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test.gml
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test.gml
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graph [
node [
id 0
label "entrez.65220"
domainIds "entrez.65220"
primaryDomainId "entrez.65220"
geneType "protein-coding"
displayName "NAD kinase"
synonyms "NAD kinase, poly(P)/ATP NAD kinase"
chromosome "1"
description "NAD kinase"
approvedSymbol "NADK"
type "Gene"
symbols "dJ283E3.1"
mapLocation "1p36.33"
graphics [
fill "#FFB6C1"
]
name "NADK"
]
node [
id 1
label "uniprot.Q6PJ22"
domainIds "uniprot.Q6PJ22"
sequence "GTRVVLRSRLKVRVVKELRGKKTAVHNGLGENGSQAAGLDMDVGKQAMQYQVLNEVVIDRGPSSYLSNVDVYLDGHLITTVQGDGVIVSTPTGSTAYAAAAGASMIHPNVPAIMITPICPHSLSFRPIVVPAGVELKIMLSPEARNTAWVSFDGRKRQEIRHGDSISITTSCYPLPSICVRDPVSDWFESLAQCLHWNVRKKQAHFEEEEEEEEEEG"
primaryDomainId "uniprot.Q6PJ22"
displayName "Q6PJ22_HUMAN"
synonyms "FLJ13052 protein {ECO:0000313, EMBL:AAH24219.1}"
taxid 9606
geneName "FLJ13052"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q6PJ22"
]
node [
id 2
label "uniprot.A0A0A0MR98"
domainIds "uniprot.A0A0A0MR98"
sequence "MGRPRVRQAWPGCCGHTGRLPAGRGYLASHMCDPAGAELIGDGMSDPTPPSNACTGHIQDPASQRLTWNKSPKSVLVIKKMRDASLLQPFKELCTHLMEENMIVYVEKKVLEDPAIASDESFGAVKKKFCTFREDYDDISNQIDFIICLGGDGTLLYASSLFQGSVPPVMAFHLGSLGFLTPFSFENFQSQVTQVIEGNAAVVLRSRLKVRVVKELRGKKTAVHNGLGENGSQAAGLDMDVGKQAMQYQVLNEVVIDRGPSSYLSNVDVYLDGHLITTVQGDGVIVSTPTGSTAYAAAAGASMIHPNVPAIMITPICPHSLSFRPIVVPAGVELKIMLSPEARNTAWVSFDGRKRQEIRHGDSISITTSCYPLPSICVRDPVSDWFESLAQCLHWNVRKKQAHFEEEEEEEEEG"
primaryDomainId "uniprot.A0A0A0MR98"
displayName "A0A0A0MR98_HUMAN"
synonyms "NAD kinase {ECO:0000313, Ensembl:ENSP00000339727}"
taxid 9606
geneName "NADK"
type "Protein"
graphics [
fill "#00FF00"
]
name "A0A0A0MR98"
]
node [
id 3
label "uniprot.A0A024R058"
domainIds "uniprot.A0A024R058"
sequence "MEMEQEKMTMNKELSPDAAAYCCSACHGDETWSYNHPIRGRAKSRSLSASPALGSTKEFRRTRSLHGPCPVTTFGPKACVLQNPQTIMHIQDPASQRLTWNKSPKSVLVIKKMRDASLLQPFKELCTHLMEENMIVYVEKKVLEDPAIASDESFGAVKKKFCTFREDYDDISNQIDFIICLGGDGTLLYASSLFQGSVPPVMAFHLGSLGFLTPFSFENFQSQVTQVIEGNAAVVLRSRLKVRVVKELRGKKTAVHNGLGENGSQAAGLDMDVGKQAMQYQVLNEVVIDRGPSSYLSNVDVYLDGHLITTVQGDGVIVSTPTGSTAYAAAAGASMIHPNVPAIMITPICPHSLSFRPIVVPAGVELKIMLSPEARNTAWVSFDGRKRQEIRHGDSISITTSCYPLPSICVRDPVSDWFESLAQCLHWNVRKKQAHFEEEEEEEEEG"
primaryDomainId "uniprot.A0A024R058"
displayName "A0A024R058_HUMAN"
synonyms "NAD kinase, isoform CRA_a {ECO:0000313, EMBL:EAW56155.1}"
taxid 9606
geneName "NADK"
type "Protein"
graphics [
fill "#00FF00"
]
name "A0A024R058"
]
node [
id 4
label "uniprot.O95544"
domainIds "uniprot.O95544"
sequence "MEMEQEKMTMNKELSPDAAAYCCSACHGDETWSYNHPIRGRAKSRSLSASPALGSTKEFRRTRSLHGPCPVTTFGPKACVLQNPQTIMHIQDPASQRLTWNKSPKSVLVIKKMRDASLLQPFKELCTHLMEENMIVYVEKKVLEDPAIASDESFGAVKKKFCTFREDYDDISNQIDFIICLGGDGTLLYASSLFQGSVPPVMAFHLGSLGFLTPFSFENFQSQVTQVIEGNAAVVLRSRLKVRVVKELRGKKTAVHNGLGENGSQAAGLDMDVGKQAMQYQVLNEVVIDRGPSSYLSNVDVYLDGHLITTVQGDGVIVSTPTGSTAYAAAAGASMIHPNVPAIMITPICPHSLSFRPIVVPAGVELKIMLSPEARNTAWVSFDGRKRQEIRHGDSISITTSCYPLPSICVRDPVSDWFESLAQCLHWNVRKKQAHFEEEEEEEEEG"
comments "CATALYTIC ACTIVITY: Reaction=ATP + NAD(+) = ADP + H(+) + NADP(+); Xref=Rhea:RHEA:18629, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57540, ChEBI:CHEBI:58349, ChEBI:CHEBI:456216; EC=2.7.1.23; Evidence={ECO:0000269|PubMed:11594753}; COFACTOR: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000269|PubMed:11594753}; BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3.3 mM for ATP {ECO:0000269|PubMed:11594753}; KM=0.54 mM for NAD {ECO:0000269|PubMed:11594753}; Vmax=6.7 umol/min/mg enzyme {ECO:0000269|PubMed:11594753}; pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:11594753}; Temperature dependence: Optimum temperature is 55 degrees Celsius. {ECO:0000269|PubMed:11594753}; INTERACTION: Q8TBB1:LNX1; NbExp=3; IntAct=EBI-743949, EBI-739832; O00560:SDCBP; NbExp=5; IntAct=EBI-743949, EBI-727004; P63104:YWHAZ; NbExp=2; IntAct=EBI-743949, EBI-347088; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=O95544-1; Sequence=Displayed; Name=2; IsoId=O95544-2; Sequence=VSP_047313, VSP_047314; Name=3; IsoId=O95544-3; Sequence=VSP_047312; TISSUE SPECIFICITY: Widely expressed but not detected in skeletal muscle. {ECO:0000269|PubMed:11594753}. SIMILARITY: Belongs to the NAD kinase family. {ECO:0000305}."
primaryDomainId "uniprot.O95544"
displayName "NADK_HUMAN"
synonyms "NAD kinase, 2.7.1.23, Poly(P)/ATP NAD kinase"
taxid 9606
geneName "NADK"
type "Protein"
graphics [
fill "#00FF00"
]
name "O95544"
]
node [
id 5
label "entrez.8450"
domainIds "entrez.8450"
primaryDomainId "entrez.8450"
geneType "protein-coding"
displayName "cullin 4B"
synonyms "cullin-4B"
chromosome "X"
description "cullin 4B"
approvedSymbol "CUL4B"
type "Gene"
symbols "CUL-4B, MRXHF2, MRXS15, MRXSC, SFM2"
mapLocation "Xq24"
graphics [
fill "#FFB6C1"
]
name "CUL4B"
]
node [
id 6
label "uniprot.K4DI93"
domainIds "uniprot.K4DI93"
sequence "MKSVCPVTSGFSSPSPSAAAAAQEVRSATDGNTSTTPPTSAKKRKLNSSSSSSSNSSNEREDFDSTSSSSSTPPLQPRDSASPSTSSFCLGVSVAASSHVPIQKKLRFEDTLEFVGFDAKMAEESSSSSSSSSPTAATSQQQQLKNKSILISSVASVHHANGLAKSSTTVSSFANSKPGSAKKLVIKNFKDKPKLPENYTDETWQKLKEAVEAIQNSTSIKYNLEELYQAVENLCSYKISANLYKQLRQICEDHIKAQIHQFREDSLDSVLFLKKIDRCWQNHCRQMIMIRSIFLFLDRTYVLQNSMLPSIWDMGLELFRAHIISDQKVQNKTIDGILLLIERERNGEAIDRSLLRSLLSMLSDLQIYQDSFEQRFLEETNRLYAAEGQKLMQEREVPEYLHHVNKRLEEEADRLITYLDQTTQKSLIATVEKQLLGEHLTAILQKGLNNLLDENRIQDLSLLYQLFSRVRGGVQVLLQQWIEYIKAFGSTIVINPEKDKTMVQELLDFKDKVDHIIDICFLKNEKFINAMKEAFETFINKRPNKPAELIAKYVDSKLRAGNKEATDEELEKMLDKIMIIFRFIYGKDVFEAFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSKLEGMFKDMELSKDIMIQFKQYMQNQNVPGNIELTVNILTMGYWPTYVPMEVHLPPEMVKLQEIFKTFYLGKHSGRKLQWQSTLGHCVLKAEFKEGKKELQVSLFQTLVLLMFNEGEEFSLEEIKQATGIEDGELRRTLQSLACGKARVLAKNPKGKDIEDGDKFICNDDFKHKLFRIKINQIQMKETVEEQASTTERVFQDRQYQIDAAIVRIMKMRKTLSHNLLVSEVYNQLKFPVKPADLKKRIESLIDRDYMERDKENPNQYNYIA"
comments "SIMILARITY: Belongs to the cullin family. {ECO:0000256|PROSITE- ProRule:PRU00330, ECO:0000256|RuleBase:RU003829, ECO:0000256|SAAS:SAAS00585788}."
primaryDomainId "uniprot.K4DI93"
displayName "K4DI93_HUMAN"
synonyms "Cullin 4B, isoform CRA_e {ECO:0000313, EMBL:EAX11880.1}, Cullin-4B {ECO:0000313, Ensembl:ENSP00000338919}"
taxid 9606
geneName "CUL4B"
type "Protein"
graphics [
fill "#00FF00"
]
name "K4DI93"
]
node [
id 7
label "mondo.0010306"
domainIds "mondo.0010306, omim.300354, orpha.85293, snomedct.719811001, umls.C1845861, umls.C1845845, doid.0060822"
primaryDomainId "mondo.0010306"
displayName "X-linked intellectual disability, Cabezas type"
synonyms "mental retardation, X-linked, with short stature, mental retardation, X-linked, syndromic 15 (Cabezas type), X-linked mental retardation with short stature, hypogonadism, and abnormal gait, X-linked mental retardation with short stature, MRSS, Cabezas syndrome, MRXSC, syndromic X-linked intellectual disability Cabezas type, MRXS15, Cabezas syndrome; syndromic X-linked mental retardation 15"
description "X-linked intellectual disability, Cabezas type is characterised by intellectual deficit, muscle wasting, short stature, a prominent lower lip, small testes, kyphosis and joint hyperextensibility. An abnormal gait, tremor, decreased fine motor coordination and impaired speech are also present. The syndrome has been described in six boys from three generations of the same family. Transmission is X-linked and the causative gene has been localised to the q24-q25 region of the X chromosome."
type "Disorder"
icd10 "Q87.8"
graphics [
fill "#FF7F00"
]
]
node [
id 8
label "uniprot.Q13620"
domainIds "uniprot.Q13620"
sequence "MMSQSSGSGDGNDDEATTSKDGGFSSPSPSAAAAAQEVRSATDGNTSTTPPTSAKKRKLNSSSSSSSNSSNEREDFDSTSSSSSTPPLQPRDSASPSTSSFCLGVSVAASSHVPIQKKLRFEDTLEFVGFDAKMAEESSSSSSSSSPTAATSQQQQLKNKSILISSVASVHHANGLAKSSTTVSSFANSKPGSAKKLVIKNFKDKPKLPENYTDETWQKLKEAVEAIQNSTSIKYNLEELYQAVENLCSYKISANLYKQLRQICEDHIKAQIHQFREDSLDSVLFLKKIDRCWQNHCRQMIMIRSIFLFLDRTYVLQNSMLPSIWDMGLELFRAHIISDQKVQNKTIDGILLLIERERNGEAIDRSLLRSLLSMLSDLQIYQDSFEQRFLEETNRLYAAEGQKLMQEREVPEYLHHVNKRLEEEADRLITYLDQTTQKSLIATVEKQLLGEHLTAILQKGLNNLLDENRIQDLSLLYQLFSRVRGGVQVLLQQWIEYIKAFGSTIVINPEKDKTMVQELLDFKDKVDHIIDICFLKNEKFINAMKEAFETFINKRPNKPAELIAKYVDSKLRAGNKEATDEELEKMLDKIMIIFRFIYGKDVFEAFYKKDLAKRLLVGKSASVDAEKSMLSKLKHECGAAFTSKLEGMFKDMELSKDIMIQFKQYMQNQNVPGNIELTVNILTMGYWPTYVPMEVHLPPEMVKLQEIFKTFYLGKHSGRKLQWQSTLGHCVLKAEFKEGKKELQVSLFQTLVLLMFNEGEEFSLEEIKQATGIEDGELRRTLQSLACGKARVLAKNPKGKDIEDGDKFICNDDFKHKLFRIKINQIQMKETVEEQASTTERVFQDRQYQIDAAIVRIMKMRKTLSHNLLVSEVYNQLKFPVKPADLKKRIESLIDRDYMERDKENPNQYNYIA"
comments "FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of- rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. With CUL4A, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:26711351}. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin- protein ligase complexes that seem to be formed of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4- associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460}. INTERACTION: Q86VP6:CAND1; NbExp=5; IntAct=EBI-456067, EBI-456077; Q16543:CDC37; NbExp=2; IntAct=EBI-456067, EBI-295634; Q16531:DDB1; NbExp=17; IntAct=EBI-456067, EBI-350322; P62877:RBX1; NbExp=5; IntAct=EBI-456067, EBI-398523; O94888:UBXN7; NbExp=3; IntAct=EBI-456067, EBI-1993627; Q9H898-2:ZMAT4; NbExp=3; IntAct=EBI-456067, EBI-11529334; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544}. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q13620-2; Sequence=Displayed; Name=2; IsoId=Q13620-1; Sequence=VSP_039085; Name=3; IsoId=Q13620-3; Sequence=VSP_039084, VSP_039086; PTM: Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. {ECO:0000269|PubMed:10597293}. DISEASE: Mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:300354]: A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span. {ECO:0000269|PubMed:17236139, ECO:0000269|PubMed:17273978, ECO:0000269|PubMed:19377476, ECO:0000269|PubMed:20002452}. Note=The disease is caused by mutations affecting the gene represented in this entry. SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE- ProRule:PRU00330}. SEQUENCE CAUTION: Sequence=AAB67315.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAK16812.1; Type=Frameshift; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q13620"
displayName "CUL4B_HUMAN"
synonyms "Cullin-4B, CUL-4B"
taxid 9606
geneName "CUL4B"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q13620"
]
node [
id 9
label "entrez.3383"
domainIds "entrez.3383"
primaryDomainId "entrez.3383"
geneType "protein-coding"
displayName "intercellular adhesion molecule 1"
synonyms "intercellular adhesion molecule 1, ICAM-1, cell surface glycoprotein P3.58, epididymis secretory sperm binding protein, intercellular adhesion molecule 1 (CD54), human rhinovirus receptor, major group rhinovirus receptor"
chromosome "19"
description "intercellular adhesion molecule 1"
approvedSymbol "ICAM1"
type "Gene"
symbols "BB2, CD54, P3.58"
mapLocation "19p13.2"
graphics [
fill "#FFB6C1"
]
name "ICAM1"
]
node [
id 10
label "uniprot.A0A384MEK5"
domainIds "uniprot.A0A384MEK5"
sequence "MAPSSPRPALPALLVLLGALFPGPGNAQTSVSPSKVILPRGGSVLVTCSTSCDQPKLLGIETPLPKKELLLPGNNRKVYELSNVQEDSQPMCYSNCPDGQSTAKTFLTVYWTPERVELAPLPSWQPVGKNLTLRCQVEGGAPRANLTVVLLRGEKELKREPAVGEPAEVTTTVLVRRDHHGANFSCRTELDLRPQGLELFENTSAPYQLQTFVLPATPPQLVSPRVLEVDTQGTVVCSLDGLFPVSEAQVHLALGDQRLNPTVTYGNDSFSAKASVSVTAEDEGTQRLTCAVILGNQSQETLQTVTIYSFPAPNVILTKPEVSEGTEVTVKCEAHPRAKVTLNGVPAQPLGPRAQLLLKATPEDNGRSFSCSATLEVAGQLIHKNQTRELRVLYGPRLDERDCPGNWTWPENSQQTPMCQAWGNPLPELKCLKDGTFPLPIGESVTVTRDLEGTYLCRARSTQGEVTRKVTVNVLSPRYEIVIITVVAAAVIMGTAGLSTYLYNRQRKIKKYRLQQAQKGTPMKPNTQATPP"
primaryDomainId "uniprot.A0A384MEK5"
displayName "A0A384MEK5_HUMAN"
synonyms "Epididymis secretory sperm binding protein {ECO:0000313, EMBL:ADO22559.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "A0A384MEK5"
]
node [
id 11
label "mondo.0021024"
domainIds "mondo.0021024, omim.611162"
type "Disorder"
primaryDomainId "mondo.0021024"
displayName "malaria, susceptibility to"
synonyms "malaria, cerebral, resistance to, malaria, cerebral, susceptibility to, malaria, Severe, resistance to, malaria, Severe, susceptibility to, malaria, resistance to, malaria, susceptibility to"
graphics [
fill "#FF7F00"
]
]
node [
id 12
label "uniprot.P05362"
domainIds "uniprot.P05362"
sequence "MAPSSPRPALPALLVLLGALFPGPGNAQTSVSPSKVILPRGGSVLVTCSTSCDQPKLLGIETPLPKKELLLPGNNRKVYELSNVQEDSQPMCYSNCPDGQSTAKTFLTVYWTPERVELAPLPSWQPVGKNLTLRCQVEGGAPRANLTVVLLRGEKELKREPAVGEPAEVTTTVLVRRDHHGANFSCRTELDLRPQGLELFENTSAPYQLQTFVLPATPPQLVSPRVLEVDTQGTVVCSLDGLFPVSEAQVHLALGDQRLNPTVTYGNDSFSAKASVSVTAEDEGTQRLTCAVILGNQSQETLQTVTIYSFPAPNVILTKPEVSEGTEVTVKCEAHPRAKVTLNGVPAQPLGPRAQLLLKATPEDNGRSFSCSATLEVAGQLIHKNQTRELRVLYGPRLDERDCPGNWTWPENSQQTPMCQAWGNPLPELKCLKDGTFPLPIGESVTVTRDLEGTYLCRARSTQGEVTRKVTVNVLSPRYEIVIITVVAAAVIMGTAGLSTYLYNRQRKIKKYRLQQAQKGTPMKPNTQATPP"
comments "FUNCTION: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. {ECO:0000269|PubMed:11173916, ECO:0000269|PubMed:17875742}. FUNCTION: (Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins. {ECO:0000269|PubMed:1968231, ECO:0000269|PubMed:2538243}. FUNCTION: (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. {ECO:0000269|PubMed:11160747, ECO:0000269|PubMed:16004874, ECO:0000269|PubMed:9539703}. FUNCTION: (Microbial infection) Upon Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T- lymphocytes and NK cell. {ECO:0000269|PubMed:11413168}. SUBUNIT: Homodimer (Probable). Interacts with MUC1 and promotes cell aggregation in epithelial cells. Interacts with ARHGEF26/SGEF. Interacts (on T cell side) with CD81, CD247 and CD9 at immunological synapses between antigen-presenting cells and T cells. {ECO:0000269|PubMed:11173916, ECO:0000269|PubMed:12526797, ECO:0000269|PubMed:15099525, ECO:0000269|PubMed:17875742, ECO:0000269|PubMed:23858057, ECO:0000305}. SUBUNIT: (Microbial infection) Interacts with major receptor group rhinovirus A-B capsid proteins (PubMed:1968231, PubMed:2538243). {ECO:0000269|PubMed:1968231, ECO:0000269|PubMed:2538243}. SUBUNIT: (Microbial infection) Interacts with Coxsackievirus A21 capsid proteins (PubMed:11160747, PubMed:16004874, PubMed:9539703). {ECO:0000269|PubMed:11160747, ECO:0000269|PubMed:16004874, ECO:0000269|PubMed:9539703}. INTERACTION: P20701:ITGAL; NbExp=2; IntAct=EBI-1035358, EBI-961214; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. PTM: Monoubiquitinated, which is promoted by MARCH9 and leads to endocytosis. POLYMORPHISM: Homozygotes with ICAM1-Kalifi Met-56 seem to have an increased risk for cerebral malaria [MIM:611162]. {ECO:0000269|PubMed:9259284}. SIMILARITY: Belongs to the immunoglobulin superfamily. ICAM family. {ECO:0000305}. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ICAM1ID40909ch19p13.html"; WEB RESOURCE: Name=Wikipedia; Note=Intercellular adhesion molecule entry; URL="https://en.wikipedia.org/wiki/Intercellular_adhesion_molecule"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/icam1/"; WEB RESOURCE: Name=Virus Particle ExploreR db; Note=Icosahedral capsid structure; URL="http://viperdb.scripps.edu/info_page.php?VDB=1z7z"; WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; Note=ICAM-1; URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_261";"
primaryDomainId "uniprot.P05362"
displayName "ICAM1_HUMAN"
synonyms "Intercellular adhesion molecule 1, ICAM-1, Major group rhinovirus receptor, CD54"
taxid 9606
geneName "ICAM1"
type "Protein"
graphics [
fill "#00FF00"
]
name "P05362"
]
node [
id 13
label "drugbank.DB08818"
primaryDataset "DrugBank"
iupacName "(2S,3S,4R,5R,6R)-3-{[(2S,3R,5S,6R)-4-{[(2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy}-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-6-{[(2R,3R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy}-4,5-dihydroxyoxane-2-carboxylic acid"
inchi "InChI=1S/C28H44N2O23/c1-5(33)29-9-18(11(35)7(3-31)47-25(9)46)49-28-17(41)15(39)20(22(53-28)24(44)45)51-26-10(30-6(2)34)19(12(36)8(4-32)48-26)50-27-16(40)13(37)14(38)21(52-27)23(42)43/h7-22,25-28,31-32,35-41,46H,3-4H2,1-2H3,(H,29,33)(H,30,34)(H,42,43)(H,44,45)/t7-,8-,9-,10-,11-,12-,13+,14+,15-,16-,17-,18?,19?,20+,21+,22+,25-,26+,27-,28-/m1/s1"
primaryDomainId "drugbank.DB08818"
smiles "CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@@H]1O[C@@H]([C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)C(O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)C(O)=O)[C@H]2NC(C)=O)[C@H](O)[C@H]1O)C(O)=O"
synonyms "Hyaluronan, Hyaluronate"
groups "approved, vet_approved"
description "Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi, and can be very large, with its molecular weight often reaching the millions. One of the chief components of the extracellular matrix, hyaluronic acid contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors."
type "SmallMoleculeDrug"
casNumber "9004-61-9"
domainIds "drugbank.DB08818"
allDatasets "DrugBank"
molecularFormula "C28H44N2O23"
name "Hyaluronic acid"
categories "Adjuvants, Immunologic, Carbohydrates, Cicatrizants, Compounds used in a research, industrial, or household setting, Dermatologicals, Glycosaminoglycans, Immunologic Factors, Lubricants, Musculo-Skeletal System, Nasal Preparations, Ophthalmologicals, Polysaccharides, Preparations for Treatment of Wounds and Ulcers, Protective Agents, Sensory Organs, Surgical Aids, Viscoelastic Substances, Viscosupplements"
indication "Used to treat knee pain in patients with joint inflammation (osteoarthritis). It is usually used in patients who have not responded to other treatments such as acetaminophen, exercise, or physical therapy. Hyaluronic acid may also be used in plastic surgery to reduce wrinkles on the face or as a filler in other parts of the body. May be used in ophthalmology to assist in the extraction of cataracts, the implantation of intraocular lenses, corneal transplants, glaucoma filtration, retinal attachment and in the treatment of dry eyes. Finally, hyaluronic acid is also used to coat the bladder lining in treating interstitial cystitis."
graphics [
fill "#34A4EB"
]
]
node [
id 14
label "drugbank.DB12598"
primaryDataset "DrugBank"
iupacName "6-carbamimidoylnaphthalen-2-yl 4-carbamimidamidobenzoate"
inchi "InChI=1S/C19H17N5O2/c20-17(21)14-2-1-13-10-16(8-5-12(13)9-14)26-18(25)11-3-6-15(7-4-11)24-19(22)23/h1-10H,(H3,20,21)(H4,22,23,24)"
primaryDomainId "drugbank.DB12598"
smiles "NC(=N)NC1=CC=C(C=C1)C(=O)OC1=CC=C2C=C(C=CC2=C1)C(N)=N"
synonyms "Nafamostatum, p-Guanidinobenzoic acid ester with 6-hydroxy-2-naphthamidine"
groups "investigational"
description "Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury."
type "SmallMoleculeDrug"
casNumber "81525-10-2"
domainIds "drugbank.DB12598"
allDatasets "DrugBank"
molecularFormula "C19H17N5O2"
name "Nafamostat"
categories "Amidines, Analgesics, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Anticoagulants, Antirheumatic Agents, Central Nervous System Agents, Complement Inactivating Agents, Enzyme Inhibitors, Fibrinolysin, antagonists & inhibitors, Hematologic Agents, Immunologic Factors, Kallikreins, antagonists & inhibitors, OCT1 substrates, OCT2 Substrates, OCT2 substrates with narrow therapeutic index, Peripheral Nervous System Agents, Protease Inhibitors, Sensory System Agents, Serine Proteinase Inhibitors, Trypsin Inhibitors"
indication "Used as an anticoagulant in patients with disseminative blood vessel coagulation, hemorrhagic lesions, and hemorrhagic tendencies. It prevents blood clot formation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation."
graphics [
fill "#34A4EB"
]
]
node [
id 15
label "drugbank.DB00108"
domainIds "drugbank.DB00108, drugbank.BTD00083, drugbank.BIOD00083"
primaryDataset "DrugBank"
allDatasets "DrugBank"
primaryDomainId "drugbank.DB00108"
synonyms "Anti-alpha4 integrin, Anti-VLA4"
name "Natalizumab"
groups "approved, investigational"
description "Humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML). It was returned to market July, 2006."
categories "Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic and Immunomodulating Agents, Blood Proteins, Globulins, Immunoglobulins, Immunologic Factors, Immunomodulatory Agents, Immunoproteins, Immunosuppressive Agents, Integrin Receptor Antagonist, Integrin Receptor Antagonists, Proteins, Selective Immunosuppressants, Serum Globulins"
indication "For treatment of multiple sclerosis."
type "BiotechDrug"
casNumber "189261-10-7"
graphics [
fill "#34A4EB"
]
]
node [
id 16
label "entrez.5711"
domainIds "entrez.5711"
primaryDomainId "entrez.5711"
geneType "protein-coding"
displayName "proteasome 26S subunit, non-ATPase 5"
synonyms "26S proteasome non-ATPase regulatory subunit 5, 26S protease subunit S5 basic, 26S proteasome subunit S5B, proteasome (prosome, macropain) 26S subunit, non-ATPase, 5"
chromosome "9"
description "proteasome 26S subunit, non-ATPase 5"
approvedSymbol "PSMD5"
type "Gene"
symbols "S5B"
mapLocation "9q33.2"
graphics [
fill "#FFB6C1"
]
name "PSMD5"
]
node [
id 17
label "uniprot.Q16401"
domainIds "uniprot.Q16401"
sequence "MAAQALALLREVARLEAPLEELRALHSVLQAVPLNELRQQAAELRLGPLFSLLNENHREKTTLCVSILERLLQAMEPVHVARNLRVDLQRGLIHPDDSVKILTLSQIGRIVENSDAVTEILNNAELLKQIVYCIGGENLSVAKAAIKSLSRISLTQAGLEALFESNLLDDLKSVMKTNDIVRYRVYELIIEISSVSPESLNYCTTSGLVTQLLRELTGEDVLVRATCIEMVTSLAYTHHGRQYLAQEGVIDQISNIIVGADSDPFSSFYLPGFVKFFGNLAVMDSPQQICERYPIFVEKVFEMIESQDPTMIGVAVDTVGILGSNVEGKQVLQKTGTRFERLLMRIGHQSKNAPVELKIRCLDAISSLLYLPPEQQTDDLLRMTESWFSSLSRDPLELFRGISSQPFPELHCAALKVFTAIANQPWAQKLMFNSPGFVEYVVDRSVEHDKASKDAKYELVKALANSKTIAEIFGNPNYLRLRTYLSEGPYYVKPVSTTAVEGAE"
comments "FUNCTION: Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5. {ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}. SUBUNIT: Interacts with PSMC1, PSMC2, PSMD1 and PSMD6. Part of transient complex containing PSMD5, PSMC2, PSMC1 and PSMD2 formed during the assembly of the 26S proteasome. {ECO:0000269|PubMed:19217412, ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}. INTERACTION: P62191:PSMC1; NbExp=10; IntAct=EBI-752143, EBI-357598; P35998:PSMC2; NbExp=21; IntAct=EBI-752143, EBI-359710; Q12800:TFCP2; NbExp=3; IntAct=EBI-752143, EBI-717422; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q16401-1; Sequence=Displayed; Name=2; IsoId=Q16401-2; Sequence=VSP_045176; DOMAIN: Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins. SIMILARITY: Belongs to the proteasome subunit S5B/HSM3 family. {ECO:0000305}. CAUTION: Was initially identified as a genuine component of the 26S proteasome. {ECO:0000305}."
primaryDomainId "uniprot.Q16401"
displayName "PSMD5_HUMAN"
synonyms "26S proteasome non-ATPase regulatory subunit 5, 26S protease subunit S5 basic, 26S proteasome subunit S5B"
taxid 9606
geneName "PSMD5"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q16401"
]
node [
id 18
label "entrez.144100"
domainIds "entrez.144100"
primaryDomainId "entrez.144100"
geneType "protein-coding"
displayName "pleckstrin homology domain containing A7"
synonyms "pleckstrin homology domain-containing family A member 7, PH domain-containing family A member 7, pleckstrin homology domain containing, family A member 2, pleckstrin homology domain containing, family A member 7, pleckstrin homology domain-containing family A member 6"
chromosome "11"
description "pleckstrin homology domain containing A7"
approvedSymbol "PLEKHA7"
type "Gene"
symbols "-"
mapLocation "11p15.2-p15.1"
graphics [
fill "#FFB6C1"
]
name "PLEKHA7"
]
node [
id 19
label "uniprot.E9PKC0"
domainIds "uniprot.E9PKC0"
sequence "MAAATVGRDTLPEHWSYGVCRDGRVFFINDQLRCTTWLHPRTGEPVNSGHMIRSDLPRGWEEGFTEEGASYFIDHNQQTTAFRHPVTGQFSPENSEFILQEEPNPHMSKQDRNQRPSSMVSETSTAGTASTLEAKPGPKIIKSSSKVHSFGKRDQAIRRNPNVPVVVRGWLHKQDSSGMRLWKRRWFVLADYCLFYYKDSREEAVLGSIPLPSYVISPVAPEDRISRKYSFKAVHTGMRALIYNSSTAGSQAEQSGMRTYYFSADTQEDMNAWVRAMNQAAQVLSRSSLKRDMEKVERQAVPQANHTESCHECGRVGPGHTRDCPHRGHDDIVNFERQEQEGEQYRSQRDPLEGKRDRSKARSPYSPAEEDALFMDLPTGPRGQQAQPQRAEKNGMLPASYGPGEQNGTGGYQRAFPPRTNPEKHSQRKSNLAQVEHWARAQKGDSRSLPLDQTLPRQGPGQSLSFPENYQTLPKSTRHPSGGSSPPPRNLPSDYKYAQDRASHLKMSSEERRAHRDGTVWQLYEWQQRQQFRHGSPTAPICLGSPEFTDQGRSRSMLEVPRSISVPPSPSDIPPPGPPRVFPPRRPHTPAERVTVKPPDQRRSVDISLGDSPRRARGHAVKNSSHVDRRSMPSMGYMTHTVSAPSLHGKSADDTYLQLKKDLEYLDLKMTGRDLLKDRSLKPVKIAESDTDVKLSIFCEQDRVLQDLEDKIRALKENKDQLESVLEVLHRQMEQYRDQPQHLEKIAYQQKLLQEDLVHIRAELSRESTEMENAWNEYLKLENDVEQLKQTLQEQHRRAFFFQEKSQIQKDLWRIEDVTAGLSANKENFRILVESVKNPERKTVPLFPHPPVPSLSTSESKPPPQPSPPTSPVRTPLEVRLFPQLQTYVPYRPHPPQLRKVTSPLQSPTKAKPKVEDEAPPRPPLPELYSPEDQPPAVPPLPREATIIRHTSVRGLKRQSDERKRDRELGQCVNGDSRVELRSYVSEPELATLSGDMAQPSLGLVGPESRYQTLPGRGLSGSTSRLQQSSTIAPYVTLRRGLNAESSKATFPRPKSALERLYSGDHQRGKMSAEEQLERMKRHQKALVRERKRTLGQGERTGLPSSRYLSRPLPGDLGSWKREQDFDLQLLERVVQGEKKDKEENGWLKVQAMPVTELDLEPQDYDLDISRELSKPEKVSIPERYVELDPEEPPSLEELQARYRKAEKIRNILARSSMCNLQPTSGQDQNSVADLDLQLQEQERIINISYALASEASQRSKQVAAQAVTDP"
primaryDomainId "uniprot.E9PKC0"
displayName "E9PKC0_HUMAN"
synonyms "Pleckstrin homology domain-containing family A member 7 {ECO:0000313, Ensembl:ENSP00000435389}"
taxid 9606
geneName "PLEKHA7"
type "Protein"
graphics [
fill "#00FF00"
]
name "E9PKC0"
]
node [
id 20
label "uniprot.Q6IQ23"
domainIds "uniprot.Q6IQ23"
sequence "MAAATVGRDTLPEHWSYGVCRDGRVFFINDQLRCTTWLHPRTGEPVNSGHMIRSDLPRGWEEGFTEEGASYFIDHNQQTTAFRHPVTGQFSPENSEFILQEEPNPHMSKQDRNQRPSSMVSETSTAGTASTLEAKPGPKIIKSSSKVHSFGKRDQAIRRNPNVPVVVRGWLHKQDSSGMRLWKRRWFVLADYCLFYYKDSREEAVLGSIPLPSYVISPVAPEDRISRKYSFKAVHTGMRALIYNSSTAGSQAEQSGMRTYYFSADTQEDMNAWVRAMNQAAQVLSRSSLKRDMEKVERQAVPQANHTESCHECGRVGPGHTRDCPHRGHDDIVNFERQEQEGEQYRSQRDPLEGKRDRSKARSPYSPAEEDALFMDLPTGPRGQQAQPQRAEKNGMLPASYGPGEQNGTGGYQRAFPPRTNPEKHSQRKSNLAQVEHWARAQKGDSRSLPLDQTLPRQGPGQSLSFPENYQTLPKSTRHPSGGSSPPPRNLPSDYKYAQDRASHLKMSSEERRAHRDGTVWQLYEWQQRQQFRHGSPTAPICLGSPEFTDQGRSRSMLEVPRSISVPPSPSDIPPPGPPRVFPPRRPHTPAERVTVKPPDQRRSVDISLGDSPRRARGHAVKNSSHVDRRSMPSMGYMTHTVSAPSLHGKSADDTYLQLKKDLEYLDLKMTGRDLLKDRSLKPVKIAESDTDVKLSIFCEQDRVLQDLEDKIRALKENKDQLESVLEVLHRQMEQYRDQPQHLEKIAYQQKLLQEDLVHIRAELSRESTEMENAWNEYLKLENDVEQLKQTLQEQHRRAFFFQEKSQIQKDLWRIEDVTAGLSANKENFRILVESVKNPERKTVPLFPHPPVPSLSTSESKPPPQPSPPTSPVRTPLEVRLFPQLQTYVPYRPHPPQLRKVTSPLQSPTKAKPKVEDEAPPRPPLPELYSPEDQPPAVPPLPREATIIRHTSVRGLKRQSDERKRDRELGQCVNGDSRVELRSYVSEPELATLSGDMAQPSLGLVGPESRYQTLPGRGLSGSTSRLQQSSTIAPYVTLRRGLNAESSKATFPRPKSALERLYSGDHQRGKMSAEEQLERMKRHQKALVRERKRTLGQGERTGLPSSRYLSRPLPGDLGSVC"
comments "FUNCTION: Required for zonula adherens biogenesis and maintenance (PubMed:19041755). Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site (PubMed:19041755). Mediates docking of ADAM10 to zonula adherens through a PDZD11- dependent interaction with the ADAM10-binding protein TSPAN33 (PubMed:30463011). {ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:30463011}. SUBUNIT: Interacts with CAMSAP3 and CTNND1 (PubMed:19041755). Interacts (via WW domains) with TSPAN33 (via cytoplasmic domain) and with PDZD11; the interaction with TSPAN33 is dependent on PDZD11 being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula adherens through interaction of TSPAN33 with ADAM10 (PubMed:30463011). {ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:30463011}. INTERACTION: Q9UKV8:AGO2; NbExp=7; IntAct=EBI-2125301, EBI-528269; O60716:CTNND1; NbExp=3; IntAct=EBI-2125301, EBI-701927; SUBCELLULAR LOCATION: Cell junction, adherens junction {ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:30463011}. Cytoplasm {ECO:0000269|PubMed:19041755}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:19041755}. Note=Localizes to zonula adherens, recruited via its interaction with CTNND1. {ECO:0000269|PubMed:19041755}. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q6IQ23-1; Sequence=Displayed; Name=2; IsoId=Q6IQ23-2; Sequence=VSP_025592; Name=3; IsoId=Q6IQ23-3; Sequence=VSP_039543, VSP_025592; SEQUENCE CAUTION: Sequence=AAH33239.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG62985.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q6IQ23"
displayName "PKHA7_HUMAN"
synonyms "Pleckstrin homology domain-containing family A member 7, PH domain-containing family A member 7"
taxid 9606
geneName "PLEKHA7"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q6IQ23"
]
node [
id 21
label "entrez.64599"
domainIds "entrez.64599"
primaryDomainId "entrez.64599"
geneType "protein-coding"
displayName "GRB10 interacting GYF protein 1"
synonyms "GRB10-interacting GYF protein 1, PERQ amino acid-rich with GYF domain-containing protein 1, postmeiotic segregation increased 2-like 12"
chromosome "7"
description "GRB10 interacting GYF protein 1"
approvedSymbol "GIGYF1"
type "Gene"
symbols "GYF1, PERQ1"
mapLocation "7q22.1"
graphics [
fill "#FFB6C1"
]
name "GIGYF1"
]
node [
id 22
label "uniprot.O75420"
domainIds "uniprot.O75420"
sequence "MAAETLNFGPEWLRALSGGGSVASPPPSPAMPKYKLADYRYGREEMLALYVKENKVPEELQDKEFAAVLQDEPLQPLALEPLTEEEQRNFSLSVNSVAVLRLMGKGAGPPLAGTSRGRGSTRSRGRGRGDSCFYQRSIEEGDGAFGRSPREIQRSQSWDDRGERRFEKSARRDGARCGFEEGGAGPRKEHARSDSENWRSLREEQEEEEEGSWRLGAGPRRDGDRWRSASPDGGPRSAGWREHGERRRKFEFDLRGDRGGCGEEEGRGGGGSSHLRRCRAPEGFEEDKDGLPEWCLDDEDEEMGTFDASGAFLPLKKGPKEPIPEEQELDFQGLEEEEEPSEGLEEEGPEAGGKELTPLPPQEEKSSSPSPLPTLGPLWGTNGDGDETAEKEPPAAEDDIRGIQLSPGVGSSAGPPGDLEDDEGLKHLQQEAEKLVASLQDSSLEEEQFTAAMQTQGLRHSAAATALPLSHGAARKWFYKDPQGEIQGPFTTQEMAEWFQAGYFSMSLLVKRGCDEGFQPLGEVIKMWGRVPFAPGPSPPPLLGNMDQERLKKQQELAAAALYQQLQHQQFLQLVSSRQLPQCALREKAALGDLTPPPPPPPQQQQQQLTAFLQQLQALKPPRGGDQNLLPTMSRSLSVPDSGRLWDVHTSASSQSGGEASLWDIPINSSTQGPILEQLQLQHKFQERREVELRAKREEEERKRREEKRRQQQQEEQKRRQEEEELFRRKHVRQQELLLKLLQQQQAVPVPPAPSSPPPLWAGLAKQGLSMKTLLELQLEGERQLHKQPPPREPARAQAPNHRVQLGGLGTAPLNQWVSEAGPLWGGPDKSGGGSSGLGLWEDTPKSGGSLVRGLGLKNSRSSPSLSDSYSHLSGRPIRKKTEEEEKLLKLLQGIPRPQDGFTQWCEQMLHTLSATGSLDVPMAVAILKEVESPYDVHDYIRSCLGDTLEAKEFAKQFLERRAKQKASQQRQQQQEAWLSSASLQTAFQANHSTKLGPGEGSKAKRRALMLHSDPSILGYSLHGSSGEIESVDDY"
comments "FUNCTION: May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:12771153}. SUBUNIT: Interacts with GRB10. This transient binding is increased under IGF1 stimulation and leads to recruitment of GIGYF1/GRB10 complex to IGF1 receptor (By similarity). {ECO:0000250}. DOMAIN: The GYF domain interacts with GRB10. {ECO:0000250}. SIMILARITY: Belongs to the GIGYF family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=AAC78792.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAL55738.1; Type=Frameshift; Evidence={ECO:0000305};"
primaryDomainId "uniprot.O75420"
displayName "GGYF1_HUMAN"
synonyms "GRB10-interacting GYF protein 1, PERQ amino acid-rich with GYF domain-containing protein 1"
taxid 9606
geneName "GIGYF1"
type "Protein"
graphics [
fill "#00FF00"
]
name "O75420"
]
node [
id 23
label "entrez.1499"
domainIds "entrez.1499"
primaryDomainId "entrez.1499"
geneType "protein-coding"
displayName "catenin beta 1"
synonyms "catenin beta-1, catenin (cadherin-associated protein), beta 1, 88kDa"
chromosome "3"
description "catenin beta 1"
approvedSymbol "CTNNB1"
type "Gene"
symbols "CTNNB, EVR7, MRD19, NEDSDV, armadillo"
mapLocation "3p22.1"
graphics [
fill "#FFB6C1"
]
name "CTNNB1"
]
node [
id 24
label "uniprot.A0A024R2Q3"
domainIds "uniprot.A0A024R2Q3"
sequence "MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL"
primaryDomainId "uniprot.A0A024R2Q3"
displayName "A0A024R2Q3_HUMAN"
synonyms "Catenin (Cadherin-associated protein), beta 1, 88kDa, isoform CRA_a {ECO:0000313, EMBL:EAW64628.1}"
taxid 9606
geneName "CTNNB1"
type "Protein"
graphics [
fill "#00FF00"
]
name "A0A024R2Q3"
]
node [
id 25
label "mondo.0033123"
domainIds "mondo.0033123, omim.617572, doid.0080264, umls.CN321863"
type "Disorder"
primaryDomainId "mondo.0033123"
displayName "exudative vitreoretinopathy 7"
graphics [
fill "#FF7F00"
]
]
node [
id 26
label "mondo.0014035"
domainIds "mondo.0014035, orpha.404473, omim.615075, doid.0070049, umls.C3554449"
primaryDomainId "mondo.0014035"
displayName "severe intellectual disability-progressive spastic diplegia syndrome"
synonyms "MRD19, mental retardation, autosomal dominant type 19, autosomal dominant mental retardation 19"
description "Severe intellectual disability-progressive spastic diplegia syndrome is a rare condition that has been described in a few people with severe intellectual disability . Other signs and symptoms include progressive microcephaly (very small head); ataxia (lack of coordination); spasticity ; and/or skin, hair and mild facial anomalies. It is caused by changes ( mutations ) in the CTNNB1 gene and it is inherited in an autosomal dominant fashion. Treatment is based on the signs and symptoms present in each person."
type "Disorder"
icd10 "G11.4"
graphics [
fill "#FF7F00"
]
]
node [
id 27
label "mondo.0007564"
domainIds "mondo.0007564, umls.C0206711, umls.C0853031, ncit.C7368, mesh.D018296, snomedct.274901004, omim.132600, orpha.91414, meddra.10035040, doid.5374"
primaryDomainId "mondo.0007564"
displayName "pilomatrixoma"
synonyms "calcifying Epitherlioma of Malherbe, pilomatrixoma, benign, pilomatrixoma, benign pilomatrixoma, pilomatricoma, epithelioma calcificans of Malherbe, benign hair follicle neoplasm, benign pilomatricoma"
description "Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome (see these terms)."
type "Disorder"
icd10 "C44.6, C44.3"
graphics [
fill "#FF7F00"
]
]
node [
id 28
label "mondo.0007256"
domainIds "mondo.0007256, omim.114550, doid.684, doid.686, mesh.D006528, ncit.C3099, meddra.10049010, orpha.88673"
primaryDomainId "mondo.0007256"
displayName "hepatocellular carcinoma"
synonyms "HCC, liver carcinoma, carcinoma, hepatocellular, malignant, liver and intrahepatic bile duct carcinoma, hepatocellular carcinoma, carcinoma of the liver cells, carcinoma of liver cells, hepatocellular adenocarcinoma, primary carcinoma of the liver cells, carcinoma of liver, hepatoma, hepatocellular cancer, primary carcinoma of liver cells, liver cell carcinoma, liver cell cancer (hepatocellular carcinoma), cancer, hepatocellular"
description "A malignant tumor that arises from hepatocytes. Hepatocellular carcinoma is relatively rare in the United States but very common in all African countries south of the Sahara and in Southeast Asia. Most cases are seen in patients over the age of 50 years, but this tumor can also occur in younger individuals and even in children. Hepatocellular carcinoma is more common in males than females and is associated with hepatitis B, hepatitis C, chronic alcohol abuse and cirrhosis. Serum elevation of alpha-fetoprotein occurs in a large percentage of patients with hepatocellular carcinoma. Grossly, hepatocellular carcinoma may present as a single mass, as multiple nodules, or as diffuse liver involvement. Microscopically, there is a wide range of differentiation from tumor to tumor (well differentiated to poorly differentiated tumors). Hepatocellular carcinomas quickly metastasize to regional lymph nodes and lung. The overall median survival of untreated liver cell carcinoma is about 4 months. The most effective treatment of hepatocellular carcinoma is complete resection of the tumor. Lately, an increasing number of tumors have been treated with liver transplantation."
type "Disorder"
icd10 "C22.0"
graphics [
fill "#FF7F00"
]
]
node [
id 29
label "mondo.0007959"
domainIds "mondo.0007959, ncit.C3222, umls.C1334410, omim.155255, umls.C0025149, snomedct.443333004, orpha.616, mesh.D008527, doid.0050902, doid.0060104, meddra.10027107"
primaryDomainId "mondo.0007959"
displayName "medulloblastoma"
synonyms "medulloblastoma, medulloblastoma, malignant, cerebellum embryonal neoplasm, brain medulloblastoma, Medulloblastomas"
description "A malignant, invasive embryonal neoplasm arising from the cerebellum. It occurs predominantly in children and has the tendency to metastasize via the cerebrospinal fluid pathways. Signs and symptoms include truncal ataxia, disturbed gait, lethargy, headache, and vomiting. There are four histologic variants: classic medulloblastoma, large cell/anaplastic medulloblastoma, desmoplastic/nodular medulloblastoma, and medulloblastoma with extensive nodularity."
type "Disorder"
icd10 "C71.6"
graphics [
fill "#FF7F00"
]
]
node [
id 30
label "mondo.0023113"
domainIds "mondo.0023113, omim.114500, umls.CN029768"
description "Familial colon cancer is a cluster of colon cancer within a family. Most cases ofcolon cancer occur sporadically in people with little to no family history of the condition. Approximately 3-5% of colon cancer is considered 'hereditary' and is thought to be caused by an inherited predisposition tocolon cancer that is passed down through a family in an autosomal dominant or autosomal recessive manner. In some of these families, the underlying genetic cause is not known; however, many of these cases are caused by changes ( mutations ) in the APC , MYH , MLH1 , MSH2 , MSH6 , PMS2 , EPCAM , PTEN , STK11 , SMAD4 , BMPR1A , NTHL1 , POLE , and POLD1 genes (which are associated with hereditary cancer syndromes). An additional 10-30% of people diagnosed with colon cancer have a significant family history of the condition but have no identifiable mutation in a gene known to cause a hereditary predisposition to colon cancer. These clusters of colon cancer are likely due to a combination of gene(s) and other shared factors such as environment and lifestyle. High-risk cancer screening and other preventative measures such as prophylactic surgeries are typically recommended in people who have an increased risk for colon cancer based on their personal and/or family histories."
type "Disorder"
primaryDomainId "mondo.0023113"
displayName "familial colorectal cancer"
synonyms "hereditary colorectal cancer"
graphics [
fill "#FF7F00"
]
]
node [
id 31
label "mondo.0008170"
domainIds "mondo.0008170, ncit.C7431, mesh.D010051, doid.2394, snomedct.363443007, omim.167000, orpha.213500"
primaryDomainId "mondo.0008170"
displayName "ovarian cancer"
synonyms "malignant neoplasm of the ovary, ovarian cancer, ovarian malignant tumor, malignant tumour of ovary, malignant tumor of the ovary, cancer of ovary, malignant ovarian neoplasm, malignant tumor of ovary, cancer of the ovary, ovary cancer, malignant ovarian tumor, malignant neoplasm of ovary, malignant ovary neoplasm"
description "A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas."
type "Disorder"
icd10 "C56"
graphics [
fill "#FF7F00"
]
]
node [
id 32
label "uniprot.P35222"
domainIds "uniprot.P35222"
sequence "MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL"
comments "FUNCTION: Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2- mediated sumoylation of PML (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22647378, PubMed:22699938, PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938}. SUBUNIT: Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E- cadherin:catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with SCRIB. Interacts with RAPGEF2. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain). Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of CDK5. Interacts with PTK6. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Interacts with FERMT2. Identified in a complex with TCF7L2/TCF4 and FERMT2. Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220 (PubMed:25266658). Interacts with CTNND2 (PubMed:25807484). Interacts (via the C-terminal region) with CBY1 (PubMed:12712206, PubMed:16424001). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Interacts with DLG5 (By similarity). Interacts with FAM53B; promoting translocation to the nucleus (PubMed:25183871). Interacts with TMEM170B (PubMed:29367600). Interacts with AHI1 (PubMed:21623382). Interacts with GID8 (PubMed:28829046). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha- catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2 (PubMed:19433865). Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1 (PubMed:29374064). Interacts with AMFR (By similarity). Interacts with LMBR1L (PubMed:31073040). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:10966653, ECO:0000269|PubMed:11279024, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11590244, ECO:0000269|PubMed:11713475, ECO:0000269|PubMed:11713476, ECO:0000269|PubMed:11751639, ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12297051, ECO:0000269|PubMed:12370829, ECO:0000269|PubMed:12408824, ECO:0000269|PubMed:12420223, ECO:0000269|PubMed:12501215, ECO:0000269|PubMed:12712206, ECO:0000269|PubMed:12830000, ECO:0000269|PubMed:14595118, ECO:0000269|PubMed:16424001, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17047063, ECO:0000269|PubMed:17052462, ECO:0000269|PubMed:17289029, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:18819930, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:19996314, ECO:0000269|PubMed:20026641, ECO:0000269|PubMed:20164195, ECO:0000269|PubMed:21132015, ECO:0000269|PubMed:21247902, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21623382, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25183871, ECO:0000269|PubMed:25266658, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:28051089, ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:29367600, ECO:0000269|PubMed:29374064, ECO:0000269|PubMed:29432739, ECO:0000269|PubMed:7982500, ECO:0000305|PubMed:31073040}. SUBUNIT: (Microbial infection) Interacts with herpes virus 8 protein vPK; this interaction inhibits the Wnt signaling pathway. {ECO:0000269|PubMed:29432739}. INTERACTION: P00519:ABL1; NbExp=2; IntAct=EBI-491549, EBI-375543; O43707:ACTN4; NbExp=7; IntAct=EBI-491549, EBI-351526; Q5JTC6:AMER1; NbExp=9; IntAct=EBI-491549, EBI-6169747; P25054:APC; NbExp=19; IntAct=EBI-491549, EBI-727707; P10275:AR; NbExp=11; IntAct=EBI-491549, EBI-608057; O15169:AXIN1; NbExp=44; IntAct=EBI-491549, EBI-710484; O35625:Axin1 (xeno); NbExp=4; IntAct=EBI-491549, EBI-2365912; Q9YGY0:axin1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-1037449; Q9Y2T1:AXIN2; NbExp=2; IntAct=EBI-491549, EBI-4400025; O00512:BCL9; NbExp=2; IntAct=EBI-491549, EBI-533127; A1Z199:BCR/ABL fusion; NbExp=2; IntAct=EBI-491549, EBI-7286259; Q9Y297:BTRC; NbExp=8; IntAct=EBI-491549, EBI-307461; P33724:CAV1 (xeno); NbExp=5; IntAct=EBI-491549, EBI-79998; Q6P1J9:CDC73; NbExp=10; IntAct=EBI-491549, EBI-930143; P12830:CDH1; NbExp=14; IntAct=EBI-491549, EBI-727477; P19022:CDH2; NbExp=8; IntAct=EBI-491549, EBI-2256711; P33151:CDH5; NbExp=7; IntAct=EBI-491549, EBI-2903122; Q92793:CREBBP; NbExp=2; IntAct=EBI-491549, EBI-81215; P35221:CTNNA1; NbExp=3; IntAct=EBI-491549, EBI-701918; P26231:Ctnna1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-647895; Q9UI47:CTNNA3; NbExp=2; IntAct=EBI-491549, EBI-3937546; Q9NSA3:CTNNBIP1; NbExp=12; IntAct=EBI-491549, EBI-747082; Q9NYF0:DACT1; NbExp=3; IntAct=EBI-491549, EBI-3951744; P26358:DNMT1; NbExp=8; IntAct=EBI-491549, EBI-719459; P18146:EGR1; NbExp=7; IntAct=EBI-491549, EBI-2834611; P50402:EMD; NbExp=3; IntAct=EBI-491549, EBI-489887; P29317:EPHA2; NbExp=2; IntAct=EBI-491549, EBI-702104; Q9UKB1:FBXW11; NbExp=4; IntAct=EBI-491549, EBI-355189; Q96AC1:FERMT2; NbExp=13; IntAct=EBI-491549, EBI-4399465; P11362:FGFR1; NbExp=2; IntAct=EBI-491549, EBI-1028277; P49789:FHIT; NbExp=4; IntAct=EBI-491549, EBI-741760; P17948:FLT1; NbExp=2; IntAct=EBI-491549, EBI-1026718; Q08050:FOXM1; NbExp=16; IntAct=EBI-491549, EBI-866480; Q9BZE0:GLIS2; NbExp=6; IntAct=EBI-491549, EBI-7251368; P49841:GSK3B; NbExp=19; IntAct=EBI-491549, EBI-373586; Q9UBN7:HDAC6; NbExp=4; IntAct=EBI-491549, EBI-301697; Q16665:HIF1A; NbExp=4; IntAct=EBI-491549, EBI-447269; P42858:HTT; NbExp=5; IntAct=EBI-491549, EBI-466029; P08069:IGF1R; NbExp=3; IntAct=EBI-491549, EBI-475981; P18012:ipaC (xeno); NbExp=4; IntAct=EBI-491549, EBI-491541; P46940:IQGAP1; NbExp=3; IntAct=EBI-491549, EBI-297509; O75564:JRK; NbExp=3; IntAct=EBI-491549, EBI-8607681; P14923:JUP; NbExp=3; IntAct=EBI-491549, EBI-702484; Q14678:KANK1; NbExp=2; IntAct=EBI-491549, EBI-2556221; Q2LD37:KIAA1109; NbExp=2; IntAct=EBI-491549, EBI-2683809; Q9UJU2:LEF1; NbExp=10; IntAct=EBI-491549, EBI-926131; P27782:Lef1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-984464; Q8WVC0:LEO1; NbExp=2; IntAct=EBI-491549, EBI-932432; Q9JHQ5:Lztfl1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-6142879; Q9GZQ8:MAP1LC3B; NbExp=5; IntAct=EBI-491549, EBI-373144; P55197:MLLT10; NbExp=4; IntAct=EBI-491549, EBI-1104952; Q92597:NDRG1; NbExp=3; IntAct=EBI-491549, EBI-716486; P19838:NFKB1; NbExp=3; IntAct=EBI-491549, EBI-300010; P29474:NOS3; NbExp=4; IntAct=EBI-491549, EBI-1391623; O00482-1:NR5A2; NbExp=5; IntAct=EBI-491549, EBI-15960777; P49757:NUMB; NbExp=2; IntAct=EBI-491549, EBI-915016; P49757-3:NUMB; NbExp=3; IntAct=EBI-491549, EBI-10692196; Q8TEW0:PARD3; NbExp=2; IntAct=EBI-491549, EBI-81968; P16284:PECAM1; NbExp=3; IntAct=EBI-491549, EBI-716404; Q99697:PITX2; NbExp=2; IntAct=EBI-491549, EBI-1175211; P14618:PKM; NbExp=4; IntAct=EBI-491549, EBI-353408; P14618-1:PKM; NbExp=3; IntAct=EBI-491549, EBI-4304679; Q03431:PTH1R; NbExp=4; IntAct=EBI-491549, EBI-2860297; Q13308:PTK7; NbExp=5; IntAct=EBI-491549, EBI-2803245; P08575:PTPRC; NbExp=2; IntAct=EBI-491549, EBI-1341; P23470:PTPRG; NbExp=2; IntAct=EBI-491549, EBI-2258115; Q12913:PTPRJ; NbExp=2; IntAct=EBI-491549, EBI-2264500; P49023:PXN; NbExp=4; IntAct=EBI-491549, EBI-702209; Q04206:RELA; NbExp=3; IntAct=EBI-491549, EBI-73886; Q13761:RUNX3; NbExp=12; IntAct=EBI-491549, EBI-925990; Q9Y265:RUVBL1; NbExp=3; IntAct=EBI-491549, EBI-353675; Q01887:Ryk (xeno); NbExp=2; IntAct=EBI-491549, EBI-16110594; Q01826:SATB1; NbExp=9; IntAct=EBI-491549, EBI-743747; P63208:SKP1; NbExp=3; IntAct=EBI-491549, EBI-307486; Q9H6I2:SOX17; NbExp=2; IntAct=EBI-491549, EBI-9106753; P12931:SRC; NbExp=2; IntAct=EBI-491549, EBI-621482; P15884:TCF4; NbExp=22; IntAct=EBI-491549, EBI-533224; P36402:TCF7; NbExp=4; IntAct=EBI-491549, EBI-2119465; Q9NQB0:TCF7L2; NbExp=27; IntAct=EBI-491549, EBI-924724; O14746:TERT; NbExp=2; IntAct=EBI-491549, EBI-1772203; Q9UKE5:TNIK; NbExp=3; IntAct=EBI-491549, EBI-1051794; P11388:TOP2A; NbExp=5; IntAct=EBI-491549, EBI-539628; Q13625:TP53BP2; NbExp=5; IntAct=EBI-491549, EBI-77642; O95071:UBR5; NbExp=6; IntAct=EBI-491549, EBI-358329; Q9GZV5:WWTR1; NbExp=4; IntAct=EBI-491549, EBI-747743; Q9EPK5:Wwtr1 (xeno); NbExp=2; IntAct=EBI-491549, EBI-1211920; P46937:YAP1; NbExp=13; IntAct=EBI-491549, EBI-1044059; P46937-3:YAP1; NbExp=2; IntAct=EBI-491549, EBI-6558686; SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25183871}. Nucleus {ECO:0000269|PubMed:24342833, ECO:0000269|PubMed:25183871, ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:29367600}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:B6V8E6}. Cell junction, adherens junction {ECO:0000250|UniProtKB:Q02248}. Cell junction {ECO:0000250|UniProtKB:B6V8E6}. Cell membrane {ECO:0000269|PubMed:24342833}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Cell junction, synapse {ECO:0000250|UniProtKB:Q02248}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q02248}. Note=Colocalized with RAPGEF2 and TJP1 at cell-cell contacts (By similarity). Cytoplasmic when it is unstabilized (high level of phosphorylation) or bound to CDH1. Translocates to the nucleus when it is stabilized (low level of phosphorylation). Interaction with GLIS2 and MUC1 promotes nuclear translocation. Interaction with EMD inhibits nuclear localization. The majority of beta-catenin is localized to the cell membrane. In interphase, colocalizes with CROCC between CEP250 puncta at the proximal end of centrioles, and this localization is dependent on CROCC and CEP250. In mitosis, when NEK2 activity increases, it localizes to centrosomes at spindle poles independent of CROCC. Colocalizes with CDK5 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Interaction with FAM53B promotes translocation to the nucleus (PubMed:25183871). {ECO:0000250|UniProtKB:B6V8E6, ECO:0000269|PubMed:25183871}. TISSUE SPECIFICITY: Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). Expressed in breast cancer tissues (at protein level) (PubMed:29367600). {ECO:0000269|PubMed:11703283, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17289029, ECO:0000269|PubMed:29367600}. PTM: Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription (By similarity). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation (PubMed:25169422). Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity. {ECO:0000250, ECO:0000269|PubMed:10966653, ECO:0000269|PubMed:11279024, ECO:0000269|PubMed:12027456, ECO:0000269|PubMed:12051714, ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12640114, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:20026641, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:25169422}. PTM: Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation. Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation (By similarity). {ECO:0000250}. PTM: S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions. {ECO:0000250|UniProtKB:Q02248}. PTM: O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1. {ECO:0000269|PubMed:24342833}. PTM: Deacetylated at Lys-49 by SIRT1. {ECO:0000269|PubMed:24824780}. DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:9065402}. Note=The gene represented in this entry may be involved in disease pathogenesis. DISEASE: Note=Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. DISEASE: Pilomatrixoma (PTR) [MIM:132600]: Common benign skin tumor. {ECO:0000269|PubMed:10192393, ECO:0000269|PubMed:11703283, ECO:0000269|PubMed:12027456}. Note=The gene represented in this entry is involved in disease pathogenesis. DISEASE: Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. {ECO:0000269|PubMed:10666372, ECO:0000269|PubMed:12027456}. Note=The gene represented in this entry may be involved in disease pathogenesis. DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:10391090}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. DISEASE: Note=A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1. DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269|PubMed:11464291}. Note=The gene represented in this entry may be involved in disease pathogenesis. DISEASE: Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) [MIM:615075]: An autosomal dominant disorder characterized by global developmental delay, severe intellectual disability with absent or very limited speech, microcephaly, spasticity, and visual abnormalities. {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:25326669, ECO:0000269|PubMed:28514307}. Note=The disease is caused by mutations affecting the gene represented in this entry. DISEASE: Vitreoretinopathy, exudative 7 (EVR7) [MIM:617572]: A form of exudative vitreoretinopathy, a disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:28575650}. Note=The disease is caused by mutations affecting the gene represented in this entry. SIMILARITY: Belongs to the beta-catenin family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=AAG35511.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=BAB93475.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CTNNB1ID71.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ctnnb1/"; WEB RESOURCE: Name=Wikipedia; Note=Beta-catenin entry; URL="https://en.wikipedia.org/wiki/Beta-catenin";"
primaryDomainId "uniprot.P35222"
displayName "CTNB1_HUMAN"
synonyms "Catenin beta-1, Beta-catenin"
taxid 9606
geneName "CTNNB1"
type "Protein"
graphics [
fill "#00FF00"
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name "P35222"
]
node [
id 33
label "drugbank.DB03904"
primaryDataset "DrugBank"
iupacName "urea"
inchi "InChI=1S/CH4N2O/c2-1(3)4/h(H4,2,3,4)"
primaryDomainId "drugbank.DB03904"
smiles "NC(N)=O"
synonyms "Carbamide, Carbonyldiamide, Harnstoff, Karbamid, Urea, Urée"
groups "approved, investigational"
description "A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids."
type "SmallMoleculeDrug"
casNumber "57-13-6"
domainIds "drugbank.DB03904, drugbank.EXPT03203"
allDatasets "DrugBank"
molecularFormula "CH4N2O"
name "Urea"
categories "Blood and Blood Forming Organs, Blood Substitutes and Perfusion Solutions, Carbamide products, Dermatologicals, Diuretics, Osmotic, Emollients and Protectives, i.v. Solutions, Keratolytic Agents, Solutions Producing Osmotic Diuresis"
indication "<ul> <li>10% hydrate skin</li> <li>15% accelerate fibrin degradation</li> <li>20-30% are antipruritic, break down keratin, decrease the thickness of the stratum corneum and are used in scaling conditions such as ichthysosis</li> <li>40% are proteolytic and may be used to dissolve and peel dystrophic nails</li> </ul> <br>[Patient Self Care, 2010]</br>"
graphics [
fill "#34A4EB"
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]
node [
id 34
label "uniprot.B4DGU4"
domainIds "uniprot.B4DGU4"
sequence "MELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL"
primaryDomainId "uniprot.B4DGU4"
displayName "B4DGU4_HUMAN"
synonyms "Catenin beta-1 {ECO:0000313, Ensembl:ENSP00000411226}, cDNA FLJ57878, highly similar to Beta-catenin {ECO:0000313, EMBL:BAG57905.1}"
taxid 9606
geneName "CTNNB1"
type "Protein"
graphics [
fill "#00FF00"
]
name "B4DGU4"
]
node [
id 35
label "entrez.57706"
domainIds "entrez.57706"
primaryDomainId "entrez.57706"
geneType "protein-coding"
displayName "DENN domain containing 1A"
synonyms "DENN domain-containing protein 1A, DENN/MADD domain containing 1A, connecdenn 1"
chromosome "9"
description "DENN domain containing 1A"
approvedSymbol "DENND1A"
type "Gene"
symbols "FAM31A, KIAA1608"
mapLocation "9q33.3"
graphics [
fill "#FFB6C1"
]
name "DENND1A"
]
node [
id 36
label "uniprot.Q9HCG4"
domainIds "uniprot.Q9HCG4"
sequence "QQTEIRVLPLIFRSEELLLYLKENQWNELLETLHKLPIPDPGVSVHLSVHSYFTVPDTRELPSIPENRNLTEYFVAVDVNNMLHLYASMLYERRILIICSKLSTLTACIHGSAAMLYPMYWQHVYIPVLPPHLLDYCCAPMPYLIGIHLSLMEKVRNMALDDVVILNVDTNTLETPFDDLQSLPNDVISSLKNRLKKVSTTTGDGVARAFLKAQAAFFGSYRNALKIEPKGSGAILNTVKTKANPAMKTVYKFAKDHAKMGIKEVKNRLKQKDIAENGCAPTPEEQLPKTAPSPLVEAKDPKLREDRRPITVHFGQVRPPRPHVVKRPKSNIAVEGRRTSVPSPEHLVKPLRHYAVFLSEDSSDDECQREEGPSSGFTESFFFSAPFEWPQPYRTLRESDSAEGDEAESPEQQVRKSTGPVPAPPDRAASIDLLEDVFSNLDMEAALQPLGQAKSLEDLRAPKDLREQPGTFDYQRLDLGGSERSRGVTVALKLTHPYNKLWSLGQDDMAIPSKPPAASPEKPSALLGNSLALPRRPQNRDSILNPSDKEEVPTPTLGSITIPRPQGRKTPELGIVPPPPIPRPAKLQAAGAALGDVSERLQTDRDRRAALSPGLLPGVVPQGPTELLQPLSPGPGAAGTSSDALLALLDPLSTAWSGSTLPSRPATPNVATPFTPQFSFPPAGTPTPFPQPPLNPFVPSMPAAPPTLPLVSTPAGPFGAPPASLGPAFASGLLLSSAGFCAPHRSQPNLSALSMPNLFGQMPMGTHTSPLQPLGPPAVAPSRIRTLPLARSSARAAETKQGLALRPGDPPLLPPRPPQGLEPTLQPSAPQQARDPFEDLLQKTKQDVSPSPALAPAPDSVEQLRKQWETFE"
primaryDomainId "uniprot.Q9HCG4"
displayName "Q9HCG4_HUMAN"
synonyms "KIAA1608 protein {ECO:0000313, EMBL:BAB13434.2}"
taxid 9606
geneName "KIAA1608"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q9HCG4"
]
node [
id 37
label "uniprot.Q8TEH3"
domainIds "uniprot.Q8TEH3"
sequence "MGSRIKQNPETTFEVYVEVAYPRTGGTLSDPEVQRQFPEDYSDQEVLQTLTKFCFPFYVDSLTVSQVGQNFTFVLTDIDSKQRFGFCRLSSGAKSCFCILSYLPWFEVFYKLLNILADYTTKRQENQWNELLETLHKLPIPDPGVSVHLSVHSYFTVPDTRELPSIPENRNLTEYFVAVDVNNMLHLYASMLYERRILIICSKLSTLTACIHGSAAMLYPMYWQHVYIPVLPPHLLDYCCAPMPYLIGIHLSLMEKVRNMALDDVVILNVDTNTLETPFDDLQSLPNDVISSLKNRLKKVSTTTGDGVARAFLKAQAAFFGSYRNALKIEPEEPITFCEEAFVSHYRSGAMRQFLQNATQLQLFKQFIDGRLDLLNSGEGFSDVFEEEINMGEYAGSDKLYHQWLSTVRKGSGAILNTVKTKANPAMKTVYKFAKDHAKMGIKEVKNRLKQKDIAENGCAPTPEEQLPKTAPSPLVEAKDPKLREDRRPITVHFGQVRPPRPHVVKRPKSNIAVEGRRTSVPSPEQPQPYRTLRESDSAEGDEAESPEQQVRKSTGPVPAPPDRAASIDLLEDVFSNLDMEAALQPLGQAKSLEDLRAPKDLREQPGTFDYQRLDLGGSERSRGVTVALKLTHPYNKLWSLGQDDMAIPSKPPAASPEKPSALLGNSLALPRRPQNRDSILNPSDKEEVPTPTLGSITIPRPQGRKTPELGIVPPPPIPRPAKLQAAGAALGDVSERLQTDRDRRAALSPGLLPGVVPQGPTELLQPLSPGPGAAGTSSDALLALLDPLSTAWSGSTLPSRPATPNVATPFTPQFSFPPAGTPTPFPQPPLNPFVPSMPAAPPTLPLVSTPAGPFGAPPASLGPAFASGLLLSSAGFCAPHRSQPNLSALSMPNLFGQMPMGTHTSPLQPLGPPAVAPSRIRTLPLARSSARAAETKQGLALRPGDPPLLPPRPPQGLEPTLQPSAPQQARDPFEDLLQKTKQDVSPSPALAPAPDSVEQLRKQWETFE"
comments "FUNCTION: Guanine nucleotide exchange factor (GEF) regulating clathrin- mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP- bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes (PubMed:20154091, PubMed:20937701). Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P (By similarity). {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}. ACTIVITY REGULATION: The guanine nucleotide exchange factor (GEF) activity is autoinhibited. Autoinhibition may be the result of intramolecular interaction between the DENN domain and the C-terminus, which is disrupted upon phosphorylation. Activation is regulated by Akt activation. {ECO:0000269|PubMed:26055712}. SUBUNIT: Interacts with RAB35 (PubMed:20154091). Interacts with clathrin and with the adapter protein complex 2, AP-2 (PubMed:20154091, PubMed:20937701). Interacts with ITSN1 AND SH3GL2 (By similarity). Interacts (when phosphorylated) with YWHAE (PubMed:26055712). {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:26055712}. SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}; Peripheral membrane protein {ECO:0000269|PubMed:20937701}. Cell junction, synapse, presynaptic cell membrane {ECO:0000269|PubMed:20937701}. Note=Associates to membranes via lipid- binding activity. {ECO:0000250|UniProtKB:Q8K382}. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=7; Name=1; IsoId=Q8TEH3-1; Sequence=Displayed; Name=2; IsoId=Q8TEH3-2; Sequence=VSP_019464, VSP_019465; Name=3; IsoId=Q8TEH3-3; Sequence=VSP_034513, VSP_034514; Name=4; IsoId=Q8TEH3-4; Sequence=VSP_034509, VSP_034512, VSP_034513, VSP_034514; Name=5; IsoId=Q8TEH3-5; Sequence=VSP_034510, VSP_034511, VSP_019464, VSP_019465; Name=6; IsoId=Q8TEH3-6; Sequence=VSP_034509, VSP_040666, VSP_040668; Name=7; IsoId=Q8TEH3-7; Sequence=VSP_040667, VSP_040668; PTM: Phosphorylated on serine and/or threonine in an Akt-dependent manner. Phosphorylation probably regulates the guanine nucleotide exchange factor (GEF) activity, possibly by disrupting an intramolecular interaction between the DENN domain and the C-terminus of the protein, thereby relieving the autoinhibition. {ECO:0000269|PubMed:26055712}. DISEASE: Note=Genetic variants in DENND1A may play a role in susceptibility to polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women. PCOS is a complex disorder characterized by infertility, hirsutism, obesity, various menstrual disturbances, and enlarged ovaries studded with atretic follicles. {ECO:0000269|PubMed:22180642, ECO:0000269|PubMed:23208300, ECO:0000269|PubMed:24086769, ECO:0000269|PubMed:25626177}. SEQUENCE CAUTION: Sequence=AAH09616.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH28061.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAH13155.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q8TEH3"
displayName "DEN1A_HUMAN"
synonyms "DENN domain-containing protein 1A {ECO:0000312, HGNC:HGNC:29324}, Connecdenn 1 {ECO:0000303, PubMed:20154091}, Connecdenn {ECO:0000303, PubMed:20154091}, Protein FAM31A"
taxid 9606
geneName "DENND1A"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q8TEH3"
]
node [
id 38
label "entrez.93185"
domainIds "entrez.93185"
primaryDomainId "entrez.93185"
geneType "protein-coding"
displayName "immunoglobulin superfamily member 8"
synonyms "immunoglobulin superfamily member 8, CD81 partner 3, glu-Trp-Ile EWI motif-containing protein 2, keratinocytes-associated transmembrane protein 4, prostaglandin regulatory-like protein"
chromosome "1"
description "immunoglobulin superfamily member 8"
approvedSymbol "IGSF8"
type "Gene"
symbols "CD316, CD81P3, EWI-2, EWI2, KCT-4, LIR-D1, PGRL"
mapLocation "1q23.2"
graphics [
fill "#FFB6C1"
]
name "IGSF8"
]
node [
id 39
label "uniprot.Q969P0"
domainIds "uniprot.Q969P0"
sequence "MGALRPTLLPPSLPLLLLLMLGMGCWAREVLVPEGPLYRVAGTAVSISCNVTGYEGPAQQNFEWFLYRPEAPDTALGIVSTKDTQFSYAVFKSRVVAGEVQVQRLQGDAVVLKIARLQAQDAGIYECHTPSTDTRYLGSYSGKVELRVLPDVLQVSAAPPGPRGRQAPTSPPRMTVHEGQELALGCLARTSTQKHTHLAVSFGRSVPEAPVGRSTLQEVVGIRSDLAVEAGAPYAERLAAGELRLGKEGTDRYRMVVGGAQAGDAGTYHCTAAEWIQDPDGSWAQIAEKRAVLAHVDVQTLSSQLAVTVGPGERRIGPGEPLELLCNVSGALPPAGRHAAYSVGWEMAPAGAPGPGRLVAQLDTEGVGSLGPGYEGRHIAMEKVASRTYRLRLEAARPGDAGTYRCLAKAYVRGSGTRLREAASARSRPLPVHVREEGVVLEAVAWLAGGTVYRGETASLLCNISVRGGPPGLRLAASWWVERPEDGELSSVPAQLVGGVGQDGVAELGVRPGGGPVSVELVGPRSHRLRLHSLGPEDEGVYHCAPSAWVQHADYSWYQAGSARSGPVTVYPYMHALDTLFVPLLVGTGVALVTGATVLGTITCCFMKRLRKR"
comments "FUNCTION: May play a key role in diverse functions ascribed to CD81 and CD9 such as oocytes fertilization or hepatitis C virus function. May regulate proliferation and differentiation of keratinocytes. May be a negative regulator of cell motility: suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. May also play a role on integrin-dependent morphology and motility functions. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain. {ECO:0000269|PubMed:11504738, ECO:0000269|PubMed:12750295, ECO:0000269|PubMed:12752121, ECO:0000269|PubMed:14662754, ECO:0000269|PubMed:15070678}. SUBUNIT: Interacts directly with CD82, CD81/tetraspanin-28 and CD9/tetraspanin-29. Also interacts with integrin alpha-3/beta-1 and integrin alpha-4/beta-1. {ECO:0000269|PubMed:11504738, ECO:0000269|PubMed:12750295, ECO:0000269|PubMed:14662754, ECO:0000269|PubMed:15070678}. INTERACTION: P60372:KRTAP10-4; NbExp=3; IntAct=EBI-8293590, EBI-10178153; P60409:KRTAP10-7; NbExp=3; IntAct=EBI-8293590, EBI-10172290; P60410:KRTAP10-8; NbExp=5; IntAct=EBI-8293590, EBI-10171774; P60411:KRTAP10-9; NbExp=3; IntAct=EBI-8293590, EBI-10172052; SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass membrane protein. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q969P0-1; Sequence=Displayed; Name=2; IsoId=Q969P0-2; Sequence=VSP_017429, VSP_017430; Name=3; IsoId=Q969P0-3; Sequence=VSP_017431; TISSUE SPECIFICITY: Expressed in brain, kidney, testis, liver and placenta with moderate expression in all other tissues. Detected on a majority of B-cells, T-cells, and natural killer cells but not on monocytes, polynuclear cells and platelets. {ECO:0000269|PubMed:11504738, ECO:0000269|PubMed:12708969, ECO:0000269|PubMed:12750295}. DOMAIN: The Ig-like C2-type domains 3 and 4 are required for interaction with CD81. {ECO:0000250}. DOMAIN: The short cytoplasmic domain is very basic, interacts with membrane PIPs, and mediates plasma membrane localization. {ECO:0000250}. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/IGSF8ID45820ch1q23.html";"
primaryDomainId "uniprot.Q969P0"
displayName "IGSF8_HUMAN"
synonyms "Immunoglobulin superfamily member 8, IgSF8, CD81 partner 3, Glu-Trp-Ile EWI motif-containing protein 2, EWI-2, Keratinocytes-associated transmembrane protein 4, KCT-4, LIR-D1, Prostaglandin regulatory-like protein, PGRL, CD316"
taxid 9606
geneName "IGSF8"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q969P0"
]
node [
id 40
label "entrez.9462"
domainIds "entrez.9462"
primaryDomainId "entrez.9462"
geneType "protein-coding"
displayName "RAS protein activator like 2"
synonyms "ras GTPase-activating protein nGAP, RASAL2/ACVR1 fusion, Ras protein activator like 1"
chromosome "1"
description "RAS protein activator like 2"
approvedSymbol "RASAL2"
type "Gene"
symbols "NGAP"
mapLocation "1q25.2"
graphics [
fill "#FFB6C1"
]
name "RASAL2"
]
node [
id 41
label "uniprot.A8K2P3"
domainIds "uniprot.A8K2P3"
sequence "MQTPEVPAERSPRRRSISGTSTSEKPNSMDTANTSPFKVPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSPRSTDDRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKPLHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKRKKKDKNNYVGLVNIPTASVTGRQFVEKWYPVSTPTPNKGKTGGPSIRIKSRFQTITILPMEQYKESAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDKGENSFLQATVAKLGPLPRVLADITKSLTNPTPIQQQLRRFTEHNSSPNVSGSLSSGLQKIFEDPTDSDLHKLKSPSQDNTDSYFRGKTLLLVQQASSQSMTYSEKDERESSLPNGRSVSLMDLQDTHAAQVEHASVMLDVPIRLTGSQLSITQVASIKQLRETQSTPQSAPQVRRPLHPALNQPGGLQPLSFQNPVYHLNNPIPAMPKASIDSSLENLSTASSRSQSNSEDFKLSGPSNSSMEDFTKRSTQSEDFSRRHTVPDRHIPLALPRQNSTGQAQIRKVDQGGLGARAKAPPSLPHSASLRSTGSMSVVSAALVAEPVQNGSRSRQQSSSSRESPVPKVRAIQRQQTQQVQSPVDSATMSPVERTAAWVLNNGQYEEDVEETEQNLDEAKHAEKYE"
primaryDomainId "uniprot.A8K2P3"
displayName "A8K2P3_HUMAN"
synonyms "cDNA FLJ77041, highly similar to Homo sapiens RAS protein activator like 2 (RASAL2), transcript variant 1, mRNA {ECO:0000313, EMBL:BAF82997.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "A8K2P3"
]
node [
id 42
label "uniprot.Q9UJF2"
domainIds "uniprot.Q9UJF2"
sequence "MQTPEVPAERSPRRRSISGTSTSEKPNSMDTANTSPFKVPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSLRSTDDRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKPLHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKKKKKDKNNYVGLVNIPTASVTGRQFVEKWYPVSTPTPNKGKTGGPSIRIKSRFQTITILPMEQYKEFAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDKGENSFLQATVAKLGPLPRVLADITKSLTNPTPIQQQLRRFTEHNSSPNVSGSLSSGLQKIFEDPTDSDLHKLKSPSQDNTDSYFRGKTLLLVQQASSQSMTYSEKDERESSLPNGRSVSLMDLQDTHAAQVEHASVMLDVPIRLTGSQLSITQVASIKQLRETQSTPQSAPQVRRPLHPALNQPGGLQPLSFQNPVYHLNNPIPAMPKASIDSSLENLSTASSRSQSNSEDFKLSGPSNSSMEDFTKRSTQSEDFSRRHTVPDRHIPLALPRQNSTGQAQIRKVDQGGLGARAKAPPSLPHSASLRSTGSMSVVSAALVAEPVQNGSRSRQQSSSSRESPVPKVRAIQRQQTQQVQSPVDSATMSPVERTAAWVLNNGQYEEDVEETEQNLDEAKHAEKYEQEITKLKERLRVSSRRLEEYERRLLVQEQQMQKLLLEYKARLEDSEERLRRQQEEKDSQMKSIISRLMAVEEELKKDHAEMQAVIDAKQKIIDAQEKRIVSLDSANTRLMSALTQVKERYSMQVRNGISPTNPTKLSITENGEFKNSSC"
comments "FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. INTERACTION: Q9WMX2:- (xeno); NbExp=2; IntAct=EBI-359444, EBI-6863741; Q96PC5:MIA2; NbExp=3; IntAct=EBI-359444, EBI-1050253; Q13077:TRAF1; NbExp=3; IntAct=EBI-359444, EBI-359224; Q8N6Y0:USHBP1; NbExp=3; IntAct=EBI-359444, EBI-739895; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9UJF2-1; Sequence=Displayed; Name=2; IsoId=Q9UJF2-2; Sequence=VSP_045777, VSP_045778; SEQUENCE CAUTION: Sequence=AAI10612.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q9UJF2"
displayName "NGAP_HUMAN"
synonyms "Ras GTPase-activating protein nGAP, RAS protein activator-like 2"
taxid 9606
geneName "RASAL2"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q9UJF2"
]
node [
id 43
label "entrez.9644"
domainIds "entrez.9644"
primaryDomainId "entrez.9644"
geneType "protein-coding"
displayName "SH3 and PX domains 2A"
synonyms "SH3 and PX domain-containing protein 2A, SH3 multiple domains 1, adapter protein TKS5, adaptor protein TKS5, five SH3 domain-containing protein, tyrosine kinase substrate with five SH3 domains"
chromosome "10"
description "SH3 and PX domains 2A"
approvedSymbol "SH3PXD2A"
type "Gene"
symbols "FISH, SH3MD1, TKS5"
mapLocation "10q24.33"
graphics [
fill "#FFB6C1"
]
name "SH3PXD2A"
]
node [
id 44
label "uniprot.B3KPL1"
domainIds "uniprot.B3KPL1"
sequence "MQLLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILEQYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEEEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKETPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSRLAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEEGPTWASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEPVEDRASGERRPAQPHRPSPASSLQRARFKVGESSEDVALEEETIYENEGFRPYAEDTLSARGSSGDSDSPGSSSLSLTRKNSPKSGSPKSSSLLKLKAEKNAQAEMGKNHSSASFSSSITINTTCCSSSSSSSSSLSKTSGDLKPRSASDAGIRGTPKVRAKKDADANAGLTSCPRAKPSVRPKPFLNRAESQSQEKMDISTLRRQLRPTGQLRGGLKGSKSEDSELPPQTASEAPSEGSRRSSSDLITLPATTPPCPTKKEWEGPATSYMTCSAYQKVQDSEISFPAGVEVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENEQPDPSGKELDTVPAKGRQNEGKSDSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKTSGTPAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFSTARSAAAEAKGRLAERAASQGSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSIADYEGDEETAGFQEGVSMEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN"
primaryDomainId "uniprot.B3KPL1"
displayName "B3KPL1_HUMAN"
synonyms "cDNA FLJ31907 fis, clone NT2RP7004396, highly similar to Homo sapiens SH3 multiple domains 1 (SH3MD1), mRNA {ECO:0000313, EMBL:BAG51723.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "B3KPL1"
]
node [
id 45
label "uniprot.Q5TCZ1"
domainIds "uniprot.Q5TCZ1"
sequence "MLAYCVQDATVVDVEKRRNPSKHYVYIINVTWSDSTSQTIYRRYSKFFDLQMQLLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILEQYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKETPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSRLAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEEGPTGASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEPVEDRASGERRPAQPHRPSPASSLQRARFKVGESSEDVALEEETIYENEGFRPYAEDTLSARGSSGDSDSPGSSSLSLTRKNSPKSGSPKSSSLLKLKAEKNAQAEMGKNHSSASFSSSITINTTCCSSSSSSSSSLSKTSGDLKPRSASDAGIRGTPKVRAKKDADANAGLTSCPRAKPSVRPKPFLNRAESQSQEKMDISTLRRQLRPTGQLRGGLKGSKSEDSELPPQTASEAPSEGSRRSSSDLITLPATTPPCPTKKEWEGPATSYMTCSAYQKVQDSEISFPAGVEVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENEQPDPSGKELDTVPAKGRQNEGKSDSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKTSGTPAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFSTARSAAAEAKGRLAERAASQGSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSIADYEGDEETAGFQEGVSMEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN"
comments "FUNCTION: Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}. SUBUNIT: Interacts (via N-terminus) with CYBA (By similarity). Interacts with ADAM12, ADAM15 and ADAM19. Interacts with NOXO1. Interacts (via SH3 domains) with NOXA1. Interacts with FASLG. {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20609497}. INTERACTION: Q13444:ADAM15; NbExp=2; IntAct=EBI-2483234, EBI-77818; P21575:Dnm1 (xeno); NbExp=2; IntAct=EBI-7014859, EBI-80070; Q07889:SOS1; NbExp=5; IntAct=EBI-7014859, EBI-297487; SUBCELLULAR LOCATION: Cytoplasm. Cell projection, podosome. Note=Cytoplasmic in normal cells and localizes to podosomes in SRC- transformed cells. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q5TCZ1-1; Sequence=Displayed; Name=2; IsoId=Q5TCZ1-2; Sequence=VSP_023312, VSP_023313; Name=3; IsoId=Q5TCZ1-3; Sequence=VSP_023313; TISSUE SPECIFICITY: Found in several cancer cell lines, particularly invasive breast carcinomas and melanomas. {ECO:0000269|PubMed:15710328}. DOMAIN: The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity). {ECO:0000250}. DOMAIN: The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328}. PTM: Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory role in the protein localization. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. MISCELLANEOUS: [Isoform 3]: and partial transcript data. {ECO:0000305}. SIMILARITY: Belongs to the SH3PXD2 family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=BAA24848.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q5TCZ1"
displayName "SPD2A_HUMAN"
synonyms "SH3 and PX domain-containing protein 2A, Adapter protein TKS5, Five SH3 domain-containing protein, SH3 multiple domains protein 1, Tyrosine kinase substrate with five SH3 domains"
taxid 9606
geneName "SH3PXD2A"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q5TCZ1"
]
node [
id 46
label "entrez.5093"
domainIds "entrez.5093"
primaryDomainId "entrez.5093"
geneType "protein-coding"
displayName "poly(rC) binding protein 1"
synonyms "poly(rC)-binding protein 1, alpha-CP1, epididymis secretory protein Li 85, heterogeneous nuclear ribonucleoprotein E1, heterogenous nuclear ribonucleoprotein E1, heterogenous nuclear ribonucleoprotein X, nucleic acid-binding protein SUB2.3"
chromosome "2"
description "poly(rC) binding protein 1"
approvedSymbol "PCBP1"
type "Gene"
symbols "HEL-S-85, HNRPE1, HNRPX, hnRNP-E1, hnRNP-X"
mapLocation "2p13.3"
graphics [
fill "#FFB6C1"
]
name "PCBP1"
]
node [
id 47
label "uniprot.Q53SS8"
domainIds "uniprot.Q53SS8"
sequence "MDAGVTESGLNVTLTIRLLMHGKEVGSIIGKKGESVKRIREESGARINISEGNCPERIITLTGPTNAIFKAFAMIIDKLEEDINSSMTNSTAASRPPVTLRLVVPATQCGSLIGKGGCKIKEIRESTGAQVQVAGDMLPNSTERAITIAGVPQSVTECVKQICLVMLETLSQSPQGRVMTIPYQPMPASSPVICAGGQDRCSDAAGYPHATHDLEGPPLDAYSIQGQHTISPLDLAKLNQVARQQSHFAMMHGGTGFAGIDSSSPEVKGYWASLDASTQTTHELTIPNNLIGCIIGRQGANINEIRQMSGAQIKIANPVEGSSGRQVTITGSAASISLAQYLINARLSSEKGMGCS"
primaryDomainId "uniprot.Q53SS8"
displayName "Q53SS8_HUMAN"
synonyms "Epididymis secretory protein Li 85 {ECO:0000313, EMBL:ACI46021.1}, Poly(RC) binding protein 1 {ECO:0000313, EMBL:EAW99834.1}, cDNA, FLJ94964, highly similar to Homo sapiens poly(rC) binding protein 1 (PCBP1), mRNA {ECO:0000313, EMBL:BAG36897.1}"
taxid 9606
geneName "PCBP1"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q53SS8"
]
node [
id 48
label "uniprot.Q15365"
domainIds "uniprot.Q15365"
sequence "MDAGVTESGLNVTLTIRLLMHGKEVGSIIGKKGESVKRIREESGARINISEGNCPERIITLTGPTNAIFKAFAMIIDKLEEDINSSMTNSTAASRPPVTLRLVVPATQCGSLIGKGGCKIKEIRESTGAQVQVAGDMLPNSTERAITIAGVPQSVTECVKQICLVMLETLSQSPQGRVMTIPYQPMPASSPVICAGGQDRCSDAAGYPHATHDLEGPPLDAYSIQGQHTISPLDLAKLNQVARQQSHFAMMHGGTGFAGIDSSSPEVKGYWASLDASTQTTHELTIPNNLIGCIIGRQGANINEIRQMSGAQIKIANPVEGSSGRQVTITGSAASISLAQYLINARLSSEKGMGCS"
comments "FUNCTION: Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943). {ECO:0000269|PubMed:12414943}. INTERACTION: O41951:GAMMAHV.ORF34 (xeno); NbExp=4; IntAct=EBI-946095, EBI-9640556; Q67020:PA (xeno); NbExp=2; IntAct=EBI-946095, EBI-11514477; Q13153:PAK1; NbExp=2; IntAct=EBI-946095, EBI-1307; Q13153-1:PAK1; NbExp=5; IntAct=EBI-946095, EBI-15628682; Q15366:PCBP2; NbExp=2; IntAct=EBI-946095, EBI-945799; Q13427:PPIG; NbExp=2; IntAct=EBI-946095, EBI-396072; Q6P2Q9:PRPF8; NbExp=2; IntAct=EBI-946095, EBI-538479; P26599:PTBP1; NbExp=2; IntAct=EBI-946095, EBI-350540; Q9UHX1:PUF60; NbExp=2; IntAct=EBI-946095, EBI-1053259; Q96PU8:QKI; NbExp=2; IntAct=EBI-946095, EBI-945792; Q14498:RBM39; NbExp=2; IntAct=EBI-946095, EBI-395290; Q14498-2:RBM39; NbExp=2; IntAct=EBI-946095, EBI-11032687; P09012:SNRPA; NbExp=5; IntAct=EBI-946095, EBI-607085; Q96EK4:THAP11; NbExp=4; IntAct=EBI-946095, EBI-1790529; Q9Y3Q8:TSC22D4; NbExp=2; IntAct=EBI-946095, EBI-739485; Q9Y2W2:WBP11; NbExp=2; IntAct=EBI-946095, EBI-714455; Q96NB3:ZNF830; NbExp=2; IntAct=EBI-946095, EBI-3920997; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Loosely bound in the nucleus. May shuttle between the nucleus and the cytoplasm. TISSUE SPECIFICITY: Abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands. PTM: Phosphorylated; lowers poly(rC)-binding activity. SEQUENCE CAUTION: Sequence=CAA82631.1; Type=Frameshift; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q15365"
displayName "PCBP1_HUMAN"
synonyms "Poly(rC)-binding protein 1, Alpha-CP1, Heterogeneous nuclear ribonucleoprotein E1, hnRNP E1, Nucleic acid-binding protein SUB2.3"
taxid 9606
geneName "PCBP1"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q15365"
]
node [
id 49
label "entrez.995"
domainIds "entrez.995"
primaryDomainId "entrez.995"
geneType "protein-coding"
displayName "cell division cycle 25C"
synonyms "M-phase inducer phosphatase 3, dual specificity phosphatase CDC25C, mitosis inducer CDC25, phosphotyrosine phosphatase, protein phosphatase 1, regulatory subunit 60"
chromosome "5"
description "cell division cycle 25C"
approvedSymbol "CDC25C"
type "Gene"
symbols "CDC25, PPP1R60"
mapLocation "5q31.2"
graphics [
fill "#FFB6C1"
]
name "CDC25C"
]
node [
id 50
label "uniprot.B4DX61"
domainIds "uniprot.B4DX61"
sequence "MSEEARFCFSPGENSKTMSTELFSSTREEGSSGSGPSFRSNQRKMLNLLLERDTSFTVCPDVPRTPVGKFLGDSANLSILSGGTPKRCLDLSNLSSGEITATQLTTSADLDETGHLDSSGLQEVHLAGMNHDQHLMKCSPAQLLCSTPNGLDRGHRKRDAMCSSSANKENDNGNLVDSEMKYLGSPITTVPKLDKNPNLGEDQAEEISDELMEFSLKDQEAKVSRSGLYRSPSMPENLNRPRLKQVEKFKDNTIPDKVKKKYFSGQGKLRKGLCLKKTVSLCDITITQMLEEDSNQGHLIGDFSKVCALPTVSGKHQDLKYVNPETVAALLSGKFQGLIEKFYVIDCRYPYEYLGGHIQGALNLYSQEELFNFFLKKPIVPLDTQKRIIIVLHCEFSSERGPRMCRCLREEDRSLNQYPALYYPELYILKGGYRDFFPEYMELCEPQSYCPMHHQDHKTELLRCRSQSKVQEGERQLREQIALLVKDMSP"
primaryDomainId "uniprot.B4DX61"
displayName "B4DX61_HUMAN"
synonyms "cDNA FLJ56262, highly similar to M-phase inducer phosphatase 3 {ECO:0000313, EMBL:BAG63273.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "B4DX61"
]
node [
id 51
label "uniprot.P30307"
domainIds "uniprot.P30307"
sequence "MSTELFSSTREEGSSGSGPSFRSNQRKMLNLLLERDTSFTVCPDVPRTPVGKFLGDSANLSILSGGTPKRCLDLSNLSSGEITATQLTTSADLDETGHLDSSGLQEVHLAGMNHDQHLMKCSPAQLLCSTPNGLDRGHRKRDAMCSSSANKENDNGNLVDSEMKYLGSPITTVPKLDKNPNLGEDQAEEISDELMEFSLKDQEAKVSRSGLYRSPSMPENLNRPRLKQVEKFKDNTIPDKVKKKYFSGQGKLRKGLCLKKTVSLCDITITQMLEEDSNQGHLIGDFSKVCALPTVSGKHQDLKYVNPETVAALLSGKFQGLIEKFYVIDCRYPYEYLGGHIQGALNLYSQEELFNFFLKKPIVPLDTQKRIIIVFHCEFSSERGPRMCRCLREEDRSLNQYPALYYPELYILKGGYRDFFPEYMELCEPQSYCPMHHQDHKTELLRCRSQSKVQEGERQLREQIALLVKDMSP"
comments "FUNCTION: Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. When phosphorylated, highly effective in activating G2 cells into prophase. Directly dephosphorylates CDK1 and activates its kinase activity. {ECO:0000269|PubMed:8119945}. CATALYTIC ACTIVITY: Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; SUBUNIT: Interacts with MAPK14 and 14-3-3 proteins. When phosphorylated on Ser-129 and/or Thr-130, interacts with PLK1. {ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:12595692}. SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpr; this interaction inactivates CDC25C phosphatase activity. {ECO:0000269|PubMed:14972559}. INTERACTION: P06493:CDK1; NbExp=2; IntAct=EBI-974439, EBI-444308; O14757:CHEK1; NbExp=2; IntAct=EBI-974439, EBI-974488; Q9Y250:LZTS1; NbExp=2; IntAct=EBI-974439, EBI-1216080; P53350:PLK1; NbExp=5; IntAct=EBI-974439, EBI-476768; P31946:YWHAB; NbExp=4; IntAct=EBI-974439, EBI-359815; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:8119945}. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=5; Name=1; Synonyms=CDC25C1; IsoId=P30307-1; Sequence=Displayed; Name=2; Synonyms=CDC25C2; IsoId=P30307-2; Sequence=VSP_000864; Name=3; Synonyms=CDC25C3; IsoId=P30307-5; Sequence=Not described; Name=4; Synonyms=CDC25C4; IsoId=P30307-3; Sequence=VSP_000863; Name=5; Synonyms=CDC25C5, Cdc25Cdm; IsoId=P30307-4; Sequence=VSP_000863, VSP_000864; DEVELOPMENTAL STAGE: Expressed predominantly in G2 phase. PTM: Phosphorylated by CHEK1 and MAPK14 at Ser-216. This phosphorylation creates a binding site for 14-3-3 protein and inhibits the phosphatase. Phosphorylated by PLK4. Phosphorylated by PLK1, leading to activate the phosphatase activity. Phosphorylation by PLK3 at Ser-191 promotes nuclear translocation. Ser-198 is a minor phosphorylation site. Was initially reported to be phosphorylated by PLK3 at Ser-216 (PubMed:10557092). However, such phosphorylation by PLK3 was not confirmed by other groups. Phosphorylation at Thr-48, Thr- 67, Ser-122, Thr-130, Ser-168 and Ser-214 occurs at G2 and G2-M transition and is probably catalyzed by CDK1. Ser-168 phosphorylation levels are lower than those at the other 5 CDK1 sites. Phosphorylation by CDK1 leads to increased activity. {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:8119945}. SIMILARITY: Belongs to the MPI phosphatase family. {ECO:0000305}. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdc25c/";"
primaryDomainId "uniprot.P30307"
displayName "MPIP3_HUMAN"
synonyms "M-phase inducer phosphatase 3, 3.1.3.48, Dual specificity phosphatase Cdc25C"
taxid 9606
geneName "CDC25C"
type "Protein"
graphics [
fill "#00FF00"
]
name "P30307"
]
node [
id 52
label "entrez.3608"
domainIds "entrez.3608"
primaryDomainId "entrez.3608"
geneType "protein-coding"
displayName "interleukin enhancer binding factor 2"
synonyms "interleukin enhancer-binding factor 2, interleukin enhancer binding factor 2, 45kD, interleukin enhancer binding factor 2, 45kDa, nuclear factor of activated T-cells, 45-kDa"
chromosome "1"
description "interleukin enhancer binding factor 2"
approvedSymbol "ILF2"
type "Gene"
symbols "NF45, PRO3063"
mapLocation "1q21.3"
graphics [
fill "#FFB6C1"
]
name "ILF2"
]
node [
id 53
label "uniprot.F4ZW62"
domainIds "uniprot.F4ZW62"
sequence "MRGDRGRGRGGRFGSRGGPGGGFRPFVPHIPFDFYLCEMAFPRVKPAPDETSFSEALLKRNQDLAPNSAEQASILSLVTKINNVIDNLIVAPGTFEVQIEEVRQVGSYKKGTMTTGHNVADLVVILKILPTLEAVAALGNKVVESLRAQDPSEVLTMLTNETGFEISSSDATVKILITTVPPNLRKLDPELHLDIKVLQSALAAIRHARWFEENASQSTVKVLIRLLKDLRIRFPGFEPLTPWILDLLGHYAVMNNPTRQPLALNVAYRRCLQILAAGLFLPGSVGITDPCESGNFRVHTVMTLEQQDMVCYTAQTLVRILSHGGFRKILGQEGDASYLASEISTWDGVIVTPSEKAYEKPPEKKEGEEEEENTEEPPQGEEEESMETQE"
comments "INTERACTION: O95273:CCNDBP1; NbExp=3; IntAct=EBI-10177680, EBI-748961; P26641-2:EEF1G; NbExp=3; IntAct=EBI-10177680, EBI-10177695;"
primaryDomainId "uniprot.F4ZW62"
displayName "F4ZW62_HUMAN"
synonyms "NF45 {ECO:0000313, EMBL:AEE02016.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "F4ZW62"
]
node [
id 54
label "uniprot.Q53FG3"
domainIds "uniprot.Q53FG3"
sequence "MRGDRGRGRGGRFGSRGGPGGGFRPFVPHIPFDFYLCEMAFPRVKPAPDETSFSEALLKRNQDLAPNSAEQASILSLVTKINNVVDNLIVAPGTFEVQIEEVRQVGSYKKGTMTTGHNVADLVVILKILPTLEAVAALGNKVVESLRAQDPSEVLTMLTNETGFEISSSDATVKILITTVPPNLRKLDPELHLDIKVLQSALAAIRHARWFEENASQSTVKVLIRLLKDLRIRFPGFEPLTPWILDLLGHYAVMNNPTRQPLALNVAYRRCLQILAAGLFLPGSVGITDPCESGNFRVHTVMTLEQQDMVCYTAQTLVRILSHGGFRKILGQEGDASYLASEISTWDGVIVTPSEKAYEKPPEKKEGEEEEENTEEPPQGEEEESMETQE"
primaryDomainId "uniprot.Q53FG3"
displayName "Q53FG3_HUMAN"
synonyms "Interleukin enhancer binding factor 2 variant {ECO:0000313, EMBL:BAD97046.1}"
taxid 9606
type "Protein"
graphics [
fill "#00FF00"
]
name "Q53FG3"
]
node [
id 55
label "uniprot.B4DY09"
domainIds "uniprot.B4DY09"
sequence "MAFPRVKPAPDETSFSEALLKRNQDLAPNSAEQASILSLVTKINNVIDNLIVAPGTFEVQIEEVRQVGSYKKGTMTTGHNVADLVVILKILPTLEAVAALGNKVVESLRAQDPSEVLTMLTNETGFEISSSDATVKILITTVPPNLRKLDPELHLDIKVLQSALAAIRHARWFEENASQSTVKVLIRLLKDLRIRFPGFEPLTPWILDLLGHYAVMNNPTRQPLALNVAYRRCLQILAAGLFLPGSVGITDPCESGNFRVHTVMTLEQQDMVCYTAQTLVRILSHGGFRKILGQEGDASYLASEISTWDGVIVTPSEKAYEKPPEKKEGEEEEENTEEPPQGEEEESMETQE"
primaryDomainId "uniprot.B4DY09"
displayName "B4DY09_HUMAN"
synonyms "Interleukin enhancer-binding factor 2 {ECO:0000313, Ensembl:ENSP00000482909}, cDNA FLJ51660, highly similar to Interleukin enhancer-binding factor 2 {ECO:0000313, EMBL:BAG63571.1}"
taxid 9606
geneName "ILF2"
type "Protein"
graphics [
fill "#00FF00"
]
name "B4DY09"
]
node [
id 56
label "uniprot.Q12905"
domainIds "uniprot.Q12905"
sequence "MRGDRGRGRGGRFGSRGGPGGGFRPFVPHIPFDFYLCEMAFPRVKPAPDETSFSEALLKRNQDLAPNSAEQASILSLVTKINNVIDNLIVAPGTFEVQIEEVRQVGSYKKGTMTTGHNVADLVVILKILPTLEAVAALGNKVVESLRAQDPSEVLTMLTNETGFEISSSDATVKILITTVPPNLRKLDPELHLDIKVLQSALAAIRHARWFEENASQSTVKVLIRLLKDLRIRFPGFEPLTPWILDLLGHYAVMNNPTRQPLALNVAYRRCLQILAAGLFLPGSVGITDPCESGNFRVHTVMTLEQQDMVCYTAQTLVRILSHGGFRKILGQEGDASYLASEISTWDGVIVTPSEKAYEKPPEKKEGEEEEENTEEPPQGEEEESMETQE"
comments "FUNCTION: Appears to function predominantly as a heterodimeric complex with ILF3. This complex may regulate transcription of the IL2 gene during T-cell activation. It can also promote the formation of stable DNA-dependent protein kinase holoenzyme complexes on DNA. Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. {ECO:0000269|PubMed:10574923, ECO:0000269|PubMed:11739746, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:9442054}. SUBUNIT: Forms heterodimers with ILF3. ILF2-ILF3 heterodimers may also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of G22P1/KU70 and XRCC5/KU80. Forms a complex with ILF3, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. {ECO:0000269|PubMed:10574923, ECO:0000269|PubMed:11739746, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:17890166, ECO:0000269|PubMed:9442054}. INTERACTION: Q08752:PPID; NbExp=4; IntAct=EBI-357925, EBI-716596; SUBCELLULAR LOCATION: Nucleus, nucleolus. Cytoplasm. Nucleus. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. SEQUENCE CAUTION: Sequence=AAA20993.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF29591.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.Q12905"
displayName "ILF2_HUMAN"
synonyms "Interleukin enhancer-binding factor 2, Nuclear factor of activated T-cells 45 kDa"
taxid 9606
geneName "ILF2"
type "Protein"
graphics [
fill "#00FF00"
]
name "Q12905"
]
node [
id 57
label "entrez.10528"
domainIds "entrez.10528"
primaryDomainId "entrez.10528"
geneType "protein-coding"
displayName "NOP56 ribonucleoprotein"
synonyms "nucleolar protein 56, NOP56 ribonucleoprotein homolog, nucleolar protein 5A (56kDa with KKE/D repeat)"
chromosome "20"
description "NOP56 ribonucleoprotein"
approvedSymbol "NOP56"
type "Gene"
symbols "NOL5A, SCA36"
mapLocation "20p13"
graphics [
fill "#FFB6C1"
]
name "NOP56"
]
node [
id 58
label "uniprot.O00567"
domainIds "uniprot.O00567"
sequence "MVLLHVLFEHAVGYALLALKEVEEISLLQPQVEESVLNLGKFHSIVRLVAFCPFASSQVALENANAVSEGVVHEDLRLLLETHLPSKKKKVLLGVGDPKIGAAIQEELGYNCQTGGVIAEILRGVRLHFHNLVKGLTDLSACKAQLGLGHSYSRAKVKFNVNRVDNMIIQSISLLDQLDKDINTFSMRVREWYGYHFPELVKIINDNATYCRLAQFIGNRRELNEDKLEKLEELTMDGAKAKAILDASRSSMGMDISAIDLINIESFSSRVVSLSEYRQSLHTYLRSKMSQVAPSLSALIGEAVGARLIAHAGSLTNLAKYPASTVQILGAEKALFRALKTRGNTPKYGLIFHSTFIGRAAAKNKGRISRYLANKCSIASRIDCFSEVPTSVFGEKLREQVEERLSFYETGEIPRKNLDVMKEAMVQAEEAAAEITRKLEKQEKKRLKKEKKRLAALALASSENSSSTPEECEEMSEKPKKKKKQKPQEVPQENGMEDPSISFSKPKKKKSFSKEELMSSDLEETAGSTSIPKRKKSTPKEETVNDPEEAGHRSGSKKKRKFSKEEPVSSGPEEAVGKSSSKKKKKFHKASQED"
comments "FUNCTION: Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs. {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333}. SUBUNIT: Part of a large pre-ribosomal ribonucleoprotein (RNP) complex, that consists of at least 62 ribosomal proteins, 45 nonribosomal proteins and both pre-rRNA and mature rRNA species. Within this complex directly interacts with TCOF1 in an RNA-independent manner. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles; the core proteins SNU13, NOP56, NOP58 and FBL assemble stepwise onto the snoRNA. Interacts NOP1 and NOP58. Interacts with NUFIP1, RUVBL1 and RUVBL2; RUVBL1:RUVBL2 seem to bridge the association of NOP56 with NUFIP1. {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:19620283}. SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:9372940}. Cytoplasm {ECO:0000250|UniProtKB:Q9D6Z1}. Nucleus, nucleoplasm {ECO:0000305|PubMed:15574333}. DISEASE: Spinocerebellar ataxia 36 (SCA36) [MIM:614153]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA36 is characterized by complicated clinical features, with ataxia as the first symptom, followed by characteristic late-onset involvement of the motor neuron system. Ataxic symptoms, such as gait and truncal instability, ataxic dysarthria, and uncoordinated limbs, start in late forties to fifties. Characteristically, affected individuals exhibit tongue atrophy with fasciculation. Progression of motor neuron involvement is typically limited to the tongue and main proximal skeletal muscles in both upper and lower extremities. {ECO:0000269|PubMed:21683323}. Note=The disease is caused by mutations affecting the gene represented in this entry. Caused by large hexanucleotide CGCCTG repeat expansions within intron 1. These expansions induce RNA foci and sequester the RNA-binding protein SRSF2. In addition, the transcription of MIR1292, a microRNA gene located just 19 bp 3' of the GGCCTG repeat, is significantly decreased. SIMILARITY: Belongs to the NOP5/NOP56 family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=CAA72789.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};"
primaryDomainId "uniprot.O00567"
displayName "NOP56_HUMAN"
synonyms "Nucleolar protein 56, Nucleolar protein 5A"
taxid 9606
geneName "NOP56"
type "Protein"
graphics [
fill "#00FF00"
]
name "O00567"