IRS4_HUMAN
ID IRS4_HUMAN Reviewed; 1257 AA.
AC O14654;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Insulin receptor substrate 4;
DE Short=IRS-4;
DE AltName: Full=160 kDa phosphotyrosine protein;
DE Short=py160;
DE AltName: Full=Phosphoprotein of 160 kDa;
DE Short=pp160;
GN Name=IRS4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 100-117; 233-240; 613-618;
RP 836-843 AND 844-852, AND PHOSPHORYLATION.
RC TISSUE=Kidney;
RX PubMed=9261155; DOI=10.1074/jbc.272.34.21403;
RA Lavan B.E., Fantin V.R., Chang E.T., Lane W.S., Keller S.R., Lienhard G.E.;
RT "A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic
RT kidney cells is a new member of the insulin receptor substrate family.";
RL J. Biol. Chem. 272:21403-21407(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GRB2 AND PIK3R1, AND
RP PHOSPHORYLATION.
RX PubMed=9553137; DOI=10.1074/jbc.273.17.10726;
RA Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E.,
RA Lavan B.E.;
RT "Characterization of insulin receptor substrate 4 in human embryonic kidney
RT 293 cells.";
RL J. Biol. Chem. 273:10726-10732(1998).
RN [5]
RP INTERACTION WITH CRK AND CRKL.
RX PubMed=9614078; DOI=10.1074/jbc.273.24.14780;
RA Koval A.P., Karas M., Zick Y., LeRoith D.;
RT "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like
RT growth factor-I receptor-mediated signal transduction.";
RL J. Biol. Chem. 273:14780-14787(1998).
RN [6]
RP FUNCTION.
RX PubMed=10531310; DOI=10.1074/jbc.274.44.31179;
RA Qu B.-H., Karas M., Koval A., LeRoith D.;
RT "Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced
RT cell proliferation.";
RL J. Biol. Chem. 274:31179-31184(1999).
RN [7]
RP FUNCTION, AND INTERACTION WITH GRB2 AND PIK3R1.
RX PubMed=10594015; DOI=10.1128/mcb.20.1.126-138.2000;
RA Uchida T., Myers M.G. Jr., White M.F.;
RT "IRS-4 mediates protein kinase B signaling during insulin stimulation
RT without promoting antiapoptosis.";
RL Mol. Cell. Biol. 20:126-138(2000).
RN [8]
RP INTERACTION WITH CRK, AND MUTAGENESIS OF TYR-700; TYR-717; TYR-743 AND
RP TYR-779.
RX PubMed=11316748; DOI=10.1210/endo.142.5.8135;
RA Karas M., Koval A.P., Zick Y., LeRoith D.;
RT "The insulin-like growth factor I receptor-induced interaction of insulin
RT receptor substrate-4 and Crk-II.";
RL Endocrinology 142:1835-1840(2001).
RN [9]
RP INTERACTION WITH NISCH.
RX PubMed=11912194; DOI=10.1074/jbc.m111838200;
RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.;
RT "Insulin receptor substrate 4 associates with the protein IRAS.";
RL J. Biol. Chem. 277:19439-19447(2002).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12639902; DOI=10.1210/en.2002-220723;
RA Schreyer S., Ledwig D., Rakatzi I., Kloeting I., Eckel J.;
RT "Insulin receptor substrate-4 is expressed in muscle tissue without acting
RT as a substrate for the insulin receptor.";
RL Endocrinology 144:1211-1218(2003).
RN [11]
RP PHOSPHORYLATION AT TYR-921, INTERACTION WITH SHC1; GRB2; PHOSPHOLIPASE
RP C-GAMMA AND PHOSPHATIDYLINOSITOL 3-KINASE, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15316024; DOI=10.1074/jbc.m404537200;
RA Hinsby A.M., Olsen J.V., Mann M.;
RT "Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role
RT for insulin receptor substrate-4.";
RL J. Biol. Chem. 279:46438-46447(2004).
RN [12]
RP INTERACTION WITH PPP4C, INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15331607; DOI=10.1074/jbc.m408067200;
RA Mihindukulasuriya K.A., Zhou G., Qin J., Tan T.-H.;
RT "Protein phosphatase 4 interacts with and down-regulates insulin receptor
RT substrate 4 following tumor necrosis factor-alpha stimulation.";
RL J. Biol. Chem. 279:46588-46594(2004).
RN [13]
RP INTERACTION WITH PTK6, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15870689; DOI=10.1038/sj.onc.1208721;
RA Qiu H., Zappacosta F., Su W., Annan R.S., Miller W.T.;
RT "Interaction between Brk kinase and insulin receptor substrate-4.";
RL Oncogene 24:5656-5664(2005).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17408801; DOI=10.1016/j.jhep.2007.01.031;
RA Cuevas E.P., Escribano O., Chiloeches A., Ramirez Rubio S., Roman I.D.,
RA Fernandez-Moreno M.D., Guijarro L.G.;
RT "Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2
RT proliferation.";
RL J. Hepatol. 46:1089-1098(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-20; GLU-215 AND ARG-557.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [17]
RP INVOLVEMENT IN CHNG9, AND VARIANT CHNG9 215-GLY--ARG-1257 DEL.
RX PubMed=30061370; DOI=10.1136/jmedgenet-2017-105113;
RA Heinen C.A., de Vries E.M., Alders M., Bikker H., Zwaveling-Soonawala N.,
RA van den Akker E.L.T., Bakker B., Hoorweg-Nijman G., Roelfsema F.,
RA Hennekam R.C., Boelen A., van Trotsenburg A.S.P., Fliers E.;
RT "Mutations in IRS4 are associated with central hypothyroidism.";
RL J. Med. Genet. 55:693-700(2018).
CC -!- FUNCTION: Acts as an interface between multiple growth factor receptors
CC possessing tyrosine kinase activity, such as insulin receptor, IGF1R
CC and FGFR1, and a complex network of intracellular signaling molecules
CC containing SH2 domains. Involved in the IGF1R mitogenic signaling
CC pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation
CC during insulin stimulation without activation of RPS6KB1 or the
CC inhibition of apoptosis. Interaction with GRB2 enhances insulin-
CC stimulated mitogen-activated protein kinase activity. May be involved
CC in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal
CC role in the proliferation/differentiation of hepatoblastoma cell
CC through EPHB2 activation upon IGF1 stimulation. May play a role in the
CC signal transduction in response to insulin and to a lesser extent in
CC response to IL4 and GH on mitogenesis. Plays a role in growth,
CC reproduction and glucose homeostasis. May act as negative regulators of
CC the IGF1 signaling pathway by suppressing the function of IRS1 and
CC IRS2. {ECO:0000269|PubMed:10531310, ECO:0000269|PubMed:10594015,
CC ECO:0000269|PubMed:12639902, ECO:0000269|PubMed:17408801,
CC ECO:0000269|PubMed:9553137}.
CC -!- SUBUNIT: Interacts with SOCS6 in response to stimulation with either
CC insulin or IGF1 (By similarity). Interacts with CRK and CRKL.
CC Interaction with CRK is stronger than with CRKL. Interacts with CRK via
CC the phosphorylated YXXM motifs. Interacts with GRB2 and PIK3R1.
CC Interacts with PLC-gamma, SHC1, PTK6, PPP4C and NISCH. {ECO:0000250,
CC ECO:0000269|PubMed:10594015, ECO:0000269|PubMed:11316748,
CC ECO:0000269|PubMed:11912194, ECO:0000269|PubMed:15316024,
CC ECO:0000269|PubMed:15331607, ECO:0000269|PubMed:15870689,
CC ECO:0000269|PubMed:9553137, ECO:0000269|PubMed:9614078}.
CC -!- INTERACTION:
CC O14654; P46108: CRK; NbExp=9; IntAct=EBI-356594, EBI-886;
CC O14654; P00533: EGFR; NbExp=2; IntAct=EBI-356594, EBI-297353;
CC O14654; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-356594, EBI-720768;
CC O14654; Q15185: PTGES3; NbExp=2; IntAct=EBI-356594, EBI-1049387;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9553137};
CC Peripheral membrane protein {ECO:0000269|PubMed:9553137}; Cytoplasmic
CC side {ECO:0000269|PubMed:9553137}.
CC -!- TISSUE SPECIFICITY: Expressed in myoblasts. Expressed in liver and
CC hepatocellular carcinoma. {ECO:0000269|PubMed:12639902,
CC ECO:0000269|PubMed:17408801}.
CC -!- INDUCTION: Down-regulated by PPP4C in a phosphatase activity-dependent
CC manner. {ECO:0000269|PubMed:15331607}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to both insulin
CC and IGF1 signaling. Phosphorylated on Tyr-921 in response to FGF2
CC signaling. Phosphorylation of Tyr-921 is required for GRB2,
CC phospholipase C-gamma and phosphatidylinositol 3-kinase interaction.
CC {ECO:0000269|PubMed:15316024, ECO:0000269|PubMed:9261155,
CC ECO:0000269|PubMed:9553137}.
CC -!- DISEASE: Hypothyroidism, congenital, non-goitrous, 9 (CHNG9)
CC [MIM:301035]: A form of central hypothyroidism, a disorder
CC characterized by sub-optimal thyroid hormone secretion, due to
CC insufficient stimulation by thyrotropin of an otherwise normal thyroid
CC gland. It may be caused by congenital or acquired disorders of the
CC pituitary gland or hypothalamus. CHNG9 is a congenital, X-linked
CC recessive form. Patients have a small thyroid gland with low free T4
CC levels and inappropriately normal levels of thyrotropin.
CC {ECO:0000269|PubMed:30061370}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF007567; AAC51738.1; -; mRNA.
DR EMBL; AL035425; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471120; EAX02682.1; -; Genomic_DNA.
DR CCDS; CCDS14544.1; -.
DR RefSeq; NP_003595.1; NM_003604.2.
DR AlphaFoldDB; O14654; -.
DR SMR; O14654; -.
DR BioGRID; 114048; 241.
DR IntAct; O14654; 131.
DR MINT; O14654; -.
DR STRING; 9606.ENSP00000361202; -.
DR GlyGen; O14654; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14654; -.
DR PhosphoSitePlus; O14654; -.
DR BioMuta; IRS4; -.
DR MassIVE; O14654; -.
DR MaxQB; O14654; -.
DR PaxDb; O14654; -.
DR PeptideAtlas; O14654; -.
DR PRIDE; O14654; -.
DR ProteomicsDB; 48151; -.
DR Antibodypedia; 15310; 172 antibodies from 31 providers.
DR DNASU; 8471; -.
DR Ensembl; ENST00000564206.2; ENSP00000505547.1; ENSG00000133124.12.
DR GeneID; 8471; -.
DR KEGG; hsa:8471; -.
DR UCSC; uc004eoc.3; human.
DR CTD; 8471; -.
DR DisGeNET; 8471; -.
DR GeneCards; IRS4; -.
DR HGNC; HGNC:6128; IRS4.
DR HPA; ENSG00000133124; Tissue enhanced (brain, choroid plexus, ovary, pituitary gland).
DR MalaCards; IRS4; -.
DR MIM; 300904; gene.
DR MIM; 301035; phenotype.
DR neXtProt; NX_O14654; -.
DR OpenTargets; ENSG00000133124; -.
DR PharmGKB; PA29923; -.
DR VEuPathDB; HostDB:ENSG00000133124; -.
DR eggNOG; ENOG502SD84; Eukaryota.
DR GeneTree; ENSGT00940000160883; -.
DR HOGENOM; CLU_290952_0_0_1; -.
DR InParanoid; O14654; -.
DR OMA; EDSRGYM; -.
DR OrthoDB; 298675at2759; -.
DR PhylomeDB; O14654; -.
DR TreeFam; TF325994; -.
DR PathwayCommons; O14654; -.
DR Reactome; R-HSA-2428928; IRS-related events triggered by IGF1R.
DR SignaLink; O14654; -.
DR SIGNOR; O14654; -.
DR BioGRID-ORCS; 8471; 19 hits in 700 CRISPR screens.
DR GeneWiki; IRS4; -.
DR GenomeRNAi; 8471; -.
DR Pharos; O14654; Tbio.
DR PRO; PR:O14654; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O14654; protein.
DR Bgee; ENSG00000133124; Expressed in pituitary gland and 27 other tissues.
DR Genevisible; O14654; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005158; F:insulin receptor binding; IBA:GO_Central.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IBA:GO_Central.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd01204; PTB_IRS; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR039011; IRS.
DR InterPro; IPR002404; IRS_PTB.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR10614; PTHR10614; 1.
DR Pfam; PF02174; IRS; 1.
DR PRINTS; PR00628; INSULINRSI.
DR SMART; SM00233; PH; 1.
DR SMART; SM00310; PTBI; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Congenital hypothyroidism; Direct protein sequencing;
KW Disease variant; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW Transducer.
FT CHAIN 1..1257
FT /note="Insulin receptor substrate 4"
FT /id="PRO_0000314678"
FT DOMAIN 78..199
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 231..335
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 406..653
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..921
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..800
FT /note="CRK-binding"
FT REGION 895..897
FT /note="GRB2-binding"
FT REGION 1179..1257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 487..490
FT /note="YXXM motif 1"
FT MOTIF 700..703
FT /note="YXXM motif 2"
FT MOTIF 717..720
FT /note="YXXM motif 3"
FT MOTIF 743..746
FT /note="YXXM motif 4"
FT MOTIF 779..782
FT /note="YXXM motif 5"
FT MOTIF 828..831
FT /note="YXXM motif 6"
FT MOTIF 921..924
FT /note="YXXM motif 7"
FT COMPBIAS 454..470
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..642
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..701
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 716..730
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 762..776
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 794..825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 904..918
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1220..1257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 921
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15316024"
FT VARIANT 20
FT /note="A -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_038042"
FT VARIANT 34
FT /note="L -> F (in dbSNP:rs1801162)"
FT /id="VAR_051078"
FT VARIANT 215..1257
FT /note="Missing (in CHNG9)"
FT /evidence="ECO:0000269|PubMed:30061370"
FT /id="VAR_083291"
FT VARIANT 215
FT /note="G -> E (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_038043"
FT VARIANT 508
FT /note="N -> K (in dbSNP:rs34287560)"
FT /id="VAR_051079"
FT VARIANT 557
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_038044"
FT VARIANT 879
FT /note="H -> D (in dbSNP:rs1801164)"
FT /id="VAR_051080"
FT VARIANT 1230
FT /note="D -> Y (in dbSNP:rs28546943)"
FT /id="VAR_061669"
FT MUTAGEN 700
FT /note="Y->F: No effect. Reduces interaction with CRK by
FT 50%; when associated with F-717. Abolishes interaction with
FT CRK; when associated with F-717; F-743 and F-779."
FT /evidence="ECO:0000269|PubMed:11316748"
FT MUTAGEN 717
FT /note="Y->F: No effect. Reduces interaction with CRK by
FT 50%; when associated with F-700. Abolishes interaction with
FT CRK; when associated with F-700; F-743 and F-779."
FT /evidence="ECO:0000269|PubMed:11316748"
FT MUTAGEN 743
FT /note="Y->F: No effect. Reduces interaction with CRK by
FT 50%; when associated with F-779. Abolishes interaction with
FT CRK; when associated with F-700; F-717 and F-779."
FT /evidence="ECO:0000269|PubMed:11316748"
FT MUTAGEN 779
FT /note="Y->F: No effect. Reduces interaction with CRK by
FT 50%; when associated with F-743. Abolishes interaction with
FT CRK; when associated with F-700; F-717 and F-743."
FT /evidence="ECO:0000269|PubMed:11316748"
SQ SEQUENCE 1257 AA; 133768 MW; 4D512D65A7A80374 CRC64;
MASCSFTRDQ ATRRLRGAAA AAAAALAAVV TTPLLSSGTP TALIGTGSSC PGAMWLSTAT
GSRSDSESEE EDLPVGEEVC KRGYLRKQKH GHRRYFVLKL ETADAPARLE YYENARKFRH
SVRAAAAAAA AAASGAAIPP LIPPRRVITL YQCFSVSQRA DARYRHLIAL FTQDEYFAMV
AENESEQESW YLLLSRLILE SKRRRCGTLG AQPDGEPAAL AAAAAAEPPF YKDVWQVIVK
PRGLGHRKEL SGVFRLCLTD EEVVFVRLNT EVASVVVQLL SIRRCGHSEQ YFFLEVGRST
VIGPGELWMQ VDDCVVAQNM HELFLEKMRA LCADEYRARC RSYSISIGAH LLTLLSARRH
LGLVPLEPGG WLRRSRFEQF CHLRAIGDGE DEMLFTRRFV TPSEPVAHSR RGRLHLPRGR
RSRRAVSVPA SFFRRLAPSP ARPRHPAEAP NNGARLSSEV SGSGSGNFGE EGNPQGKEDQ
EGSGGDYMPM NNWGSGNGRG SGGGQGSNGQ GSSSHSSGGN QCSGEGQGSR GGQGSNGQGS
GGNQCSRDGQ GTAGGHGSGG GQRPGGGHGS GGGQGPGDGH GSGGGKNSGG GKGSGSGKGS
DGDGERGKSL KKRSYFGKLT QSKQQQMPPP PPPPPPPPPA GGTGGKGKSG GRFRLYFCVD
RGATKECKEA KEVKDAEIPE GAARGPHRAR AFDEDEDDPY VPMRPGVATP LVSSSDYMPM
APQNVSASKK RHSRSPFEDS RGYMMMFPRV SPPPAPSPPK APDTNKEDDS KDNDSESDYM
FMAPGAGAIP KNPRNPQGGS SSKSWSSYFS LPNPFRSSPL GQNDNSEYVP MLPGKFLGRG
LDKEVSYNWD PKDAASKPSG EGSFSKPGDG GSPSKPSDHE PPKNKAKRPN RLSFITKGYK
IKPKPQKPTH EQREADSSSD YVNMDFTKRE SNTPAPSTQG LPDSWGIIAE PRQSAFSNYV
NVEFGVPFPN PANDLSDLLR AIPRANPLSL DSARWPLPPL PLSATGSNAI EEEGDYIEVI
FNSAMTPAMA LADSAIRYDA ETGRIYVVDP FSECCMDISL SPSRCSEPPP VARLLQEEEQ
ERRRPQSRSQ SFFAAARAAV SAFPTDSLER DLSPSSAPAV ASAAEPTLAL SQVVAAASAL
AAAPGIGAAA AAAGFDSASA RWFQPVANAA DAEAVRGAQD VAGGSNPGAH NPSANLARGD
NQAGGAAAAA AAPEPPPRSR RVPRPPERED SDNDDDTHVR MDFARRDNQF DSPKRGR
