CRK_HUMAN
ID CRK_HUMAN Reviewed; 304 AA.
AC P46108; A8MWE8; B0LPE8; D3DTH6; Q96GA9; Q96HJ0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Adapter molecule crk;
DE AltName: Full=Proto-oncogene c-Crk;
DE AltName: Full=p38;
GN Name=CRK;
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] (ISOFORM CRK-II), FUNCTION (ISOFORM CRK-II), AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Embryonic lung, and Placenta;
RX PubMed=1630456; DOI=10.1128/mcb.12.8.3482-3489.1992;
RA Matsuda M., Tanaka S., Nagata S., Kojima A., Kurata T., Shibuya M.;
RT "Two species of human CRK cDNA encode proteins with distinct biological
RT activities.";
RL Mol. Cell. Biol. 12:3482-3489(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8378094;
RA Fioretos T., Heisterkamp N., Groffen J., Benjes S., Morris C.;
RT "CRK proto-oncogene maps to human chromosome band 17p13.";
RL Oncogene 8:2853-2855(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRK-II).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRK-I).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CRK-I AND CRK-II).
RC TISSUE=Eye, Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH DOCK1.
RX PubMed=8657152; DOI=10.1128/mcb.16.4.1770;
RA Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N., Shibuya M.,
RA Kurata T., Matsuda M.;
RT "DOCK180, a major CRK-binding protein, alters cell morphology upon
RT translocation to the cell membrane.";
RL Mol. Cell. Biol. 16:1770-1776(1996).
RN [10]
RP INTERACTION WITH DOCK1; C3G AND EPS15, AND MUTAGENESIS OF ASP-150.
RX PubMed=8662907; DOI=10.1074/jbc.271.24.14468;
RA Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T.,
RA Nagashima K., Kurata T.;
RT "Interaction between the amino-terminal SH3 domain of CRK and its natural
RT target proteins.";
RL J. Biol. Chem. 271:14468-14472(1996).
RN [11]
RP INTERACTION WITH IRS4.
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 [12]
RP INTERACTION WITH CBLC.
RX PubMed=10362357; DOI=10.1038/sj.onc.1202753;
RA Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M., Penninger J.,
RA Lipkowitz S.;
RT "cbl-3: a new mammalian cbl family protein.";
RL Oncogene 18:3365-3375(1999).
RN [13]
RP INTERACTION WITH PDGFRA AND PDGFRB.
RX PubMed=10733900; DOI=10.1006/bbrc.2000.2374;
RA Matsumoto T., Yokote K., Take A., Takemoto M., Asaumi S., Hashimoto Y.,
RA Matsuda M., Saito Y., Mori S.;
RT "Differential interaction of CrkII adaptor protein with platelet-derived
RT growth factor alpha- and beta-receptors is determined by its internal
RT tyrosine phosphorylation.";
RL Biochem. Biophys. Res. Commun. 270:28-33(2000).
RN [14]
RP INTERACTION WITH SHB.
RX PubMed=10964504; DOI=10.1006/excr.2000.4984;
RA Lu L., Anneren C., Reedquist K.A., Bos J.L., Welsh M.;
RT "NGF-dependent neurite outgrowth in PC12 cells overexpressing the Src
RT homology 2-domain protein shb requires activation of the Rap1 pathway.";
RL Exp. Cell Res. 259:370-377(2000).
RN [15]
RP FUNCTION (ISOFORM CRK-II), AND INTERACTION WITH EPHA3.
RX PubMed=11870224; DOI=10.1242/jcs.115.5.1059;
RA Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M.,
RA Boyd A.W., Alewood P.F., Lackmann M.;
RT "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing
RT 293T and melanoma cells by CrkII and Rho-mediated signalling.";
RL J. Cell Sci. 115:1059-1072(2002).
RN [16]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH SH2D3C AND BCAR1, AND
RP MUTAGENESIS OF TRP-169.
RX PubMed=12432078; DOI=10.1242/jcs.00207;
RA Sakakibara A., Ohba Y., Kurokawa K., Matsuda M., Hattori S.;
RT "Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-
RT pathway-mediated Rap1 activation.";
RL J. Cell Sci. 115:4915-4924(2002).
RN [17]
RP INTERACTION WITH DOCK4.
RX PubMed=12628187; DOI=10.1016/s0092-8674(03)00155-7;
RA Yajnik V., Paulding C., Sordella R., McClatchey A.I., Saito M.,
RA Wahrer D.C.R., Reynolds P., Bell D.W., Lake R., van den Heuvel S.,
RA Settleman J., Haber D.A.;
RT "DOCK4, a GTPase activator, is disrupted during tumorigenesis.";
RL Cell 112:673-684(2003).
RN [18]
RP INTERACTION WITH KIT, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP PHOSPHORYLATION.
RX PubMed=12878163; DOI=10.1016/s0014-4827(03)00206-4;
RA Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.;
RT "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent
RT phosphorylation site mediating interaction with c-Crk.";
RL Exp. Cell Res. 288:110-118(2003).
RN [19]
RP INTERACTION WITH FLT4.
RX PubMed=16076871; DOI=10.1182/blood-2005-04-1388;
RA Salameh A., Galvagni F., Bardelli M., Bussolino F., Oliviero S.;
RT "Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation,
RT migration, and survival of endothelial cells through the activation of ERK,
RT AKT, and JNK pathways.";
RL Blood 106:3423-3431(2005).
RN [20]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [22]
RP INTERACTION WITH BCAR1; CDC42 AND TNK2.
RX PubMed=17038317; DOI=10.1074/jbc.m604342200;
RA Modzelewska K., Newman L.P., Desai R., Keely P.J.;
RT "Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas.";
RL J. Biol. Chem. 281:37527-37535(2006).
RN [23]
RP INTERACTION WITH PDPK1.
RX PubMed=18024423; DOI=10.1074/jbc.m706361200;
RA Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., Won M.,
RA Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P.,
RA Hemmings B.A., Park J.;
RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src
RT involves tyrosine phosphorylation of PDK1 and Src homology 2 domain
RT binding.";
RL J. Biol. Chem. 283:1480-1491(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74 AND SER-83, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [26]
RP FUNCTION (ISOFORM CRK-II), INTERACTION WITH DOCK5, AND MUTAGENESIS OF
RP TRP-169.
RX PubMed=19004829; DOI=10.1074/jbc.m808010200;
RA Sanders M.A., Ampasala D., Basson M.D.;
RT "DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and
RT migration on collagen IV.";
RL J. Biol. Chem. 284:27-35(2009).
RN [27]
RP IDENTIFICATION IN A COMPLEX WITH ABL1; ABL2 AND UNC119.
RX PubMed=19381274; DOI=10.1371/journal.pone.0005211;
RA Vepachedu R., Karim Z., Patel O., Goplen N., Alam R.;
RT "Unc119 protects from Shigella infection by inhibiting the Abl family
RT kinases.";
RL PLoS ONE 4:E5211-E5211(2009).
RN [28]
RP INTERACTION WITH PEAK1.
RX PubMed=20534451; DOI=10.1073/pnas.0914776107;
RA Wang Y., Kelber J.A., Tran Cao H.S., Cantin G.T., Lin R., Wang W.,
RA Kaushal S., Bristow J.M., Edgington T.S., Hoffman R.M., Bouvet M.,
RA Yates J.R. III, Klemke R.L.;
RT "Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and
RT cancer progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10920-10925(2010).
RN [29]
RP ERRATUM OF PUBMED:20534451.
RA Wang Y., Kelber J.A., Tran Cao H.S., Cantin G.T., Lin R., Wang W.,
RA Kaushal S., Bristow J.M., Edgington T.S., Hoffman R.M., Bouvet M.,
RA Yates J.R. III, Klemke R.L.;
RL Proc. Natl. Acad. Sci. U.S.A. 107:13556-13556(2010).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-74,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194 (ISOFORM CRK-I), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-41; TYR-108 AND
RP SER-125, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [37]
RP FUNCTION (ISOFORM CRK-II), INTERACTION WITH PEAK3 (ISOFORM CRK-II), AND
RP MUTAGENESIS OF TRP-169 AND TRP-275.
RX PubMed=31311869; DOI=10.1073/pnas.1906360116;
RA Lopez M.L., Lo M., Kung J.E., Dudkiewicz M., Jang G.M., Von Dollen J.,
RA Johnson J.R., Krogan N.J., Pawlowski K., Jura N.;
RT "PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits
RT CrkII through dimerization.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:15495-15504(2019).
RN [38]
RP STRUCTURE BY NMR OF 12-120 IN COMPLEX WITH ABL1, AND INTERACTION OF THE CRK
RP SH2 DOMAIN WITH PHOSPHORYLATED TYR-221.
RX PubMed=12384576; DOI=10.1073/pnas.212518799;
RA Donaldson L.W., Gish G., Pawson T., Kay L.E., Forman-Kay J.D.;
RT "Structure of a regulatory complex involving the Abl SH3 domain, the Crk
RT SH2 domain, and a Crk-derived phosphopeptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002).
RN [39]
RP STRUCTURE BY NMR (ISOFORMS CRK-I AND CRK-II), FUNCTION (ISOFORM CRK-II),
RP AND PHOSPHORYLATION AT TYR-221.
RX PubMed=17515907; DOI=10.1038/nsmb1241;
RA Kobashigawa Y., Sakai M., Naito M., Yokochi M., Kumeta H., Makino Y.,
RA Ogura K., Tanaka S., Inagaki F.;
RT "Structural basis for the transforming activity of human cancer-related
RT signaling adaptor protein CRK.";
RL Nat. Struct. Mol. Biol. 14:503-510(2007).
CC -!- FUNCTION: Involved in cell branching and adhesion mediated by BCAR1-
CC CRK-RAPGEF1 signaling and activation of RAP1.
CC {ECO:0000269|PubMed:12432078}.
CC -!- FUNCTION: [Isoform Crk-II]: Regulates cell adhesion, spreading and
CC migration (PubMed:31311869). Mediates attachment-induced MAPK8
CC activation, membrane ruffling and cell motility in a Rac-dependent
CC manner. Involved in phagocytosis of apoptotic cells and cell motility
CC via its interaction with DOCK1 and DOCK4 (PubMed:19004829). May
CC regulate the EFNA5-EPHA3 signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q64010, ECO:0000269|PubMed:11870224,
CC ECO:0000269|PubMed:1630456, ECO:0000269|PubMed:17515907,
CC ECO:0000269|PubMed:19004829, ECO:0000269|PubMed:31311869}.
CC -!- SUBUNIT: Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK
CC (PubMed:12432078). Within the complex, interacts with SH2D3C (via C-
CC terminus), and BCAR1/CAS (PubMed:12432078). Found in a complex with
CC ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK
CC phosphorylation by ABL kinases (PubMed:19381274). Interacts with ABL1,
CC C3G, DOCK3, DOCK5, MAP4K1, MAPK8 and SOS via its first SH3 domain.
CC Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1
CC upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2
CC domain) with several tyrosine-phosphorylated growth factor receptors
CC such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated).
CC Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with
CC PEAK1. Interacts with FASLG. Part of a collagen stimulated complex
CC involved in cell migration composed of CDC42, CRK, TNK2 and
CC p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9'
CC phosphorylated form of PDPK1. Interacts with CBLC.
CC {ECO:0000269|PubMed:10362357, ECO:0000269|PubMed:10964504,
CC ECO:0000269|PubMed:12384576, ECO:0000269|PubMed:12432078,
CC ECO:0000269|PubMed:12628187, ECO:0000269|PubMed:12878163,
CC ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:17038317,
CC ECO:0000269|PubMed:18024423, ECO:0000269|PubMed:19381274,
CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20534451,
CC ECO:0000269|PubMed:8657152, ECO:0000269|PubMed:8662907,
CC ECO:0000269|PubMed:9614078}.
CC -!- SUBUNIT: [Isoform Crk-II]: Interacts (via SH2 domain) with PDGFRA
CC (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated)
CC (PubMed:10733900). Interacts with EPHA3 (phosphorylated); upon
CC activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase
CC activity-dependent and mediates EFNA5-EPHA3 signaling through RHOA
CC GTPase activation (PubMed:11870224). Interacts with KIT
CC (PubMed:12878163). Interacts with PEAK3; the interaction requires PEAK3
CC homodimerization (PubMed:31311869). {ECO:0000269|PubMed:10733900,
CC ECO:0000269|PubMed:11870224, ECO:0000269|PubMed:12878163,
CC ECO:0000269|PubMed:31311869}.
CC -!- INTERACTION:
CC P46108; P00519: ABL1; NbExp=4; IntAct=EBI-886, EBI-375543;
CC P46108; P42684: ABL2; NbExp=5; IntAct=EBI-886, EBI-1102694;
CC P46108; P51825: AFF1; NbExp=2; IntAct=EBI-886, EBI-2610180;
CC P46108; Q96P48: ARAP1; NbExp=3; IntAct=EBI-886, EBI-710003;
CC P46108; A7KAX9: ARHGAP32; NbExp=4; IntAct=EBI-886, EBI-308663;
CC P46108; O15085: ARHGEF11; NbExp=2; IntAct=EBI-886, EBI-311099;
CC P46108; Q9ULH1: ASAP1; NbExp=5; IntAct=EBI-886, EBI-346622;
CC P46108; O43150: ASAP2; NbExp=2; IntAct=EBI-886, EBI-310968;
CC P46108; Q8TDY4: ASAP3; NbExp=6; IntAct=EBI-886, EBI-2609717;
CC P46108; Q96DX5: ASB9; NbExp=2; IntAct=EBI-886, EBI-745641;
CC P46108; P54253: ATXN1; NbExp=9; IntAct=EBI-886, EBI-930964;
CC P46108; P56945: BCAR1; NbExp=7; IntAct=EBI-886, EBI-702093;
CC P46108; Q9NZM4: BICRA; NbExp=3; IntAct=EBI-886, EBI-1754943;
CC P46108; O43683: BUB1; NbExp=2; IntAct=EBI-886, EBI-748936;
CC P46108; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-886, EBI-946029;
CC P46108; P22681: CBL; NbExp=10; IntAct=EBI-886, EBI-518228;
CC P46108; Q13191: CBLB; NbExp=4; IntAct=EBI-886, EBI-744027;
CC P46108; Q9P1A6: DLGAP2; NbExp=2; IntAct=EBI-886, EBI-1753397;
CC P46108; Q14185: DOCK1; NbExp=4; IntAct=EBI-886, EBI-446740;
CC P46108; Q8IZD9: DOCK3; NbExp=2; IntAct=EBI-886, EBI-1752361;
CC P46108; Q9H7D0: DOCK5; NbExp=3; IntAct=EBI-886, EBI-1773858;
CC P46108; Q7L190: DPPA4; NbExp=5; IntAct=EBI-886, EBI-710457;
CC P46108; Q86Y01: DTX1; NbExp=2; IntAct=EBI-886, EBI-1755174;
CC P46108; P00533: EGFR; NbExp=4; IntAct=EBI-886, EBI-297353;
CC P46108; P41970: ELK3; NbExp=4; IntAct=EBI-886, EBI-1758534;
CC P46108; P21860: ERBB3; NbExp=2; IntAct=EBI-886, EBI-720706;
CC P46108; Q96Q35-2: FLACC1; NbExp=3; IntAct=EBI-886, EBI-11533409;
CC P46108; P21333: FLNA; NbExp=3; IntAct=EBI-886, EBI-350432;
CC P46108; Q14315: FLNC; NbExp=2; IntAct=EBI-886, EBI-489954;
CC P46108; P36888: FLT3; NbExp=2; IntAct=EBI-886, EBI-3946257;
CC P46108; Q13480: GAB1; NbExp=2; IntAct=EBI-886, EBI-517684;
CC P46108; Q9H706: GAREM1; NbExp=4; IntAct=EBI-886, EBI-3440103;
CC P46108; P42858: HTT; NbExp=3; IntAct=EBI-886, EBI-466029;
CC P46108; O15357: INPPL1; NbExp=2; IntAct=EBI-886, EBI-1384248;
CC P46108; O14654: IRS4; NbExp=9; IntAct=EBI-886, EBI-356594;
CC P46108; P10721: KIT; NbExp=4; IntAct=EBI-886, EBI-1379503;
CC P46108; Q92918: MAP4K1; NbExp=4; IntAct=EBI-886, EBI-881;
CC P46108; Q9Y4K4: MAP4K5; NbExp=6; IntAct=EBI-886, EBI-1279;
CC P46108; P20774: OGN; NbExp=2; IntAct=EBI-886, EBI-1753690;
CC P46108; P16234: PDGFRA; NbExp=4; IntAct=EBI-886, EBI-2861522;
CC P46108; P27986: PIK3R1; NbExp=3; IntAct=EBI-886, EBI-79464;
CC P46108; O00459: PIK3R2; NbExp=5; IntAct=EBI-886, EBI-346930;
CC P46108; Q92569: PIK3R3; NbExp=4; IntAct=EBI-886, EBI-79893;
CC P46108; Q8ND30: PPFIBP2; NbExp=5; IntAct=EBI-886, EBI-744056;
CC P46108; P62333: PSMC6; NbExp=10; IntAct=EBI-886, EBI-357669;
CC P46108; Q05397: PTK2; NbExp=3; IntAct=EBI-886, EBI-702142;
CC P46108; P29074: PTPN4; NbExp=3; IntAct=EBI-886, EBI-710431;
CC P46108; Q13905: RAPGEF1; NbExp=5; IntAct=EBI-886, EBI-976876;
CC P46108; Q8TB24: RIN3; NbExp=2; IntAct=EBI-886, EBI-1570523;
CC P46108; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-886, EBI-3957636;
CC P46108; Q9UPX8: SHANK2; NbExp=2; IntAct=EBI-886, EBI-1570571;
CC P46108; O60493: SNX3; NbExp=2; IntAct=EBI-886, EBI-727209;
CC P46108; Q07889: SOS1; NbExp=7; IntAct=EBI-886, EBI-297487;
CC P46108; Q07890: SOS2; NbExp=3; IntAct=EBI-886, EBI-298181;
CC P46108; Q96T58: SPEN; NbExp=2; IntAct=EBI-886, EBI-765739;
CC P46108; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-886, EBI-750109;
CC P46108; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-886, EBI-11952721;
CC P46108; P42681: TXK; NbExp=3; IntAct=EBI-886, EBI-7877438;
CC P46108; Q70EK8: USP53; NbExp=12; IntAct=EBI-886, EBI-742050;
CC P46108; Q9BRX9: WDR83; NbExp=2; IntAct=EBI-886, EBI-7705033;
CC P46108; O40931: ORF39; Xeno; NbExp=2; IntAct=EBI-886, EBI-2608673;
CC P46108-1; P00533: EGFR; NbExp=3; IntAct=EBI-287556, EBI-297353;
CC P46108-1; P62937: PPIA; NbExp=4; IntAct=EBI-287556, EBI-437708;
CC P46108-1; Q13905: RAPGEF1; NbExp=3; IntAct=EBI-287556, EBI-976876;
CC P46108-2; P54253: ATXN1; NbExp=6; IntAct=EBI-287559, EBI-930964;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Translocated to the plasma membrane upon cell
CC adhesion. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Crk-II;
CC IsoId=P46108-1; Sequence=Displayed;
CC Name=Crk-I;
CC IsoId=P46108-2; Sequence=VSP_041153, VSP_041154;
CC -!- DOMAIN: The C-terminal SH3 domain function as a negative modulator for
CC transformation and the N-terminal SH3 domain appears to function as a
CC positive regulator for transformation. {ECO:0000250}.
CC -!- DOMAIN: The SH2 domain mediates interaction with tyrosine
CC phosphorylated proteins. Mediates interaction with SHB.
CC -!- PTM: Phosphorylated on Tyr-221 upon cell adhesion. Results in the
CC negative regulation of the association with SH2- and SH3-binding
CC partners, possibly by the formation of an intramolecular interaction of
CC phosphorylated Tyr-221 with the SH2 domain. This leads finally to the
CC down-regulation of the Crk signaling pathway (PubMed:17515907). Isoform
CC Crk-II: Phosphorylated by KIT (By similarity).
CC {ECO:0000250|UniProtKB:Q64010, ECO:0000269|PubMed:17515907}.
CC -!- PTM: Proline isomerization at Pro-237 by PPIA acts as a switch between
CC two conformations: an autoinhibitory conformation in the cis form,
CC where the tandem SH3 domains interact intramolecularly, and an
CC activated conformation in the trans form. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CRK family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CRKID40149ch17p13.html";
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DR EMBL; D10656; BAA01505.1; -; mRNA.
DR EMBL; S65701; AAB28213.1; -; Genomic_DNA.
DR EMBL; BT007277; AAP35941.1; -; mRNA.
DR EMBL; EU332838; ABY87527.1; -; Genomic_DNA.
DR EMBL; AK291060; BAF83749.1; -; mRNA.
DR EMBL; AC032044; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100748; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90621.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90624.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90625.1; -; Genomic_DNA.
DR EMBL; BC001718; AAH01718.1; -; mRNA.
DR EMBL; BC008506; AAH08506.1; -; mRNA.
DR EMBL; BC009837; AAH09837.1; -; mRNA.
DR CCDS; CCDS11002.1; -. [P46108-1]
DR CCDS; CCDS45561.1; -. [P46108-2]
DR PIR; A45022; A45022.
DR RefSeq; NP_005197.3; NM_005206.4. [P46108-2]
DR RefSeq; NP_058431.2; NM_016823.3. [P46108-1]
DR PDB; 1JU5; NMR; -; A=12-120.
DR PDB; 2DVJ; NMR; -; A=1-228.
DR PDB; 2EYV; NMR; -; A=6-124.
DR PDB; 2EYW; NMR; -; A=125-198.
DR PDB; 2EYX; NMR; -; A=232-298.
DR PDB; 2EYY; NMR; -; A=1-204.
DR PDB; 2EYZ; NMR; -; A=1-304.
DR PDB; 2MS4; NMR; -; B=216-224.
DR PDB; 5UL6; X-ray; 1.45 A; A=134-191.
DR PDB; 6ATV; X-ray; 1.75 A; A=134-191.
DR PDBsum; 1JU5; -.
DR PDBsum; 2DVJ; -.
DR PDBsum; 2EYV; -.
DR PDBsum; 2EYW; -.
DR PDBsum; 2EYX; -.
DR PDBsum; 2EYY; -.
DR PDBsum; 2EYZ; -.
DR PDBsum; 2MS4; -.
DR PDBsum; 5UL6; -.
DR PDBsum; 6ATV; -.
DR AlphaFoldDB; P46108; -.
DR BMRB; P46108; -.
DR SMR; P46108; -.
DR BioGRID; 107788; 320.
DR CORUM; P46108; -.
DR DIP; DIP-199N; -.
DR IntAct; P46108; 430.
DR MINT; P46108; -.
DR STRING; 9606.ENSP00000300574; -.
DR ChEMBL; CHEMBL5005; -.
DR MoonDB; P46108; Predicted.
DR iPTMnet; P46108; -.
DR MetOSite; P46108; -.
DR PhosphoSitePlus; P46108; -.
DR BioMuta; CRK; -.
DR DMDM; 158939322; -.
DR REPRODUCTION-2DPAGE; IPI00399054; -.
DR SWISS-2DPAGE; P46108; -.
DR EPD; P46108; -.
DR jPOST; P46108; -.
DR MassIVE; P46108; -.
DR MaxQB; P46108; -.
DR PaxDb; P46108; -.
DR PeptideAtlas; P46108; -.
DR PRIDE; P46108; -.
DR ProteomicsDB; 55732; -. [P46108-1]
DR ProteomicsDB; 55733; -. [P46108-2]
DR TopDownProteomics; P46108-1; -. [P46108-1]
DR TopDownProteomics; P46108-2; -. [P46108-2]
DR ABCD; P46108; 2 sequenced antibodies.
DR Antibodypedia; 4185; 628 antibodies from 38 providers.
DR DNASU; 1398; -.
DR Ensembl; ENST00000300574.3; ENSP00000300574.2; ENSG00000167193.8. [P46108-1]
DR Ensembl; ENST00000398970.5; ENSP00000381942.5; ENSG00000167193.8. [P46108-2]
DR GeneID; 1398; -.
DR KEGG; hsa:1398; -.
DR MANE-Select; ENST00000300574.3; ENSP00000300574.2; NM_016823.4; NP_058431.2.
DR UCSC; uc002fsl.4; human. [P46108-1]
DR CTD; 1398; -.
DR DisGeNET; 1398; -.
DR GeneCards; CRK; -.
DR HGNC; HGNC:2362; CRK.
DR HPA; ENSG00000167193; Low tissue specificity.
DR MIM; 164762; gene.
DR neXtProt; NX_P46108; -.
DR OpenTargets; ENSG00000167193; -.
DR PharmGKB; PA26880; -.
DR VEuPathDB; HostDB:ENSG00000167193; -.
DR eggNOG; KOG4792; Eukaryota.
DR GeneTree; ENSGT00820000127055; -.
DR HOGENOM; CLU_060542_1_0_1; -.
DR InParanoid; P46108; -.
DR OMA; WWNAEDG; -.
DR PhylomeDB; P46108; -.
DR TreeFam; TF321436; -.
DR PathwayCommons; P46108; -.
DR Reactome; R-HSA-170984; ARMS-mediated activation.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-HSA-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-HSA-8875656; MET receptor recycling.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; P46108; -.
DR SIGNOR; P46108; -.
DR BioGRID-ORCS; 1398; 62 hits in 1086 CRISPR screens.
DR ChiTaRS; CRK; human.
DR EvolutionaryTrace; P46108; -.
DR GeneWiki; CRK_(gene); -.
DR GenomeRNAi; 1398; -.
DR Pharos; P46108; Tchem.
DR PRO; PR:P46108; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P46108; protein.
DR Bgee; ENSG00000167193; Expressed in secondary oocyte and 217 other tissues.
DR ExpressionAtlas; P46108; baseline and differential.
DR Genevisible; P46108; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IC:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IPI:CAFA.
DR GO; GO:0008092; F:cytoskeletal protein binding; IEA:Ensembl.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0045309; F:protein phosphorylated amino acid binding; IDA:CAFA.
DR GO; GO:0043621; F:protein self-association; IDA:CAFA.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:CAFA.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IPI:CAFA.
DR GO; GO:0035591; F:signaling adaptor activity; IDA:CAFA.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IEA:Ensembl.
DR GO; GO:0060326; P:cell chemotaxis; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:1990859; P:cellular response to endothelin; IEA:Ensembl.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0098749; P:cerebellar neuron development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0016358; P:dendrite development; IEA:Ensembl.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; IEA:Ensembl.
DR GO; GO:0035685; P:helper T cell diapedesis; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl.
DR GO; GO:2000146; P:negative regulation of cell motility; IDA:CAFA.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0061045; P:negative regulation of wound healing; IDA:CAFA.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:CAFA.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0072657; P:protein localization to membrane; IEA:Ensembl.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:1902531; P:regulation of intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IMP:CAFA.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IEA:Ensembl.
DR GO; GO:0009966; P:regulation of signal transduction; IDA:CAFA.
DR GO; GO:2000404; P:regulation of T cell migration; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0061847; P:response to cholecystokinin; IEA:Ensembl.
DR GO; GO:0035728; P:response to hepatocyte growth factor; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0001878; P:response to yeast; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd11759; SH3_CRK_C; 1.
DR CDD; cd11758; SH3_CRK_N; 1.
DR DisProt; DP00748; -.
DR DisProt; DP00973; -. [P46108-2]
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035458; CRK_SH3_C.
DR InterPro; IPR035457; CRK_SH3_N.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm;
KW Membrane; Phosphoprotein; Proto-oncogene; Reference proteome; Repeat;
KW SH2 domain; SH3 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..304
FT /note="Adapter molecule crk"
FT /id="PRO_0000079351"
FT DOMAIN 13..118
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 132..192
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 235..296
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 61..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..82
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 237
FT /note="Proline switch"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 108
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 221
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:17515907"
FT MOD_RES 239
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT VAR_SEQ 204
FT /note="N -> R (in isoform Crk-I)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041153"
FT VAR_SEQ 205..304
FT /note="Missing (in isoform Crk-I)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041154"
FT MUTAGEN 150
FT /note="D->K: Abolishes interaction with DOCK1."
FT /evidence="ECO:0000269|PubMed:8662907"
FT MUTAGEN 169
FT /note="W->K: Abolishes interaction with PEAK3."
FT /evidence="ECO:0000269|PubMed:31311869"
FT MUTAGEN 169
FT /note="W->L: Abolishes interaction with DOCK5. Abolishes
FT RAP1 activation."
FT /evidence="ECO:0000269|PubMed:12432078,
FT ECO:0000269|PubMed:19004829"
FT MUTAGEN 275
FT /note="W->K: No effect on interaction with PEAK3."
FT /evidence="ECO:0000269|PubMed:31311869"
FT CONFLICT 109
FT /note="L -> W (in Ref. 1; BAA01505 and 2; AAB28213)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="G -> P (in Ref. 1; BAA01505 and 2; AAB28213)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="E -> G (in Ref. 1; BAA01505 and 2; AAB28213)"
FT /evidence="ECO:0000305"
FT STRAND 7..13
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:2EYY"
FT HELIX 20..27
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 70..77
FT /evidence="ECO:0007829|PDB:2DVJ"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:1JU5"
FT HELIX 97..106
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1JU5"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:2EYV"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:2EYY"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:5UL6"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:5UL6"
FT STRAND 165..173
FT /evidence="ECO:0007829|PDB:5UL6"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:5UL6"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:5UL6"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:5UL6"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:2DVJ"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:2EYZ"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:2EYZ"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:2EYX"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:2EYX"
FT STRAND 260..269
FT /evidence="ECO:0007829|PDB:2EYX"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:2EYX"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:2EYX"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:2EYX"
FT MOD_RES P46108-2:194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
SQ SEQUENCE 304 AA; 33831 MW; 4CFBFB65BFC2E265 CRC64;
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY
IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR
SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG
MIPVPYVEKY RPASASVSAL IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA
RVIQKRVPNA YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPD
EDFS
