RBCC

Full text data of CRK

CRK [Confidence: low (only semi-automatic identification from reviews)]
Adapter molecule crk (Proto-oncogene c-Crk; p38)

UniProt P46108
ID CRK_HUMAN Reviewed; 304 AA.
AC P46108; A8MWE8; B0LPE8; D3DTH6; Q96GA9; Q96HJ0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 24-JUL-2007, sequence version 2.
DT 22-JAN-2014, entry version 148.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRK-II), FUNCTION, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Embryonic lung, and Placenta;
RX PubMed=1630456;
RA Matsuda M., Tanaka S., Nagata S., Kojima A., Kurata T., Shibuya M.;
RT "Two species of human CRK cDNA encode proteins with distinct
RT biological 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH DOCK1.
RX PubMed=8657152;
RA Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N.,
RA Shibuya M., 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
RT natural 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-
RT like 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.,
RA Penninger J., 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.,
RA Hashimoto Y., Matsuda M., Saito Y., Mori S.;
RT "Differential interaction of CrkII adaptor protein with platelet-
RT derived growth factor alpha- and beta-receptors is determined by its
RT internal 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
RT pathway.";
RL Exp. Cell Res. 259:370-377(2000).
RN [15]
RP FUNCTION IN CELL-CELL ADHESION, AND INTERACTION WITH EPHA3.
RX PubMed=11870224;
RA Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M.,
RA Down M., Boyd A.W., Alewood P.F., Lackmann M.;
RT "Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-
RT expressing 293T and melanoma cells by CrkII and Rho-mediated
RT signalling.";
RL J. Cell Sci. 115:1059-1072(2002).
RN [16]
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 [17]
RP INTERACTION WITH KIT, MASS SPECTROMETRY, AND 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-
RT dependent phosphorylation site mediating interaction with c-Crk.";
RL Exp. Cell Res. 288:110-118(2003).
RN [18]
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
RT ERK, AKT, and JNK pathways.";
RL Blood 106:3423-3431(2005).
RN [19]
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
RT receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, AND MASS
RP SPECTROMETRY.
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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
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
RT p130Cas.";
RL J. Biol. Chem. 281:37527-37535(2006).
RN [22]
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.,
RA Won M., Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T.,
RA Brazil D.P., Hemmings B.A., Park J.;
RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by
RT Src involves tyrosine phosphorylation of PDK1 and Src homology 2
RT domain binding.";
RL J. Biol. Chem. 283:1480-1491(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74 AND SER-83, AND MASS
RP SPECTROMETRY.
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 [24]
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
RT (CD178) by phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [25]
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
RT and cancer progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10920-10925(2010).
RN [26]
RP ERRATUM.
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-74,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194 (ISOFORM CRK-I), AND
RP MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
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.,
RA Buerckstuemmer T., 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 [29]
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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP STRUCTURE BY NMR OF 12-120 IN COMPLEX WITH ABL1, AND INTERACTION OF
RP THE CRK 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
RT Crk SH2 domain, and a Crk-derived phosphopeptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002).
RN [32]
RP STRUCTURE BY NMR (ISOFORMS CRK-I AND CRK-II), FUNCTION, AND
RP 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-
RT related signaling adaptor protein CRK.";
RL Nat. Struct. Mol. Biol. 14:503-510(2007).
CC -!- FUNCTION: The Crk-I and Crk-II forms differ in their biological
CC activities. Crk-II has less transforming activity than Crk-I. Crk-
CC II mediates attachment-induced MAPK8 activation, membrane ruffling
CC and cell motility in a Rac-dependent manner. Involved in
CC phagocytosis of apoptotic cells and cell motility via its
CC interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3
CC signaling.
CC -!- SUBUNIT: Interacts with ABL1, C3G, DOCK3, MAP4K1, MAPK8 and SOS
CC via its first SH3 domain. Interacts (via SH2 domain) with BCAR1,
CC CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine
CC phosphorylation. Interacts (via SH2 domain) with several tyrosine-
CC phosphorylated growth factor receptors such as EGFR and INSR.
CC Interacts with FLT1 (tyrosine-phosphorylated). Interacts with
CC DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1.
CC Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts
CC with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3
CC tyrosine kinase activity-dependent. Interacts with EPHA3
CC (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA
CC GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated).
CC Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine
CC phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a
CC collagen stimulated complex involved in cell migration composed of
CC CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain)
CC with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with
CC CBLC.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-886, EBI-375543;
CC P42684:ABL2; NbExp=5; IntAct=EBI-886, EBI-1102694;
CC O15085:ARHGEF11; NbExp=2; IntAct=EBI-886, EBI-311099;
CC Q9ULH1:ASAP1; NbExp=2; IntAct=EBI-886, EBI-346622;
CC P54253:ATXN1; NbExp=3; IntAct=EBI-886, EBI-930964;
CC P56945:BCAR1; NbExp=5; IntAct=EBI-886, EBI-702093;
CC P22681:CBL; NbExp=6; IntAct=EBI-886, EBI-518228;
CC P00533:EGFR; NbExp=2; IntAct=EBI-886, EBI-297353;
CC P21860:ERBB3; NbExp=2; IntAct=EBI-886, EBI-720706;
CC P21333:FLNA; NbExp=2; IntAct=EBI-886, EBI-350432;
CC Q14315:FLNC; NbExp=2; IntAct=EBI-886, EBI-489954;
CC O14654:IRS4; NbExp=8; IntAct=EBI-886, EBI-356594;
CC P35968:KDR; NbExp=2; IntAct=EBI-886, EBI-1005487;
CC Q92918:MAP4K1; NbExp=3; IntAct=EBI-886, EBI-881;
CC Q9Y4K4:MAP4K5; NbExp=5; IntAct=EBI-886, EBI-1279;
CC P20774:OGN; NbExp=2; IntAct=EBI-886, EBI-1753690;
CC P16234:PDGFRA; NbExp=3; IntAct=EBI-886, EBI-2861522;
CC P29074:PTPN4; NbExp=3; IntAct=EBI-886, EBI-710431;
CC Q13905:RAPGEF1; NbExp=3; IntAct=EBI-886, EBI-976876;
CC Q9UPX8:SHANK2; NbExp=2; IntAct=EBI-886, EBI-1570571;
CC P29353:SHC1; NbExp=3; IntAct=EBI-886, EBI-78835;
CC O60493:SNX3; NbExp=2; IntAct=EBI-886, EBI-727209;
CC Q07889:SOS1; NbExp=2; IntAct=EBI-886, EBI-297487;
CC Q07890:SOS2; NbExp=2; IntAct=EBI-886, EBI-298181;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By
CC similarity). Note=Translocated to the plasma membrane upon cell
CC adhesion (By similarity).
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 Note=Contains a phosphoserine at position 194;
CC -!- DOMAIN: The C-terminal SH3 domain function as a negative modulator
CC for transformation and the N-terminal SH3 domain appears to
CC function as a positive regulator for transformation (By
CC similarity).
CC -!- DOMAIN: The SH2 domain mediates interaction with tyrosine
CC phosphorylated proteins. Mediates interaction with SHB.
CC -!- PTM: Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa
CC form. Isoform Crk-II is phosphorylated by KIT.
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
CC interaction of phosphorylated Tyr-221 with the SH2 domain. This
CC leads finally to the down-regulation of the Crk signaling pathway.
CC -!- PTM: Proline isomerization at Pro-237 by PPIA acts as a switch
CC between two conformations: an autoinhibitory conformation in the
CC cis form, where the tandem SH3 domains interact intramolecularly,
CC and an activated conformation in the trans form (By similarity).
CC -!- SIMILARITY: Belongs to the CRK family.
CC -!- SIMILARITY: Contains 1 SH2 domain.
CC -!- SIMILARITY: Contains 2 SH3 domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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 PIR; A45022; A45022.
DR RefSeq; NP_005197.3; NM_005206.4.
DR RefSeq; NP_058431.2; NM_016823.3.
DR UniGene; Hs.461896; -.
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=124-198.
DR PDB; 2EYX; NMR; -; A=232-298.
DR PDB; 2EYY; NMR; -; A=1-204.
DR PDB; 2EYZ; NMR; -; A=1-304.
DR PDBsum; 1JU5; -.
DR PDBsum; 2DVJ; -.
DR PDBsum; 2EYV; -.
DR PDBsum; 2EYW; -.
DR PDBsum; 2EYX; -.
DR PDBsum; 2EYY; -.
DR PDBsum; 2EYZ; -.
DR DisProt; DP00748; -.
DR ProteinModelPortal; P46108; -.
DR SMR; P46108; 1-304.
DR DIP; DIP-199N; -.
DR IntAct; P46108; 171.
DR MINT; MINT-1208745; -.
DR STRING; 9606.ENSP00000300574; -.
DR ChEMBL; CHEMBL5005; -.
DR PhosphoSite; P46108; -.
DR DMDM; 158939322; -.
DR REPRODUCTION-2DPAGE; IPI00399054; -.
DR SWISS-2DPAGE; P46108; -.
DR PaxDb; P46108; -.
DR PRIDE; P46108; -.
DR DNASU; 1398; -.
DR Ensembl; ENST00000300574; ENSP00000300574; ENSG00000167193.
DR Ensembl; ENST00000398970; ENSP00000381942; ENSG00000167193.
DR GeneID; 1398; -.
DR KEGG; hsa:1398; -.
DR UCSC; uc002fsl.3; human.
DR CTD; 1398; -.
DR GeneCards; GC17M001323; -.
DR HGNC; HGNC:2362; CRK.
DR HPA; CAB010485; -.
DR MIM; 164762; gene.
DR neXtProt; NX_P46108; -.
DR PharmGKB; PA26880; -.
DR eggNOG; NOG292767; -.
DR HOGENOM; HOG000236288; -.
DR HOVERGEN; HBG105616; -.
DR InParanoid; P46108; -.
DR KO; K04438; -.
DR OMA; NQDSSHP; -.
DR OrthoDB; EOG7NW69P; -.
DR PhylomeDB; P46108; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P46108; -.
DR ChiTaRS; CRK; human.
DR EvolutionaryTrace; P46108; -.
DR GeneWiki; CRK_(gene); -.
DR GenomeRNAi; 1398; -.
DR NextBio; 5721; -.
DR PRO; PR:P46108; -.
DR ArrayExpress; P46108; -.
DR Bgee; P46108; -.
DR CleanEx; HS_CRK; -.
DR Genevestigator; P46108; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IEA:Ensembl.
DR GO; GO:0032319; P:regulation of Rho GTPase activity; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR011511; SH3_2.
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; 3.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Complete proteome; Cytoplasm; Membrane; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Repeat; SH2 domain; SH3 domain.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 304 Adapter molecule crk.
FT /FTId=PRO_0000079351.
FT DOMAIN 13 118 SH2.
FT DOMAIN 132 192 SH3 1.
FT DOMAIN 237 296 SH3 2.
FT SITE 237 237 Proline switch (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 41 41 Phosphoserine.
FT MOD_RES 74 74 Phosphoserine.
FT MOD_RES 83 83 Phosphoserine.
FT MOD_RES 221 221 Phosphotyrosine; by ABL1.
FT MOD_RES 239 239 Phosphotyrosine.
FT VAR_SEQ 204 204 N -> R (in isoform Crk-I).
FT /FTId=VSP_041153.
FT VAR_SEQ 205 304 Missing (in isoform Crk-I).
FT /FTId=VSP_041154.
FT MUTAGEN 150 150 D->K: Abolishes interaction with DOCK1.
FT CONFLICT 109 109 L -> W (in Ref. 1; BAA01505 and 2;
FT AAB28213).
FT CONFLICT 215 215 G -> P (in Ref. 1; BAA01505 and 2;
FT AAB28213).
FT CONFLICT 278 278 E -> G (in Ref. 1; BAA01505 and 2;
FT AAB28213).
FT STRAND 7 13
FT STRAND 14 16
FT HELIX 20 27
FT STRAND 30 33
FT STRAND 34 39
FT STRAND 41 43
FT STRAND 46 52
FT STRAND 54 56
FT STRAND 57 63
FT STRAND 66 69
FT STRAND 70 77
FT TURN 78 80
FT STRAND 87 89
FT STRAND 92 96
FT HELIX 97 106
FT STRAND 109 112
FT STRAND 116 118
FT STRAND 120 123
FT HELIX 126 128
FT STRAND 135 138
FT STRAND 146 150
FT STRAND 158 166
FT STRAND 167 173
FT STRAND 179 183
FT HELIX 184 186
FT STRAND 187 189
FT STRAND 208 210
FT STRAND 224 227
FT STRAND 229 231
FT STRAND 239 242
FT STRAND 253 255
FT STRAND 260 269
FT STRAND 273 279
FT STRAND 282 287
FT HELIX 288 290
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
//

MIM 164762
*RECORD*
*FIELD* NO
164762
*FIELD* TI
*164762 V-CRK AVIAN SARCOMA VIRUS CT10 ONCOGENE HOMOLOG; CRK
;;ONCOGENE CRK;;
CRKII
read more*FIELD* TX

CLONING

The CRK oncogene was originally identified as a transforming component
of the avian sarcoma virus CT10. A cDNA encoding the chicken cellular
homolog of v-crk was isolated by Reichman et al. (1992) and shown to
consist primarily of the SRC (190090) homology domains SH2 and SH3.
Matsuda et al. (1992) isolated 2 distinct human CRK cDNA species and
showed that the deduced amino acid sequences of the corresponding
polypeptides differed in their C termini. The 2 cDNA species were
considered to derive from the same genomic locus by alternative
splicing.

MAPPING

Fioretos et al. (1993) used fluorescence in situ hybridization to map
the CRK gene to chromosome 17p13. Deletion of this region of chromosome
17 is one of the most frequent chromosomal abnormalities in human
cancer. The TP53 gene (191170) maps to 17p13.1; Fioretos et al. (1993)
mapped the CRK oncogene to 17p13.3, which is a second region on 17p that
has been shown to manifest frequent loss of heterozygosity (LOH) in a
number of different tumor types. Thus, the region is presumed to harbor
a tumor suppressor gene.

GENE FUNCTION

Feller et al. (1994) described the SRC homology domains SH2 and SH3 as
molecular adhesives on many proteins involved in signal transduction.
They reviewed the interactions of ABL (189980) and CRK as a model of SH2
and SH3 interaction.

Hallock et al. (2010) found that Crk and Crkl (602007) were recruited to
mouse skeletal muscle synapses and played redundant roles in synaptic
differentiation. Crk and Crkl bound the same tyrosine-phosphorylated
sequences in Dok7 (610285), a protein that functions downstream of agrin
(AGRN; 103320) and muscle-specific receptor kinase (MUSK; 601296) in
synapse formation.

MOLECULAR GENETICS

Cardoso et al. (2003) completed a physical and transcriptional map of
the 17p13.3 region from LIS1 to the telomere. Using Cardoso et al.
(2003), they mapped the deletion size in 19 children with ILS (607432),
11 children with Miller-Dieker syndrome (MDS; 164762), and 4 children
with 17p13.3 deletions not involving LIS1. They showed that the critical
region that differentiates ILS from MDS at the molecular level can be
reduced to 400 kb. Using somatic cell hybrids from selected patients,
the authors identified 8 genes that are consistently deleted in patients
classified as having MDS. These genes include ABR (600365),
14-3-3-epsilon (605066), CRK, MYO1C (606538), SKIP (603055), PITPNA
(600174), SCARF1, RILP, PRP8 (607300), and SERPINF1 (172860). In
addition, deletion of the genes CRK and 14-3-3-epsilon delineates
patients with the most severe lissencephaly grade. On the basis of
recent functional data and the creation of a mouse model suggesting a
role for 14-3-3-epsilon in cortical development, Cardoso et al. (2003)
suggested that deletion of 1 or both of these genes in combination with
deletion of LIS1 may contribute to the more severe form of lissencephaly
seen only in patients with MDS.

ANIMAL MODEL

Hallock et al. (2010) found that knockout of both Crk and Crkl in mouse
skeletal muscle, but not of either gene alone, caused perinatal
lethality. Lungs from Crk- and Crkl-deficient newborns failed to expand.
Embryonic day-18.5 muscle from Crk- and Crkl-deficient mice lacked
innervation and showed severe defects in presynaptic and postsynaptic
differentiation.

*FIELD* RF
1. Cardoso, C.; Leventer, R. J.; Ward, H. L.; Toyo-oka, K.; Chung,
J.; Gross, A.; Martin, C. L.; Allanson, J.; Pilz, D. T.; Olney, A.
H.; Mutchinick, O. M.; Hirotsune, S.; Wynshaw-Boris, A.; Dobyns, W.
B.; Ledbetter, D. H.: Refinement of a 400-kb critical region allows
genotypic differentiation between isolated lissencephaly, Miller-Dieker
syndrome, and other phenotypes secondary to deletions of 17p13.3. Am.
J. Hum. Genet. 72: 918-930, 2003.

2. Feller, S. M.; Ren, R. B.; Hanafusa, H.; Baltimore, D.: SH2 and
SH3 domains as molecular adhesives: the interactions of crk and abl. Trends
Biochem. Sci. 19: 453-458, 1994.

3. Fioretos, T.; Heisterkamp, N.; Groffen, J.; Benjes, S.; Morris,
C.: CRK proto-oncogene maps to human chromosome band 17p13. Oncogene 8:
2853-2855, 1993.

4. Hallock, P. T.; Xu, C.-F.; Park, T.-J.; Neubert, T. A.; Curran,
T.; Burden, S. J.: Dok-7 regulates neuromuscular synapse formation
by recruiting Crk and Crk-L. Genes Dev. 24: 2451-2461, 2010.

5. Matsuda, M.; Tanaka, S.; Nagata, S.; Kojima, A.; Kurata, T.; Shibuya,
M.: Two species of human CRK cDNA encode proteins with distinct biological
activities. Molec. Cell. Biol. 12: 3482-3489, 1992.

6. Reichman, C. T.; Mayer, B. J.; Keshav, S.; Hanafusa, H.: The product
of the cellular crk gene consists primarily of SH2 and SH3 regions. Cell
Growth Differ. 3: 451-460, 1992.

*FIELD* CN
Patricia A. Hartz - updated: 9/24/2013
Ada Hamosh - updated: 5/9/2003
Mark H. Paalman - updated: 8/29/1996

*FIELD* CD
Victor A. McKusick: 11/2/1993

*FIELD* ED
mgross: 11/08/2013
tpirozzi: 9/24/2013
cwells: 5/13/2003
terry: 5/9/2003
mgross: 10/30/2001
dkim: 10/28/1998
mark: 8/29/1996
mark: 6/9/1996
carol: 11/3/1993
carol: 11/2/1993

RBCC Red Blood Cell Collection

Full text data of CRK