ID NCK1_HUMAN Reviewed; 377 AA. AC P16333; B7Z751; D3DNE3; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 11-JUL-2012, entry version 140. DE RecName: Full=Cytoplasmic protein NCK1; DE AltName: Full=NCK adaptor protein 1; DE Short=Nck-1; DE AltName: Full=SH2/SH3 adaptor protein NCK-alpha; GN Name=NCK1; Synonyms=NCK; 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 1). RX MEDLINE=90192089; PubMed=2107526; DOI=10.1093/nar/18.4.1048; RA Lehmann J.M., Riethmueller G., Johnson J.P.; RT "Nck, a melanoma cDNA encoding a cytoplasmic protein consisting of the RT src homology units SH2 and SH3."; RL Nucleic Acids Res. 18:1048-1048(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Synovium; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; 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 [6] RP PHOSPHORYLATION, AND PARTIAL PROTEIN SEQUENCE. RX MEDLINE=93078783; PubMed=1333046; RA Park D., Rhee S.G.; RT "Phosphorylation of Nck in response to a variety of receptors, phorbol RT myristate acetate, and cyclic AMP."; RL Mol. Cell. Biol. 12:5816-5823(1992). RN [7] RP PHOSPHORYLATION. RX MEDLINE=93078786; PubMed=1448108; RA Meisenhelder J., Hunter T.; RT "The SH2/SH3 domain-containing protein Nck is recognized by certain RT anti-phospholipase C-gamma 1 monoclonal antibodies, and its RT phosphorylation on tyrosine is stimulated by platelet-derived growth RT factor and epidermal growth factor treatment."; RL Mol. Cell. Biol. 12:5843-5856(1992). RN [8] RP INTERACTION WITH PDGFRB, AND PHOSPHORYLATION. RX PubMed=7692233; RA Nishimura R., Li W., Kashishian A., Mondino A., Zhou M., Cooper J., RA Schlessinger J.; RT "Two signaling molecules share a phosphotyrosine-containing binding RT site in the platelet-derived growth factor receptor."; RL Mol. Cell. Biol. 13:6889-6896(1993). RN [9] RP INTERACTION WITH SOCS7. RX MEDLINE=98008866; PubMed=9344857; DOI=10.1006/bbrc.1997.7492; RA Matuoka K., Miki H., Takahashi K., Takenawa T.; RT "A novel ligand for an SH3 domain of the adaptor protein Nck bears an RT SH2 domain and nuclear signaling motifs."; RL Biochem. Biophys. Res. Commun. 239:488-492(1997). RN [10] RP INTERACTION WITH FLT1. RX PubMed=9600074; DOI=10.1006/bbrc.1998.8578; RA Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I.; RT "Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2."; RL Biochem. Biophys. Res. Commun. 246:95-99(1998). RN [11] RP INTERACTION WITH BLNK; GRB2; PLCG1 AND VAV. RX MEDLINE=98361304; PubMed=9697839; DOI=10.1016/S1074-7613(00)80591-9; RA Fu C., Turck C.W., Kurosaki T., Chan A.C.; RT "BLNK: a central linker protein in B cell activation."; RL Immunity 9:93-103(1998). RN [12] RP INTERACTION WITH EPHB1. RC TISSUE=Kidney; RX PubMed=9430661; DOI=10.1074/jbc.273.3.1303; RA Stein E., Huynh-Do U., Lane A.A., Cerretti D.P., Daniel T.O.; RT "Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation RT to c-Jun kinase."; RL J. Biol. Chem. 273:1303-1308(1998). RN [13] RP FUNCTION, INTERACTION WITH EGFR; PAK1; PKN2 AND SOS1, AND RP PHOSPHORYLATION. RX PubMed=10026169; DOI=10.1074/jbc.274.9.5542; RA Braverman L.E., Quilliam L.A.; RT "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain- RT containing adapter protein having similar binding and biological RT properties to Nck."; RL J. Biol. Chem. 274:5542-5549(1999). RN [14] RP INTERACTION WITH RALGPS1. RX MEDLINE=20250892; PubMed=10747847; DOI=10.1074/jbc.C000085200; RA Rebhun J.F., Chen H., Quilliam L.A.; RT "Identification and characterization of a new family of guanine RT nucleotide exchange factors for the ras-related GTPase Ral."; RL J. Biol. Chem. 275:13406-13410(2000). RN [15] RP INTERACTION WITH CAV2. RX MEDLINE=22206546; PubMed=12091389; DOI=10.1074/jbc.M204367200; RA Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., RA Lisanti M.P.; RT "Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho- RT caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains RT associated with lipid rafts/caveolae, but no longer forms a high RT molecular mass hetero-oligomer with caveolin-1."; RL J. Biol. Chem. 277:34556-34567(2002). RN [16] RP INTERACTION WITH CAV2. RX PubMed=15504032; DOI=10.1021/bi049295+; RA Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., RA Campos-Gonzalez R., Lisanti M.P.; RT "Tyrosine phosphorylation of caveolin-2 at residue 27: differences in RT the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)."; RL Biochemistry 43:13694-13706(2004). RN [17] RP INTERACTION WITH MINK1. RX PubMed=15469942; DOI=10.1074/jbc.M404497200; RA Hu Y., Leo C., Yu S., Huang B.C., Wang H., Shen M., Luo Y., RA Daniel-Issakani S., Payan D.G., Xu X.; RT "Identification and functional characterization of a novel human RT misshapen/Nck interacting kinase-related kinase, hMINK beta."; RL J. Biol. Chem. 279:54387-54397(2004). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary epithelium; RX PubMed=15951569; DOI=10.1074/mcp.M500089-MCP200; RA Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., RA Lauffenburger D.A., White F.M.; RT "Time-resolved mass spectrometry of tyrosine phosphorylation sites in RT the epidermal growth factor receptor signaling network reveals dynamic RT modules."; RL Mol. Cell. Proteomics 4:1240-1250(2005). RN [19] RP IDENTIFICATION IN COMPLEX WITH PP1 AND PPP1R15B, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=16835242; DOI=10.1074/jbc.M513556200; RA Latreille M., Larose L.; RT "Nck in a complex containing the catalytic subunit of protein RT phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling RT and cell survival to endoplasmic reticulum stress."; RL J. Biol. Chem. 281:26633-26644(2006). RN [20] RP INTERACTION WITH KDR. RX PubMed=16966330; DOI=10.1074/jbc.M603928200; RA Lamalice L., Houle F., Huot J.; RT "Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of RT Nck and activation of Fyn leading to SAPK2/p38 activation and RT endothelial cell migration in response to VEGF."; RL J. Biol. Chem. 281:34009-34020(2006). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SOCS7. RX PubMed=17803907; DOI=10.1016/j.cell.2007.06.053; RA Kremer B.E., Adang L.A., Macara I.G.; RT "Septins regulate actin organization and cell-cycle arrest through RT nuclear accumulation of NCK mediated by SOCS7."; RL Cell 130:837-850(2007). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-96 AND TYR-105, RP AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=17287340; DOI=10.1073/pnas.0611217104; RA Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.; RT "Global proteomic profiling of phosphopeptides using electron transfer RT dissociation tandem mass spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary epithelium; RX PubMed=17389395; DOI=10.1073/pnas.0608638104; RA Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.; RT "Multiple reaction monitoring for robust quantitative proteomic RT analysis of cellular signaling networks."; RL Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND MASS RP SPECTROMETRY. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [25] RP INTERACTION WITH ADAM15. RX PubMed=18296648; DOI=10.1158/1541-7786.MCR-07-2028; RA Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M., RA Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C., RA Edwards D.R.; RT "Distinct functions of natural ADAM-15 cytoplasmic domain variants in RT human mammary carcinoma."; RL Mol. Cancer Res. 6:383-394(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-91 AND SER-96, RP AND MASS 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 [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [28] 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary epithelium; RX PubMed=19534553; DOI=10.1021/pr900044c; RA Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., RA Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., RA Wiley H.S., Qian W.-J.; RT "An extensive survey of tyrosine phosphorylation revealing new sites RT in human mammary epithelial cells."; RL J. Proteome Res. 8:3852-3861(2009). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-96 AND TYR-105, RP AND MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). 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., 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 [32] RP INTERACTION WITH RASA1, AND MUTAGENESIS OF TRP-38; TRP-143; TRP-229 RP AND ARG-308. RX PubMed=21664272; DOI=10.1016/j.cellsig.2011.05.019; RA Ger M., Zitkus Z., Valius M.; RT "Adaptor protein Nck1 interacts with p120 Ras GTPase-activating RT protein and regulates its activity."; RL Cell. Signal. 23:1651-1658(2011). RN [33] RP STRUCTURE BY NMR OF 99-174. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH3 domain of the human cytoplasmic protein RT NCK1."; RL Submitted (NOV-2005) to the PDB data bank. RN [34] RP STRUCTURE BY NMR OF 1-61 AND 107-165, AND INTERACTION WITH EGFR. RX PubMed=18269246; DOI=10.1021/bi701549a; RA Hake M.J., Choowongkomon K., Kostenko O., Carlin C.R., RA Sonnichsen F.D.; RT "Specificity determinants of a novel Nck interaction with the RT juxtamembrane domain of the epidermal growth factor receptor."; RL Biochemistry 47:3096-3108(2008). CC -!- FUNCTION: Adapter protein which associates with tyrosine- CC phosphorylated growth factor receptors, such as KDR and PDGFRB, or CC their cellular substrates. Maintains low levels of EIF2S1 CC phosphorylation by promoting its dephosphorylation by PP1. Plays a CC role in the DNA damage response, not in the detection of the CC damage by ATM/ATR, but for efficient activation of downstream CC effectors, such as that of CHEK2. Plays a role in ELK1-dependent CC transcriptional activation in response to activated Ras signaling. CC -!- SUBUNIT: Interacts (via SH2 domain and SH3 domain 2) with EGFR. CC Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with CC PKN2. Associates with BLNK, PLCG1, VAV1 and NCK1 in a B-cell CC antigen receptor-dependent fashion. Interacts with SOCS7. This CC interaction is required for nuclear import. Part of a complex CC containing PPP1R15B, PP1 and NCK1. Interacts with RALGPS1. CC Interacts with CAV2 (tyrosine phosphorylated form). Interacts with CC ADAM15. Interacts with FASLG. Directly interacts with RASA1. CC Interacts with isoform 4 of MINK1. Interacts with FLT1 (tyrosine. CC phosphorylated). Interacts with KDR (tyrosine phosphorylated). CC Interacts (via SH2 domain) with EPHB1; activates the JUN cascade CC to regulate cell adhesion. Interacts (via SH2 domain) with PDGFRB CC (tyrosine phosphorylated). CC -!- INTERACTION: CC Q9H222:ABCG5; NbExp=2; IntAct=EBI-389883, EBI-1761423; CC P00519:ABL1; NbExp=2; IntAct=EBI-389883, EBI-375543; CC P42684:ABL2; NbExp=3; IntAct=EBI-389883, EBI-1102694; CC Q15109:AGER; NbExp=2; IntAct=EBI-389883, EBI-1646426; CC O43918:AIRE; NbExp=2; IntAct=EBI-389883, EBI-1753081; CC O15085:ARHGEF11; NbExp=3; IntAct=EBI-389883, EBI-311099; CC Q9ULH1:ASAP1; NbExp=5; IntAct=EBI-389883, EBI-346622; CC Q96NS5:ASB16; NbExp=2; IntAct=EBI-389883, EBI-1751918; CC Q9UIF9:BAZ2A; NbExp=2; IntAct=EBI-389883, EBI-934890; CC O60885:BRD4; NbExp=2; IntAct=EBI-389883, EBI-723869; CC Q9ULD4:BRPF3; NbExp=3; IntAct=EBI-389883, EBI-1753470; CC P13671:C6; NbExp=2; IntAct=EBI-389883, EBI-1753221; CC P20810:CAST; NbExp=2; IntAct=EBI-389883, EBI-1268770; CC P30260:CDC27; NbExp=3; IntAct=EBI-389883, EBI-994813; CC Q9NYQ7:CELSR3; NbExp=2; IntAct=EBI-389883, EBI-308417; CC Q13111:CHAF1A; NbExp=2; IntAct=EBI-389883, EBI-1020839; CC Q14008:CKAP5; NbExp=3; IntAct=EBI-389883, EBI-310585; CC P78357:CNTNAP1; NbExp=2; IntAct=EBI-389883, EBI-1751903; CC Q8WX92:COBRA1; NbExp=6; IntAct=EBI-389883, EBI-347721; CC P78329:CYP4F2; NbExp=2; IntAct=EBI-389883, EBI-1752413; CC P98082:DAB2; NbExp=2; IntAct=EBI-389883, EBI-1171238; CC Q14118:DAG1; NbExp=2; IntAct=EBI-389883, EBI-1755945; CC O14490:DLGAP1; NbExp=4; IntAct=EBI-389883, EBI-1753207; CC Q9P1A6:DLGAP2; NbExp=4; IntAct=EBI-389883, EBI-1753397; CC O95886:DLGAP3; NbExp=2; IntAct=EBI-389883, EBI-1752541; CC Q9Y2H0:DLGAP4; NbExp=5; IntAct=EBI-389883, EBI-722139; CC Q92988:DLX4; NbExp=3; IntAct=EBI-389883, EBI-1752755; CC Q05193:DNM1; NbExp=2; IntAct=EBI-389883, EBI-713135; CC Q8IZD9:DOCK3; NbExp=3; IntAct=EBI-389883, EBI-1752361; CC Q9H1R2:DUSP15; NbExp=2; IntAct=EBI-389883, EBI-1752795; CC Q9H8V3:ECT2; NbExp=3; IntAct=EBI-389883, EBI-1054039; CC P41970:ELK3; NbExp=3; IntAct=EBI-389883, EBI-1758534; CC P42566:EPS15; NbExp=2; IntAct=EBI-389883, EBI-396684; CC O00254:F2RL2; NbExp=2; IntAct=EBI-389883, EBI-1751853; CC Q9BQ89:FAM110A; NbExp=2; IntAct=EBI-389883, EBI-1752811; CC P31994:FCGR2B; NbExp=2; IntAct=EBI-389883, EBI-724784; CC P31995:FCGR2C; NbExp=2; IntAct=EBI-389883, EBI-1396036; CC O75369:FLNB; NbExp=3; IntAct=EBI-389883, EBI-352089; CC O75593:FOXH1; NbExp=2; IntAct=EBI-389883, EBI-1759806; CC O15117:FYB; NbExp=2; IntAct=EBI-389883, EBI-1753267; CC Q9UBS5:GABBR1; NbExp=3; IntAct=EBI-389883, EBI-724156; CC Q99259:GAD1; NbExp=2; IntAct=EBI-389883, EBI-743184; CC P10912:GHR; NbExp=2; IntAct=EBI-389883, EBI-286316; CC Q9NZM4:GLTSCR1; NbExp=3; IntAct=EBI-389883, EBI-1754943; CC P15586:GNS; NbExp=2; IntAct=EBI-389883, EBI-1752200; CC O43708:GSTZ1; NbExp=2; IntAct=EBI-389883, EBI-748043; CC P10412:HIST1H1E; NbExp=2; IntAct=EBI-389883, EBI-358163; CC O43390:HNRNPR; NbExp=2; IntAct=EBI-389883, EBI-713419; CC P47928:ID4; NbExp=3; IntAct=EBI-389883, EBI-1754719; CC Q9H9L3:ISG20L2; NbExp=2; IntAct=EBI-389883, EBI-751335; CC O60674:JAK2; NbExp=2; IntAct=EBI-389883, EBI-518647; CC Q9BY71:LRRC3; NbExp=2; IntAct=EBI-389883, EBI-1761329; CC P27816:MAP4; NbExp=2; IntAct=EBI-389883, EBI-715255; CC Q92918:MAP4K1; NbExp=2; IntAct=EBI-389883, EBI-881; CC Q9Y4K4:MAP4K5; NbExp=2; IntAct=EBI-389883, EBI-1279; CC Q9NQ76:MEPE; NbExp=3; IntAct=EBI-389883, EBI-1753293; CC Q15746:MYLK; NbExp=2; IntAct=EBI-389883, EBI-968482; CC P43699:NKX2-1; NbExp=2; IntAct=EBI-389883, EBI-1391923; CC O60500:NPHS1; NbExp=3; IntAct=EBI-389883, EBI-996920; CC Q13087:PDIA2; NbExp=3; IntAct=EBI-389883, EBI-1752525; CC O75167:PHACTR2; NbExp=2; IntAct=EBI-389883, EBI-1754409; CC O00750:PIK3C2B; NbExp=3; IntAct=EBI-389883, EBI-641107; CC Q9UL42:PNMA2; NbExp=2; IntAct=EBI-389883, EBI-302355; CC Q9BXM0:PRX; NbExp=2; IntAct=EBI-389883, EBI-1753064; CC P29074:PTPN4; NbExp=3; IntAct=EBI-389883, EBI-710431; CC P15918:RAG1; NbExp=2; IntAct=EBI-389883, EBI-1755109; CC Q13905:RAPGEF1; NbExp=2; IntAct=EBI-389883, EBI-976876; CC P20936:RASA1; NbExp=6; IntAct=EBI-389883, EBI-1026476; CC Q9UQ26:RIMS2; NbExp=2; IntAct=EBI-389883, EBI-1756749; CC Q8TB24:RIN3; NbExp=2; IntAct=EBI-389883, EBI-1570523; CC P26373:RPL13; NbExp=2; IntAct=EBI-389883, EBI-356849; CC P78345:RPP38; NbExp=2; IntAct=EBI-389883, EBI-366493; CC P10301:RRAS; NbExp=3; IntAct=EBI-389883, EBI-968703; CC Q96GP6:SCARF2; NbExp=2; IntAct=EBI-389883, EBI-1752088; CC O75326:SEMA7A; NbExp=2; IntAct=EBI-389883, EBI-1753538; CC Q9NZV5:SEPN1; NbExp=2; IntAct=EBI-389883, EBI-1751965; CC Q9UPX8:SHANK2; NbExp=6; IntAct=EBI-389883, EBI-1570571; CC Q9BYB0:SHANK3; NbExp=4; IntAct=EBI-389883, EBI-1752330; CC Q13796:SHROOM2; NbExp=2; IntAct=EBI-389883, EBI-1644065; CC Q9UHI7:SLC23A1; NbExp=2; IntAct=EBI-389883, EBI-1759386; CC O60721:SLC24A1; NbExp=3; IntAct=EBI-389883, EBI-1753504; CC Q9UMY4:SNX12; NbExp=3; IntAct=EBI-389883, EBI-1752602; CC Q15036:SNX17; NbExp=3; IntAct=EBI-389883, EBI-1752620; CC Q9Y5X2:SNX8; NbExp=2; IntAct=EBI-389883, EBI-1752557; CC Q07889:SOS1; NbExp=5; IntAct=EBI-389883, EBI-297487; CC Q07890:SOS2; NbExp=3; IntAct=EBI-389883, EBI-298181; CC P08047:SP1; NbExp=2; IntAct=EBI-389883, EBI-298336; CC Q96T58:SPEN; NbExp=3; IntAct=EBI-389883, EBI-765739; CC Q9H5I1:SUV39H2; NbExp=2; IntAct=EBI-389883, EBI-723127; CC O15056:SYNJ2; NbExp=3; IntAct=EBI-389883, EBI-310513; CC O43493:TGOLN2; NbExp=3; IntAct=EBI-389883, EBI-1752146; CC P42167:TMPO; NbExp=2; IntAct=EBI-389883, EBI-455283; CC Q15661:TPSAB1; NbExp=2; IntAct=EBI-389883, EBI-1761369; CC Q9ULW0:TPX2; NbExp=4; IntAct=EBI-389883, EBI-1037322; CC Q9BWF2:TRAIP; NbExp=3; IntAct=EBI-389883, EBI-1756205; CC Q9HCM9:TRIM39; NbExp=2; IntAct=EBI-389883, EBI-739510; CC O00294:TULP1; NbExp=2; IntAct=EBI-389883, EBI-1756778; CC Q96RL7:VPS13A; NbExp=3; IntAct=EBI-389883, EBI-1752583; CC Q9UMN6:WBP7; NbExp=2; IntAct=EBI-389883, EBI-765774; CC O43516:WIPF1; NbExp=2; IntAct=EBI-389883, EBI-346356; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. Nucleus. CC Note=Mostly cytoplasmic, but shuttles between the cytoplasm and CC the nucleus. Import into the nucleus requires the interaction with CC SOCS7. Predominantly nuclear following genotoxic stresses, such as CC UV irradiation, hydroxyurea or mitomycin C treatments. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P16333-1; Sequence=Displayed; CC Name=2; CC IsoId=P16333-2; Sequence=VSP_043122; CC Note=No experimental confirmation available; CC -!- DOMAIN: Only the first and third SH3 domains seem to be involved CC in RASA1-binding; the second SH3 domain and the SH2 domains do not CC seeem to be involved. CC -!- PTM: Phosphorylated on Ser and Tyr residues. Phosphorylated in CC response to activation of EGFR and FcERI. Phosphorylated by CC activated PDGFRB. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- SIMILARITY: Contains 3 SH3 domains. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X17576; CAA35599.1; -; mRNA. DR EMBL; AK301460; BAH13487.1; -; mRNA. DR EMBL; AC011597; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79105.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79108.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79109.1; -; Genomic_DNA. DR EMBL; BC006403; AAH06403.1; -; mRNA. DR IPI; IPI00028065; -. DR IPI; IPI00793968; -. DR PIR; S08636; S08636. DR RefSeq; NP_001177725.1; NM_001190796.1. DR RefSeq; NP_006144.1; NM_006153.4. DR UniGene; Hs.477693; -. DR PDB; 2CI8; X-ray; 1.80 A; A=281-377. DR PDB; 2CI9; X-ray; 1.50 A; A/B=281-377. DR PDB; 2CUB; NMR; -; A=99-173. DR PDB; 2JS0; NMR; -; A=107-165. DR PDB; 2JS2; NMR; -; A=1-61. DR PDB; 2JW4; NMR; -; A=1-63. DR PDBsum; 2CI8; -. DR PDBsum; 2CI9; -. DR PDBsum; 2CUB; -. DR PDBsum; 2JS0; -. DR PDBsum; 2JS2; -. DR PDBsum; 2JW4; -. DR ProteinModelPortal; P16333; -. DR SMR; P16333; 1-61, 99-174, 193-250, 279-377. DR DIP; DIP-639N; -. DR IntAct; P16333; 170. DR MINT; MINT-92747; -. DR STRING; P16333; -. DR PhosphoSite; P16333; -. DR DMDM; 127962; -. DR PeptideAtlas; P16333; -. DR PRIDE; P16333; -. DR DNASU; 4690; -. DR Ensembl; ENST00000288986; ENSP00000288986; ENSG00000158092. DR Ensembl; ENST00000469404; ENSP00000419631; ENSG00000158092. DR Ensembl; ENST00000481752; ENSP00000417273; ENSG00000158092. DR GeneID; 4690; -. DR KEGG; hsa:4690; -. DR UCSC; uc003erh.3; human. DR CTD; 4690; -. DR GeneCards; GC03P136581; -. DR HGNC; HGNC:7664; NCK1. DR HPA; CAB005063; -. DR MIM; 600508; gene. DR neXtProt; NX_P16333; -. DR PharmGKB; PA31466; -. DR eggNOG; NOG261435; -. DR GeneTree; ENSGT00550000074482; -. DR HOGENOM; HOG000290684; -. DR HOVERGEN; HBG000719; -. DR InParanoid; P16333; -. DR KO; K07365; -. DR OMA; AIVKYNY; -. DR OrthoDB; EOG40ZQXR; -. DR PhylomeDB; P16333; -. DR Pathway_Interaction_DB; angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling. DR Pathway_Interaction_DB; ephbfwdpathway; EPHB forward signaling. DR Pathway_Interaction_DB; insulin_pathway; Insulin Pathway. DR Pathway_Interaction_DB; pdgfrbpathway; PDGFR-beta signaling pathway. DR Pathway_Interaction_DB; met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met). DR Pathway_Interaction_DB; vegfr1_2_pathway; Signaling events mediated by VEGFR1 and VEGFR2. DR Pathway_Interaction_DB; ret_pathway; Signaling events regulated by Ret tyrosine kinase. DR Pathway_Interaction_DB; tcrpathway; TCR signaling in naive CD4+ T cells. DR Pathway_Interaction_DB; vegfr1_pathway; VEGFR1 specific signals. DR Reactome; REACT_111045; Developmental Biology. DR Reactome; REACT_111102; Signal Transduction. DR Reactome; REACT_111155; Cell-Cell communication. DR Reactome; REACT_6900; Immune System. DR EvolutionaryTrace; P16333; -. DR NextBio; 18086; -. DR PMAP-CutDB; P16333; -. DR ArrayExpress; P16333; -. DR Bgee; P16333; -. DR CleanEx; HS_NCK1; -. DR Genevestigator; P16333; -. DR GermOnline; ENSG00000158092; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0012506; C:vesicle membrane; IEA:Compara. DR GO; GO:0007015; P:actin filament organization; IEA:Compara. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0016477; P:cell migration; IEA:Compara. DR GO; GO:0030032; P:lamellipodium assembly; IEA:Compara. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR GO; GO:0007172; P:signal complex assembly; NAS:UniProtKB. DR GO; GO:0042110; P:T cell activation; IMP:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR Gene3D; G3DSA:3.30.505.10; SH2; 1. DR InterPro; IPR017304; Cytoplasmic_NCK. DR InterPro; IPR000980; SH2. DR InterPro; IPR001452; SH3_domain. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 3. DR PIRSF; PIRSF037874; Cytoplasmic_NCK; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 3. DR SUPFAM; SSF50044; SH3; 3. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 3. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Cytoplasm; Direct protein sequencing; Endoplasmic reticulum; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH2 domain; KW SH3 domain; Translation regulation. FT INIT_MET 1 1 Removed. FT CHAIN 2 377 Cytoplasmic protein NCK1. FT /FTId=PRO_0000096766. FT DOMAIN 2 61 SH3 1. FT DOMAIN 115 165 SH3 2. FT DOMAIN 190 252 SH3 3. FT DOMAIN 282 376 SH2. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 85 85 Phosphoserine. FT MOD_RES 91 91 Phosphoserine. FT MOD_RES 96 96 Phosphoserine. FT MOD_RES 105 105 Phosphotyrosine. FT VAR_SEQ 1 76 MAEEVVVVAKFDYVAQQEQELDIKKNERLWLLDDSKSWWRV FT RNSMNKTGFVPSNYVERKNSARKASIVKNLKDTLG -> MD FT WLNVFKDFFS (in isoform 2). FT /FTId=VSP_043122. FT VARIANT 180 180 A -> V (in dbSNP:rs13320485). FT /FTId=VAR_051228. FT MUTAGEN 38 38 W->K: Small decrease in RASA1-binding. FT Almost complete loss of RASA1-binding; FT when associated with K-143 and K-229. FT MUTAGEN 143 143 W->K: No effect on RASA1-binding. Almost FT complete loss of RASA1-binding; when FT associated with K-38 and K-229. FT MUTAGEN 229 229 W->K: Small decrease in RASA1-binding. FT Almost complete loss of RASA1-binding; FT when associated with K-38 and K-229. FT MUTAGEN 308 308 R->K: No effect on RASA1-binding. FT STRAND 5 11 FT STRAND 28 33 FT STRAND 35 42 FT STRAND 48 51 FT TURN 53 55 FT STRAND 56 58 FT STRAND 99 101 FT STRAND 109 115 FT STRAND 131 138 FT STRAND 142 148 FT STRAND 151 156 FT HELIX 157 159 FT STRAND 160 162 FT STRAND 168 170 FT HELIX 289 299 FT STRAND 304 309 FT STRAND 311 313 FT STRAND 316 321 FT STRAND 324 326 FT STRAND 328 335 FT STRAND 338 341 FT STRAND 344 348 FT HELIX 349 358 FT STRAND 361 363 SQ SEQUENCE 377 AA; 42864 MW; 554E9B1A936AEF30 CRC64; MAEEVVVVAK FDYVAQQEQE LDIKKNERLW LLDDSKSWWR VRNSMNKTGF VPSNYVERKN SARKASIVKN LKDTLGIGKV KRKPSVPDSA SPADDSFVDP GERLYDLNMP AYVKFNYMAE REDELSLIKG TKVIVMEKCS DGWWRGSYNG QVGWFPSNYV TEEGDSPLGD HVGSLSEKLA AVVNNLNTGQ VLHVVQALYP FSSSNDEELN FEKGDVMDVI EKPENDPEWW KCRKINGMVG LVPKNYVTVM QNNPLTSGLE PSPPQCDYIR PSLTGKFAGN PWYYGKVTRH QAEMALNERG HEGDFLIRDS ESSPNDFSVS LKAQGKNKHF KVQLKETVYC IGQRKFSTME ELVEHYKKAP IFTSEQGEKL YLVKHLS //