NCK1_HUMAN
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 03-AUG-2022, entry version 232.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX 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 src
RT 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., 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 [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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., 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., 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 [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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1333046; DOI=10.1128/mcb.12.12.5816-5823.1992;
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 PubMed=1448108; DOI=10.1128/mcb.12.12.5843-5856.1992;
RA Meisenhelder J., Hunter T.;
RT "The SH2/SH3 domain-containing protein Nck is recognized by certain anti-
RT phospholipase C-gamma 1 monoclonal antibodies, and its phosphorylation on
RT tyrosine is stimulated by platelet-derived growth factor and epidermal
RT growth factor treatment.";
RL Mol. Cell. Biol. 12:5843-5856(1992).
RN [8]
RP INTERACTION WITH PDGFRB, AND PHOSPHORYLATION.
RX PubMed=7692233; DOI=10.1128/mcb.13.11.6889-6896.1993;
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 site in
RT the platelet-derived growth factor receptor.";
RL Mol. Cell. Biol. 13:6889-6896(1993).
RN [9]
RP INTERACTION WITH SOCS7.
RX 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 SH2
RT 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 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 FUNCTION IN CELL ADHESION, AND 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 to
RT c-Jun kinase.";
RL J. Biol. Chem. 273:1303-1308(1998).
RN [13]
RP FUNCTION, INTERACTION WITH EGFR; PAK1; PKN2 AND SOS1, AND 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-containing
RT adapter protein having similar binding and biological properties to Nck.";
RL J. Biol. Chem. 274:5542-5549(1999).
RN [14]
RP INTERACTION WITH RALGPS1.
RX 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 nucleotide
RT exchange factors for the ras-related GTPase Ral.";
RL J. Biol. Chem. 275:13406-13410(2000).
RN [15]
RP INTERACTION WITH CAV2.
RX PubMed=12091389; DOI=10.1074/jbc.m204367200;
RA Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., 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 associated
RT with lipid rafts/caveolae, but no longer forms a high molecular mass
RT 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 the
RT 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [19]
RP IDENTIFICATION IN COMPLEX WITH PP1 AND PPP1R15B, FUNCTION, AND SUBCELLULAR
RP 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 phosphatase 1
RT regulates eukaryotic initiation factor 2alpha signaling and cell survival
RT 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 Nck
RT and activation of Fyn leading to SAPK2/p38 activation and endothelial cell
RT 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 nuclear
RT accumulation of NCK mediated by SOCS7.";
RL Cell 130:837-850(2007).
RN [22]
RP FUNCTION, INTERACTION WITH EIF2AK2, AND PHOSPHORYLATION.
RX PubMed=18835251; DOI=10.1016/j.bbrc.2008.09.112;
RA Cardin E., Larose L.;
RT "Nck-1 interacts with PKR and modulates its activation by dsRNA.";
RL Biochem. Biophys. Res. Commun. 377:231-235(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [24]
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 human
RT mammary carcinoma.";
RL Mol. Cancer Res. 6:383-394(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-91 AND SER-96, 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 [26]
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND TYR-105, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND IDENTIFICATION BY
RP 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 [29]
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 [30]
RP INTERACTION WITH RASA1, AND MUTAGENESIS OF TRP-38; TRP-143; TRP-229 AND
RP 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 protein and
RT regulates its activity.";
RL Cell. Signal. 23:1651-1658(2011).
RN [31]
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 [32]
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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-91; SER-96 AND
RP SER-166, 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 [34]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH EPHA2.
RX PubMed=23358419; DOI=10.1128/mcb.01708-12;
RA Lee H., Bennett A.M.;
RT "Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate
RT screen identifies EphA2 as a target for LAR in cell migration.";
RL Mol. Cell. Biol. 33:1430-1441(2013).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-89 AND SER-166, AND
RP IDENTIFICATION BY 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 [36]
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 [37]
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., Sonnichsen F.D.;
RT "Specificity determinants of a novel Nck interaction with the juxtamembrane
RT domain of the epidermal growth factor receptor.";
RL Biochemistry 47:3096-3108(2008).
CC -!- FUNCTION: Adapter protein which associates with tyrosine-phosphorylated
CC growth factor receptors, such as KDR and PDGFRB, or their cellular
CC substrates. Maintains low levels of EIF2S1 phosphorylation by promoting
CC its dephosphorylation by PP1. Plays a role in the DNA damage response,
CC not in the detection of the damage by ATM/ATR, but for efficient
CC activation of downstream effectors, such as that of CHEK2. Plays a role
CC in ELK1-dependent transcriptional activation in response to activated
CC Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May
CC play a role in cell adhesion and migration through interaction with
CC ephrin receptors. {ECO:0000269|PubMed:10026169,
CC ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907,
CC ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419,
CC ECO:0000269|PubMed:9430661}.
CC -!- SUBUNIT: Interacts (via SH2 domain and SH3 domain 2) with EGFR.
CC Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2.
CC Associates with BLNK, PLCG1, VAV1 and NCK1 in a B-cell antigen
CC receptor-dependent fashion. Interacts with SOCS7. This interaction is
CC required for nuclear import. Part of a complex containing PPP1R15B, PP1
CC and NCK1. Interacts with RALGPS1. Interacts with CAV2 (tyrosine
CC phosphorylated form). Interacts with ADAM15. Interacts with FASLG.
CC Directly interacts with RASA1. Interacts with isoform 4 of MINK1.
CC Interacts with FLT1 (tyrosine phosphorylated). Interacts with KDR
CC (tyrosine phosphorylated). Interacts (via SH2 domain) with EPHB1;
CC activates the JUN cascade to regulate cell adhesion. Interacts with
CC EPHA2. Interacts (via SH2 domain) with PDGFRB (tyrosine
CC phosphorylated). Interacts with the inactive form of EIF2AK2/PKR.
CC {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:10747847,
CC ECO:0000269|PubMed:12091389, ECO:0000269|PubMed:15469942,
CC ECO:0000269|PubMed:15504032, ECO:0000269|PubMed:16835242,
CC ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17803907,
CC ECO:0000269|PubMed:18269246, ECO:0000269|PubMed:18296648,
CC ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:21664272, ECO:0000269|PubMed:23358419,
CC ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:9344857,
CC ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9600074,
CC ECO:0000269|PubMed:9697839}.
CC -!- INTERACTION:
CC P16333; Q9H222: ABCG5; NbExp=2; IntAct=EBI-389883, EBI-1761423;
CC P16333; P00519: ABL1; NbExp=2; IntAct=EBI-389883, EBI-375543;
CC P16333; P42684: ABL2; NbExp=4; IntAct=EBI-389883, EBI-1102694;
CC P16333; Q15109: AGER; NbExp=2; IntAct=EBI-389883, EBI-1646426;
CC P16333; O43918: AIRE; NbExp=2; IntAct=EBI-389883, EBI-1753081;
CC P16333; O15085: ARHGEF11; NbExp=3; IntAct=EBI-389883, EBI-311099;
CC P16333; Q9ULH1: ASAP1; NbExp=6; IntAct=EBI-389883, EBI-346622;
CC P16333; Q96NS5: ASB16; NbExp=2; IntAct=EBI-389883, EBI-1751918;
CC P16333; Q9UIF9: BAZ2A; NbExp=2; IntAct=EBI-389883, EBI-934890;
CC P16333; Q9NZM4: BICRA; NbExp=3; IntAct=EBI-389883, EBI-1754943;
CC P16333; O60885: BRD4; NbExp=2; IntAct=EBI-389883, EBI-723869;
CC P16333; Q9ULD4: BRPF3; NbExp=3; IntAct=EBI-389883, EBI-1753470;
CC P16333; P13671: C6; NbExp=2; IntAct=EBI-389883, EBI-1753221;
CC P16333; P20810: CAST; NbExp=2; IntAct=EBI-389883, EBI-1268770;
CC P16333; Q13191: CBLB; NbExp=4; IntAct=EBI-389883, EBI-744027;
CC P16333; P20963: CD247; NbExp=2; IntAct=EBI-389883, EBI-1165705;
CC P16333; P07766: CD3E; NbExp=6; IntAct=EBI-389883, EBI-1211297;
CC P16333; P30260: CDC27; NbExp=3; IntAct=EBI-389883, EBI-994813;
CC P16333; Q9NYQ7: CELSR3; NbExp=2; IntAct=EBI-389883, EBI-308417;
CC P16333; Q13111: CHAF1A; NbExp=2; IntAct=EBI-389883, EBI-1020839;
CC P16333; P52757: CHN2; NbExp=3; IntAct=EBI-389883, EBI-714925;
CC P16333; Q14008: CKAP5; NbExp=3; IntAct=EBI-389883, EBI-310585;
CC P16333; P78357: CNTNAP1; NbExp=2; IntAct=EBI-389883, EBI-1751903;
CC P16333; P78329: CYP4F2; NbExp=2; IntAct=EBI-389883, EBI-1752413;
CC P16333; P98082: DAB2; NbExp=2; IntAct=EBI-389883, EBI-1171238;
CC P16333; Q14118: DAG1; NbExp=2; IntAct=EBI-389883, EBI-1755945;
CC P16333; O14490: DLGAP1; NbExp=4; IntAct=EBI-389883, EBI-1753207;
CC P16333; Q9P1A6: DLGAP2; NbExp=4; IntAct=EBI-389883, EBI-1753397;
CC P16333; O95886: DLGAP3; NbExp=2; IntAct=EBI-389883, EBI-1752541;
CC P16333; Q9Y2H0: DLGAP4; NbExp=5; IntAct=EBI-389883, EBI-722139;
CC P16333; Q9Y2H0-1: DLGAP4; NbExp=3; IntAct=EBI-389883, EBI-12000556;
CC P16333; Q92988: DLX4; NbExp=3; IntAct=EBI-389883, EBI-1752755;
CC P16333; Q05193: DNM1; NbExp=2; IntAct=EBI-389883, EBI-713135;
CC P16333; Q8IZD9: DOCK3; NbExp=3; IntAct=EBI-389883, EBI-1752361;
CC P16333; Q9H1R2: DUSP15; NbExp=2; IntAct=EBI-389883, EBI-1752795;
CC P16333; Q9H8V3: ECT2; NbExp=3; IntAct=EBI-389883, EBI-1054039;
CC P16333; P00533: EGFR; NbExp=4; IntAct=EBI-389883, EBI-297353;
CC P16333; P41970: ELK3; NbExp=3; IntAct=EBI-389883, EBI-1758534;
CC P16333; P42566: EPS15; NbExp=2; IntAct=EBI-389883, EBI-396684;
CC P16333; O00254: F2RL2; NbExp=2; IntAct=EBI-389883, EBI-1751853;
CC P16333; Q9BQ89: FAM110A; NbExp=2; IntAct=EBI-389883, EBI-1752811;
CC P16333; P31994: FCGR2B; NbExp=2; IntAct=EBI-389883, EBI-724784;
CC P16333; P31995: FCGR2C; NbExp=2; IntAct=EBI-389883, EBI-1396036;
CC P16333; O75369: FLNB; NbExp=3; IntAct=EBI-389883, EBI-352089;
CC P16333; O75593: FOXH1; NbExp=2; IntAct=EBI-389883, EBI-1759806;
CC P16333; O15117: FYB1; NbExp=3; IntAct=EBI-389883, EBI-1753267;
CC P16333; Q13480: GAB1; NbExp=3; IntAct=EBI-389883, EBI-517684;
CC P16333; Q9UBS5: GABBR1; NbExp=3; IntAct=EBI-389883, EBI-724156;
CC P16333; Q99259: GAD1; NbExp=2; IntAct=EBI-389883, EBI-743184;
CC P16333; P10912: GHR; NbExp=3; IntAct=EBI-389883, EBI-286316;
CC P16333; P15586: GNS; NbExp=2; IntAct=EBI-389883, EBI-1752200;
CC P16333; O43708: GSTZ1; NbExp=2; IntAct=EBI-389883, EBI-748043;
CC P16333; P10412: H1-4; NbExp=2; IntAct=EBI-389883, EBI-358163;
CC P16333; O43390: HNRNPR; NbExp=2; IntAct=EBI-389883, EBI-713419;
CC P16333; P47928: ID4; NbExp=3; IntAct=EBI-389883, EBI-1754719;
CC P16333; Q9H9L3: ISG20L2; NbExp=2; IntAct=EBI-389883, EBI-751335;
CC P16333; O60674: JAK2; NbExp=2; IntAct=EBI-389883, EBI-518647;
CC P16333; P35968: KDR; NbExp=3; IntAct=EBI-389883, EBI-1005487;
CC P16333; P10721: KIT; NbExp=3; IntAct=EBI-389883, EBI-1379503;
CC P16333; Q9UMN6: KMT2B; NbExp=2; IntAct=EBI-389883, EBI-765774;
CC P16333; Q13094: LCP2; NbExp=21; IntAct=EBI-389883, EBI-346946;
CC P16333; Q9BY71: LRRC3; NbExp=2; IntAct=EBI-389883, EBI-1761329;
CC P16333; P27816: MAP4; NbExp=2; IntAct=EBI-389883, EBI-715255;
CC P16333; Q92918: MAP4K1; NbExp=4; IntAct=EBI-389883, EBI-881;
CC P16333; Q9Y4K4: MAP4K5; NbExp=2; IntAct=EBI-389883, EBI-1279;
CC P16333; Q9NQ76: MEPE; NbExp=3; IntAct=EBI-389883, EBI-1753293;
CC P16333; P08581: MET; NbExp=2; IntAct=EBI-389883, EBI-1039152;
CC P16333; Q15746: MYLK; NbExp=2; IntAct=EBI-389883, EBI-968482;
CC P16333; Q8WX92: NELFB; NbExp=6; IntAct=EBI-389883, EBI-347721;
CC P16333; Q5HYW2: NHSL2; NbExp=3; IntAct=EBI-389883, EBI-2859639;
CC P16333; P43699: NKX2-1; NbExp=2; IntAct=EBI-389883, EBI-1391923;
CC P16333; O60500: NPHS1; NbExp=3; IntAct=EBI-389883, EBI-996920;
CC P16333; Q13177: PAK2; NbExp=5; IntAct=EBI-389883, EBI-1045887;
CC P16333; Q13087: PDIA2; NbExp=3; IntAct=EBI-389883, EBI-1752525;
CC P16333; O75167: PHACTR2; NbExp=2; IntAct=EBI-389883, EBI-1754409;
CC P16333; Q6ZUJ8-3: PIK3AP1; NbExp=3; IntAct=EBI-389883, EBI-11981743;
CC P16333; O00750: PIK3C2B; NbExp=3; IntAct=EBI-389883, EBI-641107;
CC P16333; Q9UL42: PNMA2; NbExp=2; IntAct=EBI-389883, EBI-302355;
CC P16333; Q9BXM0: PRX; NbExp=2; IntAct=EBI-389883, EBI-1753064;
CC P16333; P29074: PTPN4; NbExp=3; IntAct=EBI-389883, EBI-710431;
CC P16333; P15918: RAG1; NbExp=2; IntAct=EBI-389883, EBI-1755109;
CC P16333; Q13905: RAPGEF1; NbExp=2; IntAct=EBI-389883, EBI-976876;
CC P16333; P20936: RASA1; NbExp=6; IntAct=EBI-389883, EBI-1026476;
CC P16333; Q9UQ26: RIMS2; NbExp=2; IntAct=EBI-389883, EBI-1756749;
CC P16333; Q8TB24: RIN3; NbExp=2; IntAct=EBI-389883, EBI-1570523;
CC P16333; P26373: RPL13; NbExp=2; IntAct=EBI-389883, EBI-356849;
CC P16333; P78345: RPP38; NbExp=2; IntAct=EBI-389883, EBI-366493;
CC P16333; P10301: RRAS; NbExp=3; IntAct=EBI-389883, EBI-968703;
CC P16333; Q96GP6: SCARF2; NbExp=2; IntAct=EBI-389883, EBI-1752088;
CC P16333; Q9NZV5: SELENON; NbExp=2; IntAct=EBI-389883, EBI-1751965;
CC P16333; O75326: SEMA7A; NbExp=2; IntAct=EBI-389883, EBI-1753538;
CC P16333; Q9UPX8: SHANK2; NbExp=6; IntAct=EBI-389883, EBI-1570571;
CC P16333; Q9BYB0: SHANK3; NbExp=4; IntAct=EBI-389883, EBI-1752330;
CC P16333; Q13796: SHROOM2; NbExp=2; IntAct=EBI-389883, EBI-1644065;
CC P16333; Q9UHI7: SLC23A1; NbExp=2; IntAct=EBI-389883, EBI-1759386;
CC P16333; O60721: SLC24A1; NbExp=3; IntAct=EBI-389883, EBI-1753504;
CC P16333; Q9UMY4: SNX12; NbExp=3; IntAct=EBI-389883, EBI-1752602;
CC P16333; Q15036: SNX17; NbExp=3; IntAct=EBI-389883, EBI-1752620;
CC P16333; Q9Y5X2: SNX8; NbExp=2; IntAct=EBI-389883, EBI-1752557;
CC P16333; Q07889: SOS1; NbExp=5; IntAct=EBI-389883, EBI-297487;
CC P16333; Q07890: SOS2; NbExp=3; IntAct=EBI-389883, EBI-298181;
CC P16333; P08047: SP1; NbExp=2; IntAct=EBI-389883, EBI-298336;
CC P16333; Q96T58: SPEN; NbExp=3; IntAct=EBI-389883, EBI-765739;
CC P16333; Q15208: STK38; NbExp=3; IntAct=EBI-389883, EBI-458376;
CC P16333; Q9H5I1: SUV39H2; NbExp=2; IntAct=EBI-389883, EBI-723127;
CC P16333; O15056: SYNJ2; NbExp=3; IntAct=EBI-389883, EBI-310513;
CC P16333; O43493: TGOLN2; NbExp=3; IntAct=EBI-389883, EBI-1752146;
CC P16333; P42167: TMPO; NbExp=2; IntAct=EBI-389883, EBI-455283;
CC P16333; Q15661: TPSAB1; NbExp=2; IntAct=EBI-389883, EBI-1761369;
CC P16333; Q9ULW0: TPX2; NbExp=4; IntAct=EBI-389883, EBI-1037322;
CC P16333; Q9BWF2: TRAIP; NbExp=3; IntAct=EBI-389883, EBI-1756205;
CC P16333; Q9HCM9: TRIM39; NbExp=2; IntAct=EBI-389883, EBI-739510;
CC P16333; O00294: TULP1; NbExp=2; IntAct=EBI-389883, EBI-1756778;
CC P16333; Q96RL7: VPS13A; NbExp=3; IntAct=EBI-389883, EBI-1752583;
CC P16333; O00401: WASL; NbExp=2; IntAct=EBI-389883, EBI-957615;
CC P16333; O43516: WIPF1; NbExp=2; IntAct=EBI-389883, EBI-346356;
CC P16333-1; P48023: FASLG; NbExp=4; IntAct=EBI-15578122, EBI-495538;
CC P16333-1; O60942: RNGTT; NbExp=2; IntAct=EBI-15578122, EBI-1237132;
CC P16333-1; O00401: WASL; NbExp=2; IntAct=EBI-15578122, EBI-957615;
CC P16333-1; O55236: Rngtt; Xeno; NbExp=3; IntAct=EBI-15578122, EBI-16118241;
CC P16333-1; O54967: Tnk2; Xeno; NbExp=2; IntAct=EBI-15578122, EBI-7780354;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. Nucleus.
CC Note=Mostly cytoplasmic, but shuttles between the cytoplasm and the
CC nucleus. Import into the nucleus requires the interaction with SOCS7.
CC Predominantly nuclear following genotoxic stresses, such as UV
CC 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 -!- DOMAIN: Only the first and third SH3 domains seem to be involved in
CC RASA1-binding; the second SH3 domain and the SH2 domains do not seem to
CC be involved.
CC -!- PTM: Phosphorylated on Ser and Tyr residues. Phosphorylated in response
CC to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB.
CC {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:1333046,
CC ECO:0000269|PubMed:1448108, ECO:0000269|PubMed:18835251,
CC ECO:0000269|PubMed:7692233}.
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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 CCDS; CCDS3092.1; -. [P16333-1]
DR CCDS; CCDS54644.1; -. [P16333-2]
DR PIR; S08636; S08636.
DR RefSeq; NP_001177725.1; NM_001190796.2. [P16333-2]
DR RefSeq; NP_001278928.1; NM_001291999.1. [P16333-1]
DR RefSeq; NP_006144.1; NM_006153.5. [P16333-1]
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 PDB; 5QU1; X-ray; 1.08 A; A/B=4-59.
DR PDB; 5QU2; X-ray; 1.04 A; A/B=1-59.
DR PDB; 5QU3; X-ray; 1.02 A; A/B=4-59.
DR PDB; 5QU4; X-ray; 1.05 A; A/B/C/D=1-61.
DR PDB; 5QU5; X-ray; 1.11 A; A/B=1-61.
DR PDB; 5QU6; X-ray; 1.82 A; 1/2/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z=1-61.
DR PDB; 5QU7; X-ray; 1.27 A; A/B=4-59.
DR PDB; 5QU8; X-ray; 0.93 A; A=1-61.
DR PDB; 5QUA; X-ray; 1.51 A; A/B=1-61.
DR PDBsum; 2CI8; -.
DR PDBsum; 2CI9; -.
DR PDBsum; 2CUB; -.
DR PDBsum; 2JS0; -.
DR PDBsum; 2JS2; -.
DR PDBsum; 2JW4; -.
DR PDBsum; 5QU1; -.
DR PDBsum; 5QU2; -.
DR PDBsum; 5QU3; -.
DR PDBsum; 5QU4; -.
DR PDBsum; 5QU5; -.
DR PDBsum; 5QU6; -.
DR PDBsum; 5QU7; -.
DR PDBsum; 5QU8; -.
DR PDBsum; 5QUA; -.
DR AlphaFoldDB; P16333; -.
DR BMRB; P16333; -.
DR SMR; P16333; -.
DR BioGRID; 110770; 171.
DR DIP; DIP-639N; -.
DR ELM; P16333; -.
DR IntAct; P16333; 254.
DR MINT; P16333; -.
DR STRING; 9606.ENSP00000417273; -.
DR BindingDB; P16333; -.
DR ChEMBL; CHEMBL4846; -.
DR MoonDB; P16333; Predicted.
DR iPTMnet; P16333; -.
DR PhosphoSitePlus; P16333; -.
DR BioMuta; NCK1; -.
DR DMDM; 127962; -.
DR EPD; P16333; -.
DR jPOST; P16333; -.
DR MassIVE; P16333; -.
DR MaxQB; P16333; -.
DR PaxDb; P16333; -.
DR PeptideAtlas; P16333; -.
DR PRIDE; P16333; -.
DR ProteomicsDB; 53345; -. [P16333-1]
DR ProteomicsDB; 53346; -. [P16333-2]
DR Antibodypedia; 3567; 559 antibodies from 39 providers.
DR DNASU; 4690; -.
DR Ensembl; ENST00000288986.6; ENSP00000288986.2; ENSG00000158092.7. [P16333-1]
DR Ensembl; ENST00000469404.1; ENSP00000419631.1; ENSG00000158092.7. [P16333-2]
DR Ensembl; ENST00000481752.6; ENSP00000417273.1; ENSG00000158092.7. [P16333-1]
DR GeneID; 4690; -.
DR KEGG; hsa:4690; -.
DR MANE-Select; ENST00000481752.6; ENSP00000417273.1; NM_001291999.2; NP_001278928.1.
DR UCSC; uc003erh.3; human. [P16333-1]
DR CTD; 4690; -.
DR DisGeNET; 4690; -.
DR GeneCards; NCK1; -.
DR HGNC; HGNC:7664; NCK1.
DR HPA; ENSG00000158092; Low tissue specificity.
DR MIM; 600508; gene.
DR neXtProt; NX_P16333; -.
DR OpenTargets; ENSG00000158092; -.
DR PharmGKB; PA31466; -.
DR VEuPathDB; HostDB:ENSG00000158092; -.
DR eggNOG; KOG4226; Eukaryota.
DR GeneTree; ENSGT00940000156601; -.
DR HOGENOM; CLU_025160_0_1_1; -.
DR InParanoid; P16333; -.
DR OMA; KTGMRET; -.
DR OrthoDB; 1097449at2759; -.
DR PhylomeDB; P16333; -.
DR TreeFam; TF351631; -.
DR PathwayCommons; P16333; -.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR Reactome; R-HSA-428540; Activation of RAC1.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P16333; -.
DR SIGNOR; P16333; -.
DR BioGRID-ORCS; 4690; 40 hits in 1083 CRISPR screens.
DR ChiTaRS; NCK1; human.
DR EvolutionaryTrace; P16333; -.
DR GeneWiki; NCK1; -.
DR GenomeRNAi; 4690; -.
DR Pharos; P16333; Tbio.
DR PRO; PR:P16333; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P16333; protein.
DR Bgee; ENSG00000158092; Expressed in penis and 206 other tissues.
DR ExpressionAtlas; P16333; baseline and differential.
DR Genevisible; P16333; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005840; C:ribosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0008093; F:cytoskeletal anchor activity; NAS:UniProtKB.
DR GO; GO:0046875; F:ephrin receptor binding; IBA:GO_Central.
DR GO; GO:0071074; F:eukaryotic initiation factor eIF2 binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:FlyBase.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; NAS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030032; P:lamellipodium assembly; IEA:Ensembl.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:UniProtKB.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990441; P:negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:1903676; P:positive regulation of cap-dependent translational initiation; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903679; P:positive regulation of cap-independent translational initiation; IDA:ParkinsonsUK-UCL.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0036493; P:positive regulation of translation in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0051707; P:response to other organism; IEA:Ensembl.
DR GO; GO:0007172; P:signal complex assembly; NAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; IEA:Ensembl.
DR GO; GO:0042110; P:T cell activation; IMP:UniProtKB.
DR CDD; cd10408; SH2_Nck1; 1.
DR CDD; cd11900; SH3_Nck1_1; 1.
DR CDD; cd11901; SH3_Nck1_2; 1.
DR CDD; cd11904; SH3_Nck1_3; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR017304; NCK.
DR InterPro; IPR028526; NCK1.
DR InterPro; IPR035882; Nck1_SH2.
DR InterPro; IPR035562; Nck1_SH3_1.
DR InterPro; IPR035564; Nck1_SH3_2.
DR InterPro; IPR035565; Nck1_SH3_3.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR19969:SF16; PTHR19969:SF16; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 2.
DR Pfam; PF14604; SH3_9; 1.
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; SSF50044; 3.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Endoplasmic reticulum; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..377
FT /note="Cytoplasmic protein NCK1"
FT /id="PRO_0000096766"
FT DOMAIN 2..61
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 106..165
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 190..252
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 282..376
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 105
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..76
FT /note="MAEEVVVVAKFDYVAQQEQELDIKKNERLWLLDDSKSWWRVRNSMNKTGFVP
FT SNYVERKNSARKASIVKNLKDTLG -> MDWLNVFKDFFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043122"
FT VARIANT 180
FT /note="A -> V (in dbSNP:rs13320485)"
FT /id="VAR_051228"
FT MUTAGEN 38
FT /note="W->K: Small decrease in RASA1-binding. Almost
FT complete loss of RASA1-binding; when associated with K-143
FT and K-229."
FT /evidence="ECO:0000269|PubMed:21664272"
FT MUTAGEN 143
FT /note="W->K: No effect on RASA1-binding. Almost complete
FT loss of RASA1-binding; when associated with K-38 and K-
FT 229."
FT /evidence="ECO:0000269|PubMed:21664272"
FT MUTAGEN 229
FT /note="W->K: Small decrease in RASA1-binding. Almost
FT complete loss of RASA1-binding; when associated with K-38
FT and K-229."
FT /evidence="ECO:0000269|PubMed:21664272"
FT MUTAGEN 308
FT /note="R->K: No effect on RASA1-binding."
FT /evidence="ECO:0000269|PubMed:21664272"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:5QU8"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:5QU8"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:5QU8"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:5QU8"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:5QU8"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:5QU8"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:5QU2"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:2CUB"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2CUB"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:2CUB"
FT HELIX 289..299
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 304..309
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 328..335
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 338..341
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:2CI9"
FT HELIX 349..358
FT /evidence="ECO:0007829|PDB:2CI9"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:2CI9"
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
