NCK1_MOUSE
ID NCK1_MOUSE Reviewed; 377 AA.
AC Q99M51; O55032; Q9Z279;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Cytoplasmic protein NCK1;
DE AltName: Full=NCK adaptor protein 1;
DE Short=Nck-1;
GN Name=Nck1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Miyoshi-Akiyama T., Mayer B.J.;
RT "Mus musculus SH2/SH3 adaptor protein (Nck) mRNA, complete cds.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen M., She H.Y., Li W.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 INTERACTION WITH FLT1.
RX PubMed=9722576; DOI=10.1074/jbc.273.36.23410;
RA Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.;
RT "Identification of vascular endothelial growth factor receptor-1 tyrosine
RT phosphorylation sites and binding of SH2 domain-containing molecules.";
RL J. Biol. Chem. 273:23410-23418(1998).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; TYR-105 AND SER-166, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: 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 MINK1. 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 (via SH2 domain and SH3 domain 2) with EGFR.
CC Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2 (By
CC similarity). Interacts with FLT1 (tyrosine phosphorylated). Interacts
CC with the inactive form of EIF2AK2/PKR (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q99M51; P00520: Abl1; NbExp=2; IntAct=EBI-642202, EBI-914519;
CC Q99M51; P97465: Dok1; NbExp=5; IntAct=EBI-642202, EBI-914917;
CC Q99M51; O54967: Tnk2; NbExp=2; IntAct=EBI-642202, EBI-7780354;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Endoplasmic reticulum
CC {ECO:0000250}. Nucleus {ECO:0000250}. Note=Mostly cytoplasmic, but
CC shuttles between the cytoplasm and the nucleus. Import into the nucleus
CC requires interaction with SOCS7. Predominantly nuclear following
CC genotoxic stresses, such as UV irradiation, hydroxyurea or mitomycin C
CC treatments (By similarity). {ECO:0000250}.
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. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser and Tyr residues. Phosphorylated in response
CC to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB (By
CC similarity). {ECO:0000250}.
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DR EMBL; AF084183; AAD13752.1; -; mRNA.
DR EMBL; AF043259; AAC06352.1; -; mRNA.
DR EMBL; AC129223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466560; EDL21028.1; -; Genomic_DNA.
DR EMBL; CH466560; EDL21029.1; -; Genomic_DNA.
DR EMBL; CH466560; EDL21031.1; -; Genomic_DNA.
DR EMBL; BC002015; AAH02015.1; -; mRNA.
DR CCDS; CCDS23440.1; -.
DR RefSeq; NP_035008.2; NM_010878.3.
DR RefSeq; XP_006510903.1; XM_006510840.2.
DR AlphaFoldDB; Q99M51; -.
DR BMRB; Q99M51; -.
DR SMR; Q99M51; -.
DR BioGRID; 201704; 49.
DR DIP; DIP-37524N; -.
DR IntAct; Q99M51; 17.
DR MINT; Q99M51; -.
DR STRING; 10090.ENSMUSP00000112221; -.
DR iPTMnet; Q99M51; -.
DR PhosphoSitePlus; Q99M51; -.
DR REPRODUCTION-2DPAGE; IPI00453999; -.
DR EPD; Q99M51; -.
DR jPOST; Q99M51; -.
DR MaxQB; Q99M51; -.
DR PaxDb; Q99M51; -.
DR PeptideAtlas; Q99M51; -.
DR PRIDE; Q99M51; -.
DR ProteomicsDB; 286159; -.
DR Antibodypedia; 3567; 559 antibodies from 39 providers.
DR DNASU; 17973; -.
DR Ensembl; ENSMUST00000116522; ENSMUSP00000112221; ENSMUSG00000032475.
DR GeneID; 17973; -.
DR KEGG; mmu:17973; -.
DR UCSC; uc009rex.1; mouse.
DR CTD; 4690; -.
DR MGI; MGI:109601; Nck1.
DR VEuPathDB; HostDB:ENSMUSG00000032475; -.
DR eggNOG; KOG4226; Eukaryota.
DR GeneTree; ENSGT00940000156601; -.
DR HOGENOM; CLU_025160_0_1_1; -.
DR InParanoid; Q99M51; -.
DR OMA; KTGMRET; -.
DR OrthoDB; 1097449at2759; -.
DR PhylomeDB; Q99M51; -.
DR TreeFam; TF351631; -.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-373753; Nephrin family interactions.
DR Reactome; R-MMU-418885; DCC mediated attractive signaling.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 17973; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Nck1; mouse.
DR PRO; PR:Q99M51; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q99M51; protein.
DR Bgee; ENSMUSG00000032475; Expressed in granulocyte and 242 other tissues.
DR ExpressionAtlas; Q99M51; baseline and differential.
DR Genevisible; Q99M51; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; ISO:MGI.
DR GO; GO:0005840; C:ribosome; ISO:MGI.
DR GO; GO:0012506; C:vesicle membrane; IDA:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:MGI.
DR GO; GO:0071074; F:eukaryotic initiation factor eIF2 binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; IMP:MGI.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IMP:MGI.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; IGI:ParkinsonsUK-UCL.
DR GO; GO:1990441; P:negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IGI:ParkinsonsUK-UCL.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IGI:MGI.
DR GO; GO:1903676; P:positive regulation of cap-dependent translational initiation; ISO:MGI.
DR GO; GO:1903679; P:positive regulation of cap-independent translational initiation; ISO:MGI.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0036493; P:positive regulation of translation in response to endoplasmic reticulum stress; IGI:ParkinsonsUK-UCL.
DR GO; GO:0030334; P:regulation of cell migration; IGI:MGI.
DR GO; GO:0051707; P:response to other organism; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; IGI:MGI.
DR GO; GO:0042110; P:T cell activation; ISO:MGI.
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 Acetylation; Cytoplasm; Endoplasmic reticulum; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P16333"
FT CHAIN 2..377
FT /note="Cytoplasmic protein NCK1"
FT /id="PRO_0000413801"
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:0000250|UniProtKB:P16333"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16333"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16333"
FT MOD_RES 105
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 4
FT /note="E -> G (in Ref. 1; AAD13752 and 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="W -> C (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="T -> N (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="P -> T (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="A -> E (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 155..157
FT /note="FPS -> LPC (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="S -> G (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="D -> N (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="I -> V (in Ref. 2; AAC06352)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 377 AA; 42891 MW; 671BBFC870A88EB9 CRC64;
MAEEVVVVAK FDYVAQQEQE LDIKKNERLW LLDDSKSWWR VRNSMNKTGF VPSNYVERKN
SARKASIVKN LKDTLGIGKV KRKPSVPDTA SPADDSFVDP GERLYDLNMP AFVKFNYMAE
REDELSLIKG TKVIVMEKCS DGWWRGSYNG QIGWFPSNYV TEEGDSPLGD HVGSLSEKLA
AVVNNLNTGQ VLHVVQALYP FSSSNDEELN FEKGDVMDVI EKPENDPEWW KCRKINGMVG
LVPKNYVTIM QNNPLTSGLE PSPPQCDYIR PSLTGKFAGN PWYYGKVTRH QAEMALNERG
HEGDFLIRDS ESSPNDFSVS LKAQGKNKHF KVQLKETVYC IGQRKFSTME ELVEHYKKAP
IFTSEQGEKL YLVKHLS
