ID NCK2_MOUSE Reviewed; 380 AA.
AC O55033;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 27-MAR-2024, entry version 183.
DE RecName: Full=Cytoplasmic protein NCK2;
DE AltName: Full=Growth factor receptor-bound protein 4;
DE AltName: Full=NCK adaptor protein 2;
DE Short=Nck-2;
DE AltName: Full=SH2/SH3 adaptor protein NCK-beta;
GN Name=Nck2; Synonyms=Grb4;
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 She H.Y., Chen M., Li W.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110, 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-90; SER-94 AND TYR-110, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC 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 or their cellular substrates. Maintains low
CC levels of EIF2S1 phosphorylation by promoting its dephosphorylation by
CC PP1. Plays a role in ELK1-dependent transcriptional activation in
CC response to activated Ras signaling (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with DOCK1, LIMS1 and TGFB1I1. Part of a complex
CC containing PPP1R15B, PP1 and NCK2. Interacts with FASLG. Interacts with
CC AXL. Interacts with PAK1, PKN2 and SOS1. Interacts (via SH2 domain)
CC with EGFR. Interacts (via SH2 domain) with DDR1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Endoplasmic reticulum
CC {ECO:0000250}.
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; AF043260; AAC06353.1; -; mRNA.
DR EMBL; AC107865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466589; EDK96908.1; -; Genomic_DNA.
DR EMBL; BC011071; AAH11071.1; -; mRNA.
DR EMBL; BC034255; AAH34255.1; -; mRNA.
DR CCDS; CCDS14924.1; -.
DR RefSeq; NP_035009.3; NM_010879.3.
DR AlphaFoldDB; O55033; -.
DR BMRB; O55033; -.
DR SMR; O55033; -.
DR BioGRID; 201705; 19.
DR IntAct; O55033; 8.
DR MINT; O55033; -.
DR STRING; 10090.ENSMUSP00000083611; -.
DR iPTMnet; O55033; -.
DR PhosphoSitePlus; O55033; -.
DR SwissPalm; O55033; -.
DR EPD; O55033; -.
DR jPOST; O55033; -.
DR MaxQB; O55033; -.
DR PaxDb; 10090-ENSMUSP00000083611; -.
DR PeptideAtlas; O55033; -.
DR ProteomicsDB; 293631; -.
DR Pumba; O55033; -.
DR Antibodypedia; 4240; 402 antibodies from 37 providers.
DR DNASU; 17974; -.
DR Ensembl; ENSMUST00000086421.9; ENSMUSP00000083611.6; ENSMUSG00000066877.12.
DR GeneID; 17974; -.
DR KEGG; mmu:17974; -.
DR UCSC; uc007avo.2; mouse.
DR AGR; MGI:1306821; -.
DR CTD; 8440; -.
DR MGI; MGI:1306821; Nck2.
DR VEuPathDB; HostDB:ENSMUSG00000066877; -.
DR eggNOG; KOG4226; Eukaryota.
DR GeneTree; ENSGT00940000157728; -.
DR HOGENOM; CLU_025160_0_1_1; -.
DR InParanoid; O55033; -.
DR OMA; TWYYGAI; -.
DR OrthoDB; 25798at2759; -.
DR PhylomeDB; O55033; -.
DR TreeFam; TF351631; -.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-373753; Nephrin family interactions.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR BioGRID-ORCS; 17974; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Nck2; mouse.
DR PRO; PR:O55033; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O55033; Protein.
DR Bgee; ENSMUSG00000066877; Expressed in cortical plate and 141 other cell types or tissues.
DR ExpressionAtlas; O55033; baseline and differential.
DR Genevisible; O55033; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0012506; C:vesicle membrane; IDA:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IMP:MGI.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0060996; P:dendritic spine development; ISO:MGI.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:MGI.
DR GO; GO:0001771; P:immunological synapse formation; ISO:MGI.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:MGI.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IGI:ParkinsonsUK-UCL.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:ParkinsonsUK-UCL.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISO:MGI.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:1902310; P:positive regulation of peptidyl-serine dephosphorylation; IEA:Ensembl.
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; ISO:MGI.
DR GO; GO:0036493; P:positive regulation of translation in response to endoplasmic reticulum stress; IGI:ParkinsonsUK-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IGI:ParkinsonsUK-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd10409; SH2_Nck2; 1.
DR CDD; cd11899; SH3_Nck2_1; 1.
DR CDD; cd11902; SH3_Nck2_2; 1.
DR CDD; cd11903; SH3_Nck2_3; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 3.
DR InterPro; IPR017304; NCK.
DR InterPro; IPR035883; Nck2_SH2.
DR InterPro; IPR035559; Nck2_SH3_1.
DR InterPro; IPR035560; Nck2_SH3_2.
DR InterPro; IPR035561; Nck2_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:SF12; CYTOPLASMIC PROTEIN NCK2; 1.
DR PANTHER; PTHR19969; SH2-SH3 ADAPTOR PROTEIN-RELATED; 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; SSF55550; SH2 domain; 1.
DR SUPFAM; SSF50044; SH3-domain; 3.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 3.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Endoplasmic reticulum; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; SH3 domain; Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O43639"
FT CHAIN 2..380
FT /note="Cytoplasmic protein NCK2"
FT /id="PRO_0000415287"
FT DOMAIN 2..61
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 111..170
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 195..257
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 285..379
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 78..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:O43639"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 92
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43639"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 110
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:21183079"
SQ SEQUENCE 380 AA; 42879 MW; 7B3404B976F0A54D CRC64;
MTEEVIVIAK WDYTAQQDQE LDIRKNERLW LLDDSKTWWR VRNAANRTGY VPSNYVERKN
SLKKGSLVKN LKDTLGLGKT RRKPSARDAS PTPSTDAEYP ANGSGADRIY DLNIPAFVKF
AYVAEREDEL SLVKGSRVTV MEKCSDGWWR GSFNGQIGWF PSNYVLEEAD EAAAEAPSFL
SLRRGTALSN GQGARVLHVV QTLYPFSSVT EEELSFEKGE TMEVIEKPEN DPEWWKCKNA
RGQVGLVPKN YVVVLSDGPA LHPAHTPQIS YTGPSASGRF AGREWYYGNV TRHQAECALN
ERGVEGDFLI RDSESSPSDF SVSLKASGRN KHFKVQLVDS VYCIGQRRFH SMDELVEHYK
KAPIFTSEHG EKLYLVRALQ
//
