P16333 B7Z751 D3DNE3 NCK1_HUMAN Cytoplasmic protein NCK1 NCK adaptor protein 1 Nck-1 SH2/SH3 adaptor protein NCK-alpha NCK1 NCK Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo Nck, a melanoma cDNA encoding a cytoplasmic protein consisting of the src homology units SH2 and SH3. NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) Complete sequencing and characterization of 21,243 full-length human cDNAs. NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2) Synovium The DNA sequence, annotation and analysis of human chromosome 3. NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1) Uterus Phosphorylation of Nck in response to a variety of receptors, phorbol myristate acetate, and cyclic AMP. PHOSPHORYLATION PARTIAL PROTEIN SEQUENCE The SH2/SH3 domain-containing protein Nck is recognized by certain anti-phospholipase C-gamma 1 monoclonal antibodies, and its phosphorylation on tyrosine is stimulated by platelet-derived growth factor and epidermal growth factor treatment. PHOSPHORYLATION Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor. INTERACTION WITH PDGFRB PHOSPHORYLATION A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs. INTERACTION WITH SOCS7 Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2. INTERACTION WITH FLT1 BLNK: a central linker protein in B cell activation. INTERACTION WITH BLNK; GRB2; PLCG1 AND VAV Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. INTERACTION WITH EPHB1 Kidney Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. FUNCTION INTERACTION WITH EGFR; PAK1; PKN2 AND SOS1 PHOSPHORYLATION Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral. INTERACTION WITH RALGPS1 Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1. INTERACTION WITH CAV2 Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27). INTERACTION WITH CAV2 Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta. INTERACTION WITH MINK1 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS] Cervix carcinoma Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. IDENTIFICATION IN COMPLEX WITH PP1 AND PPP1R15B FUNCTION SUBCELLULAR LOCATION Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF. INTERACTION WITH KDR Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. FUNCTION SUBCELLULAR LOCATION INTERACTION WITH SOCS7 Phosphoproteome of resting human platelets. PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105 MASS SPECTROMETRY Platelet Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma. INTERACTION WITH ADAM15 A quantitative atlas of mitotic phosphorylation. PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-91 AND SER-96 MASS SPECTROMETRY Cervix carcinoma Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. INTERACTION WITH FASLG Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND TYR-105 MASS SPECTROMETRY Leukemic T-cell Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105 MASS SPECTROMETRY Cervix carcinoma Initial characterization of the human central proteome. IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS] Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity. INTERACTION WITH RASA1 MUTAGENESIS OF TRP-38; TRP-143; TRP-229 AND ARG-308 Solution structure of the SH3 domain of the human cytoplasmic protein NCK1. STRUCTURE BY NMR OF 99-174 Specificity determinants of a novel Nck interaction with the juxtamembrane domain of the epidermal growth factor receptor. STRUCTURE BY NMR OF 1-61 AND 107-165 INTERACTION WITH EGFR Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Interacts (via SH2 domain and SH3 domain 2) with EGFR. Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2. Associates with BLNK, PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with SOCS7. This interaction is required for nuclear import. Part of a complex containing PPP1R15B, PP1 and NCK1. Interacts with RALGPS1. Interacts with CAV2 (tyrosine phosphorylated form). Interacts with ADAM15. Interacts with FASLG. Directly interacts with RASA1. Interacts with isoform 4 of MINK1. Interacts with FLT1 (tyrosine. phosphorylated). Interacts with KDR (tyrosine phosphorylated). Interacts (via SH2 domain) with EPHB1; activates the JUN cascade to regulate cell adhesion. Interacts (via SH2 domain) with PDGFRB (tyrosine phosphorylated). Q9H222 false 2 P00519 false 2 P42684 false 3 Q15109 false 2 O43918 false 2 O15085 false 3 Q9ULH1 false 5 Q96NS5 false 2 Q9UIF9 false 2 O60885 false 2 Q9ULD4 false 3 P13671 false 2 P20810 false 2 P30260 false 3 Q9NYQ7 false 2 Q13111 false 2 Q14008 false 3 P78357 false 2 Q8WX92 false 6 P78329 false 2 P98082 false 2 Q14118 false 2 O14490 false 4 Q9P1A6 false 4 O95886 false 2 Q9Y2H0 false 5 Q92988 false 3 Q05193 false 2 Q8IZD9 false 3 Q9H1R2 false 2 Q9H8V3 false 3 P41970 false 3 P42566 false 2 O00254 false 2 Q9BQ89 false 2 P31994 false 2 P31995 false 2 O75369 false 3 O75593 false 2 O15117 false 3 Q9UBS5 false 3 Q99259 false 2 P10912 false 2 Q9NZM4 false 3 P15586 false 2 O43708 false 2 P10412 false 2 O43390 false 2 P47928 false 3 Q9H9L3 false 2 O60674 false 2 Q9BY71 false 2 P27816 false 2 Q92918 false 2 Q9Y4K4 false 2 Q9NQ76 false 3 Q15746 false 2 P43699 false 2 O60500 false 3 Q13087 false 3 O75167 false 2 O00750 false 3 Q9UL42 false 2 Q9BXM0 false 2 P29074 false 3 P15918 false 2 Q13905 false 2 P20936 false 6 Q9UQ26 false 2 Q8TB24 false 2 P26373 false 2 P78345 false 2 P10301 false 3 Q96GP6 false 2 O75326 false 2 Q9NZV5 false 2 Q9UPX8 false 6 Q9BYB0 false 4 Q13796 false 2 Q9UHI7 false 2 O60721 false 3 Q9UMY4 false 3 Q15036 false 3 Q9Y5X2 false 2 Q07889 false 5 Q07890 false 3 P08047 false 2 Q96T58 false 3 Q9H5I1 false 2 O15056 false 3 O43493 false 3 P42167 false 2 Q15661 false 2 Q9ULW0 false 4 Q9BWF2 false 3 Q9HCM9 false 2 O00294 false 2 Q96RL7 false 3 Q9UMN6 false 2 O43516 false 2 Cytoplasm Endoplasmic reticulum Nucleus Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Import into the nucleus requires the interaction with SOCS7. Predominantly nuclear following genotoxic stresses, such as UV irradiation, hydroxyurea or mitomycin C treatments. P16333-1 1 P16333-2 2 No experimental confirmation available. Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seeem to be involved. Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB. Contains 1 SH2 domain. Contains 3 SH3 domains. 3D-structure Alternative splicing Complete proteome Cytoplasm Direct protein sequencing Endoplasmic reticulum Nucleus Phosphoprotein Polymorphism Reference proteome Repeat SH2 domain SH3 domain Translation regulation MAEEVVVVAKFDYVAQQEQELDIKKNERLWLLDDSKSWWRVRNSMNKTGFVPSNYVERKNSARKASIVKNLKDTLG MDWLNVFKDFFS A V W K W K W K R K MAEEVVVVAKFDYVAQQEQELDIKKNERLWLLDDSKSWWRVRNSMNKTGFVPSNYVERKN SARKASIVKNLKDTLGIGKVKRKPSVPDSASPADDSFVDPGERLYDLNMPAYVKFNYMAE REDELSLIKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYVTEEGDSPLGDHVGSLSEKLA AVVNNLNTGQVLHVVQALYPFSSSNDEELNFEKGDVMDVIEKPENDPEWWKCRKINGMVG LVPKNYVTVMQNNPLTSGLEPSPPQCDYIRPSLTGKFAGNPWYYGKVTRHQAEMALNERG HEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKETVYCIGQRKFSTMEELVEHYKKAP IFTSEQGEKLYLVKHLS Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms Distributed under the Creative Commons Attribution-NoDerivs License