Human Gene NCK1 (ENST00000288986.6_2) from GENCODE V47lift37
Description: 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. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. (from UniProt P16333)
Gencode Transcript: ENST00000288986.6_2
Gencode Gene: ENSG00000158092.7_13
Transcript (Including UTRs)
Position: hg19 chr3:136,581,050-136,667,968 Size: 86,919 Total Exon Count: 4 Strand: +
Coding Region
Position: hg19 chr3:136,646,844-136,667,295 Size: 20,452 Coding Exon Count: 3
Data last updated at UCSC: 2024-08-22 23:36:26
Sequence and Links to Tools and Databases
Comments and Description Text from UniProtKB
ID: NCK1_HUMAN
DESCRIPTION: RecName: Full=Cytoplasmic protein NCK1; AltName: Full=NCK adaptor protein 1; Short=Nck-1; AltName: Full=SH2/SH3 adaptor protein NCK-alpha;
FUNCTION: 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.SUBUNIT: 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).INTERACTION: Q9H222:ABCG5; NbExp=2; IntAct=EBI-389883, EBI-1761423; P00519:ABL1; NbExp=2; IntAct=EBI-389883, EBI-375543; P42684:ABL2; NbExp=3; IntAct=EBI-389883, EBI-1102694; Q15109:AGER; NbExp=2; IntAct=EBI-389883, EBI-1646426; O43918:AIRE; NbExp=2; IntAct=EBI-389883, EBI-1753081; O15085:ARHGEF11; NbExp=3; IntAct=EBI-389883, EBI-311099; Q9ULH1:ASAP1; NbExp=5; IntAct=EBI-389883, EBI-346622; Q96NS5:ASB16; NbExp=2; IntAct=EBI-389883, EBI-1751918; Q9UIF9:BAZ2A; NbExp=2; IntAct=EBI-389883, EBI-934890; O60885:BRD4; NbExp=2; IntAct=EBI-389883, EBI-723869; Q9ULD4:BRPF3; NbExp=3; IntAct=EBI-389883, EBI-1753470; P13671:C6; NbExp=2; IntAct=EBI-389883, EBI-1753221; P20810:CAST; NbExp=2; IntAct=EBI-389883, EBI-1268770; P30260:CDC27; NbExp=3; IntAct=EBI-389883, EBI-994813; Q9NYQ7:CELSR3; NbExp=2; IntAct=EBI-389883, EBI-308417; Q13111:CHAF1A; NbExp=2; IntAct=EBI-389883, EBI-1020839; Q14008:CKAP5; NbExp=3; IntAct=EBI-389883, EBI-310585; P78357:CNTNAP1; NbExp=2; IntAct=EBI-389883, EBI-1751903; Q8WX92:COBRA1; NbExp=6; IntAct=EBI-389883, EBI-347721; P78329:CYP4F2; NbExp=2; IntAct=EBI-389883, EBI-1752413; P98082:DAB2; NbExp=2; IntAct=EBI-389883, EBI-1171238; Q14118:DAG1; NbExp=2; IntAct=EBI-389883, EBI-1755945; O14490:DLGAP1; NbExp=4; IntAct=EBI-389883, EBI-1753207; Q9P1A6:DLGAP2; NbExp=4; IntAct=EBI-389883, EBI-1753397; O95886:DLGAP3; NbExp=2; IntAct=EBI-389883, EBI-1752541; Q9Y2H0:DLGAP4; NbExp=5; IntAct=EBI-389883, EBI-722139; Q92988:DLX4; NbExp=3; IntAct=EBI-389883, EBI-1752755; Q05193:DNM1; NbExp=2; IntAct=EBI-389883, EBI-713135; Q8IZD9:DOCK3; NbExp=3; IntAct=EBI-389883, EBI-1752361; Q9H1R2:DUSP15; NbExp=2; IntAct=EBI-389883, EBI-1752795; Q9H8V3:ECT2; NbExp=3; IntAct=EBI-389883, EBI-1054039; P41970:ELK3; NbExp=3; IntAct=EBI-389883, EBI-1758534; P42566:EPS15; NbExp=2; IntAct=EBI-389883, EBI-396684; O00254:F2RL2; NbExp=2; IntAct=EBI-389883, EBI-1751853; Q9BQ89:FAM110A; NbExp=2; IntAct=EBI-389883, EBI-1752811; P31994:FCGR2B; NbExp=2; IntAct=EBI-389883, EBI-724784; P31995:FCGR2C; NbExp=2; IntAct=EBI-389883, EBI-1396036; O75369:FLNB; NbExp=3; IntAct=EBI-389883, EBI-352089; O75593:FOXH1; NbExp=2; IntAct=EBI-389883, EBI-1759806; O15117:FYB; NbExp=3; IntAct=EBI-389883, EBI-1753267; Q9UBS5:GABBR1; NbExp=3; IntAct=EBI-389883, EBI-724156; Q99259:GAD1; NbExp=2; IntAct=EBI-389883, EBI-743184; P10912:GHR; NbExp=2; IntAct=EBI-389883, EBI-286316; Q9NZM4:GLTSCR1; NbExp=3; IntAct=EBI-389883, EBI-1754943; P15586:GNS; NbExp=2; IntAct=EBI-389883, EBI-1752200; O43708:GSTZ1; NbExp=2; IntAct=EBI-389883, EBI-748043; P10412:HIST1H1E; NbExp=2; IntAct=EBI-389883, EBI-358163; O43390:HNRNPR; NbExp=2; IntAct=EBI-389883, EBI-713419; P47928:ID4; NbExp=3; IntAct=EBI-389883, EBI-1754719; Q9H9L3:ISG20L2; NbExp=2; IntAct=EBI-389883, EBI-751335; O60674:JAK2; NbExp=2; IntAct=EBI-389883, EBI-518647; Q9BY71:LRRC3; NbExp=2; IntAct=EBI-389883, EBI-1761329; P27816:MAP4; NbExp=2; IntAct=EBI-389883, EBI-715255; Q92918:MAP4K1; NbExp=2; IntAct=EBI-389883, EBI-881; Q9Y4K4:MAP4K5; NbExp=2; IntAct=EBI-389883, EBI-1279; Q9NQ76:MEPE; NbExp=3; IntAct=EBI-389883, EBI-1753293; Q15746:MYLK; NbExp=2; IntAct=EBI-389883, EBI-968482; P43699:NKX2-1; NbExp=2; IntAct=EBI-389883, EBI-1391923; O60500:NPHS1; NbExp=3; IntAct=EBI-389883, EBI-996920; Q13087:PDIA2; NbExp=3; IntAct=EBI-389883, EBI-1752525; O75167:PHACTR2; NbExp=2; IntAct=EBI-389883, EBI-1754409; O00750:PIK3C2B; NbExp=3; IntAct=EBI-389883, EBI-641107; Q9UL42:PNMA2; NbExp=2; IntAct=EBI-389883, EBI-302355; Q9BXM0:PRX; NbExp=2; IntAct=EBI-389883, EBI-1753064; P29074:PTPN4; NbExp=3; IntAct=EBI-389883, EBI-710431; P15918:RAG1; NbExp=2; IntAct=EBI-389883, EBI-1755109; Q13905:RAPGEF1; NbExp=2; IntAct=EBI-389883, EBI-976876; P20936:RASA1; NbExp=6; IntAct=EBI-389883, EBI-1026476; Q9UQ26:RIMS2; NbExp=2; IntAct=EBI-389883, EBI-1756749; Q8TB24:RIN3; NbExp=2; IntAct=EBI-389883, EBI-1570523; P26373:RPL13; NbExp=2; IntAct=EBI-389883, EBI-356849; P78345:RPP38; NbExp=2; IntAct=EBI-389883, EBI-366493; P10301:RRAS; NbExp=3; IntAct=EBI-389883, EBI-968703; Q96GP6:SCARF2; NbExp=2; IntAct=EBI-389883, EBI-1752088; O75326:SEMA7A; NbExp=2; IntAct=EBI-389883, EBI-1753538; Q9NZV5:SEPN1; NbExp=2; IntAct=EBI-389883, EBI-1751965; Q9UPX8:SHANK2; NbExp=6; IntAct=EBI-389883, EBI-1570571; Q9BYB0:SHANK3; NbExp=4; IntAct=EBI-389883, EBI-1752330; Q13796:SHROOM2; NbExp=2; IntAct=EBI-389883, EBI-1644065; Q9UHI7:SLC23A1; NbExp=2; IntAct=EBI-389883, EBI-1759386; O60721:SLC24A1; NbExp=3; IntAct=EBI-389883, EBI-1753504; Q9UMY4:SNX12; NbExp=3; IntAct=EBI-389883, EBI-1752602; Q15036:SNX17; NbExp=3; IntAct=EBI-389883, EBI-1752620; Q9Y5X2:SNX8; NbExp=2; IntAct=EBI-389883, EBI-1752557; Q07889:SOS1; NbExp=5; IntAct=EBI-389883, EBI-297487; Q07890:SOS2; NbExp=3; IntAct=EBI-389883, EBI-298181; P08047:SP1; NbExp=2; IntAct=EBI-389883, EBI-298336; Q96T58:SPEN; NbExp=3; IntAct=EBI-389883, EBI-765739; Q9H5I1:SUV39H2; NbExp=2; IntAct=EBI-389883, EBI-723127; O15056:SYNJ2; NbExp=3; IntAct=EBI-389883, EBI-310513; O43493:TGOLN2; NbExp=3; IntAct=EBI-389883, EBI-1752146; P42167:TMPO; NbExp=2; IntAct=EBI-389883, EBI-455283; Q15661:TPSAB1; NbExp=2; IntAct=EBI-389883, EBI-1761369; Q9ULW0:TPX2; NbExp=4; IntAct=EBI-389883, EBI-1037322; Q9BWF2:TRAIP; NbExp=3; IntAct=EBI-389883, EBI-1756205; Q9HCM9:TRIM39; NbExp=2; IntAct=EBI-389883, EBI-739510; O00294:TULP1; NbExp=2; IntAct=EBI-389883, EBI-1756778; Q96RL7:VPS13A; NbExp=3; IntAct=EBI-389883, EBI-1752583; Q9UMN6:WBP7; NbExp=2; IntAct=EBI-389883, EBI-765774; O43516:WIPF1; NbExp=2; IntAct=EBI-389883, EBI-346356;SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. Nucleus. Note=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.DOMAIN: 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.PTM: Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB.SIMILARITY: Contains 1 SH2 domain.SIMILARITY: Contains 3 SH3 domains.
Primer design for this transcript
MalaCards Disease Associations
Comparative Toxicogenomics Database (CTD)
The following chemicals interact with this gene
Common Gene Haplotype Alleles
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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Protein Domain and Structure Information
InterPro Domains: Graphical view of domain structure IPR017304 - Cytoplasmic_NCK
IPR000980 - SH2
IPR001452 - SH3_domain
Pfam Domains: PF00017 - SH2 domain
PF00018 - SH3 domain
PF07653 - Variant SH3 domain
PF14604 - Variant SH3 domain
SCOP Domains: 50044 - SH3-domain
55550 - SH2 domain
Protein Data Bank (PDB) 3-D Structure
ModBase Predicted Comparative 3D Structure on P16333
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004860 protein kinase inhibitor activity
GO:0005070 SH3/SH2 adaptor activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0008093 cytoskeletal adaptor activity
GO:0019904 protein domain specific binding
GO:0030159 receptor signaling complex scaffold activity
GO:0030674 protein binding, bridging
GO:0030971 receptor tyrosine kinase binding
GO:0045296 cadherin binding
GO:0046875 ephrin receptor binding
GO:0060090 binding, bridging
GO:0071074 eukaryotic initiation factor eIF2 binding
Biological Process: GO:0006417 regulation of translation
GO:0006469 negative regulation of protein kinase activity
GO:0006930 substrate-dependent cell migration, cell extension
GO:0007015 actin filament organization
GO:0007172 signal complex assembly
GO:0010976 positive regulation of neuron projection development
GO:0016477 cell migration
GO:0030032 lamellipodium assembly
GO:0030334 regulation of cell migration
GO:0030838 positive regulation of actin filament polymerization
GO:0033137 negative regulation of peptidyl-serine phosphorylation
GO:0036493 positive regulation of translation in response to endoplasmic reticulum stress
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T cell activation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0051707 response to other organism
GO:0060548 negative regulation of cell death
GO:0070262 peptidyl-serine dephosphorylation
GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1903676 positive regulation of cap-dependent translational initiation
GO:1903679 positive regulation of cap-independent translational initiation
GO:1903898 negative regulation of PERK-mediated unfolded protein response
GO:1903912 negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
GO:1990441 negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
Cellular Component: GO:0000164 protein phosphatase type 1 complex
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005829 cytosol
GO:0005840 ribosome
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0012506 vesicle membrane
Descriptions from all associated GenBank mRNAs
BC006403 - Homo sapiens NCK adaptor protein 1, mRNA (cDNA clone MGC:12668 IMAGE:4304621), complete cds.X17576 - Human melanoma mRNA for nck protein, showing homology to src.AK312692 - Homo sapiens cDNA, FLJ93089, highly similar to Homo sapiens NCK adaptor protein 1 (NCK1), mRNA.JD309118 - Sequence 290142 from Patent EP1572962.AB463920 - Synthetic construct DNA, clone: pF1KB6577, Homo sapiens NCK1 gene for NCK adaptor protein 1, without stop codon, in Flexi system.KU178218 - Homo sapiens NCK adaptor protein 1 isoform 1 (NCK1) mRNA, partial cds.KU178219 - Homo sapiens NCK adaptor protein 1 isoform 2 (NCK1) mRNA, complete cds, alternatively spliced.KU178220 - Homo sapiens NCK adaptor protein 1 isoform 3 (NCK1) mRNA, partial cds, alternatively spliced.DQ893094 - Synthetic construct clone IMAGE:100005724; FLH193694.01X; RZPDo839B0179D NCK adaptor protein 1 (NCK1) gene, encodes complete protein.EU832751 - Synthetic construct Homo sapiens clone HAIB:100067780; DKFZo004H0532 NCK adaptor protein 1 protein (NCK1) gene, encodes complete protein.KJ891668 - Synthetic construct Homo sapiens clone ccsbBroadEn_01062 NCK1 gene, encodes complete protein.EU832672 - Synthetic construct Homo sapiens clone HAIB:100067701; DKFZo008H0531 NCK adaptor protein 1 protein (NCK1) gene, encodes complete protein.LF384589 - JP 2014500723-A/192092: Polycomb-Associated Non-Coding RNAs.AK301460 - Homo sapiens cDNA FLJ50895 complete cds, highly similar to Cytoplasmic protein NCK1.LF378322 - JP 2014500723-A/185825: Polycomb-Associated Non-Coding RNAs.LF378321 - JP 2014500723-A/185824: Polycomb-Associated Non-Coding RNAs.LF378319 - JP 2014500723-A/185822: Polycomb-Associated Non-Coding RNAs.LF378318 - JP 2014500723-A/185821: Polycomb-Associated Non-Coding RNAs.LF378317 - JP 2014500723-A/185820: Polycomb-Associated Non-Coding RNAs.JD509776 - Sequence 490800 from Patent EP1572962.JD083922 - Sequence 64946 from Patent EP1572962.JD313256 - Sequence 294280 from Patent EP1572962.JD166604 - Sequence 147628 from Patent EP1572962.JD301294 - Sequence 282318 from Patent EP1572962.JD083621 - Sequence 64645 from Patent EP1572962.JD516171 - Sequence 497195 from Patent EP1572962.JD095993 - Sequence 77017 from Patent EP1572962.MA620166 - JP 2018138019-A/192092: Polycomb-Associated Non-Coding RNAs.MA613899 - JP 2018138019-A/185825: Polycomb-Associated Non-Coding RNAs.MA613898 - JP 2018138019-A/185824: Polycomb-Associated Non-Coding RNAs.MA613896 - JP 2018138019-A/185822: Polycomb-Associated Non-Coding RNAs.MA613895 - JP 2018138019-A/185821: Polycomb-Associated Non-Coding RNAs.MA613894 - JP 2018138019-A/185820: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Other Names for This Gene
Alternate Gene Symbols: B7Z751, BC006403, D3DNE3, ENST00000288986.1, ENST00000288986.2, ENST00000288986.3, ENST00000288986.4, ENST00000288986.5, NCK, NCK1_HUMAN, P16333, uc317kra.1UCSC ID: ENST00000288986.6_2RefSeq Accession: NM_006153.6
Protein: P16333
(aka NCK1_HUMAN)
Gene Model Information
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for a detailed description of the fields of the table above.
Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.