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Protein

Cytoplasmic protein NCK1

Gene

Nck1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

  • eukaryotic initiation factor eIF2 binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: MGI
  • protein kinase inhibitor activity Source: UniProtKB
  • receptor binding Source: MGI
  • receptor tyrosine kinase binding Source: MGI

GO - Biological processi

  • actin filament organization Source: MGI
  • cell migration Source: MGI
  • lamellipodium assembly Source: MGI
  • negative regulation of cell death Source: UniProtKB
  • negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation Source: ParkinsonsUK-UCL
  • negative regulation of peptidyl-serine phosphorylation Source: MGI
  • negative regulation of PERK-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • peptidyl-serine dephosphorylation Source: MGI
  • positive regulation of actin filament polymerization Source: MGI
  • positive regulation of cap-dependent translational initiation Source: MGI
  • positive regulation of cap-independent translational initiation Source: MGI
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of T cell proliferation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of translation in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation Source: Ensembl
  • response to other organism Source: MGI
  • substrate-dependent cell migration, cell extension Source: MGI
  • T cell activation Source: MGI
Complete GO annotation...

Keywords - Biological processi

Translation regulation

Enzyme and pathway databases

ReactomeiREACT_271639. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_277280. Activation of Rac.
REACT_278498. Downstream signal transduction.
REACT_293748. Nephrin interactions.
REACT_295531. DCC mediated attractive signaling.
REACT_315885. VEGFA-VEGFR2 Pathway.
REACT_334692. Generation of second messenger molecules.
REACT_344463. Regulation of actin dynamics for phagocytic cup formation.
REACT_358608. RHO GTPases Activate WASPs and WAVEs.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytoplasmic protein NCK1
Alternative name(s):
NCK adaptor protein 1
Short name:
Nck-1
Gene namesi
Name:Nck1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:109601. Nck1.

Subcellular locationi

  • Cytoplasm By similarity
  • Endoplasmic reticulum By similarity
  • Nucleus By similarity

  • Note: Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Import into the nucleus requires interaction with SOCS7. Predominantly nuclear following genotoxic stresses, such as UV irradiation, hydroxyurea or mitomycin C treatments (By similarity).By similarity

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • protein phosphatase type 1 complex Source: MGI
  • ribosome Source: MGI
  • vesicle membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 377376Cytoplasmic protein NCK1PRO_0000413801Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei85 – 851PhosphoserineBy similarity
Modified residuei91 – 911PhosphoserineBy similarity
Modified residuei96 – 961PhosphoserineBy similarity
Modified residuei105 – 1051Phosphotyrosine1 Publication
Modified residuei166 – 1661PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ99M51.
PRIDEiQ99M51.

2D gel databases

REPRODUCTION-2DPAGEIPI00453999.

PTM databases

PhosphoSiteiQ99M51.

Expressioni

Gene expression databases

BgeeiQ99M51.
ExpressionAtlasiQ99M51. baseline and differential.
GenevisibleiQ99M51. MM.

Interactioni

Subunit structurei

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 MINK1. Interacts with KDR (tyrosine phosphorylated). Interacts (via SH2 domain) with EPHB1; activates the JUN cascade to regulate cell adhesion. Interacts with EPHA2. Interacts (via SH2 domain) with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain and SH3 domain 2) with EGFR. Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2 (By similarity). Interacts with FLT1 (tyrosine phosphorylated). Interacts with the inactive form of EIF2AK2/PKR (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Abl1P005202EBI-642202,EBI-914519
Dok1P974655EBI-642202,EBI-914917

Protein-protein interaction databases

BioGridi201704. 5 interactions.
DIPiDIP-37524N.
IntActiQ99M51. 15 interactions.
MINTiMINT-193264.
STRINGi10090.ENSMUSP00000112221.

Structurei

3D structure databases

ProteinModelPortaliQ99M51.
SMRiQ99M51. Positions 1-61, 99-174, 193-250, 279-377.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 6160SH3 1PROSITE-ProRule annotationAdd
BLAST
Domaini106 – 16560SH3 2PROSITE-ProRule annotationAdd
BLAST
Domaini190 – 25263SH3 3PROSITE-ProRule annotationAdd
BLAST
Domaini282 – 37695SH2PROSITE-ProRule annotationAdd
BLAST

Domaini

Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seem to be involved.By similarity

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 3 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiNOG261435.
GeneTreeiENSGT00550000074482.
HOGENOMiHOG000290684.
HOVERGENiHBG000719.
InParanoidiQ99M51.
KOiK07365.
OMAiNGNRVLH.
OrthoDBiEOG7SV0VJ.
PhylomeDBiQ99M51.
TreeFamiTF351631.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR017304. NCK.
IPR028526. NCK1.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR22820:SF11. PTHR22820:SF11. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
PF14604. SH3_9. 1 hit.
[Graphical view]
PIRSFiPIRSF037874. Cytoplasmic_NCK. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99M51-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEEVVVVAK FDYVAQQEQE LDIKKNERLW LLDDSKSWWR VRNSMNKTGF
60 70 80 90 100
VPSNYVERKN SARKASIVKN LKDTLGIGKV KRKPSVPDTA SPADDSFVDP
110 120 130 140 150
GERLYDLNMP AFVKFNYMAE REDELSLIKG TKVIVMEKCS DGWWRGSYNG
160 170 180 190 200
QIGWFPSNYV TEEGDSPLGD HVGSLSEKLA AVVNNLNTGQ VLHVVQALYP
210 220 230 240 250
FSSSNDEELN FEKGDVMDVI EKPENDPEWW KCRKINGMVG LVPKNYVTIM
260 270 280 290 300
QNNPLTSGLE PSPPQCDYIR PSLTGKFAGN PWYYGKVTRH QAEMALNERG
310 320 330 340 350
HEGDFLIRDS ESSPNDFSVS LKAQGKNKHF KVQLKETVYC IGQRKFSTME
360 370
ELVEHYKKAP IFTSEQGEKL YLVKHLS
Length:377
Mass (Da):42,891
Last modified:June 1, 2001 - v1
Checksum:i671BBFC870A88EB9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41E → G in AAD13752 (Ref. 1) Curated
Sequence conflicti4 – 41E → G in AAC06352 (Ref. 2) Curated
Sequence conflicti30 – 301W → C in AAC06352 (Ref. 2) Curated
Sequence conflicti74 – 741T → N in AAC06352 (Ref. 2) Curated
Sequence conflicti84 – 841P → T in AAC06352 (Ref. 2) Curated
Sequence conflicti90 – 901A → E in AAC06352 (Ref. 2) Curated
Sequence conflicti155 – 1573FPS → LPC in AAC06352 (Ref. 2) Curated
Sequence conflicti202 – 2021S → G in AAC06352 (Ref. 2) Curated
Sequence conflicti206 – 2061D → N in AAC06352 (Ref. 2) Curated
Sequence conflicti307 – 3071I → V in AAC06352 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084183 mRNA. Translation: AAD13752.1.
AF043259 mRNA. Translation: AAC06352.1.
AC129223 Genomic DNA. No translation available.
CH466560 Genomic DNA. Translation: EDL21028.1.
CH466560 Genomic DNA. Translation: EDL21029.1.
CH466560 Genomic DNA. Translation: EDL21031.1.
BC002015 mRNA. Translation: AAH02015.1.
CCDSiCCDS23440.1.
RefSeqiNP_035008.2. NM_010878.2.
XP_006510903.1. XM_006510840.1.
UniGeneiMm.181485.

Genome annotation databases

EnsembliENSMUST00000116522; ENSMUSP00000112221; ENSMUSG00000032475.
GeneIDi17973.
KEGGimmu:17973.
UCSCiuc009rex.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084183 mRNA. Translation: AAD13752.1.
AF043259 mRNA. Translation: AAC06352.1.
AC129223 Genomic DNA. No translation available.
CH466560 Genomic DNA. Translation: EDL21028.1.
CH466560 Genomic DNA. Translation: EDL21029.1.
CH466560 Genomic DNA. Translation: EDL21031.1.
BC002015 mRNA. Translation: AAH02015.1.
CCDSiCCDS23440.1.
RefSeqiNP_035008.2. NM_010878.2.
XP_006510903.1. XM_006510840.1.
UniGeneiMm.181485.

3D structure databases

ProteinModelPortaliQ99M51.
SMRiQ99M51. Positions 1-61, 99-174, 193-250, 279-377.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201704. 5 interactions.
DIPiDIP-37524N.
IntActiQ99M51. 15 interactions.
MINTiMINT-193264.
STRINGi10090.ENSMUSP00000112221.

PTM databases

PhosphoSiteiQ99M51.

2D gel databases

REPRODUCTION-2DPAGEIPI00453999.

Proteomic databases

MaxQBiQ99M51.
PRIDEiQ99M51.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000116522; ENSMUSP00000112221; ENSMUSG00000032475.
GeneIDi17973.
KEGGimmu:17973.
UCSCiuc009rex.1. mouse.

Organism-specific databases

CTDi4690.
MGIiMGI:109601. Nck1.

Phylogenomic databases

eggNOGiNOG261435.
GeneTreeiENSGT00550000074482.
HOGENOMiHOG000290684.
HOVERGENiHBG000719.
InParanoidiQ99M51.
KOiK07365.
OMAiNGNRVLH.
OrthoDBiEOG7SV0VJ.
PhylomeDBiQ99M51.
TreeFamiTF351631.

Enzyme and pathway databases

ReactomeiREACT_271639. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_277280. Activation of Rac.
REACT_278498. Downstream signal transduction.
REACT_293748. Nephrin interactions.
REACT_295531. DCC mediated attractive signaling.
REACT_315885. VEGFA-VEGFR2 Pathway.
REACT_334692. Generation of second messenger molecules.
REACT_344463. Regulation of actin dynamics for phagocytic cup formation.
REACT_358608. RHO GTPases Activate WASPs and WAVEs.

Miscellaneous databases

NextBioi292925.
PROiQ99M51.
SOURCEiSearch...

Gene expression databases

BgeeiQ99M51.
ExpressionAtlasiQ99M51. baseline and differential.
GenevisibleiQ99M51. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR017304. NCK.
IPR028526. NCK1.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR22820:SF11. PTHR22820:SF11. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
PF14604. SH3_9. 1 hit.
[Graphical view]
PIRSFiPIRSF037874. Cytoplasmic_NCK. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mus musculus SH2/SH3 adaptor protein (Nck) mRNA, complete cds."
    Miyoshi-Akiyama T., Mayer B.J.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Chen M., She H.Y., Li W.
    Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  6. "Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules."
    Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.
    J. Biol. Chem. 273:23410-23418(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLT1.
  7. "Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
    Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
    J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

Entry informationi

Entry nameiNCK1_MOUSE
AccessioniPrimary (citable) accession number: Q99M51
Secondary accession number(s): O55032, Q9Z279
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2011
Last sequence update: June 1, 2001
Last modified: June 24, 2015
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.