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Q99M51 (NCK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytoplasmic protein NCK1
Alternative name(s):
NCK adaptor protein 1
Short name=Nck-1
Gene names
Name:Nck1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Modulates the activation of EIF2AK2/PKR by dsRNA By similarity.

Subunit structure

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 (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. Ref.6

Subcellular location

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.

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 seem to be involved By similarity.

Post-translational modification

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

Sequence similarities

Contains 1 SH2 domain.

Contains 3 SH3 domains.

Ontologies

Keywords
   Biological processTranslation regulation
   Cellular componentCytoplasm
Endoplasmic reticulum
Nucleus
   DomainRepeat
SH2 domain
SH3 domain
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from electronic annotation. Source: Ensembl

actin filament organization

Inferred from mutant phenotype PubMed 12637565. Source: MGI

cell migration

Inferred from mutant phenotype PubMed 12637565. Source: MGI

lamellipodium assembly

Inferred from mutant phenotype PubMed 12808099. Source: MGI

negative regulation of cell death

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of actin filament polymerization

Inferred from genetic interaction PubMed 17923684. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

response to other organism

Inferred from mutant phenotype PubMed 22966049. Source: MGI

   Cellular_componentendoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

vesicle membrane

Inferred from direct assay PubMed 12147689. Source: MGI

   Molecular_functionprotein domain specific binding

Inferred from physical interaction PubMed 8438166. Source: MGI

protein kinase inhibitor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 377376Cytoplasmic protein NCK1
PRO_0000413801

Regions

Domain2 – 6160SH3 1
Domain106 – 16560SH3 2
Domain190 – 25263SH3 3
Domain282 – 37695SH2

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue851Phosphoserine By similarity
Modified residue911Phosphoserine By similarity
Modified residue961Phosphoserine By similarity
Modified residue1051Phosphotyrosine Ref.7

Experimental info

Sequence conflict41E → G in AAD13752. Ref.1
Sequence conflict41E → G in AAC06352. Ref.2
Sequence conflict301W → C in AAC06352. Ref.2
Sequence conflict741T → N in AAC06352. Ref.2
Sequence conflict841P → T in AAC06352. Ref.2
Sequence conflict901A → E in AAC06352. Ref.2
Sequence conflict155 – 1573FPS → LPC in AAC06352. Ref.2
Sequence conflict2021S → G in AAC06352. Ref.2
Sequence conflict2061D → N in AAC06352. Ref.2
Sequence conflict3071I → V in AAC06352. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q99M51 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 671BBFC870A88EB9

FASTA37742,891
        10         20         30         40         50         60 
MAEEVVVVAK FDYVAQQEQE LDIKKNERLW LLDDSKSWWR VRNSMNKTGF VPSNYVERKN 

        70         80         90        100        110        120 
SARKASIVKN LKDTLGIGKV KRKPSVPDTA SPADDSFVDP GERLYDLNMP AFVKFNYMAE 

       130        140        150        160        170        180 
REDELSLIKG TKVIVMEKCS DGWWRGSYNG QIGWFPSNYV TEEGDSPLGD HVGSLSEKLA 

       190        200        210        220        230        240 
AVVNNLNTGQ VLHVVQALYP FSSSNDEELN FEKGDVMDVI EKPENDPEWW KCRKINGMVG 

       250        260        270        280        290        300 
LVPKNYVTIM QNNPLTSGLE PSPPQCDYIR PSLTGKFAGN PWYYGKVTRH QAEMALNERG 

       310        320        330        340        350        360 
HEGDFLIRDS ESSPNDFSVS LKAQGKNKHF KVQLKETVYC IGQRKFSTME ELVEHYKKAP 

       370 
IFTSEQGEKL YLVKHLS 

« Hide

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_035008.2. NM_010878.2.
XP_006510903.1. XM_006510840.1.
UniGeneMm.181485.

3D structure databases

ProteinModelPortalQ99M51.
SMRQ99M51. Positions 1-61, 99-174, 193-250, 279-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201704. 5 interactions.
IntActQ99M51. 15 interactions.
MINTMINT-193264.
STRING10090.ENSMUSP00000112221.

PTM databases

PhosphoSiteQ99M51.

2D gel databases

REPRODUCTION-2DPAGEIPI00453999.

Proteomic databases

PRIDEQ99M51.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000116522; ENSMUSP00000112221; ENSMUSG00000032475.
GeneID17973.
KEGGmmu:17973.
UCSCuc009rex.1. mouse.

Organism-specific databases

CTD4690.
MGIMGI:109601. Nck1.

Phylogenomic databases

eggNOGNOG261435.
GeneTreeENSGT00550000074482.
HOGENOMHOG000290684.
HOVERGENHBG000719.
InParanoidQ9Z279.
KOK07365.
OMANGNRVLH.
OrthoDBEOG7SV0VJ.
PhylomeDBQ99M51.
TreeFamTF351631.

Gene expression databases

ArrayExpressQ99M51.
BgeeQ99M51.
GenevestigatorQ99M51.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR017304. NCK.
IPR028526. NCK1.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR22820:SF11. PTHR22820:SF11. 1 hit.
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]
PIRSFPIRSF037874. Cytoplasmic_NCK. 1 hit.
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 3 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
PS50002. SH3. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio292925.
PROQ99M51.
SOURCESearch...

Entry information

Entry nameNCK1_MOUSE
AccessionPrimary (citable) accession number: Q99M51
Secondary accession number(s): O55032, Q9Z279
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2011
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot