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O43639 (NCK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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 NCK2
Alternative name(s):
Growth factor receptor-bound protein 4
NCK adaptor protein 2
Short name=Nck-2
SH2/SH3 adaptor protein NCK-beta
Gene names
Name:NCK2
Synonyms:GRB4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length380 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 or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Ref.5 Ref.10

Subunit structure

Interacts with DOCK1, LIMS1 and TGFB1I1. Part of a complex containing PPP1R15B, PP1 and NCK2. Interacts with FASLG By similarity. Interacts with AXL. Interacts with PAK1, PKN2 and SOS1. Interacts (via SH2 domain) with EGFR. Interacts (via SH2 domain) with DDR1. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12

Subcellular location

Cytoplasm. Endoplasmic reticulum Ref.10.

Tissue specificity

Ubiquitous.

Post-translational modification

Phosphorylated. Ref.5

Sequence similarities

Contains 1 SH2 domain.

Contains 3 SH3 domains.

Ontologies

Keywords
   Biological processTranslation regulation
   Cellular componentCytoplasm
Endoplasmic reticulum
   DomainRepeat
SH2 domain
SH3 domain
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Non-traceable author statement PubMed 12110186. Source: UniProtKB

actin filament organization

Inferred from electronic annotation. Source: Ensembl

axon guidance

Traceable author statement. Source: Reactome

cell migration

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

lamellipodium assembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Traceable author statement Ref.1. Source: ProtInc

positive regulation of T cell proliferation

Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of epidermal growth factor-activated receptor activity

Traceable author statement Ref.1. Source: ProtInc

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

signal complex assembly

Non-traceable author statement PubMed 12110186. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasm

Non-traceable author statement PubMed 12110186. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

vesicle membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncytoskeletal adaptor activity

Non-traceable author statement PubMed 12110186. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5PubMed 12110186. Source: UniProtKB

receptor signaling complex scaffold activity

Non-traceable author statement PubMed 12110186. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 380379Cytoplasmic protein NCK2
PRO_0000096767

Regions

Domain2 – 6160SH3 1
Domain111 – 17060SH3 2
Domain195 – 25763SH3 3
Domain285 – 38096SH2

Amino acid modifications

Modified residue21N-acetylthreonine Ref.15
Modified residue901Phosphoserine Ref.13
Modified residue1101Phosphotyrosine Ref.11

Experimental info

Mutagenesis1481W → K: Abolishes interaction with DOCK1. Ref.7
Mutagenesis2341W → K: Abolishes interaction with DOCK1. Ref.7
Sequence conflict251K → KV in AAC04831. Ref.1
Sequence conflict1001P → A in AAC80284. Ref.2
Sequence conflict2961E → Q in AAC04831. Ref.1

Secondary structure

............................................................ 380
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43639 [UniParc].

Last modified May 10, 2002. Version 2.
Checksum: 3A211085E46F4452

FASTA38042,915
        10         20         30         40         50         60 
MTEEVIVIAK WDYTAQQDQE LDIKKNERLW LLDDSKTWWR VRNAANRTGY VPSNYVERKN 

        70         80         90        100        110        120 
SLKKGSLVKN LKDTLGLGKT RRKTSARDAS PTPSTDAEYP ANGSGADRIY DLNIPAFVKF 

       130        140        150        160        170        180 
AYVAEREDEL SLVKGSRVTV MEKCSDGWWR GSYNGQIGWF PSNYVLEEVD EAAAESPSFL 

       190        200        210        220        230        240 
SLRKGASLSN GQGSRVLHVV QTLYPFSSVT EEELNFEKGE TMEVIEKPEN DPEWWKCKNA 

       250        260        270        280        290        300 
RGQVGLVPKN YVVVLSDGPA LHPAHAPQIS YTGPSSSGRF AGREWYYGNV TRHQAECALN 

       310        320        330        340        350        360 
ERGVEGDFLI RDSESSPSDF SVSLKASGKN KHFKVQLVDN VYCIGQRRFH TMDELVEHYK 

       370        380 
KAPIFTSEHG EKLYLVRALQ 

« Hide

References

« Hide 'large scale' references
[1]"Identification of Nck family genes, chromosomal localization, expression, and signaling specificity."
Chen M., She H., Davis E.M., Spicer C.M., Kim L., Ren R., LeBeau M.M., Li W.
J. Biol. Chem. 273:25171-25178(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways."
Tu Y., Li F., Wu C.
Mol. Biol. Cell 9:3367-3382(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH LIMS1.
Tissue: Lung.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Placenta and Uterus.
[5]"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck."
Braverman L.E., Quilliam L.A.
J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EGFR; PAK1; PKN2 AND SOS1, PHOSPHORYLATION.
[6]"Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: a role in cytoskeletal remodeling."
Turner C.E., Brown M.C., Perrotta J.A., Riedy M.C., Nikolopoulos S.N., McDonald A.R., Bagrodia S., Thomas S.M., Leventhal P.S.
J. Cell Biol. 145:851-863(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[7]"Identification and kinetic analysis of the interaction between Nck-2 and DOCK180."
Tu Y., Kucik D.F., Wu C.
FEBS Lett. 491:193-199(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DOCK1, MUTAGENESIS OF TRP-148 AND TRP-234.
[8]"Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin."
Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.
Biochem. Biophys. Res. Commun. 299:793-800(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AXL.
[9]"Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1."
Koo D.H., McFadden C., Huang Y., Abdulhussein R., Friese-Hamim M., Vogel W.F.
FEBS Lett. 580:15-22(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDR1.
[10]"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."
Latreille M., Larose L.
J. Biol. Chem. 281:26633-26644(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN COMPLEX WITH PP1 AND PPP1R15B, FUNCTION, SUBCELLULAR LOCATION.
[11]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[12]"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
Voss M., Lettau M., Janssen O.
BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FASLG.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[16]"Solution structure of the SH3 domain of the human cytoplasmic protein NCK2."
RIKEN structural genomics initiative (RSGI)
Submitted (JUL-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 188-265.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF043119 mRNA. Translation: AAC04831.1.
AF047487 mRNA. Translation: AAC80284.1.
CH471127 Genomic DNA. Translation: EAX01753.1.
CH471127 Genomic DNA. Translation: EAX01754.1.
BC000103 mRNA. Translation: AAH00103.1.
BC007195 mRNA. Translation: AAH07195.1.
CCDSCCDS33266.1.
RefSeqNP_001004720.1. NM_001004720.2.
NP_003572.2. NM_003581.4.
XP_006712860.1. XM_006712797.1.
UniGeneHs.529244.
Hs.735723.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1U5SNMR-A192-262[»]
1WX6NMR-A188-265[»]
1Z3KNMR-A283-380[»]
2B86NMR-A1-59[»]
2CIAX-ray1.45A284-380[»]
2FRWNMR-A114-170[»]
2FRYNMR-A198-256[»]
2JXBNMR-A1-59[»]
4E6RX-ray2.20A/B114-170[»]
ProteinModelPortalO43639.
SMRO43639. Positions 1-59, 114-170, 192-261, 284-380.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114020. 45 interactions.
IntActO43639. 39 interactions.
MINTMINT-190960.
STRING9606.ENSP00000233154.

PTM databases

PhosphoSiteO43639.

Proteomic databases

MaxQBO43639.
PaxDbO43639.
PRIDEO43639.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233154; ENSP00000233154; ENSG00000071051.
ENST00000393349; ENSP00000377018; ENSG00000071051.
GeneID8440.
KEGGhsa:8440.
UCSCuc002tdg.3. human.

Organism-specific databases

CTD8440.
GeneCardsGC02P106361.
HGNCHGNC:7665. NCK2.
HPACAB016116.
HPA031004.
MIM604930. gene.
neXtProtNX_O43639.
PharmGKBPA31467.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG261435.
HOGENOMHOG000290684.
HOVERGENHBG000719.
InParanoidO43639.
KOK07365.
OMAYYGNITR.
OrthoDBEOG7SV0VJ.
PhylomeDBO43639.
TreeFamTF351631.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
SignaLinkO43639.

Gene expression databases

ArrayExpressO43639.
BgeeO43639.
CleanExHS_NCK2.
GenevestigatorO43639.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR017304. NCK.
IPR028524. NCK2.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR22820:SF29. PTHR22820:SF29. 1 hit.
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
PF14604. SH3_9. 1 hit.
[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

EvolutionaryTraceO43639.
GeneWikiNCK2.
GenomeRNAi8440.
NextBio31578.
PROO43639.
SOURCESearch...

Entry information

Entry nameNCK2_HUMAN
AccessionPrimary (citable) accession number: O43639
Secondary accession number(s): D3DVK1, Q9BWN9, Q9UIC3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2002
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM