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O43639

- NCK2_HUMAN

UniProt

O43639 - NCK2_HUMAN

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Protein

Cytoplasmic protein NCK2

Gene

NCK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. cytoskeletal adaptor activity Source: UniProtKB
  2. receptor signaling complex scaffold activity Source: UniProtKB

GO - Biological processi

  1. actin filament organization Source: Ensembl
  2. axon guidance Source: Reactome
  3. cell migration Source: Ensembl
  4. epidermal growth factor receptor signaling pathway Source: ProtInc
  5. lamellipodium assembly Source: Ensembl
  6. negative regulation of cell proliferation Source: ProtInc
  7. positive regulation of actin filament polymerization Source: UniProtKB
  8. positive regulation of T cell proliferation Source: UniProtKB
  9. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  10. regulation of epidermal growth factor-activated receptor activity Source: ProtInc
  11. regulation of translation Source: UniProtKB-KW
  12. signal complex assembly Source: UniProtKB
  13. signal transduction Source: ProtInc
  14. T cell activation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Translation regulation

Enzyme and pathway databases

ReactomeiREACT_17025. Downstream signal transduction.
REACT_19226. Activation of Rac.
REACT_23832. Nephrin interactions.
SignaLinkiO43639.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:NCK2
Synonyms:GRB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:7665. NCK2.

Subcellular locationi

Cytoplasm 1 Publication. Endoplasmic reticulum 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. endoplasmic reticulum Source: UniProtKB-KW
  4. vesicle membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi148 – 1481W → K: Abolishes interaction with DOCK1. 1 Publication
Mutagenesisi234 – 2341W → K: Abolishes interaction with DOCK1. 1 Publication

Organism-specific databases

PharmGKBiPA31467.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 380379Cytoplasmic protein NCK2PRO_0000096767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonine1 Publication
Modified residuei90 – 901Phosphoserine1 Publication
Modified residuei110 – 1101Phosphotyrosine1 Publication

Post-translational modificationi

Phosphorylated.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO43639.
PaxDbiO43639.
PRIDEiO43639.

PTM databases

PhosphoSiteiO43639.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiO43639.
CleanExiHS_NCK2.
ExpressionAtlasiO43639. baseline and differential.
GenevestigatoriO43639.

Organism-specific databases

HPAiCAB016116.
HPA031004.

Interactioni

Subunit structurei

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.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DDR1Q083453EBI-713635,EBI-711879
EFNB2P527997EBI-713635,EBI-7532268
ERBB2P046262EBI-713635,EBI-641062
ERBB3P218602EBI-713635,EBI-720706
GAB1Q134805EBI-713635,EBI-517684
KITP107212EBI-713635,EBI-1379503
LIMS1P480592EBI-713635,EBI-306928
METP085812EBI-713635,EBI-1039152
RHOUQ7L0Q86EBI-713635,EBI-1638043
RHOVQ96L334EBI-713635,EBI-8538631
RTN4Q9NQC32EBI-713635,EBI-715945
UBCP0CG482EBI-713635,EBI-3390054

Protein-protein interaction databases

BioGridi114020. 88 interactions.
IntActiO43639. 40 interactions.
MINTiMINT-190960.
STRINGi9606.ENSP00000233154.

Structurei

Secondary structure

1
380
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 117
Beta strandi17 – 204
Beta strandi28 – 336
Beta strandi35 – 384
Beta strandi40 – 423
Beta strandi48 – 503
Beta strandi55 – 584
Beta strandi115 – 1184
Beta strandi137 – 1437
Beta strandi147 – 1537
Beta strandi156 – 1616
Helixi162 – 1643
Beta strandi165 – 1673
Beta strandi196 – 2049
Beta strandi210 – 2134
Beta strandi222 – 2265
Turni230 – 2323
Beta strandi234 – 2396
Turni240 – 2423
Beta strandi243 – 2486
Beta strandi251 – 2544
Helixi292 – 30211
Beta strandi307 – 3126
Beta strandi314 – 3163
Beta strandi320 – 3245
Beta strandi327 – 3293
Beta strandi331 – 3388
Beta strandi341 – 3444
Beta strandi347 – 3515
Helixi352 – 36110
Beta strandi364 – 3663
Turni368 – 3703

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliO43639.
SMRiO43639. Positions 1-59, 114-170, 192-261, 284-380.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43639.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 6160SH3 1PROSITE-ProRule annotationAdd
BLAST
Domaini111 – 17060SH3 2PROSITE-ProRule annotationAdd
BLAST
Domaini195 – 25763SH3 3PROSITE-ProRule annotationAdd
BLAST
Domaini285 – 38096SH2PROSITE-ProRule annotationAdd
BLAST

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.
InParanoidiO43639.
KOiK07365.
OMAiYYGNITR.
OrthoDBiEOG7SV0VJ.
PhylomeDBiO43639.
TreeFamiTF351631.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR017304. NCK.
IPR028524. NCK2.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR22820:SF29. PTHR22820:SF29. 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.

O43639-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTEEVIVIAK WDYTAQQDQE LDIKKNERLW LLDDSKTWWR VRNAANRTGY
60 70 80 90 100
VPSNYVERKN SLKKGSLVKN LKDTLGLGKT RRKTSARDAS PTPSTDAEYP
110 120 130 140 150
ANGSGADRIY DLNIPAFVKF AYVAEREDEL SLVKGSRVTV MEKCSDGWWR
160 170 180 190 200
GSYNGQIGWF PSNYVLEEVD EAAAESPSFL SLRKGASLSN GQGSRVLHVV
210 220 230 240 250
QTLYPFSSVT EEELNFEKGE TMEVIEKPEN DPEWWKCKNA RGQVGLVPKN
260 270 280 290 300
YVVVLSDGPA LHPAHAPQIS YTGPSSSGRF AGREWYYGNV TRHQAECALN
310 320 330 340 350
ERGVEGDFLI RDSESSPSDF SVSLKASGKN KHFKVQLVDN VYCIGQRRFH
360 370 380
TMDELVEHYK KAPIFTSEHG EKLYLVRALQ
Length:380
Mass (Da):42,915
Last modified:May 10, 2002 - v2
Checksum:i3A211085E46F4452
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251K → KV in AAC04831. (PubMed:9737977)Curated
Sequence conflicti100 – 1001P → A in AAC80284. (PubMed:9843575)Curated
Sequence conflicti296 – 2961E → Q in AAC04831. (PubMed:9737977)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS33266.1.
RefSeqiNP_001004720.1. NM_001004720.2.
NP_003572.2. NM_003581.4.
XP_006712860.1. XM_006712797.1.
UniGeneiHs.529244.
Hs.735723.

Genome annotation databases

EnsembliENST00000233154; ENSP00000233154; ENSG00000071051.
ENST00000393349; ENSP00000377018; ENSG00000071051.
GeneIDi8440.
KEGGihsa:8440.
UCSCiuc002tdg.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS33266.1.
RefSeqi NP_001004720.1. NM_001004720.2.
NP_003572.2. NM_003581.4.
XP_006712860.1. XM_006712797.1.
UniGenei Hs.529244.
Hs.735723.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1U5S NMR - A 192-262 [» ]
1WX6 NMR - A 188-265 [» ]
1Z3K NMR - A 283-380 [» ]
2B86 NMR - A 1-59 [» ]
2CIA X-ray 1.45 A 284-380 [» ]
2FRW NMR - A 114-170 [» ]
2FRY NMR - A 198-256 [» ]
2JXB NMR - A 1-59 [» ]
4E6R X-ray 2.20 A/B 114-170 [» ]
ProteinModelPortali O43639.
SMRi O43639. Positions 1-59, 114-170, 192-261, 284-380.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114020. 88 interactions.
IntActi O43639. 40 interactions.
MINTi MINT-190960.
STRINGi 9606.ENSP00000233154.

PTM databases

PhosphoSitei O43639.

Proteomic databases

MaxQBi O43639.
PaxDbi O43639.
PRIDEi O43639.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000233154 ; ENSP00000233154 ; ENSG00000071051 .
ENST00000393349 ; ENSP00000377018 ; ENSG00000071051 .
GeneIDi 8440.
KEGGi hsa:8440.
UCSCi uc002tdg.3. human.

Organism-specific databases

CTDi 8440.
GeneCardsi GC02P106361.
HGNCi HGNC:7665. NCK2.
HPAi CAB016116.
HPA031004.
MIMi 604930. gene.
neXtProti NX_O43639.
PharmGKBi PA31467.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG261435.
GeneTreei ENSGT00550000074482.
HOGENOMi HOG000290684.
HOVERGENi HBG000719.
InParanoidi O43639.
KOi K07365.
OMAi YYGNITR.
OrthoDBi EOG7SV0VJ.
PhylomeDBi O43639.
TreeFami TF351631.

Enzyme and pathway databases

Reactomei REACT_17025. Downstream signal transduction.
REACT_19226. Activation of Rac.
REACT_23832. Nephrin interactions.
SignaLinki O43639.

Miscellaneous databases

EvolutionaryTracei O43639.
GeneWikii NCK2.
GenomeRNAii 8440.
NextBioi 31578.
PROi O43639.
SOURCEi Search...

Gene expression databases

Bgeei O43639.
CleanExi HS_NCK2.
ExpressionAtlasi O43639. baseline and differential.
Genevestigatori O43639.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR017304. NCK.
IPR028524. NCK2.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view ]
PANTHERi PTHR22820:SF29. PTHR22820:SF29. 1 hit.
Pfami PF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
PF14604. SH3_9. 1 hit.
[Graphical view ]
PIRSFi PIRSF037874. Cytoplasmic_NCK. 1 hit.
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 3 hits.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 1 hit.
PROSITEi PS50001. SH2. 1 hit.
PS50002. SH3. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiNCK2_HUMAN
AccessioniPrimary (citable) accession number: O43639
Secondary accession number(s): D3DVK1, Q9BWN9, Q9UIC3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2002
Last modified: October 29, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3