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Protein

Cytoplasmic protein NCK2

Gene

NCK2

Organism
Homo sapiens (Human)
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 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

  • ARF guanyl-nucleotide exchange factor activity Source: GO_Central
  • cytoskeletal adaptor activity Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: ParkinsonsUK-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Translation regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000071051-MONOMER.
ReactomeiR-HSA-186763. Downstream signal transduction.
R-HSA-373753. Nephrin interactions.
R-HSA-3928664. Ephrin signaling.
R-HSA-428540. Activation of Rac.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
SignaLinkiO43639.
SIGNORiO43639.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:7665. NCK2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Endoplasmic reticulum 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endoplasmic reticulum Source: ParkinsonsUK-UCL
  • synapse Source: Ensembl
  • trans-Golgi network Source: GO_Central
  • vesicle membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi148W → K: Abolishes interaction with DOCK1. 1 Publication1
Mutagenesisi234W → K: Abolishes interaction with DOCK1. 1 Publication1

Organism-specific databases

DisGeNETi8440.
OpenTargetsiENSG00000071051.
PharmGKBiPA31467.

Polymorphism and mutation databases

BioMutaiNCK2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000967672 – 380Cytoplasmic protein NCK2Add BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei90PhosphoserineCombined sources1
Modified residuei92PhosphothreonineCombined sources1
Modified residuei94PhosphoserineBy similarity1
Modified residuei110PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO43639.
MaxQBiO43639.
PaxDbiO43639.
PeptideAtlasiO43639.
PRIDEiO43639.

PTM databases

iPTMnetiO43639.
PhosphoSitePlusiO43639.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000071051.
CleanExiHS_NCK2.
ExpressionAtlasiO43639. baseline and differential.
GenevisibleiO43639. HS.

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
ABI2Q9NYB94EBI-713635,EBI-743598
ABI3Q9P2A45EBI-713635,EBI-742038
ARHGAP32A7KAX93EBI-713635,EBI-308663
BCL11AQ9H165-25EBI-713635,EBI-10183342
CBLBQ131914EBI-713635,EBI-744027
CHN1P158828EBI-713635,EBI-718947
CHN2P527574EBI-713635,EBI-714925
CPSF7Q8N6844EBI-713635,EBI-746909
DDR1Q083453EBI-713635,EBI-711879
DLGAP4Q9Y2H0-14EBI-713635,EBI-12000556
DRAP1Q149193EBI-713635,EBI-712941
DVL1Q86TH33EBI-713635,EBI-10185025
EFHC2Q5JST63EBI-713635,EBI-2349927
EFNB2P527997EBI-713635,EBI-7532268
EIF3S3Q6IB983EBI-713635,EBI-10184995
ERBB2P046262EBI-713635,EBI-641062
ERBB3P218602EBI-713635,EBI-720706
FAM53CQ9NYF33EBI-713635,EBI-1644252
FASLGP480233EBI-713635,EBI-495538
FCRL2Q96LA53EBI-713635,EBI-10185081
FYBO151173EBI-713635,EBI-1753267
GAB1Q134805EBI-713635,EBI-517684
HOMEZQ8IX15-33EBI-713635,EBI-10172004
HOXC4Q86TF73EBI-713635,EBI-10185009
KITP107212EBI-713635,EBI-1379503
LCP2Q130944EBI-713635,EBI-346946
LIMS1P480592EBI-713635,EBI-306928
LNX1Q8TBB13EBI-713635,EBI-739832
LRRIQ3A6PVS83EBI-713635,EBI-10184751
LZTS2Q9BRK43EBI-713635,EBI-741037
MAGEA6P433605EBI-713635,EBI-1045155
MEOX2A4D1273EBI-713635,EBI-10172134
METP085812EBI-713635,EBI-1039152
NR5A1Q132853EBI-713635,EBI-874629
PAK1Q131536EBI-713635,EBI-1307
PRR20CP864795EBI-713635,EBI-10172814
RASSF7Q028333EBI-713635,EBI-929013
RBM26Q5T8P63EBI-713635,EBI-3232077
RELQ048643EBI-713635,EBI-307352
RHOUQ7L0Q86EBI-713635,EBI-1638043
RHOVQ96L334EBI-713635,EBI-8538631
RTN4Q9NQC32EBI-713635,EBI-715945
SF3B4Q154276EBI-713635,EBI-348469
SORBS2O948753EBI-713635,EBI-311323
SPRY2O435973EBI-713635,EBI-742487
TCF4P158843EBI-713635,EBI-533224
TNRA1L3063EBI-713635,EBI-10182881
TRIM27P143735EBI-713635,EBI-719493
TRIM41Q8WV445EBI-713635,EBI-725997
TRIP6Q156546EBI-713635,EBI-742327
UBCP0CG482EBI-713635,EBI-3390054
VARS2Q5ST30-43EBI-713635,EBI-10244997
VPS37BQ9H9H45EBI-713635,EBI-4400866
WASP427683EBI-713635,EBI-346375
WASLO004013EBI-713635,EBI-957615
ZBTB7BO151563EBI-713635,EBI-740434

GO - Molecular functioni

  • cytoskeletal adaptor activity Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi114020. 131 interactors.
IntActiO43639. 103 interactors.
MINTiMINT-190960.
STRINGi9606.ENSP00000233154.

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 11Combined sources7
Beta strandi17 – 20Combined sources4
Beta strandi28 – 33Combined sources6
Beta strandi35 – 38Combined sources4
Beta strandi40 – 42Combined sources3
Beta strandi48 – 50Combined sources3
Beta strandi55 – 58Combined sources4
Beta strandi115 – 118Combined sources4
Beta strandi137 – 143Combined sources7
Beta strandi147 – 153Combined sources7
Beta strandi156 – 161Combined sources6
Helixi162 – 164Combined sources3
Beta strandi165 – 167Combined sources3
Beta strandi196 – 204Combined sources9
Beta strandi210 – 213Combined sources4
Beta strandi222 – 226Combined sources5
Turni230 – 232Combined sources3
Beta strandi234 – 239Combined sources6
Turni240 – 242Combined sources3
Beta strandi243 – 248Combined sources6
Beta strandi251 – 254Combined sources4
Helixi292 – 302Combined sources11
Beta strandi307 – 312Combined sources6
Beta strandi314 – 316Combined sources3
Beta strandi320 – 324Combined sources5
Beta strandi327 – 329Combined sources3
Beta strandi331 – 338Combined sources8
Beta strandi341 – 344Combined sources4
Beta strandi347 – 351Combined sources5
Helixi352 – 361Combined sources10
Beta strandi364 – 366Combined sources3
Turni368 – 370Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43639.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 61SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini111 – 170SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini195 – 257SH3 3PROSITE-ProRule annotationAdd BLAST63
Domaini285 – 380SH2PROSITE-ProRule annotationAdd BLAST96

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

eggNOGiKOG4226. Eukaryota.
ENOG410XRPF. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000290684.
HOVERGENiHBG000719.
InParanoidiO43639.
KOiK19862.
OMAiQPALDCG.
OrthoDBiEOG091G0AD0.
PhylomeDBiO43639.
TreeFamiTF351631.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR017304. NCK.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10663:SF159. PTHR10663:SF159. 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)DescriptionActionsGraphical viewLength
Sequence conflicti25K → KV in AAC04831 (PubMed:9737977).Curated1
Sequence conflicti100P → A in AAC80284 (PubMed:9843575).Curated1
Sequence conflicti296E → Q in AAC04831 (PubMed:9737977).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006712797.3.
XP_011510293.1. XM_011511991.2.
XP_016860592.1. XM_017005103.1.
XP_016860593.1. XM_017005104.1.
XP_016860594.1. XM_017005105.1.
UniGeneiHs.529244.
Hs.735723.

Genome annotation databases

EnsembliENST00000233154; ENSP00000233154; ENSG00000071051.
ENST00000393349; ENSP00000377018; ENSG00000071051.
GeneIDi8440.
KEGGihsa:8440.
UCSCiuc002tdg.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006712797.3.
XP_011510293.1. XM_011511991.2.
XP_016860592.1. XM_017005103.1.
XP_016860593.1. XM_017005104.1.
XP_016860594.1. XM_017005105.1.
UniGeneiHs.529244.
Hs.735723.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114020. 131 interactors.
IntActiO43639. 103 interactors.
MINTiMINT-190960.
STRINGi9606.ENSP00000233154.

PTM databases

iPTMnetiO43639.
PhosphoSitePlusiO43639.

Polymorphism and mutation databases

BioMutaiNCK2.

Proteomic databases

EPDiO43639.
MaxQBiO43639.
PaxDbiO43639.
PeptideAtlasiO43639.
PRIDEiO43639.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233154; ENSP00000233154; ENSG00000071051.
ENST00000393349; ENSP00000377018; ENSG00000071051.
GeneIDi8440.
KEGGihsa:8440.
UCSCiuc002tdg.4. human.

Organism-specific databases

CTDi8440.
DisGeNETi8440.
GeneCardsiNCK2.
HGNCiHGNC:7665. NCK2.
HPAiCAB016116.
HPA031004.
MIMi604930. gene.
neXtProtiNX_O43639.
OpenTargetsiENSG00000071051.
PharmGKBiPA31467.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4226. Eukaryota.
ENOG410XRPF. LUCA.
GeneTreeiENSGT00820000126999.
HOGENOMiHOG000290684.
HOVERGENiHBG000719.
InParanoidiO43639.
KOiK19862.
OMAiQPALDCG.
OrthoDBiEOG091G0AD0.
PhylomeDBiO43639.
TreeFamiTF351631.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000071051-MONOMER.
ReactomeiR-HSA-186763. Downstream signal transduction.
R-HSA-373753. Nephrin interactions.
R-HSA-3928664. Ephrin signaling.
R-HSA-428540. Activation of Rac.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
SignaLinkiO43639.
SIGNORiO43639.

Miscellaneous databases

ChiTaRSiNCK2. human.
EvolutionaryTraceiO43639.
GeneWikiiNCK2.
GenomeRNAii8440.
PROiO43639.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000071051.
CleanExiHS_NCK2.
ExpressionAtlasiO43639. baseline and differential.
GenevisibleiO43639. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR017304. NCK.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10663:SF159. PTHR10663:SF159. 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...

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: November 30, 2016
This is version 170 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

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 one 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.