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Protein

Cytoplasmic protein NCK1

Gene

Nck1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • actin filament organization Source: MGI
  • cell migration Source: MGI
  • ephrin receptor signaling pathway 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 insulin receptor signaling pathway Source: MGI
  • negative regulation of peptidyl-serine phosphorylation Source: MGI
  • negative regulation of PERK-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • 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 neuron projection development Source: MGI
  • positive regulation of T cell proliferation Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of translation in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • regulation of cell migration Source: MGI
  • response to other organism Source: MGI
  • substrate-dependent cell migration, cell extension Source: MGI
  • T cell activation Source: MGI

Keywordsi

Biological processTranslation regulation

Enzyme and pathway databases

ReactomeiR-MMU-186763 Downstream signal transduction
R-MMU-202433 Generation of second messenger molecules
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-373753 Nephrin family interactions
R-MMU-418885 DCC mediated attractive signaling
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-5663213 RHO GTPases Activate WASPs and WAVEs
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:109601 Nck1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004138012 – 377Cytoplasmic protein NCK1Add BLAST376

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei85PhosphoserineCombined sources1
Modified residuei91PhosphoserineBy similarity1
Modified residuei96PhosphoserineBy similarity1
Modified residuei105PhosphotyrosineCombined sources1
Modified residuei166PhosphoserineCombined sources1

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

EPDiQ99M51
MaxQBiQ99M51
PaxDbiQ99M51
PeptideAtlasiQ99M51
PRIDEiQ99M51

2D gel databases

REPRODUCTION-2DPAGEiIPI00453999

PTM databases

iPTMnetiQ99M51
PhosphoSitePlusiQ99M51

Expressioni

Gene expression databases

BgeeiENSMUSG00000032475
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

Show more details

GO - Molecular functioni

  • cadherin binding Source: MGI
  • ephrin receptor binding Source: MGI
  • eukaryotic initiation factor eIF2 binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: MGI
  • receptor tyrosine kinase binding Source: MGI
  • SH3/SH2 adaptor activity Source: InterPro
  • signaling receptor binding Source: MGI

Protein-protein interaction databases

BioGridi201704, 7 interactors
DIPiDIP-37524N
IntActiQ99M51, 17 interactors
MINTiQ99M51
STRINGi10090.ENSMUSP00000112221

Structurei

3D structure databases

ProteinModelPortaliQ99M51
SMRiQ99M51
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 61SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini106 – 165SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini190 – 252SH3 3PROSITE-ProRule annotationAdd BLAST63
Domaini282 – 376SH2PROSITE-ProRule annotationAdd BLAST95

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

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4226 Eukaryota
ENOG410XRPF LUCA
GeneTreeiENSGT00820000126999
HOGENOMiHOG000290684
HOVERGENiHBG000719
InParanoidiQ99M51
KOiK07365
OMAiKNYVTIM
OrthoDBiEOG091G0AD0
PhylomeDBiQ99M51
TreeFamiTF351631

Family and domain databases

CDDicd10408 SH2_Nck1, 1 hit
cd11900 SH3_Nck1_1, 1 hit
cd11901 SH3_Nck1_2, 1 hit
cd11904 SH3_Nck1_3, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR017304 NCK
IPR035882 Nck1_SH2
IPR035562 Nck1_SH3_1
IPR035564 Nck1_SH3_2
IPR035565 Nck1_SH3_3
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 2 hits
PF14604 SH3_9, 1 hit
PIRSFiPIRSF037874 Cytoplasmic_NCK, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 3 hits
SUPFAMiSSF50044 SSF50044, 3 hits
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 3 hits

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)DescriptionActionsGraphical viewLength
Sequence conflicti4E → G in AAD13752 (Ref. 1) Curated1
Sequence conflicti4E → G in AAC06352 (Ref. 2) Curated1
Sequence conflicti30W → C in AAC06352 (Ref. 2) Curated1
Sequence conflicti74T → N in AAC06352 (Ref. 2) Curated1
Sequence conflicti84P → T in AAC06352 (Ref. 2) Curated1
Sequence conflicti90A → E in AAC06352 (Ref. 2) Curated1
Sequence conflicti155 – 157FPS → LPC in AAC06352 (Ref. 2) Curated3
Sequence conflicti202S → G in AAC06352 (Ref. 2) Curated1
Sequence conflicti206D → N in AAC06352 (Ref. 2) Curated1
Sequence conflicti307I → V in AAC06352 (Ref. 2) Curated1

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_010878.3
XP_006510903.1, XM_006510840.2
UniGeneiMm.181485

Genome annotation databases

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

Entry informationi

Entry nameiNCK1_MOUSE
AccessioniPrimary (citable) accession number: Q99M51
Secondary accession number(s): O55032, Q9Z279
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2011
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 144 of the entry and version 1 of the sequence. See 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

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