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NCK2 NCK adaptor protein 2 [ Homo sapiens (human) ]

Gene ID: 8440, updated on 11-Sep-2019

Summary

Official Symbol
NCK2provided by HGNC
Official Full Name
NCK adaptor protein 2provided by HGNC
Primary source
HGNC:HGNC:7665
See related
Ensembl:ENSG00000071051 MIM:604930
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GRB4; NCKbeta
Summary
This gene encodes a member of the NCK family of adaptor proteins. The protein contains three SH3 domains and one SH2 domain. The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in duodenum (RPKM 14.7), spleen (RPKM 14.6) and 25 other tissues See more
Orthologs

Genomic context

See NCK2 in Genome Data Viewer
Location:
2q12.2
Exon count:
9
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (105744649..105894274)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (106361520..106510730)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC285000 Neighboring gene uncharacterized LOC107985929 Neighboring gene uncharacterized LOC105373530 Neighboring gene uncharacterized LOC105373531

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide meta-analysis of systolic blood pressure in children with sickle cell disease.
NHGRI GWA Catalog
NCK2 is significantly associated with opiates addiction in African-origin men.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of NCK adaptor protein 2 (NCK2) in human B cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Activation of Rac, organism-specific biosystem (from REACTOME)
    Activation of Rac, organism-specific biosystemA low level of Rac activity is essential to maintain axon outgrowth and Robo activation recruits Sos, a dual specificity GEF to the plasma membrane via Dock to activate Rac during midline repulsion.
  • Axon guidance, organism-specific biosystem (from KEGG)
    Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, conserved biosystem (from KEGG)
    Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystem (from WikiPathways)
    Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
  • Cell-Cell communication, organism-specific biosystem (from REACTOME)
    Cell-Cell communication, organism-specific biosystemCell-to-Cell communication is crucial for multicellular organisms because it allows organisms to coordinate the activity of their cells. Some cell-to-cell communication requires direct cell-cell cont...
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • Downstream signal transduction, organism-specific biosystem (from REACTOME)
    Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
  • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
  • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
    EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
  • Ephrin B reverse signaling, organism-specific biosystem (from Pathway Interaction Database)
    Ephrin B reverse signaling, organism-specific biosystem
    Ephrin B reverse signaling
  • Ephrin signaling, organism-specific biosystem (from REACTOME)
    Ephrin signaling, organism-specific biosystemThe interaction between ephrin (EFN) ligands and EPH receptors results not only in forward signaling through the EPH receptor, but also in 'reverse' signaling through the EFN ligand itself. Reverse s...
  • ErbB signaling pathway, organism-specific biosystem (from KEGG)
    ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
  • ErbB signaling pathway, conserved biosystem (from KEGG)
    ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
  • IGF1 pathway, organism-specific biosystem (from Pathway Interaction Database)
    IGF1 pathway, organism-specific biosystem
    IGF1 pathway
  • Insulin Pathway, organism-specific biosystem (from Pathway Interaction Database)
    Insulin Pathway, organism-specific biosystem
    Insulin Pathway
  • Nephrin interactions, organism-specific biosystem (from REACTOME)
    Nephrin interactions, organism-specific biosystemNephrin is a member of the Super-IgG-Molecule family and is most prominently expressed in kidney podocytes. It is a major if not the most important structural component of the slit diaphragm, a modif...
  • Nephrin/Neph1 signaling in the kidney podocyte, organism-specific biosystem (from Pathway Interaction Database)
    Nephrin/Neph1 signaling in the kidney podocyte, organism-specific biosystem
    Nephrin/Neph1 signaling in the kidney podocyte
  • PDGFR-beta signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    PDGFR-beta signaling pathway, organism-specific biosystem
    PDGFR-beta signaling pathway
  • Pathogenic Escherichia coli infection, organism-specific biosystem (from KEGG)
    Pathogenic Escherichia coli infection, organism-specific biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
  • Pathogenic Escherichia coli infection, conserved biosystem (from KEGG)
    Pathogenic Escherichia coli infection, conserved biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
  • Pathogenic Escherichia coli infection, organism-specific biosystem (from WikiPathways)
    Pathogenic Escherichia coli infection, organism-specific biosystemSources: [http://www.genome.jp/kegg/pathway/hsa/hsa05130.html KEGG]
  • Reelin signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Reelin signaling pathway, organism-specific biosystem
    Reelin signaling pathway
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by PDGF, organism-specific biosystem (from REACTOME)
    Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
  • Signaling by Robo receptor, organism-specific biosystem (from REACTOME)
    Signaling by Robo receptor, organism-specific biosystemThe Roundabout (Robo) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growt...
  • Signaling by VEGF, organism-specific biosystem (from REACTOME)
    Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
  • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
  • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
    T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T cell receptor signaling pathway, conserved biosystem (from KEGG)
    T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
    VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SH3/SH2 adaptor activity NAS
Non-traceable Author Statement
more info
PubMed 
cytoskeletal adaptor activity NAS
Non-traceable Author Statement
more info
PubMed 
phosphotyrosine residue binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
 
receptor signaling complex scaffold activity NAS
Non-traceable Author Statement
more info
PubMed 
scaffold protein binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
T cell activation NAS
Non-traceable Author Statement
more info
PubMed 
actin filament organization IEA
Inferred from Electronic Annotation
more info
 
cell migration IEA
Inferred from Electronic Annotation
more info
 
dendritic spine development IEA
Inferred from Electronic Annotation
more info
 
ephrin receptor signaling pathway TAS
Traceable Author Statement
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
immunological synapse formation IEA
Inferred from Electronic Annotation
more info
 
lamellipodium assembly IEA
Inferred from Electronic Annotation
more info
 
negative regulation of PERK-mediated unfolded protein response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of actin filament polymerization IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of translation in response to endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
more info
 
regulation of epidermal growth factor-activated receptor activity TAS
Traceable Author Statement
more info
PubMed 
signal complex assembly NAS
Non-traceable Author Statement
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm NAS
Non-traceable Author Statement
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
postsynaptic density IEA
Inferred from Electronic Annotation
more info
 
vesicle membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
cytoplasmic protein NCK2
Names
SH2/SH3 adaptor protein NCK-beta
growth factor receptor-bound protein 4
noncatalytic region of tyrosine kinase, beta

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001004720.3NP_001004720.1  cytoplasmic protein NCK2 isoform A

    See identical proteins and their annotated locations for NP_001004720.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (A).
    Source sequence(s)
    AC009505, BC000103, DB456958
    Consensus CDS
    CCDS33266.1
    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Related
    ENSP00000377018.2, ENST00000393349.2
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  2. NM_001004722.3NP_001004722.1  cytoplasmic protein NCK2 isoform B

    See identical proteins and their annotated locations for NP_001004722.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an exon, which results in a frameshift, compared to variant 1. The resulting protein (isoform B) is shorter and has a distinct C-terminus, compared to isoform A.
    Source sequence(s)
    AC009505, AC010978, BG480643
    UniProtKB/TrEMBL
    E7ERP6
    Related
    ENSP00000410428.2, ENST00000451463.6
    Conserved Domains (1) summary
    cl17036
    Location:259
    SH3; Src Homology 3 domain superfamily
  3. NM_003581.5NP_003572.2  cytoplasmic protein NCK2 isoform A

    See identical proteins and their annotated locations for NP_003572.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (A). Variants 1 and 2 both encode isoform A.
    Source sequence(s)
    AC009505, AC010978, BC007195
    Consensus CDS
    CCDS33266.1
    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Related
    ENSP00000233154.4, ENST00000233154.9
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    105744649..105894274
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017005105.1XP_016860594.1  cytoplasmic protein NCK2 isoform X1

    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  2. XM_011511991.3XP_011510293.1  cytoplasmic protein NCK2 isoform X1

    See identical proteins and their annotated locations for XP_011510293.1

    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  3. XM_017005103.1XP_016860592.1  cytoplasmic protein NCK2 isoform X1

    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  4. XM_006712797.3XP_006712860.1  cytoplasmic protein NCK2 isoform X1

    See identical proteins and their annotated locations for XP_006712860.1

    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  5. XM_017005104.1XP_016860593.1  cytoplasmic protein NCK2 isoform X1

    UniProtKB/Swiss-Prot
    O43639
    UniProtKB/TrEMBL
    A0A0S2Z4M6
    Conserved Domains (4) summary
    cd10409
    Location:283380
    SH2_Nck2; Src homology 2 (SH2) domain found in Nck
    cd11899
    Location:259
    SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein
    cd11902
    Location:114168
    SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein
    cd11903
    Location:198256
    SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
  6. XM_011511992.2XP_011510294.2  cytoplasmic protein NCK2 isoform X2

    UniProtKB/TrEMBL
    E7ERP6
    Conserved Domains (1) summary
    cl17036
    Location:259
    SH3; Src Homology 3 domain superfamily
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