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

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; AllianceGenome:HGNC:7665
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: mouse all
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Genomic context

Location:: 2q12.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (105744453..105894272)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (106205667..106355582)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (106361369..106510728)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[CBL inhibits proliferation and invasion of breast cancer cells by ubiquitylation-mediated degradation of NCK2].
Title: [CBL inhibits proliferation and invasion of breast cancer cells by ubiquitylation-mediated degradation of NCK2].
Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling.
Title: Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling.
Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion.
Title: Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion.
The minor allele frequency (MAF) of rs678350 was significantly higher in NTG patients (MAF = 0.32) than in controls (MAF = 0.23) (OR, 1.586; 95% CI, 1.058 to 2.375; P = 0.028). This trend was more significant in the dominant model (OR, 1.908; 95% CI, 1.144 to 3.180; P = 0.015).
Title: Association of HK2 and NCK2 with normal-tension glaucoma in a population from the Republic of Korea.
This study provides evidence of a possible role of NCK2 as biomarker of ovarian cancer progression.
Title: Non-catalytic region of tyrosine kinase adaptor protein 2 (NCK2) pathways as factor promoting aggressiveness in ovarian cancer.
There was no difference in the Nck2 mRNA expression between the SLE patients and the healthy subjects.
Title: A Study of Interleukin-2 Production and Nck Adaptor Molecule Gene Expression in Systemic Lupus Erythematosus Patients.
Nck1 and Nck2 Interact with WTIP. Nck1/2 integrates nephrin with the Hippo kinase cascade through association with the adaptor protein WTIP.
Title: Nephrin Suppresses Hippo Signaling through the Adaptor Proteins Nck and WTIP.
Data suggest that PINCH1 and Nck2 critically participate in the regulation of cellular radiosensitivity and EGFR function and downstream signaling in a cellular model of human squamous cell carcinoma.
Title: Targeting of the EGFR/β1 integrin connecting proteins PINCH1 and Nck2 radiosensitizes three-dimensional SCC cell cultures.
Tir-Intimin interaction recruits the Nck adaptor to a Tir tyrosine phosphorylated residue where it activates neural Wiskott-Aldrich syndrome protein (N-WASP).
Title: Nck adaptors, besides promoting N-WASP mediated actin-nucleation activity at pedestals, influence the cellular levels of enteropathogenic Escherichia coli Tir effector.
Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics.
Title: Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytoskeletal anchor activity	NAS Non-traceable Author Statement more info	PubMed
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables scaffold protein binding	IEA Inferred from Electronic Annotation more info
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling adaptor activity	NAS Non-traceable Author Statement more info	PubMed
enables signaling receptor complex adaptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell activation	NAS Non-traceable Author Statement more info	PubMed
involved_in actin filament organization	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in dendritic spine development	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in immunological synapse formation	IEA Inferred from Electronic Annotation more info
involved_in lamellipodium assembly	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of PERK-mediated unfolded protein response	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of translation in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal complex assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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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)

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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)

NM_001004720.3 → NP_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

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Related

ENSP00000377018.2, ENST00000393349.2

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
NM_001004722.4 → NP_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:2 → 59

SH3; Src Homology 3 domain superfamily
NM_003581.5 → NP_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

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Related

ENSP00000233154.4, ENST00000233154.9

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

105744453..105894272

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017005105.2 → XP_016860594.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
XM_017005103.2 → XP_016860592.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
XM_011511991.4 → XP_011510293.1 cytoplasmic protein NCK2 isoform X1

See identical proteins and their annotated locations for XP_011510293.1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
XM_047446021.1 → XP_047301977.1 cytoplasmic protein NCK2 isoform X2

UniProtKB/TrEMBL

E7ERP6

Related

ENSP00000431109.1, ENST00000522586.5
XM_006712797.4 → XP_006712860.1 cytoplasmic protein NCK2 isoform X1

See identical proteins and their annotated locations for XP_006712860.1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
XM_047446019.1 → XP_047301975.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6
XM_017005104.2 → XP_016860593.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6, Q53TG4

Conserved Domains (4) summary

cd10409
Location:283 → 380

SH2_Nck2; Src homology 2 (SH2) domain found in Nck

cd11899
Location:2 → 59

SH3_Nck2_1; First Src Homology 3 domain of Nck2 adaptor protein

cd11902
Location:114 → 168

SH3_Nck2_2; Second Src Homology 3 domain of Nck2 adaptor protein

cd11903
Location:198 → 256

SH3_Nck2_3; Third Src Homology 3 domain of Nck2 adaptor protein
XM_047446020.1 → XP_047301976.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6
XM_047446017.1 → XP_047301973.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6
XM_047446018.1 → XP_047301974.1 cytoplasmic protein NCK2 isoform X1

UniProtKB/Swiss-Prot

D3DVK1, O43639, Q9BWN9, Q9UIC3

UniProtKB/TrEMBL

A0A0S2Z4M6
XM_011511992.3 → XP_011510294.2 cytoplasmic protein NCK2 isoform X2

UniProtKB/TrEMBL

E7ERP6

Conserved Domains (1) summary

cl17036
Location:2 → 59

SH3; Src Homology 3 domain superfamily