NCK1 NCK adaptor protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NCK1provided by HGNC
Official Full Name: NCK adaptor protein 1provided by HGNC
Primary source: HGNC:HGNC:7664
See related: Ensembl:ENSG00000158092 MIM:600508; AllianceGenome:HGNC:7664
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: NCK; nck-1; NCKalpha
Summary: The protein encoded by this gene is one of the signaling and transforming proteins containing Src homology 2 and 3 (SH2 and SH3) domains. It is located in the cytoplasm and is an adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jun 2010]
Expression: Ubiquitous expression in lymph node (RPKM 10.1), fat (RPKM 9.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q22.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (136862208..136951606)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (139602861..139692274)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (136581050..136670448)

Chromosome 3 - NC_000003.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Long noncoding RNA LINC00885 upregulates NCK1 to promote cell viability and migration of triple-negative breast cancer cells through sponging miR-654-3p.
Title: Long noncoding RNA LINC00885 upregulates NCK1 to promote cell viability and migration of triple-negative breast cancer cells through sponging miR-654-3p.
Lack of Nck1 protein and Nck-CD3 interaction caused the increment of lipid content in Jurkat T cells.
Title: Lack of Nck1 protein and Nck-CD3 interaction caused the increment of lipid content in Jurkat T cells.
LncRNA NCK1-AS1 Promotes Malignant Cellular Phenotypes of Laryngeal Squamous Cell Carcinoma via miR-137/NCK1 Axis.
Title: LncRNA NCK1-AS1 Promotes Malignant Cellular Phenotypes of Laryngeal Squamous Cell Carcinoma via miR-137/NCK1 Axis.
STAT3-induced NCK1 elevation promotes migration of triple-negative breast cancer cells via regulating ERK1/2 signaling.
Title: STAT3-induced NCK1 elevation promotes migration of triple-negative breast cancer cells via regulating ERK1/2 signaling.
NCK1-AS1 promotes the progression of lung squamous cell carcinoma through transcriptionally upregulating NCK1 via interacting with MYC.
Title: NCK1-AS1 promotes the progression of lung squamous cell carcinoma through transcriptionally upregulating NCK1 via interacting with MYC.
Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling.
Title: Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling.
LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/beta-catenin signaling.
Title: LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/β-catenin signaling.
Nck1, But Not Nck2, Mediates Disturbed Flow-Induced p21-Activated Kinase Activation and Endothelial Permeability.
Title: Nck1, But Not Nck2, Mediates Disturbed Flow-Induced p21-Activated Kinase Activation and Endothelial Permeability.
Overactivated Cdc42 acts through Cdc42EP3/Borg2 and NCK to trigger DNA damage response signaling and sensitize cells to DNA-damaging agents.
Title: Overactivated Cdc42 acts through Cdc42EP3/Borg2 and NCK to trigger DNA damage response signaling and sensitize cells to DNA-damaging agents.
Selective role of Nck1 in atherogenic inflammation and plaque formation.
Title: Selective role of Nck1 in atherogenic inflammation and plaque formation.

Submit: New GeneRIF Correction See all GeneRIFs (80)

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
Biological insights from 108 schizophrenia-associated genetic loci. 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)

Protein	Gene	Interaction	Pubs
Nef	nef	The association of HIV-1 Nef with Vav1, Pak2, and Nck1 is greatly reduced in SLP76-deficient T cells	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-77376 (e-PCR)
- UniSTS:65188

D3S3349 (e-PCR)
- UniSTS:72396

D3S4077 (e-PCR)
- UniSTS:66519

D3S3617 (e-PCR), detects polymorphism
- UniSTS:27362

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	HDA more info	PubMed
enables cytoskeletal anchor activity	NAS Non-traceable Author Statement more info	PubMed
enables ephrin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ephrin receptor binding	IEA Inferred from Electronic Annotation more info
enables eukaryotic initiation factor eIF2 binding	IEA Inferred from Electronic Annotation more info
enables eukaryotic initiation factor eIF2 binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular condensate scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction 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	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within actin filament organization	IEA Inferred from Electronic Annotation more info
involved_in antiviral innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cell migration	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within 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 PERK-mediated unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of PERK-mediated unfolded protein response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
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	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cap-dependent translational initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cap-independent translational initiation	IDA Inferred from Direct Assay 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 endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of macromolecule biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of neuron projection development	IEA Inferred from Electronic Annotation 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 positive regulation of translation in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of translation in response to endoplasmic reticulum stress	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in regulation of translation initiation in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of translation initiation in response to endoplasmic reticulum stress	IEA Inferred from Electronic Annotation more info
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to other organism	IEA Inferred from Electronic Annotation more info
involved_in signal complex assembly	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within substrate-dependent cell migration, cell extension	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein phosphatase type 1 complex	IDA Inferred from Direct Assay more info	PubMed
located_in ribosome	IDA Inferred from Direct Assay more info	PubMed
located_in vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: SH2/SH3 adapter protein NCK1

Names: NCK adapter protein 1; NCK tyrosine kinase; SH2/SH3 adapter protein NCK-alpha; SH2/SH3 adaptor protein NCK-alpha; cytoplasmic protein NCK1; melanoma NCK protein; non-catalytic region of tyrosine kinase

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_001190796.3 → NP_001177725.1 SH2/SH3 adapter protein NCK1 isoform 2

See identical proteins and their annotated locations for NP_001177725.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' sequence compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC011597, AK301460, BC006403, BP339594

Consensus CDS

CCDS54644.1

UniProtKB/TrEMBL

B2R6S4

Related

ENSP00000419631.1, ENST00000469404.1

Conserved Domains (3) summary

cd10408
Location:216 → 312

SH2_Nck1; Src homology 2 (SH2) domain found in Nck

cd11901
Location:44 → 98

SH3_Nck1_2; Second Src Homology 3 domain of Nck1 adaptor protein

cd11904
Location:129 → 185

SH3_Nck1_3; Third Src Homology 3 domain of Nck1 adaptor protein
NM_001291999.2 → NP_001278928.1 SH2/SH3 adapter protein NCK1 isoform 1

See identical proteins and their annotated locations for NP_001278928.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC011597, BC006403, DA855124

Consensus CDS

CCDS3092.1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000417273.1, ENST00000481752.6

Conserved Domains (4) summary

cd10408
Location:280 → 376

SH2_Nck1; Src homology 2 (SH2) domain found in Nck

cd11900
Location:3 → 61

SH3_Nck1_1; First Src Homology 3 domain of Nck1 adaptor protein

cd11901
Location:108 → 162

SH3_Nck1_2; Second Src Homology 3 domain of Nck1 adaptor protein

cd11904
Location:193 → 249

SH3_Nck1_3; Third Src Homology 3 domain of Nck1 adaptor protein
NM_006153.6 → NP_006144.1 SH2/SH3 adapter protein NCK1 isoform 1

See identical proteins and their annotated locations for NP_006144.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer protein (isoform 1). Variants 1 and 3 encode the same protein.

Source sequence(s)

AC011597, BC006403, DB117533

Consensus CDS

CCDS3092.1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000288986.2, ENST00000288986.6

Conserved Domains (4) summary

cd10408
Location:280 → 376

SH2_Nck1; Src homology 2 (SH2) domain found in Nck

cd11900
Location:3 → 61

SH3_Nck1_1; First Src Homology 3 domain of Nck1 adaptor protein

cd11901
Location:108 → 162

SH3_Nck1_2; Second Src Homology 3 domain of Nck1 adaptor protein

cd11904
Location:193 → 249

SH3_Nck1_3; Third Src Homology 3 domain of Nck1 adaptor protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

136862208..136951606

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448189.1 → XP_047304145.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000568774.1, ENST00000898715.1
XM_024453538.2 → XP_024309306.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000568779.1, ENST00000898720.1

Conserved Domains (4) summary

cd10408
Location:280 → 376

SH2_Nck1; Src homology 2 (SH2) domain found in Nck

cd11900
Location:3 → 61

SH3_Nck1_1; First Src Homology 3 domain of Nck1 adaptor protein

cd11901
Location:108 → 162

SH3_Nck1_2; Second Src Homology 3 domain of Nck1 adaptor protein

cd11904
Location:193 → 249

SH3_Nck1_3; Third Src Homology 3 domain of Nck1 adaptor protein
XM_047448191.1 → XP_047304147.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000568780.1, ENST00000898721.1
XM_047448190.1 → XP_047304146.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4

Related

ENSP00000568776.1, ENST00000898717.1

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

139602861..139692274

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346632.1 → XP_054202607.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4
XM_054346631.1 → XP_054202606.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4
XM_054346633.1 → XP_054202608.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4
XM_054346634.1 → XP_054202609.1 SH2/SH3 adapter protein NCK1 isoform X1

UniProtKB/Swiss-Prot

B7Z751, D3DNE3, P16333

UniProtKB/TrEMBL

A0A0S2Z4Y3, B2R6S4