CSK C-terminal Src kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: CSKprovided by HGNC
Official Full Name: C-terminal Src kinaseprovided by HGNC
Primary source: HGNC:HGNC:2444
See related: Ensembl:ENSG00000103653 MIM:124095; AllianceGenome:HGNC:2444
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
Summary: The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]
Expression: Broad expression in lymph node (RPKM 63.0), spleen (RPKM 47.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q24.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (74782080..74803197)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (72651992..72673091)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (75074421..75095538)

Chromosome 15 - NC_000015.10 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?

SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.
Title: SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding.
Molecular mapping of platelet hyperreactivity in diabetes: the stress proteins complex HSPA8/Hsp90/CSK2alpha and platelet aggregation in diabetic and normal platelets.
Title: Molecular mapping of platelet hyperreactivity in diabetes: the stress proteins complex HSPA8/Hsp90/CSK2α and platelet aggregation in diabetic and normal platelets.
Depletion of Csk preferentially reduces the protein level of LynA in a Cbl-dependent manner in cancer cells.
Title: Depletion of Csk preferentially reduces the protein level of LynA in a Cbl-dependent manner in cancer cells.
CSK promotes innate immune response to DNA virus by phosphorylating MITA.
Title: CSK promotes innate immune response to DNA virus by phosphorylating MITA.
CD28 functions as a novel adaptor protein for CSK, and CSK regulates signaling downstream of CD28
Title: Carboxyl-Terminal Src Kinase Binds CD28 upon Activation and Mutes Downstream Signaling.
Here we report that Csk is covalently modified by SUMO1 at lysine 53 (K53) both in vitro and in vivo. Treatment with hydrogen peroxide inhibited this modification to a certain extent, but PIAS3, identified as the main specific SUMO E3 ligase for Csk, could significantly enhance SUMO1-Csk level
Title: SUMOylation of Csk Negatively Modulates its Tumor Suppressor Function.
results demonstrate that c-Src directly phosphorylates the Notch intracellular domain at specific tyrosine residues and that mutation of these phosphorylation sites increases Notch responsive transcriptional activity.
Title: Src kinase phosphorylates Notch1 to inhibit MAML binding.
This study demonstrate that in FcepsilonRI-activated mast cells CSK is a negative regulator of degranulation and chemotaxis, but a positive regulator of adhesion to fibronectin and production of proinflammatory cytokines.
Title: Positive and Negative Regulatory Roles of C-Terminal Src Kinase (CSK) in FcεRI-Mediated Mast Cell Activation, Independent of the Transmembrane Adaptor PAG/CSK-Binding Protein.
identified a novel and critical role of c-Src in guiding human neural stem cells differentiation to an oligodendrocyte lineage
Title: Oligodendrocyte differentiation from human neural stem cells: A novel role for c-Src.
CSK is down-regulated in patients with rheumatoid arthritis.
Title: Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis.

Submit: New GeneRIF Correction See all GeneRIFs (115)

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
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies eight loci associated with blood pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of blood pressure and hypertension. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. 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	DC-SIGN engagement by HIV-1 gp120 on dendritic cell (DC) surface activates Src kinases, leading to an increase in membrane extensions at the DC surface	PubMed
Tat	tat	HIV-1 Tat stimulates the tyrosine phosphorylation and activation of c-Src kinase resulting in the activation of the intrinsic kinase activity of c-Src, an effect associated with Tat-induced angiogenesis and Kaposi's sarcoma	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH77839 (e-PCR)
- UniSTS:67364

CSK_3956 (e-PCR)
- UniSTS:462130

RH70899 (e-PCR)
- UniSTS:77652

RH69961 (e-PCR)
- UniSTS:26230

PMC193924P3 (e-PCR)
- UniSTS:271765

MARC_5011-5012:991939428:1 (e-PCR)
- UniSTS:231136

MARC_5011-5012:996690037:1 (e-PCR)
- UniSTS:231136

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables proline-rich region binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase A catalytic subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info
enables protein tyrosine kinase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell costimulation	TAS Traceable Author Statement more info
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in adherens junction organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to peptide hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of Golgi to plasma membrane protein transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of bone resorption	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of low-density lipoprotein particle clearance	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of Fc receptor mediated stimulatory signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IPI Inferred from Physical Interaction more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tyrosine-protein kinase CSK

Names: C-Src kinase; CSK, non-receptor tyrosine kinase; c-src tyrosine kinase; protein-tyrosine kinase CYL

NP_001120662.1

EC 2.7.10.2

NP_001341917.1

EC 2.7.10.2

NP_001374018.1

EC 2.7.10.2

NP_001374019.1

EC 2.7.10.2

NP_001374020.1

EC 2.7.10.2

NP_001374021.1

EC 2.7.10.2

NP_001374022.1

EC 2.7.10.2

NP_001374023.1

EC 2.7.10.2

NP_001374024.1

EC 2.7.10.2

NP_001374025.1

EC 2.7.10.2

NP_001374026.1

EC 2.7.10.2

NP_001374027.1

EC 2.7.10.2

NP_004374.1

EC 2.7.10.2

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_001127190.2 → NP_001120662.1 tyrosine-protein kinase CSK isoform 1

See identical proteins and their annotated locations for NP_001120662.1

Status: REVIEWED

Source sequence(s)

AC091230, AK290531, AW575209, AY007162

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Related

ENSP00000414764.2, ENST00000439220.6

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001354988.2 → NP_001341917.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AK127672, AW575209

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Related

ENSP00000454906.1, ENST00000567571.5

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387089.1 → NP_001374018.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387090.1 → NP_001374019.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387091.1 → NP_001374020.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387092.1 → NP_001374021.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387093.1 → NP_001374022.1 tyrosine-protein kinase CSK isoform 1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387094.1 → NP_001374023.1 tyrosine-protein kinase CSK isoform 6

Status: REVIEWED

Source sequence(s)

AC091230

UniProtKB/TrEMBL

B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:187 → 442

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387095.1 → NP_001374024.1 tyrosine-protein kinase CSK isoform 2

Status: REVIEWED

Source sequence(s)

AC091230

UniProtKB/TrEMBL

B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:188 → 442

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase
NM_001387096.1 → NP_001374025.1 tyrosine-protein kinase CSK isoform 3

Status: REVIEWED

Source sequence(s)

AC091230

UniProtKB/TrEMBL

Q53EL3

Conserved Domains (3) summary

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase

cl21453
Location:188 → 429

PKc_like; Protein Kinases, catalytic domain
NM_001387097.1 → NP_001374026.1 tyrosine-protein kinase CSK isoform 4

Status: REVIEWED

Source sequence(s)

AC091230

UniProtKB/TrEMBL

A8K3B6, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:155 → 410

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:53 → 142

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cl17036
Location:11 → 57

SH3; Src Homology 3 domain superfamily
NM_001387098.1 → NP_001374027.1 tyrosine-protein kinase CSK isoform 5

Status: REVIEWED

Source sequence(s)

AC091230

UniProtKB/TrEMBL

A8K3B6, B5BU52, Q53EL3

Conserved Domains (3) summary

cd05082
Location:145 → 400

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:43 → 132

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cl17036
Location:11 → 43

SH3; Src Homology 3 domain superfamily
NM_004383.3 → NP_004374.1 tyrosine-protein kinase CSK isoform 1

See identical proteins and their annotated locations for NP_004374.1

Status: REVIEWED

Source sequence(s)

AC091230

Consensus CDS

CCDS10269.1

UniProtKB/Swiss-Prot

P41240, Q2M3N2, Q6FGZ6

UniProtKB/TrEMBL

B2R6Q4, B5BU52, Q53EL3

Related

ENSP00000220003.9, ENST00000220003.14

Conserved Domains (3) summary

cd05082
Location:188 → 443

PTKc_Csk; Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase

cd09937
Location:78 → 175

SH2_csk_like; Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk)

cd11769
Location:11 → 67

SH3_CSK; Src Homology 3 domain of C-terminal Src kinase