CISH cytokine inducible SH2 containing protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: CISHprovided by HGNC
Official Full Name: cytokine inducible SH2 containing proteinprovided by HGNC
Primary source: HGNC:HGNC:1984
See related: Ensembl:ENSG00000114737 MIM:602441; AllianceGenome:HGNC:1984
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: CIS; G18; SOCS; CIS-1; BACTS2
Summary: The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Expression: Broad expression in thyroid (RPKM 9.8), kidney (RPKM 7.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (50606489..50611774, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (50636358..50641643, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (50643920..50649205, complement)

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: 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?

CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma.
Title: CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma.
CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging.
Title: CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging.
MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.
Title: MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.
Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of a CISH Enhancer.
Title: Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of a CISH Enhancer.
NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS.
Title: NK cell-derived GM-CSF potentiates inflammatory arthritis and is negatively regulated by CIS.
We conclude that the Cish-SH2 domain is essential for PLC-gamma1 regulation in TCR-stimulated CD8(+) T cells.
Title: The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8(+) T cells.
The CISH rs414171 polymorphism is associated significantly with susceptibility to sepsis and multiple organ dysfunction syndrome in traumatic patients, which might prove to be a novel biomarker for indicating risk of infectious outcomes in critically injured patients.
Title: Genetic contribution of suppressor of cytokine signalling polymorphisms to the susceptibility to infection after traumatic injury.
These findings suggest that CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL-13-induced CCL26 production.
Title: CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts.
identified P2RX2, KCNQ5, ERBB3 and SOCS3 to be associated with the progression of age-related hearing impairment
Title: Down-expression of P2RX2, KCNQ5, ERBB3 and SOCS3 through DNA hypermethylation in elderly women with presbycusis.
CIS interacted with phosphorylated EpoR at Y401, which was critical for the activation of STAT5 and ERK.
Title: Phosphorylated CIS suppresses the Epo or JAK2 V617F mutant-triggered cell proliferation through binding to EpoR.

Submit: New GeneRIF Correction See all GeneRIFs (39)

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

Associated conditions

Description	Tests
Bacteremia, susceptibility to, 2 MedGen: C3280647 OMIM: 614383 GeneReviews: Not available	Compare labs
Malaria, susceptibility to MedGen: C1970028 OMIM: 611162 GeneReviews: Not available	Compare labs
Mycobacterium tuberculosis, susceptibility to MedGen: C1834752 OMIM: 607948 GeneReviews: Not available	Compare labs

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-treated vaginal epithelial cells show downregulation of cytokine inducible SH2-containing protein (CISH) expression as compared to untreated control	PubMed
Tat	tat	HIV-1 Tat recruits CISH (CIS) to the cytoplasmic tail of CD127; recruitment is dependent upon the basic region in Tat	PubMed
	tat	HIV-1 Tat upregulates the expression of cytokine inducible SH2-containing protein (CISH) in human primary T 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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Markers

RH94332 (e-PCR)
- UniSTS:89624

CISH_308 (e-PCR)
- UniSTS:277099

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 1-phosphatidylinositol-3-kinase regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables molecular_function	ND No biological Data available more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in intracellular signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of signal transduction	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol phosphate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein kinase C-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell growth	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cellular_component	ND No biological Data available more info
located_in cytosol	TAS Traceable Author Statement more info
part_of phosphatidylinositol 3-kinase complex	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cytokine-inducible SH2-containing protein

Names: cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signaling

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.

Genomic

NG_023194.1 RefSeqGene

Range

5058..10343

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_013324.7 → NP_037456.5 cytokine-inducible SH2-containing protein isoform 1

See identical proteins and their annotated locations for NP_037456.5

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents a longer transcript, and encodes an isoform (1) with a distinct N-terminus.

Source sequence(s)

AC096920, AF132297, CA435538, DA957793

Consensus CDS

CCDS46834.1

UniProtKB/TrEMBL

Q71V34

Related

ENSP00000409346.2, ENST00000443053.6

Conserved Domains (2) summary

cd10718
Location:94 → 181

SH2_CIS; Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS)

cd03734
Location:235 → 275

SOCS_CIS1; SOCS (suppressors of cytokine signaling) box of CIS (cytokine-inducible SH2 protein) 1-like proteins. Together with the SOCS proteins, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. ...
NM_145071.4 → NP_659508.1 cytokine-inducible SH2-containing protein isoform 2

See identical proteins and their annotated locations for NP_659508.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a segment in the 5' UTR and coding region compared to variant 1. The translation begins at an in-frame upstream start codon, and results in an isoform (2) with a different N-terminus, as compared to isoform 1.

Source sequence(s)

BC031590, BC064354, DA957793

Consensus CDS

CCDS2831.1

UniProtKB/Swiss-Prot

B2R9N1, G5E9R1, Q9NS38, Q9NSE2, Q9Y5R1

UniProtKB/TrEMBL

Q71V34

Related

ENSP00000294173.3, ENST00000348721.4

Conserved Domains (2) summary

cd10718
Location:77 → 164

SH2_CIS; Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS)

cd03734
Location:218 → 258

SOCS_CIS1; SOCS (suppressors of cytokine signaling) box of CIS (cytokine-inducible SH2 protein) 1-like proteins. Together with the SOCS proteins, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. ...