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 gen... See more...

Aliases for CISH Gene

Aliases for CISH Gene

  • Cytokine Inducible SH2 Containing Protein 2 3 5
  • CIS-1 2 3 4
  • SOCS 2 3 4
  • CIS 2 3 4
  • G18 2 3 4
  • Cytokine-Inducible SH2-Containing Protein 3 4
  • Suppressor Of Cytokine Signaling 3 4
  • Cytokine-Inducible Inhibitor Of Signaling Type 1B 3
  • Cytokine Inducible SH2-Containing Protein 2
  • Protein G18 4
  • BACTS2 3
  • CISH 5

External Ids for CISH Gene

Previous GeneCards Identifiers for CISH Gene

  • GC03P049337
  • GC03P049507
  • GC03M050498
  • GC03M050602

Summaries for CISH Gene

Entrez Gene Summary for CISH Gene

  • 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]

GeneCards Summary for CISH Gene

CISH (Cytokine Inducible SH2 Containing Protein) is a Protein Coding gene. Diseases associated with CISH include Bacteremia 2 and Malaria. Among its related pathways are IL-2 Signaling Pathway and Prolactin Signaling Pathway. Gene Ontology (GO) annotations related to this gene include protein kinase inhibitor activity. An important paralog of this gene is SOCS2.

UniProtKB/Swiss-Prot Summary for CISH Gene

  • SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).

Gene Wiki entry for CISH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CISH Gene

Genomics for CISH Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CISH Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CISH on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CISH

Top Transcription factor binding sites by QIAGEN in the CISH gene promoter:
  • GR
  • GR-alpha
  • GR-beta
  • NRSF form 1
  • STAT3
  • STAT5A
  • STAT5B

Genomic Locations for CISH Gene

Latest Assembly
chr3:50,606,454-50,611,774
(GRCh38/hg38)
Size:
5,321 bases
Orientation:
Minus strand

Previous Assembly
chr3:50,643,920-50,649,205
(GRCh37/hg19 by Entrez Gene)
Size:
5,286 bases
Orientation:
Minus strand

chr3:50,643,921-50,649,262
(GRCh37/hg19 by Ensembl)
Size:
5,342 bases
Orientation:
Minus strand

Genomic View for CISH Gene

Genes around CISH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CISH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CISH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CISH Gene

Proteins for CISH Gene

  • Protein details for CISH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NSE2-CISH_HUMAN
    Recommended name:
    Cytokine-inducible SH2-containing protein
    Protein Accession:
    Q9NSE2
    Secondary Accessions:
    • B2R9N1
    • G5E9R1
    • Q9NS38
    • Q9Y5R1

    Protein attributes for CISH Gene

    Size:
    258 amino acids
    Molecular mass:
    28663 Da
    Quaternary structure:
    • Stably associated with the tyrosine-phosphorylated IL3 receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR).
    SequenceCaution:
    • Sequence=AAD28471.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for CISH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CISH Gene

Post-translational modifications for CISH Gene

  • Association with EPOR may target the protein for proteolysis by the ubiquitin-dependent proteasome pathway. CIS is mainly monubiquitinated (37 kDa form) but may also exist in a polyubiquitinated form (45 kDa).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CISH Gene

No data available for DME Specific Peptides for CISH Gene

Domains & Families for CISH Gene

Gene Families for CISH Gene

Protein Domains for CISH Gene

InterPro:
Blocks:
  • SH2 domain signature
  • SOCS protein, C-terminal

Suggested Antigen Peptide Sequences for CISH Gene

GenScript: Design optimal peptide antigens:
  • Suppressor of cytokine signaling (CISH_HUMAN)
genes like me logo Genes that share domains with CISH: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CISH Gene

Function for CISH Gene

Molecular function for CISH Gene

UniProtKB/Swiss-Prot Function:
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).
UniProtKB/Swiss-Prot Induction:
By a subset of cytokines including EPO/erythropoietin.
GENATLAS Biochemistry:
cytokine inducible SH2-containing protein gene,binding to IL3 and EPOR,predominantly expressed in fetal and adult liver and kidney,negative regulator of the JAK signaling pathway

Phenotypes From GWAS Catalog for CISH Gene

Gene Ontology (GO) - Molecular Function for CISH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005515 protein binding IPI 16273093
GO:0046935 1-phosphatidylinositol-3-kinase regulator activity IBA 21873635
genes like me logo Genes that share ontologies with CISH: view
genes like me logo Genes that share phenotypes with CISH: view

Animal Models for CISH Gene

MGI Knock Outs for CISH:
  • Cish Cish<tm1.2Cdon>
  • Cish Cish<tm1a(KOMP)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CISH

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CISH Gene

Localization for CISH Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CISH gene
Compartment Confidence
cytosol 5
plasma membrane 3
extracellular 3
cytoskeleton 3
nucleus 3
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytokinetic bridge (2)
  • Microtubules (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CISH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0005942 phosphatidylinositol 3-kinase complex IBA 21873635
genes like me logo Genes that share ontologies with CISH: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CISH Gene

Pathways & Interactions for CISH Gene

PathCards logo

SuperPathways for CISH Gene

SuperPathway Contained pathways
1 Prolactin Signaling Pathway
2 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.42
.36
3 Development EPO-induced Jak-STAT pathway
.42
4 Immune response IL-2 activation and signaling pathway
.41
.41
5 IL-2 Signaling Pathway
genes like me logo Genes that share pathways with CISH: view

Pathways by source for CISH Gene

5 GeneGo (Thomson Reuters) pathways for CISH Gene
  • Development EPO-induced Jak-STAT pathway
  • Development_Thrombopoetin signaling via JAK-STAT pathway
  • Immune response IL-2 activation and signaling pathway
  • Immune response IL-3 activation and signaling pathway
  • Immune response IL-9 signaling pathway
2 Qiagen pathways for CISH Gene
  • IL-9 Pathway
  • SOCS Pathway
1 Cell Signaling Technology pathway for CISH Gene
1 GeneTex pathway for CISH Gene

UniProtKB/Swiss-Prot Q9NSE2-CISH_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for CISH Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CISH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth NAS 9465889
GO:0007205 protein kinase C-activating G protein-coupled receptor signaling pathway IEA --
GO:0009968 negative regulation of signal transduction IEA --
GO:0016567 protein ubiquitination IEA --
GO:0035556 intracellular signal transduction NAS 10902923
genes like me logo Genes that share ontologies with CISH: view

Drugs & Compounds for CISH Gene

(9) Drugs for CISH Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(12) Additional Compounds for CISH Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CISH: view

Transcripts for CISH Gene

mRNA/cDNA for CISH Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CISH

Alternative Splicing Database (ASD) splice patterns (SP) for CISH Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c
SP1:
SP2: -
SP3: - -
SP4: - - -
SP5:

Relevant External Links for CISH Gene

GeneLoc Exon Structure for
CISH

Expression for CISH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CISH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CISH Gene

This gene is overexpressed in Liver (x5.1) and Kidney - Cortex (x4.5).

Protein differential expression in normal tissues from HIPED for CISH Gene

This gene is overexpressed in Adipocyte (66.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CISH Gene



Protein tissue co-expression partners for CISH Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CISH

SOURCE GeneReport for Unigene cluster for CISH Gene:

Hs.655334

mRNA Expression by UniProt/SwissProt for CISH Gene:

Q9NSE2-CISH_HUMAN
Tissue specificity: Expressed in various epithelial tissues. Abundantly expressed in liver and kidney, and to a lesser extent in lung. The tissue distribution of isoforms 1 and 1B is distinct.

Evidence on tissue expression from TISSUES for CISH Gene

  • Lung(4.5)
  • Intestine(4.5)
  • Skin(4.5)
  • Liver(3.4)
  • Kidney(2.8)
  • Lymph node(2.6)
  • Muscle(2.6)
  • Spleen(2.6)
  • Blood(2.5)
  • Heart(2.5)
  • Nervous system(2.5)
  • Thyroid gland(2.4)
  • Bone marrow(2.3)
  • Pancreas(2.2)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with CISH: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CISH Gene

Orthologs for CISH Gene

This gene was present in the common ancestor of chordates.

Orthologs for CISH Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CISH 29 30
  • 99.74 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CISH 29 30
  • 89.23 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CISH 29 30
  • 87.93 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Cish 29 16 30
  • 84.82 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cish 29
  • 84.57 (n)
Oppossum
(Monodelphis domestica)
Mammalia CISH 30
  • 70 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CISH 30
  • 66 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CISH 29 30
  • 71.26 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CISH 30
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cish 29
  • 60.85 (n)
Zebrafish
(Danio rerio)
Actinopterygii cishb 29 30
  • 53.93 (n)
OneToMany
cish 30
  • 43 (a)
OneToMany
Species where no ortholog for CISH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CISH Gene

ENSEMBL:
Gene Tree for CISH (if available)
TreeFam:
Gene Tree for CISH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CISH: view image
Alliance of Genome Resources:
Additional Orthologs for CISH

Paralogs for CISH Gene

Paralogs for CISH Gene

(1) SIMAP similar genes for CISH Gene using alignment to 1 proteins:

  • CISH_HUMAN
genes like me logo Genes that share paralogs with CISH: view

Variants for CISH Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for CISH Gene

CISH_HUMAN-Q9NSE2
CISH polymorphisms are involved in susceptibility to malaria [MIM:611162].
CISH_HUMAN-Q9NSE2
Genetic variations in CISH are involved in susceptibility to tuberculosis [MIM:607948].
CISH_HUMAN-Q9NSE2
Genetic variations in CISH are associated with susceptibility to bacterial invasion of the blood and define the bacteremia susceptibility locus 2 (BACTS2) [MIM:614383].

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CISH Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs148162012 Likely Benign: not provided 50,608,381(-) C/T
NM_013324.6(CISH):c.284G>A (p.Arg95Gln)
MISSENSE
rs414171 Affects, Risk Factor: Bacteremia, susceptibility to, 2; Susceptibility to malaria; Tuberculosis, susceptibility to 50,612,068(-) A/T
NM_001243926.1(MAPKAPK3):c.-436A>T
FIVE_PRIME_UTR
rs61737505 Benign: not provided 50,607,865(-) G/A
NM_013324.6(CISH):c.570C>T (p.Ser190=)
SYNONYMOUS
rs76541284 Benign: not provided 50,607,715(-) C/T
NM_013324.6(CISH):c.720G>A (p.Leu240=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CISH Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CISH Gene

Variant ID Type Subtype PubMed ID
esv3584502 CNV gain 24956385
nsv460533 CNV loss 19166990
nsv482083 CNV gain 20164927
nsv508919 CNV insertion 20534489
nsv590273 CNV loss 21841781

Variation tolerance for CISH Gene

Residual Variation Intolerance Score: 60.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.27; 25.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CISH Gene

Human Gene Mutation Database (HGMD)
CISH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CISH
Leiden Open Variation Database (LOVD)
CISH

SNP Genotyping and Copy Number Assays for research

Disorders for CISH Gene

MalaCards: The human disease database

(11) MalaCards diseases for CISH Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
bacteremia 2
  • bacteremia, susceptibility to, 2
malaria
  • malaria, susceptibility to
mycobacterium tuberculosis 1
  • mycobacterium tuberculosis, susceptibility to, 1
myeloproliferative neoplasm
  • chronic myeloproliferative disease
infectious anterior uveitis
  • infectious secondary iridocyclitis
- elite association - COSMIC cancer census association via MalaCards
Search CISH in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CISH

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CISH: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CISH Gene

Publications for CISH Gene

  1. CISH and susceptibility to infectious diseases. (PMID: 20484391) Khor CC … Hill AV (The New England journal of medicine 2010) 3 4 22 40 72
  2. Cloning and characterization of CIS 1b (cytokine inducible SH2-containing protein 1b), an alternative splicing form of CIS 1 gene. (PMID: 10902923) Jiang C … Zhao S (DNA sequence : the journal of DNA sequencing and mapping 2000) 3 4 22
  3. Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated Cis protein. (PMID: 9774439) Verdier F … Mayeux P (The Journal of biological chemistry 1998) 3 4 22
  4. Molecular cloning of CISH, chromosome assignment to 3p21.3, and analysis of expression in fetal and adult tissues. (PMID: 9465889) Uchida K … Takahashi T (Cytogenetics and cell genetics 1997) 2 3 4
  5. A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. (PMID: 7796808) Yoshimura A … Miyajima A (The EMBO journal 1995) 2 3 22

Products for CISH Gene

Sources for CISH Gene