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Aliases for CISH Gene

Aliases for CISH Gene

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

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 and Mycobacterium Tuberculosis, Susceptibility To Mycobacterium Tuberculosis, Protection Against, Included. Among its related pathways are Development EPO-induced Jak-STAT pathway and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. GO annotations related to this gene include protein kinase inhibitor activity. An important paralog of this gene is SOCS2.

UniProtKB/Swiss-Prot 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 , fRNAdb sequence ontologies and piRNA Summary for CISH Gene

Genomics for CISH Gene

Regulatory Elements for CISH Gene

Enhancers for CISH Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03G050566 2.1 FANTOM5 Ensembl ENCODE dbSUPER 38.5 +39.9 39928 10.0 CREB3L1 AGO1 DMAP1 YY1 ZNF143 ZNF263 SP3 NFYC TBX21 SSRP1 CISH RAD54L2 SEMA3F-AS1 MAPKAPK3 TMEM115 HEMK1 DOCK3 NAT6 TRAIP RASSF1
GH03G050598 2.5 VISTA FANTOM5 Ensembl ENCODE dbSUPER 7.8 +5.3 5345 15.0 MLX CREB3L1 AGO1 ZFP64 DMAP1 YBX1 YY1 ZNF143 ZNF263 SP3 TMEM115 HEMK1 RAD54L2 C3orf18 SEMA3F-AS1 DOCK3 MANF GMPPB NAT6 TRAIP
GH03G050581 1.1 ENCODE dbSUPER 12.8 +27.7 27677 5.8 HDGF ZSCAN4 RAD21 YY1 RELB IKZF2 CREM CEBPB JUNB TBX21 CISH MAPKAPK3 PIR34243 C3orf18
GH03G050577 1 ENCODE dbSUPER 12.5 +34.3 34292 0.9 CTCF ZSCAN4 ZNF766 SCRT2 NFE2 IKZF2 EGR2 ZBTB11 MNT DPF2 MAPKAPK3 CISH HEMK1 C3orf18 PIR34243
GH03G050652 0.9 Ensembl ENCODE 11.5 -41.1 -41070 0.6 CTCF FOXA2 FOXA3 HLF REST DPF2 RAD21 ZKSCAN1 ZBTB48 ZKSCAN8 MAPKAPK3 CISH C3orf18 HEMK1 LSMEM2 LINC02019
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CISH on UCSC Golden Path with GeneCards custom track

Promoters for CISH Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000152388 31 1601 PKNOX1 ARNT CREB3L1 ARID4B SIN3A FEZF1 DMAP1 YY1 ZNF143 FOS

Genomic Location for CISH Gene

Chromosome:
3
Start:
50,606,454 bp from pter
End:
50,611,831 bp from pter
Size:
5,378 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=Translation N-terminally extended.; 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

Protein Domains for CISH Gene

Suggested Antigen Peptide Sequences for CISH Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with CISH: view

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

Function for CISH Gene

Molecular function for CISH Gene

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
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.

Gene Ontology (GO) - Molecular Function for CISH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0004860 protein kinase inhibitor activity IBA --
GO:0005515 protein binding IPI 16273093
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:

Animal Model Products

CRISPR Products

miRNA for CISH Gene

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones 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
cytoskeleton 3
nucleus 3
extracellular 2
endoplasmic reticulum 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for CISH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
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

genes like me logo Genes that share pathways with CISH: view

UniProtKB/Swiss-Prot Q9NSE2-CISH_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

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:0006469 negative regulation of protein kinase activity IBA --
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 --
genes like me logo Genes that share ontologies with CISH: view

No data available for SIGNOR curated interactions for CISH Gene

Drugs & Compounds for CISH Gene

(10) Drugs for CISH Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) 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

Unigene Clusters for CISH Gene

Cytokine inducible SH2-containing protein:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones 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
ECgene alternative splicing isoforms for
CISH

Expression for CISH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP 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, PaxDb, MaxQB, and MOPED for CISH Gene



Protein tissue co-expression partners for CISH Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CISH Gene:

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(4.4)
  • Skin(4.4)
  • Intestine(4.3)
  • Liver(3.2)
  • Muscle(2.3)
  • Blood(2.2)
  • Kidney(2.2)
  • Heart(2)
  • Lymph node(2)
  • Spleen(2)
  • Nervous system(2)
genes like me logo Genes that share expression patterns with CISH: view

Primer Products

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 34 35
  • 99.74 (n)
dog
(Canis familiaris)
Mammalia CISH 34 35
  • 89.23 (n)
cow
(Bos Taurus)
Mammalia CISH 34 35
  • 87.93 (n)
mouse
(Mus musculus)
Mammalia Cish 34 16 35
  • 84.82 (n)
rat
(Rattus norvegicus)
Mammalia Cish 34
  • 84.57 (n)
oppossum
(Monodelphis domestica)
Mammalia CISH 35
  • 70 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CISH 35
  • 66 (a)
OneToOne
chicken
(Gallus gallus)
Aves CISH 34 35
  • 71.26 (n)
lizard
(Anolis carolinensis)
Reptilia CISH 35
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cish 34
  • 60.85 (n)
zebrafish
(Danio rerio)
Actinopterygii cishb 34 35
  • 53.93 (n)
cish 35
  • 43 (a)
OneToMany
Species where no ortholog for CISH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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)

Paralogs for CISH Gene

Paralogs for CISH Gene

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

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

Sequence variations from dbSNP and Humsavar for CISH Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs414171 other 50,612,068(-) ACCGC(A/T)CGGCT upstream-variant-2KB, utr-variant-5-prime
rs1000420183 -- 50,611,502(+) GCTCC(C/T)GAGGT intron-variant, upstream-variant-2KB, utr-variant-5-prime
rs1000516669 -- 50,606,810(+) GAGGG(A/G)GTGAG utr-variant-3-prime
rs1001025462 -- 50,609,518(+) GCCGA(C/T)CAAAA intron-variant, utr-variant-5-prime
rs1001523882 -- 50,606,117(+) CAGCT(C/G)TCTCT downstream-variant-500B

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)

Relevant External Links for CISH Gene

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

Disorders for CISH Gene

MalaCards: The human disease database

(5) MalaCards diseases for CISH Gene - From: OMIM, ClinVar, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
bacteremia
  • bacteremia, susceptibility to, 2
mycobacterium tuberculosis, susceptibility to mycobacterium tuberculosis, protection against, included
  • tuberculosis
malaria
  • malaria, severe
breast secretory carcinoma
  • juvenile breast carcinoma
central nervous system disease
  • cns
- elite association - COSMIC cancer census association via MalaCards
Search CISH in MalaCards View complete list of genes associated with diseases

Relevant External Links for CISH

Genetic Association Database (GAD)
CISH
Human Genome Epidemiology (HuGE) Navigator
CISH
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CISH
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 C.C. … Hill A.V. (N. Engl. J. Med. 2010) 3 4 22 46 64
  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 Seq. 2000) 3 4 22 64
  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. (J. Biol. Chem. 1998) 3 4 22 64
  4. Molecular cloning of CISH, chromosome assignment to 3p21.3, and analysis of expression in fetal and adult tissues. (PMID: 9465889) Uchida K. … Takahashi K. (Cytogenet. Cell Genet. 1997) 2 3 4 64
  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. (EMBO J. 1995) 2 3 22 64

Products for CISH Gene

Sources for CISH Gene

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