Seroatlas · Human Serome Atlas

CISH

Cytokine-inducible SH2-containing protein

Also known as: CIS, CIS-1, CISH_HUMAN, G18, SOCS

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9NSE2
Gene: CISH
Ensembl: ENSG00000114737
Chromosome: 3
Canonical length: 258 aa
Protein class: Predicted intracellular proteins
Subcellular location: Microtubules,Cytokinetic bridge

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

258 residues, UniProt reviewed canonical sequence.

>Q9NSE2|CISH
     1  MVLCVQGPRP LLAVERTGQR PLWAPSLELP KPVMQPLPAG AFLEEVAEGT PAQTESEPKV
    61  LDPEEDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP EGTFLVRDST HPSYLFTLSV
   121  KTTRGPTNVR IEYADSSFRL DSNCLSRPRI LAFPDVVSLV QHYVASCTAD TRSDSPDPAP
   181  TPALPMPKED APSDPALPAP PPATAVHLKL VQPFVRRSSA RSLQHLCRLV INRLVADVDC
   241  LPLPRRMADY LRQYPFQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CISH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.47
Highest tissue expression: 59 nTPM

Expression across tissuesHPA

Tissue

liver: 59 nTPM
kidney: 46 nTPM
skeletal muscle: 39 nTPM
thyroid gland: 35 nTPM
lung: 27 nTPM
breast: 24 nTPM

Single-cell type

alveolar cells type 2: 82 nCPM
breast lactating cells: 79 nCPM
epididymal efferent duct absorptive cells: 46 nCPM
transitional alveolar cells: 41 nCPM
alveolar cells type 1: 33 nCPM
fallopian tube ciliated cells: 32 nCPM

Immune cell

memory CD4 T-cell: 54 nTPM
MAIT T-cell: 51 nTPM
memory CD8 T-cell: 42 nTPM
naive CD8 T-cell: 41 nTPM
naive CD4 T-cell: 41 nTPM
T-reg: 35 nTPM

Brain region

medulla oblongata: 4 nTPM
choroid plexus: 2.8 nTPM
pons: 2.5 nTPM
midbrain: 2.4 nTPM
hypothalamus: 2.3 nTPM
spinal cord: 2.2 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.34
gnomAD pLI: 0
gnomAD missense Z: 0.89
DepMap mean gene effect: -0.05
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

cytokine receptor binding

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CISH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

EGFR

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CISH as an antibody target. Whether an autoantibody or antibody against CISH could matter depends on whether native CISH is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CISH is annotated at the cell surface, where native CISH is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label CISH as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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