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Protein

Cytokine-inducible SH2-containing protein

Gene

CISH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionSignal transduction inhibitor
Biological processGrowth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1266695 Interleukin-7 signaling
R-HSA-8951664 Neddylation
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiQ9NSE2
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cytokine-inducible SH2-containing protein
Short name:
CIS
Alternative name(s):
CIS-1
Protein G18
Suppressor of cytokine signaling
Short name:
SOCS
Gene namesi
Name:CISH
Synonyms:G18
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114737.15
HGNCiHGNC:1984 CISH
MIMi602441 gene
neXtProtiNX_Q9NSE2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi1154
MalaCardsiCISH
MIMi607948 phenotype
611162 phenotype
614383 phenotype
OpenTargetsiENSG00000114737
PharmGKBiPA26521

Polymorphism and mutation databases

BioMutaiCISH
DMDMi13124022

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812311 – 258Cytokine-inducible SH2-containing proteinAdd BLAST258

Post-translational modificationi

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).1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ9NSE2
PaxDbiQ9NSE2
PeptideAtlasiQ9NSE2
PRIDEiQ9NSE2

PTM databases

iPTMnetiQ9NSE2
PhosphoSitePlusiQ9NSE2

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

By a subset of cytokines including EPO/erythropoietin.

Gene expression databases

BgeeiENSG00000114737
CleanExiHS_CISH
GenevisibleiQ9NSE2 HS

Organism-specific databases

HPAiCAB034039
HPA040812

Interactioni

Subunit structurei

Stably associated with the tyrosine-phosphorylated IL3 receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR).

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi10757426 interactors.
IntActiQ9NSE2 9 interactors.
MINTiQ9NSE2
STRINGi9606.ENSP00000409346

Structurei

3D structure databases

ProteinModelPortaliQ9NSE2
SMRiQ9NSE2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 163SH2PROSITE-ProRule annotationAdd BLAST82
Domaini209 – 257SOCS boxPROSITE-ProRule annotationAdd BLAST49

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG4566 Eukaryota
ENOG4111V4J LUCA
GeneTreeiENSGT00760000119136
HOGENOMiHOG000236320
HOVERGENiHBG002457
InParanoidiQ9NSE2
KOiK04701
OMAiQHYVTSC
OrthoDBiEOG091G0J75
PhylomeDBiQ9NSE2
TreeFamiTF321368

Family and domain databases

CDDicd10718 SH2_CIS, 1 hit
Gene3Di3.30.505.101 hit
InterProiView protein in InterPro
IPR028425 CIS
IPR035887 CIS_SH2
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR001496 SOCS_box
IPR036036 SOCS_box-like_dom_sf
PANTHERiPTHR44649 PTHR44649, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF07525 SOCS_box, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00253 SOCS, 1 hit
SM00969 SOCS_box, 1 hit
SUPFAMiSSF158235 SSF158235, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50225 SOCS, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NSE2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVLCVQGPRP LLAVERTGQR PLWAPSLELP KPVMQPLPAG AFLEEVAEGT
60 70 80 90 100
PAQTESEPKV LDPEEDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP
110 120 130 140 150
EGTFLVRDST HPSYLFTLSV KTTRGPTNVR IEYADSSFRL DSNCLSRPRI
160 170 180 190 200
LAFPDVVSLV QHYVASCTAD TRSDSPDPAP TPALPMPKED APSDPALPAP
210 220 230 240 250
PPATAVHLKL VQPFVRRSSA RSLQHLCRLV INRLVADVDC LPLPRRMADY

LRQYPFQL
Length:258
Mass (Da):28,663
Last modified:October 1, 2000 - v1
Checksum:i0BA97804E3B0F608
GO
Isoform 1B (identifier: Q9NSE2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MVLCVQG → MGPPLTAHPLPSR

Show »
Length:264
Mass (Da):29,288
Checksum:i0C1C5791EAFE56DC
GO
Isoform 1C (identifier: Q9NSE2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MVLCVQG → MYLEHTSHCPHHDDDTAMDTPLPR

Show »
Length:275
Mass (Da):30,734
Checksum:i6F9A0020F2D27A19
GO

Sequence cautioni

The sequence AAD28471 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Polymorphismi

Note: CISH polymorphisms are involved in susceptibilty to malaria [MIMi:611162].1 Publication
Note: Genetic variations in CISH are involved in susceptibilty to tuberculosis [MIMi:607948].1 Publication
Note: Genetic variations in CISH are associated with susceptibility to bacterial invasion of the blood and define the bacteremia susceptibility locus 2 (BACTS2) [MIMi:614383].1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0061941 – 7MVLCVQG → MGPPLTAHPLPSR in isoform 1B. 1 Publication7
Alternative sequenceiVSP_0061951 – 7MVLCVQG → MYLEHTSHCPHHDDDTAMDT PLPR in isoform 1C. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D83532 mRNA Translation: BAA92328.1
AF035947 mRNA Translation: AAF97410.1
AF132297 mRNA Translation: AAD28471.2 Different initiation.
AK313850 mRNA Translation: BAG36578.1
AC096920 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW65128.1
CH471055 Genomic DNA Translation: EAW65129.1
BC031590 mRNA Translation: AAH31590.1
BC064354 mRNA Translation: AAH64354.1
CCDSiCCDS2831.1 [Q9NSE2-1]
CCDS46834.1 [Q9NSE2-3]
PIRiJC7512
RefSeqiNP_037456.5, NM_013324.5 [Q9NSE2-3]
NP_659508.1, NM_145071.2 [Q9NSE2-1]
XP_011531631.1, XM_011533329.2 [Q9NSE2-2]
UniGeneiHs.655334

Genome annotation databases

EnsembliENST00000348721; ENSP00000294173; ENSG00000114737 [Q9NSE2-1]
ENST00000443053; ENSP00000409346; ENSG00000114737 [Q9NSE2-3]
GeneIDi1154
KEGGihsa:1154
UCSCiuc003dax.4 human [Q9NSE2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCISH_HUMAN
AccessioniPrimary (citable) accession number: Q9NSE2
Secondary accession number(s): B2R9N1
, G5E9R1, Q9NS38, Q9Y5R1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 1, 2000
Last modified: February 28, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome