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Protein

Cytokine-inducible SH2-containing protein

Gene

Cish

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 similarity1 Publication

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

Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-982772. Growth hormone receptor signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytokine-inducible SH2-containing protein
Short name:
CIS
Alternative name(s):
CIS-1
Suppressor of cytokine signaling
Short name:
SOCS
Gene namesi
Name:Cish
Synonyms:Cis
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:103159. Cish.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • plasma membrane Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 257257Cytokine-inducible SH2-containing proteinPRO_0000181232Add
BLAST

Proteomic databases

EPDiQ62225.
PaxDbiQ62225.
PRIDEiQ62225.

PTM databases

iPTMnetiQ62225.
PhosphoSiteiQ62225.

Expressioni

Tissue specificityi

Expressed in kidney, lung and liver. Detected to a lower extent in stomach and heart.

Developmental stagei

In the developing brain, expressed at low levels from E10 stages to young adulthood (P25) with peak levels from E14 to P8.

Inductioni

By a subset of cytokines including interleukins 2, 3 and 6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO).

Gene expression databases

BgeeiQ62225.
CleanExiMM_CISH.
ExpressionAtlasiQ62225. baseline and differential.
GenevisibleiQ62225. MM.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
EPORP192354EBI-617489,EBI-617321From a different organism.

Protein-protein interaction databases

BioGridi198717. 11 interactions.
DIPiDIP-907N.
IntActiQ62225. 3 interactions.
MINTiMINT-2577033.
STRINGi10090.ENSMUSP00000082183.

Structurei

3D structure databases

ProteinModelPortaliQ62225.
SMRiQ62225. Positions 61-257.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 16382SH2PROSITE-ProRule annotationAdd
BLAST
Domaini208 – 25649SOCS boxPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SOCS box domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiQ62225.
KOiK04701.
OMAiQHYVTSC.
OrthoDBiEOG71RXKX.
PhylomeDBiQ62225.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
InterProiIPR028425. CIS.
IPR000980. SH2.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF65. PTHR24369:SF65. 2 hits.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q62225-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLCVQGSCP LLAVEQIGRR PLWAQSLELP GPAMQPLPTG AFPEEVTEET
60 70 80 90 100
PVQAENEPKV LDPEGDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP
110 120 130 140 150
EGTFLVRDST HPSYLFTLSV KTTRGPTNVR IEYADSSFRL DSNCLSRPRI
160 170 180 190 200
LAFPDVVSLV QHYVASCAAD TRSDSPDPAP TPALPMSKQD APSDSVLPIP
210 220 230 240 250
VATAVHLKLV QPFVRRSSAR SLQHLCRLVI NRLVADVDCL PLPRRMADYL

RQYPFQL
Length:257
Mass (Da):28,537
Last modified:November 1, 1996 - v1
Checksum:iF14FD8B370B9A005
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31943 mRNA. Translation: BAA06713.1.
AK077338 mRNA. Translation: BAC36758.1.
AK170554 mRNA. Translation: BAE41877.1.
AK170877 mRNA. Translation: BAE42087.1.
AK171431 mRNA. Translation: BAE42448.1.
BC003783 mRNA. Translation: AAH03783.1.
BC022178 mRNA. Translation: AAH22178.1.
CCDSiCCDS40761.1.
PIRiS55551.
RefSeqiNP_001304283.1. NM_001317354.1.
NP_034025.1. NM_009895.4.
UniGeneiMm.4592.

Genome annotation databases

EnsembliENSMUST00000085102; ENSMUSP00000082183; ENSMUSG00000032578.
GeneIDi12700.
KEGGimmu:12700.
UCSCiuc009rlc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31943 mRNA. Translation: BAA06713.1.
AK077338 mRNA. Translation: BAC36758.1.
AK170554 mRNA. Translation: BAE41877.1.
AK170877 mRNA. Translation: BAE42087.1.
AK171431 mRNA. Translation: BAE42448.1.
BC003783 mRNA. Translation: AAH03783.1.
BC022178 mRNA. Translation: AAH22178.1.
CCDSiCCDS40761.1.
PIRiS55551.
RefSeqiNP_001304283.1. NM_001317354.1.
NP_034025.1. NM_009895.4.
UniGeneiMm.4592.

3D structure databases

ProteinModelPortaliQ62225.
SMRiQ62225. Positions 61-257.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198717. 11 interactions.
DIPiDIP-907N.
IntActiQ62225. 3 interactions.
MINTiMINT-2577033.
STRINGi10090.ENSMUSP00000082183.

PTM databases

iPTMnetiQ62225.
PhosphoSiteiQ62225.

Proteomic databases

EPDiQ62225.
PaxDbiQ62225.
PRIDEiQ62225.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000085102; ENSMUSP00000082183; ENSMUSG00000032578.
GeneIDi12700.
KEGGimmu:12700.
UCSCiuc009rlc.1. mouse.

Organism-specific databases

CTDi1154.
MGIiMGI:103159. Cish.

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiQ62225.
KOiK04701.
OMAiQHYVTSC.
OrthoDBiEOG71RXKX.
PhylomeDBiQ62225.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-982772. Growth hormone receptor signaling.

Miscellaneous databases

ChiTaRSiCish. mouse.
PROiQ62225.
SOURCEiSearch...

Gene expression databases

BgeeiQ62225.
CleanExiMM_CISH.
ExpressionAtlasiQ62225. baseline and differential.
GenevisibleiQ62225. MM.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
InterProiIPR028425. CIS.
IPR000980. SH2.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF65. PTHR24369:SF65. 2 hits.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors."
    Yoshimura A., Ohkubo T., Kiguchi T., Jenkins N.A., Gilbert D.J., Copeland N.G., Hara T., Miyajima A.
    EMBO J. 14:2816-2826(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Pituitary.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Mammary gland and Salivary gland.
  4. "CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation."
    Matsumoto A., Masuhara M., Mitsui K., Yokouchi M., Ohtsubo M., Misawa H., Miyajima A., Yoshimura A.
    Blood 89:3148-3154(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCISH_MOUSE
AccessioniPrimary (citable) accession number: Q62225
Secondary accession number(s): Q3TC70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.