Reviewed, UniProtKB/Swiss-Prot Q62225 (CISH_MOUSE)

Names and origin

Protein names

Recommended name:
    Cytokine-inducible SH2-containing protein
      Short name=CIS
Alternative name(s):
    CIS-1
    Suppressor of cytokine signaling
      Short name=SOCS

Gene names

Name:	Cish
Synonyms:	Cis

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Stably associated with the tyrosine-phosphorylated IL3 receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR).
Tissue specificity	Expressed in kidney, lung and liver. Detected to a lower extent in stomach and heart.
Developmental stage	In the developing brain, expressed at low levels from E10 stages to young adulthood (P25) with peak levels from E14 to P8.
Induction	By a subset of cytokines including interleukins 2, 3 and 6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO).
Sequence similarities	Contains 1 SH2 domain. Contains 1 SOCS box domain.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from direct assay. Source: MGI intracellular signaling cascade Inferred from electronic annotation. Source: InterPro modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	plasma membrane Inferred from direct assay. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPOR	P19235	3	EBI-617489,EBI-617321	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 257	257	Cytokine-inducible SH2-containing protein		PRO_0000181232
Regions
	Domain	82 – 163	82	SH2
	Domain	208 – 256	49	SOCS box

Sequences

	Sequence		Length	Mass (Da)
	Q62225-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: F14FD8B370B9A005	FASTA	257	28,537
	10 20 30 40 50 60 MVLCVQGSCP LLAVEQIGRR PLWAQSLELP GPAMQPLPTG AFPEEVTEET PVQAENEPKV 70 80 90 100 110 120 LDPEGDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP EGTFLVRDST HPSYLFTLSV 130 140 150 160 170 180 KTTRGPTNVR IEYADSSFRL DSNCLSRPRI LAFPDVVSLV QHYVASCAAD TRSDSPDPAP 190 200 210 220 230 240 TPALPMSKQD APSDSVLPIP VATAVHLKLV QPFVRRSSAR SLQHLCRLVI NRLVADVDCL 250 PLPRRMADYL RQYPFQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 7796808] [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: 16141072] [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: 15489334] [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: 9129017] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00123312.
PIR	S55551.
RefSeq	NP_034025.1.
UniGene	Mm.4592
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:907N.
IntAct	Q62225. 1 interaction.
STRING	Q62225.
Proteomic databases
PRIDE	Q62225.
Genome annotation databases
Ensembl	ENSMUST00000085102; ENSMUSP00000082183; ENSMUSG00000032578; Mus musculus. [Genome view]
GeneID	12700.
KEGG	mmu:12700.
UCSC	uc009rlc.1. mouse.
Organism-specific databases
CTD	12700.
MGI	MGI:103159. Cish.
Phylogenomic databases
HOGENOM	Q62225.
HOVERGEN	Q62225.
OMA	PRILAFP
OrthoDB	EOG9T7BNJ
Gene expression databases
ArrayExpress	Q62225.
Bgee	Q62225.
CleanEx	MM_CISH.
Genevestigator	Q62225.
GermOnline	ENSMUSG00000032578. Mus musculus.
Family and domain databases
InterPro	IPR000980. SH2. IPR001496. SOCS_C. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF07525. SOCS_box. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00252. SH2. 1 hit. SM00253. SOCS. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. PS50225. SOCS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	281954.
SOURCE	Search...

Entry information

Entry name

CISH_MOUSE

Accession

Primary (citable) accession number: Q62225
Secondary accession number(s): Q3TC70

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1996
Last modified:	November 24, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)