Q9NSE2 (CISH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CISH
Synonyms:	G18

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	258 AA.
Sequence status	Complete.
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 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. Ref.4
Induction	By a subset of cytokines including EPO/erythropoietin.
Post-translational modification	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).
Polymorphism	Note=CISH polymorphisms are involved in susceptibilty to malaria [MIM:611162]. Note=Genetic variations in CISH are involved in susceptibilty to tuberculosis [MIM:607948].
Sequence similarities	Contains 1 SH2 domain. Contains 1 SOCS box domain.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Non-traceable author statement Ref.2. Source: UniProtKB negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell growth Non-traceable author statement Ref.1. Source: UniProtKB
Cellular component	intracellular Non-traceable author statement Ref.2. Source: GOC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NSE2-1)

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.

Isoform 1B (identifier: Q9NSE2-2)

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

Isoform 1C (identifier: Q9NSE2-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 258	258	Cytokine-inducible SH2-containing protein		PRO_0000181231
Regions
	Domain	82 – 163	82	SH2
	Domain	209 – 257	49	SOCS box
Natural variations
	Alternative sequence	1 – 7	7	MVLCVQG → MGPPLTAHPLPSR in isoform 1B.		VSP_006194
	Alternative sequence	1 – 7	7	MVLCVQG → MDTPLPR in isoform 1C.		VSP_006195

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 0BA97804E3B0F608	FASTA	258	28,663
	10 20 30 40 50 60 MVLCVQGPRP LLAVERTGQR PLWAPSLELP KPVMQPLPAG AFLEEVAEGT PAQTESEPKV 70 80 90 100 110 120 LDPEEDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP EGTFLVRDST HPSYLFTLSV 130 140 150 160 170 180 KTTRGPTNVR IEYADSSFRL DSNCLSRPRI LAFPDVVSLV QHYVASCTAD TRSDSPDPAP 190 200 210 220 230 240 TPALPMPKED APSDPALPAP PPATAVHLKL VQPFVRRSSA RSLQHLCRLV INRLVADVDC 250 LPLPRRMADY LRQYPFQL
	Isoform 1B [UniParc]. Checksum: 0C1C5791EAFE56DC	FASTA	264	29,288
	10 20 30 40 50 60 MGPPLTAHPL PSRPRPLLAV ERTGQRPLWA PSLELPKPVM QPLPAGAFLE EVAEGTPAQT 70 80 90 100 110 120 ESEPKVLDPE EDLLCIAKTF SYLRESGWYW GSITASEARQ HLQKMPEGTF LVRDSTHPSY 130 140 150 160 170 180 LFTLSVKTTR GPTNVRIEYA DSSFRLDSNC LSRPRILAFP DVVSLVQHYV ASCTADTRSD 190 200 210 220 230 240 SPDPAPTPAL PMPKEDAPSD PALPAPPPAT AVHLKLVQPF VRRSSARSLQ HLCRLVINRL 250 260 VADVDCLPLP RRMADYLRQY PFQL
	Isoform 1C [UniParc]. Checksum: 00B4844614490098	FASTA	258	28,743
	10 20 30 40 50 60 MDTPLPRPRP LLAVERTGQR PLWAPSLELP KPVMQPLPAG AFLEEVAEGT PAQTESEPKV 70 80 90 100 110 120 LDPEEDLLCI AKTFSYLRES GWYWGSITAS EARQHLQKMP EGTFLVRDST HPSYLFTLSV 130 140 150 160 170 180 KTTRGPTNVR IEYADSSFRL DSNCLSRPRI LAFPDVVSLV QHYVASCTAD TRSDSPDPAP 190 200 210 220 230 240 TPALPMPKED APSDPALPAP PPATAVHLKL VQPFVRRSSA RSLQHLCRLV INRLVADVDC 250 LPLPRRMADY LRQYPFQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of CISH, chromosome assignment to 3p21.3, and analysis of expression in fetal and adult tissues." Uchida K., Yoshimura A., Inazawa J., Yanagisawa K., Osada H., Masuda A., Saito T., Takahashi T., Miyajima A., Takahashi K. Cytogenet. Cell Genet. 78:209-212(1997) [PubMed: 9465889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal lung.
[2]	"Cloning and characterization of CIS 1b (cytokine inducible SH2-containing protein 1b), an alternative splicing form of CIS 1 gene." Jiang C., Yu L., Zhao Y., Zhang M., Liu Q., Mao N., Geng Z., Zhao S. DNA Seq. 11:149-154(2000) [PubMed: 10902923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1B). Tissue: Placenta.
[3]	"The human G18 is an ortholog of the rodent gene CIS-2 and is located in 3p21.3 and homozygously deleted in lung cancer." Wei M.-H., Minna J.D., Lerman M.I. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1C).
[4]	"cDNA representational difference analysis of human neutrophils stimulated by GM-CSF." Yousefi S., Cooper P.R., Mueck B., Potter S.L., Jarai G. Biochem. Biophys. Res. Commun. 277:401-409(2000) [PubMed: 11032736] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Colon and Skin.
[8]	"Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated CIS protein." Verdier F., Chretien S., Muller O., Varlet P., Yoshimura A., Gisselbrecht S., Lacombe C., Mayeux P. J. Biol. Chem. 273:28185-28190(1998) [PubMed: 9774439] [Abstract] Cited for: INTERACTION WITH EPOR, UBIQUITINATION.
[9]	"CISH and susceptibility to infectious diseases." Khor C.C., Vannberg F.O., Chapman S.J., Guo H., Wong S.H., Walley A.J., Vukcevic D., Rautanen A., Mills T.C., Chang K.C., Kam K.M., Crampin A.C., Ngwira B., Leung C.C., Tam C.M., Chan C.Y., Sung J.J., Yew W.W. , Toh K.Y., Tay S.K., Kwiatkowski D., Lienhardt C., Hien T.T., Day N.P., Peshu N., Marsh K., Maitland K., Scott J.A., Williams T.N., Berkley J.A., Floyd S., Tang N.L., Fine P.E., Goh D.L., Hill A.V. N. Engl. J. Med. 362:2092-2101(2010) [PubMed: 20484391] [Abstract] Cited for: POLYMORPHISM, INVOLVEMENT IN SUSCEPTIBILITY TO TUBERCULOSIS AND MALARIA.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D83532 mRNA. Translation: BAA92328.1. AF035947 mRNA. Translation: AAF97410.1. AF132297 mRNA. Translation: AAD28471.2. AK313850 mRNA. Translation: BAG36578.1. CH471055 Genomic DNA. Translation: EAW65128.1. BC031590 mRNA. Translation: AAH31590.1. BC064354 mRNA. Translation: AAH64354.1.
IPI	IPI00017281. IPI00221337. IPI00412214.
PIR	JC7512.
RefSeq	NP_037456.5. NM_013324.5. NP_659508.1. NM_145071.2.
UniGene	Hs.655334.
3D structure databases
ProteinModelPortal	Q9NSE2.
SMR	Q9NSE2. Positions 69-258.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NSE2. 5 interactions.
MINT	MINT-1191268.
STRING	Q9NSE2.
PTM databases
PhosphoSite	Q9NSE2.
Polymorphism databases
DMDM	13124022.
Proteomic databases
PRIDE	Q9NSE2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000348721; ENSP00000294173; ENSG00000114737.
GeneID	1154.
KEGG	hsa:1154.
UCSC	uc003dax.1. human. uc010hlq.1. human.
Organism-specific databases
CTD	1154.
GeneCards	GC03M050618.
HGNC	HGNC:1984. CISH.
HPA	CAB034039.
MIM	602441. gene. 607948. phenotype. 611162. phenotype.
neXtProt	NX_Q9NSE2.
PharmGKB	PA26521.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00550000074283.
HOVERGEN	HBG002457.
InParanoid	Q9NSE2.
Enzyme and pathway databases
Pathway_Interaction_DB	il2_1pathway. IL2-mediated signaling events.
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NSE2.
Bgee	Q9NSE2.
CleanEx	HS_CISH.
Genevestigator	Q9NSE2.
GermOnline	ENSG00000114737. Homo sapiens.
Family and domain databases
InterPro	IPR000980. SH2. IPR001496. SOCS_C. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
KO	K04701.
Pfam	PF00017. SH2. 1 hit. PF07525. SOCS_box. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00252. SH2. 1 hit. SM00253. SOCS. 1 hit. SM00969. SOCS_box. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. PS50225. SOCS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	4792.
SOURCE	Search...

Entry information

Entry name

CISH_HUMAN

Accession

Primary (citable) accession number: Q9NSE2
Secondary accession number(s): B2R9N1, Q9NS38, Q9Y5R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	October 1, 2000
Last modified:	December 14, 2011
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.