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Q9NSE2 (CISH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length258 AA.
Sequence statusComplete.
Protein existenceEvidence 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].

Note=Genetic variations in CISH are associated with susceptibility to bacterial invasion of the blood and define the bacteremia susceptibility locus 2 (BACTS2) [MIM:614383].

Sequence similarities

Contains 1 SH2 domain.

Contains 1 SOCS box domain.

Sequence caution

The sequence AAD28471.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ERBB2P046264EBI-617866,EBI-641062

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 → MYLEHTSHCPHHDDDTAMDTPLPR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 258258Cytokine-inducible SH2-containing protein
PRO_0000181231

Regions

Domain82 – 16382SH2
Domain209 – 25749SOCS box

Natural variations

Alternative sequence1 – 77MVLCVQG → MGPPLTAHPLPSR in isoform 1B.
VSP_006194
Alternative sequence1 – 77MVLCVQG → MYLEHTSHCPHHDDDTAMDT PLPR in isoform 1C.
VSP_006195

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 0BA97804E3B0F608

FASTA25828,663
        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 

« Hide

Isoform 1B [UniParc].

Checksum: 0C1C5791EAFE56DC
Show »

FASTA26429,288
Isoform 1C [UniParc].

Checksum: 6F9A0020F2D27A19
Show »

FASTA27530,734

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[6]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]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. expand/collapse author list , 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].
[8]"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] (ISOFORM 1).
Tissue: Colon and Skin.
[9]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPOR, UBIQUITINATION.
[10]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM, INVOLVEMENT IN SUSCEPTIBILITY TO TUBERCULOSIS; MALARIA AND BACTS2.
+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. 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.
CCDSCCDS2831.1. [Q9NSE2-1]
CCDS46834.1. [Q9NSE2-3]
PIRJC7512.
RefSeqNP_037456.5. NM_013324.5. [Q9NSE2-3]
NP_659508.1. NM_145071.2. [Q9NSE2-1]
XP_005264903.1. XM_005264846.2. [Q9NSE2-3]
UniGeneHs.655334.

3D structure databases

ProteinModelPortalQ9NSE2.
SMRQ9NSE2. Positions 61-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107574. 21 interactions.
IntActQ9NSE2. 9 interactions.
MINTMINT-1191268.
STRING9606.ENSP00000409346.

PTM databases

PhosphoSiteQ9NSE2.

Polymorphism databases

DMDM13124022.

Proteomic databases

MaxQBQ9NSE2.
PaxDbQ9NSE2.
PRIDEQ9NSE2.

Protocols and materials databases

DNASU1154.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000348721; ENSP00000294173; ENSG00000114737. [Q9NSE2-1]
ENST00000443053; ENSP00000409346; ENSG00000114737. [Q9NSE2-3]
GeneID1154.
KEGGhsa:1154.
UCSCuc003dax.3. human. [Q9NSE2-1]
uc010hlq.3. human.

Organism-specific databases

CTD1154.
GeneCardsGC03M050618.
HGNCHGNC:1984. CISH.
HPACAB034039.
HPA040812.
MIM602441. gene.
607948. phenotype.
611162. phenotype.
614383. phenotype.
neXtProtNX_Q9NSE2.
PharmGKBPA26521.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301272.
HOGENOMHOG000236320.
HOVERGENHBG002457.
InParanoidQ9NSE2.
KOK04701.
OMAEYADSKF.
OrthoDBEOG71RXKX.
PhylomeDBQ9NSE2.
TreeFamTF321368.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ9NSE2.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9NSE2.
BgeeQ9NSE2.
CleanExHS_CISH.
GenevestigatorQ9NSE2.

Family and domain databases

Gene3D3.30.505.10. 2 hits.
InterProIPR028425. CIS.
IPR000980. SH2.
IPR028413. SOCS.
IPR001496. SOCS_C.
[Graphical view]
PANTHERPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF7. PTHR10385:SF7. 1 hit.
PfamPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCISH.
GenomeRNAi1154.
NextBio4792.
PROQ9NSE2.
SOURCESearch...

Entry information

Entry nameCISH_HUMAN
AccessionPrimary (citable) accession number: Q9NSE2
Secondary accession number(s): B2R9N1 expand/collapse secondary AC list , G5E9R1, Q9NS38, Q9Y5R1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM