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O14508 (SOCS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Suppressor of cytokine signaling 2

Short name=SOCS-2
Alternative name(s):
Cytokine-inducible SH2 protein 2
Short name=CIS-2
STAT-induced STAT inhibitor 2
Short name=SSI-2
Gene names
Name:SOCS2
Synonyms:CIS2, SSI2, STATI2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length198 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. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable 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.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with IGF1 receptor, prolactin receptor and growth hormone (GH) receptor. Associates with the Elongin BC complex.

Tissue specificity

High expression in heart, placenta, lung, kidney and prostate.

Induction

By a subset of cytokines, including EPO/erythropoietin and CSF2/GM-CSF.

Domain

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

Sequence similarities

Contains 1 SH2 domain.

Contains 1 SOCS box domain.

Ontologies

Keywords
   Biological processGrowth regulation
Ubl conjugation pathway
   Coding sequence diversityPolymorphism
   DomainSH2 domain
   Molecular functionSignal transduction inhibitor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJAK-STAT cascade

Traceable author statement Ref.1. Source: ProtInc

JAK-STAT cascade involved in growth hormone signaling pathway

Traceable author statement. Source: Reactome

aging

Inferred from electronic annotation. Source: Ensembl

cellular response to hormone stimulus

Inferred from direct assay PubMed 12552091. Source: BHF-UCL

growth hormone receptor signaling pathway

Inferred from direct assay PubMed 12552091. Source: BHF-UCL

negative regulation of apoptotic process

Traceable author statement Ref.1. Source: ProtInc

negative regulation of signal transduction

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of signal transduction

Traceable author statement Ref.2. Source: GOC

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of JAK-STAT cascade

Traceable author statement. Source: GOC

regulation of cell growth

Non-traceable author statement Ref.4. Source: UniProtKB

regulation of signal transduction

Non-traceable author statement Ref.4. Source: UniProtKB

response to estradiol

Inferred from direct assay PubMed 12552091. Source: BHF-UCL

   Cellular_componentcytoplasm

Non-traceable author statement Ref.4. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionJAK pathway signal transduction adaptor activity

Traceable author statement Ref.1. Source: ProtInc

SH3/SH2 adaptor activity

Traceable author statement Ref.2. Source: ProtInc

growth hormone receptor binding

Non-traceable author statement PubMed 12135564. Source: UniProtKB

insulin-like growth factor receptor binding

Inferred from physical interaction Ref.4. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11781573PubMed 16643902PubMed 19159283PubMed 24728074. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 198198Suppressor of cytokine signaling 2
PRO_0000181238

Regions

Domain48 – 156109SH2
Domain151 – 19747SOCS box

Natural variations

Natural variant521S → N.
Corresponds to variant rs3741676 [ dbSNP | Ensembl ].
VAR_052032

Experimental info

Sequence conflict21T → N in AAC98896. Ref.3
Sequence conflict51C → R in BAA22536. Ref.2
Sequence conflict31 – 399PQAARLAKA → RRRRVWRR in AAC98896. Ref.3

Secondary structure

............................ 198
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14508 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: DAFC4AD97F8182BF

FASTA19822,172
        10         20         30         40         50         60 
MTLRCLEPSG NGGEGTRSQW GTAGSAEEPS PQAARLAKAL RELGQTGWYW GSMTVNEAKE 

        70         80         90        100        110        120 
KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ DGKFRLDSII CVKSKLKQFD 

       130        140        150        160        170        180 
SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL YLTKPLYTSA PSLQHLCRLT INKCTGAIWG 

       190 
LPLPTRLKDY LEEYKFQV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3."
Minamoto S., Ikegame K., Ueno K., Narazaki M., Naka T., Yamamoto H., Matsumoto T., Saito H., Hosoe S., Kishimoto T.
Biochem. Biophys. Res. Commun. 237:79-83(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: T-cell lymphoma.
[2]"Cloning and characterization of novel CIS family genes."
Masuhara M., Sakamoto H., Matsumoto A., Suzuki R., Yasukawa H., Mitsui K., Wakioka T., Tanimura S., Sasaki A., Misawa H., Yokouchi M., Ohtsubo M., Yoshimura A.
Biochem. Biophys. Res. Commun. 239:439-446(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of a novel human gene coding human suppressor of cytokine signaling-2 (HsSOCS-2)."
Tu Q., Yu L., Zhang Q.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor."
Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.
J. Biol. Chem. 273:24095-24101(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[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].
Tissue: Brain and Lung.
[6]Mural R.J., Istrail S., Sutton 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].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[8]"Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively."
Yandava C.N., Pillari A., Drazen J.M.
Genomics 61:108-111(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 173-198.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase."
Bullock A.N., Debreczeni J.E., Edwards A.M., Sundstrom M., Knapp S.
Proc. Natl. Acad. Sci. U.S.A. 103:7637-7642(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH THE ELONGIN BC COMPLEX.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB004903 mRNA. Translation: BAA22429.1.
AB006966 mRNA. Translation: BAA22536.1.
AF020590 mRNA. Translation: AAC98896.1.
AF037989 mRNA. Translation: AAC34745.1.
AK290546 mRNA. Translation: BAF83235.1.
AK313165 mRNA. Translation: BAG35983.1.
CH471054 Genomic DNA. Translation: EAW97492.1.
BC010399 mRNA. Translation: AAH10399.1.
AF132441 Genomic DNA. Translation: AAD27710.1.
CCDSCCDS9047.1.
PIRJC5626.
JC5760.
RefSeqNP_001257396.1. NM_001270467.1.
NP_001257397.1. NM_001270468.1.
NP_001257398.1. NM_001270469.1.
NP_001257399.1. NM_001270470.1.
NP_001257400.1. NM_001270471.1.
NP_003868.1. NM_003877.4.
UniGeneHs.485572.
Hs.594327.
Hs.736572.
Hs.737206.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2C9WX-ray1.90A32-198[»]
4JGHX-ray3.00A32-198[»]
ProteinModelPortalO14508.
SMRO14508. Positions 28-198.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114362. 22 interactions.
DIPDIP-29569N.
IntActO14508. 10 interactions.
MINTMINT-1459522.
STRING9606.ENSP00000339428.

Proteomic databases

MaxQBO14508.
PaxDbO14508.
PRIDEO14508.

Protocols and materials databases

DNASU8835.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.
GeneID8835.
KEGGhsa:8835.
UCSCuc001tcw.2. human.

Organism-specific databases

CTD8835.
GeneCardsGC12P093963.
HGNCHGNC:19382. SOCS2.
HPACAB010356.
MIM605117. gene.
neXtProtNX_O14508.
PharmGKBPA128394542.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320153.
HOGENOMHOG000236320.
HOVERGENHBG002457.
InParanoidO14508.
KOK04695.
OMAWELPLPT.
OrthoDBEOG71RXKX.
PhylomeDBO14508.
TreeFamTF321368.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkO14508.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO14508.
BgeeO14508.
CleanExHS_SOCS2.
GenevestigatorO14508.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
IPR028413. SOCS.
IPR028410. SOCS2.
IPR001496. SOCS_C.
[Graphical view]
PANTHERPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF27. PTHR10385:SF27. 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

ChiTaRSSOCS2. human.
EvolutionaryTraceO14508.
GeneWikiSOCS2.
GenomeRNAi8835.
NextBio33160.
PROO14508.
SOURCESearch...

Entry information

Entry nameSOCS2_HUMAN
AccessionPrimary (citable) accession number: O14508
Secondary accession number(s): A8K3D1 expand/collapse secondary AC list , O14542, O95102, Q9UKS5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 130 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM