Reviewed, UniProtKB/Swiss-Prot O14508 (SOCS2_HUMAN)

Names and origin

Protein names

Recommended 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

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	198 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. 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 erythropoietin and granulocyte-macrophage colony stimulating factor (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 process	Growth regulation Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	3D-structure
Gene Ontology (GO)
Biological process	JAK-STAT cascade Ref.1 Traceable author statement. Source: ProtInc anti-apoptosis Ref.1 Traceable author statement. Source: ProtInc cellular response to hormone stimulus Inferred from direct assay. Source: UniProtKB growth hormone receptor signaling pathway Inferred from direct assay. Source: UniProtKB 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 cell growth Ref.4 Non-traceable author statement. Source: UniProtKB response to estradiol stimulus Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.4 Non-traceable author statement. Source: UniProtKB
Molecular function	JAK pathway signal transduction adaptor activity Ref.1 Traceable author statement. Source: ProtInc SH3/SH2 adaptor activity Ref.2 Traceable author statement. Source: ProtInc growth hormone receptor binding Non-traceable author statement. Source: UniProtKB insulin-like growth factor receptor binding Ref.4 Inferred from physical interaction. Source: UniProtKB prolactin receptor binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPOR	P19235	3	EBI-617737,EBI-617321

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 198

198

Suppressor of cytokine signaling 2

PRO_0000181238

Regions

Domain

48 – 156

109

SH2

Domain

151 – 197

47

SOCS box

Natural variations

Natural variant

52

1

S → N: dbSNP rs3741676.

VAR_052032

Experimental info

Sequence conflict

2

1

T → N in AAC98896. Ref.3

Sequence conflict

5

1

C → R in BAA22536. Ref.2

Sequence conflict

31 – 39

9

PQAARLAKA → RRRRVWRR in AAC98896. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

198

Helix Strand Turn

Details...

Helix

33 – 45

13

Helix

55 – 62

8

Beta strand

70 – 74

5

Beta strand

81 – 88

8

Beta strand

91 – 100

10

Beta strand

103 – 106

4

Turn

108 – 112

5

Helix

113 – 115

3

Helix

122 – 132

11

Helix

163 – 174

12

Helix

178 – 180

3

Beta strand

181 – 183

3

Helix

185 – 192

8

Sequences

	Sequence		Length	Mass (Da)
	O14508-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: DAFC4AD97F8182BF	FASTA	198	22,172
	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

References

	« Hide 'large scale' referencesShow '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: 9266833] [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: 9344848] [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: 9727029] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[5]	"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]. Tissue: Brain.
[6]	"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: 10512686] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 173-198.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"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: 16675548] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH THE ELONGIN BC COMPLEX.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB004903 mRNA. Translation: BAA22429.1.
AB006966 mRNA. Translation: BAA22536.1.
AF020590 mRNA. Translation: AAC98896.1.
AF037989 mRNA. Translation: AAC34745.1.
BC010399 mRNA. Translation: AAH10399.1.
AF132441 Genomic DNA. Translation: AAD27710.1.

IPI

IPI00033944.

PIR

JC5626.
JC5760.

RefSeq

NP_003868.1.

UniGene

Hs.485572

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C9W	X-ray	1.90	A	32-198	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O14508. 1 interaction.

Proteomic databases

PRIDE

O14508.

Genome annotation databases

Ensembl

ENSG00000120833. Homo sapiens. [Contig view]

GeneID

8835.

KEGG

hsa:8835.

Organism-specific databases

GeneCards

GC12P092466.

H-InvDB

HIX0010881.

HGNC

HGNC:19382. SOCS2.

HPA

CAB010356.

MIM

605117. gene.

PharmGKB

PA128394542.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O14508.

HOVERGEN

O14508.

OMA

O14508. EGTRSQW.

Enzyme and pathway databases

Pathway_Interaction_DB

il2_1pathway. IL2-mediated signaling events.

Gene expression databases

ArrayExpress

O14508.

Bgee

O14508.

CleanEx

HS_SOCS2.

GermOnline

ENSG00000120833. Homo sapiens.

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.

ProDom

PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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

33160.

SOURCE

Search...

Entry information

Entry name

SOCS2_HUMAN

Accession

Primary (citable) accession number: O14508
Secondary accession number(s): O14542, O95102, Q9UKS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	January 1, 1998
Last modified:	June 16, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)