O14508 (SOCS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	198 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. 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 process	Growth regulation Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade involved in growth hormone signaling pathway Traceable author statement. Source: Reactome aging Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Traceable author statement Ref.1. Source: ProtInc negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of cell growth Non-traceable author statement Ref.4. Source: UniProtKB response to estradiol stimulus Inferred from direct assay PubMed 12552091. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	JAK 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 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.
Corresponds to variant rs3741676 [ dbSNP | Ensembl ].

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 [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] [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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00033944.

PIR

JC5626.
JC5760.

RefSeq

NP_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.

UniGene

Hs.485572.
Hs.594327.
Hs.736572.
Hs.737206.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

O14508.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29569N.

IntAct

O14508. 7 interactions.

MINT

MINT-1459522.

STRING

9606.ENSP00000339428.

Proteomic databases

PaxDb

O14508.

PRIDE

O14508.

Protocols and materials databases

DNASU

8835.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.

GeneID

8835.

KEGG

hsa:8835.

UCSC

uc001tcw.1. human.

Organism-specific databases

CTD

8835.

GeneCards

GC12P093963.

HGNC

HGNC:19382. SOCS2.

HPA

CAB010356.

MIM

605117. gene.

neXtProt

NX_O14508.

PharmGKB

PA128394542.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG320153.

HOGENOM

HOG000236320.

HOVERGEN

HBG002457.

InParanoid

O14508.

KO

K04695.

OMA

WELPLPT.

OrthoDB

EOG48WC31.

PhylomeDB

O14508.

Enzyme and pathway databases

Pathway_Interaction_DB

il2_1pathway. IL2-mediated signaling events.

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

O14508.

Bgee

O14508.

CleanEx

HS_SOCS2.

Genevestigator

O14508.

GermOnline

ENSG00000120833. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
IPR001496. SOCS_C.
[Graphical view]

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

ChiTaRS

SOCS2. human.

EvolutionaryTrace

O14508.

GenomeRNAi

8835.

NextBio

33160.

SOURCE

Search...

Entry information

Entry name

SOCS2_HUMAN

Accession

Primary (citable) accession number: O14508
Secondary accession number(s): A8K3D1 , O14542, O95102, Q9UKS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 118 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.