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Protein

Suppressor of cytokine signaling 2

Gene

SOCS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • growth hormone receptor binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: UniProtKB
  • JAK pathway signal transduction adaptor activity Source: ProtInc
  • protein kinase inhibitor activity Source: GO_Central
  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  • aging Source: Ensembl
  • cellular response to hormone stimulus Source: BHF-UCL
  • cytokine-mediated signaling pathway Source: GO_Central
  • growth hormone receptor signaling pathway Source: BHF-UCL
  • JAK-STAT cascade Source: ProtInc
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of insulin receptor signaling pathway Source: GO_Central
  • negative regulation of JAK-STAT cascade Source: GO_Central
  • negative regulation of protein kinase activity Source: GO_Central
  • positive regulation of signal transduction Source: GOC
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of cell growth Source: UniProtKB
  • regulation of signal transduction Source: UniProtKB
  • response to estradiol Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_111133. Growth hormone receptor signaling.
SignaLinkiO14508.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SOCS2
Synonyms:CIS2, SSI2, STATI2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:19382. SOCS2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA128394542.

Polymorphism and mutation databases

BioMutaiSOCS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 198198Suppressor of cytokine signaling 2PRO_0000181238Add
BLAST

Proteomic databases

MaxQBiO14508.
PaxDbiO14508.
PRIDEiO14508.

Expressioni

Tissue specificityi

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

Inductioni

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

Gene expression databases

BgeeiO14508.
CleanExiHS_SOCS2.
ExpressionAtlasiO14508. baseline and differential.
GenevisibleiO14508. HS.

Organism-specific databases

HPAiCAB010356.

Interactioni

Subunit structurei

Interacts with IGF1 receptor, prolactin receptor and growth hormone (GH) receptor. Associates with the Elongin BC complex.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
EPORP192353EBI-617737,EBI-617321
KITP107214EBI-617737,EBI-1379503
TCEB1Q153692EBI-617737,EBI-301231

Protein-protein interaction databases

BioGridi114362. 22 interactions.
DIPiDIP-29569N.
IntActiO14508. 10 interactions.
MINTiMINT-1459522.
STRINGi9606.ENSP00000339428.

Structurei

Secondary structure

1
198
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi33 – 4513Combined sources
Helixi55 – 628Combined sources
Beta strandi70 – 745Combined sources
Beta strandi76 – 794Combined sources
Beta strandi81 – 888Combined sources
Beta strandi91 – 10010Combined sources
Beta strandi103 – 1064Combined sources
Turni108 – 1125Combined sources
Helixi113 – 1153Combined sources
Beta strandi119 – 1213Combined sources
Helixi122 – 13211Combined sources
Helixi163 – 17412Combined sources
Helixi178 – 1803Combined sources
Beta strandi181 – 1833Combined sources
Helixi185 – 1928Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C9WX-ray1.90A32-198[»]
4JGHX-ray3.00A32-198[»]
ProteinModelPortaliO14508.
SMRiO14508. Positions 28-198.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14508.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 156109SH2PROSITE-ProRule annotationAdd
BLAST
Domaini151 – 19747SOCS boxPROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SOCS box domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG320153.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO14508.
KOiK04695.
OMAiWELPLPT.
OrthoDBiEOG71RXKX.
PhylomeDBiO14508.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR028410. SOCS2.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF27. PTHR10385:SF27. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14508-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLRCLEPSG NGGEGTRSQW GTAGSAEEPS PQAARLAKAL RELGQTGWYW
60 70 80 90 100
GSMTVNEAKE KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ
110 120 130 140 150
DGKFRLDSII CVKSKLKQFD SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL
160 170 180 190
YLTKPLYTSA PSLQHLCRLT INKCTGAIWG LPLPTRLKDY LEEYKFQV
Length:198
Mass (Da):22,172
Last modified:January 1, 1998 - v1
Checksum:iDAFC4AD97F8182BF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21T → N in AAC98896 (Ref. 3) Curated
Sequence conflicti5 – 51C → R in BAA22536 (PubMed:9344848).Curated
Sequence conflicti31 – 399PQAARLAKA → RRRRVWRR in AAC98896 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti52 – 521S → N.
Corresponds to variant rs3741676 [ dbSNP | Ensembl ].
VAR_052032

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9047.1.
PIRiJC5626.
JC5760.
RefSeqiNP_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.
UniGeneiHs.485572.
Hs.594327.
Hs.736572.
Hs.737206.

Genome annotation databases

EnsembliENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.
ENST00000622746; ENSP00000481249; ENSG00000120833.
GeneIDi8835.
KEGGihsa:8835.
UCSCiuc001tcw.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9047.1.
PIRiJC5626.
JC5760.
RefSeqiNP_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.
UniGeneiHs.485572.
Hs.594327.
Hs.736572.
Hs.737206.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C9WX-ray1.90A32-198[»]
4JGHX-ray3.00A32-198[»]
ProteinModelPortaliO14508.
SMRiO14508. Positions 28-198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114362. 22 interactions.
DIPiDIP-29569N.
IntActiO14508. 10 interactions.
MINTiMINT-1459522.
STRINGi9606.ENSP00000339428.

Polymorphism and mutation databases

BioMutaiSOCS2.

Proteomic databases

MaxQBiO14508.
PaxDbiO14508.
PRIDEiO14508.

Protocols and materials databases

DNASUi8835.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.
ENST00000622746; ENSP00000481249; ENSG00000120833.
GeneIDi8835.
KEGGihsa:8835.
UCSCiuc001tcw.2. human.

Organism-specific databases

CTDi8835.
GeneCardsiGC12P093963.
HGNCiHGNC:19382. SOCS2.
HPAiCAB010356.
MIMi605117. gene.
neXtProtiNX_O14508.
PharmGKBiPA128394542.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG320153.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO14508.
KOiK04695.
OMAiWELPLPT.
OrthoDBiEOG71RXKX.
PhylomeDBiO14508.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_111133. Growth hormone receptor signaling.
SignaLinkiO14508.

Miscellaneous databases

ChiTaRSiSOCS2. human.
EvolutionaryTraceiO14508.
GeneWikiiSOCS2.
GenomeRNAii8835.
NextBioi33160.
PROiO14508.
SOURCEiSearch...

Gene expression databases

BgeeiO14508.
CleanExiHS_SOCS2.
ExpressionAtlasiO14508. baseline and differential.
GenevisibleiO14508. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR028410. SOCS2.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF27. PTHR10385:SF27. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. 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.

Entry informationi

Entry nameiSOCS2_HUMAN
AccessioniPrimary (citable) accession number: O14508
Secondary accession number(s): A8K3D1
, O14542, O95102, Q9UKS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: June 24, 2015
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.