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O14508

- SOCS2_HUMAN

UniProt

O14508 - SOCS2_HUMAN

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Protein

Suppressor of cytokine signaling 2

Gene
SOCS2, CIS2, SSI2, STATI2
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Pathwayi

GO - Molecular functioni

  1. growth hormone receptor binding Source: UniProtKB
  2. insulin-like growth factor receptor binding Source: UniProtKB
  3. JAK pathway signal transduction adaptor activity Source: ProtInc
  4. protein binding Source: IntAct
  5. SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  1. aging Source: Ensembl
  2. cellular response to hormone stimulus Source: BHF-UCL
  3. growth hormone receptor signaling pathway Source: BHF-UCL
  4. JAK-STAT cascade Source: ProtInc
  5. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  6. negative regulation of apoptotic process Source: ProtInc
  7. negative regulation of JAK-STAT cascade Source: InterPro
  8. positive regulation of signal transduction Source: GOC
  9. protein ubiquitination Source: UniProtKB-UniPathway
  10. regulation of cell growth Source: UniProtKB
  11. regulation of signal transduction Source: UniProtKB
  12. 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: Chromosome 12

Organism-specific databases

HGNCiHGNC:19382. SOCS2.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA128394542.

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

ArrayExpressiO14508.
BgeeiO14508.
CleanExiHS_SOCS2.
GenevestigatoriO14508.

Organism-specific databases

HPAiCAB010356.

Interactioni

Subunit structurei

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

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 – 4513
Helixi55 – 628
Beta strandi70 – 745
Beta strandi76 – 794
Beta strandi81 – 888
Beta strandi91 – 10010
Beta strandi103 – 1064
Turni108 – 1125
Helixi113 – 1153
Beta strandi119 – 1213
Helixi122 – 13211
Helixi163 – 17412
Helixi178 – 1803
Beta strandi181 – 1833
Helixi185 – 1928

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiO14508.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 156109SH2Add
BLAST
Domaini151 – 19747SOCS boxAdd
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.
Contains 1 SOCS box domain.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG320153.
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

MTLRCLEPSG NGGEGTRSQW GTAGSAEEPS PQAARLAKAL RELGQTGWYW    50
GSMTVNEAKE KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ 100
DGKFRLDSII CVKSKLKQFD SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL 150
YLTKPLYTSA PSLQHLCRLT INKCTGAIWG LPLPTRLKDY LEEYKFQV 198
Length:198
Mass (Da):22,172
Last modified:January 1, 1998 - v1
Checksum:iDAFC4AD97F8182BF
GO

Natural variant

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21T → N in AAC98896. 1 Publication
Sequence conflicti5 – 51C → R in BAA22536. 1 Publication
Sequence conflicti31 – 399PQAARLAKA → RRRRVWRR in AAC98896. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS9047.1.
PIRi JC5626.
JC5760.
RefSeqi 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.
UniGenei Hs.485572.
Hs.594327.
Hs.736572.
Hs.737206.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2C9W X-ray 1.90 A 32-198 [» ]
4JGH X-ray 3.00 A 32-198 [» ]
ProteinModelPortali O14508.
SMRi O14508. Positions 28-198.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114362. 22 interactions.
DIPi DIP-29569N.
IntActi O14508. 10 interactions.
MINTi MINT-1459522.
STRINGi 9606.ENSP00000339428.

Proteomic databases

MaxQBi O14508.
PaxDbi O14508.
PRIDEi O14508.

Protocols and materials databases

DNASUi 8835.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000340600 ; ENSP00000339428 ; ENSG00000120833 .
ENST00000536696 ; ENSP00000442898 ; ENSG00000120833 .
ENST00000549122 ; ENSP00000447161 ; ENSG00000120833 .
ENST00000549206 ; ENSP00000448815 ; ENSG00000120833 .
ENST00000551556 ; ENSP00000449227 ; ENSG00000120833 .
GeneIDi 8835.
KEGGi hsa:8835.
UCSCi uc001tcw.2. human.

Organism-specific databases

CTDi 8835.
GeneCardsi GC12P093963.
HGNCi HGNC:19382. SOCS2.
HPAi CAB010356.
MIMi 605117. gene.
neXtProti NX_O14508.
PharmGKBi PA128394542.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG320153.
HOGENOMi HOG000236320.
HOVERGENi HBG002457.
InParanoidi O14508.
KOi K04695.
OMAi WELPLPT.
OrthoDBi EOG71RXKX.
PhylomeDBi O14508.
TreeFami TF321368.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_111133. Growth hormone receptor signaling.
SignaLinki O14508.

Miscellaneous databases

ChiTaRSi SOCS2. human.
EvolutionaryTracei O14508.
GeneWikii SOCS2.
GenomeRNAii 8835.
NextBioi 33160.
PROi O14508.
SOURCEi Search...

Gene expression databases

ArrayExpressi O14508.
Bgeei O14508.
CleanExi HS_SOCS2.
Genevestigatori O14508.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR000980. SH2.
IPR028413. SOCS.
IPR028410. SOCS2.
IPR001496. SOCS_C.
[Graphical view ]
PANTHERi PTHR10385. PTHR10385. 1 hit.
PTHR10385:SF27. PTHR10385:SF27. 1 hit.
Pfami PF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
SMARTi SM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 1 hit.
PROSITEi PS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 131 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

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