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Protein

Suppressor of cytokine signaling 5

Gene

Socs5

Organism
Mus musculus (Mouse)
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. May be a 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. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T-helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes differentiation into the Th2 phenotype. Can also partially inhibit IL6 and LIF signaling.1 Publication

Pathwayi: 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

  • epidermal growth factor receptor binding Source: MGI
  • kinase inhibitor activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: MGI

GO - Biological processi

  • cell growth Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: MGI
  • JAK-STAT cascade Source: UniProtKB
  • negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • negative regulation of signal transduction Source: UniProtKB
  • negative regulation of T-helper 2 cell differentiation Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of T-helper 1 cell differentiation Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of growth Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of cytokine signaling 5
Short name:
SOCS-5
Alternative name(s):
Cytokine-inducible SH2-containing protein 5
Gene namesi
Name:Socs5
Synonyms:Cish5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:2385459. Socs5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 536536Suppressor of cytokine signaling 5PRO_0000181250Add
BLAST

Post-translational modificationi

Phosphorylated. Phosphorylation is induced by EGF (By similarity).By similarity

Proteomic databases

PaxDbiO54928.
PRIDEiO54928.

PTM databases

PhosphoSiteiO54928.

Expressioni

Tissue specificityi

Widely expressed. Expressed in TH1 but not TH2 cells.1 Publication

Developmental stagei

During embryonic development, expressed from mid-to-late gestation and in yolk sac.

Inductioni

By a subset of cytokines including IL6 and LIF.

Gene expression databases

BgeeiO54928.
CleanExiMM_SOCS5.
GenevisibleiO54928. MM.

Interactioni

Subunit structurei

Interacts with EGFR. Interacts with TCEB1 AND TCEB2; mediates EGFR ubiquitination and degradation (By similarity). Interacts with IL4R; inhibits IL4 signaling.By similarity1 Publication

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: MGI
  • receptor tyrosine kinase binding Source: MGI

Protein-protein interaction databases

BioGridi208004. 9 interactions.
MINTiMINT-1323800.
STRINGi10090.ENSMUSP00000038591.

Structurei

Secondary structure

1
536
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi225 – 2339Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N34NMR-A175-244[»]
ProteinModelPortaliO54928.
SMRiO54928. Positions 175-244, 369-524.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini381 – 47696SH2PROSITE-ProRule annotationAdd
BLAST
Domaini471 – 52050SOCS boxPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5050Required for interaction with IL4RAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000027791.
HOVERGENiHBG054138.
InParanoidiO54928.
KOiK04698.
OMAiQVSGDSH.
OrthoDBiEOG7XH6QR.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR022252. SOCS4/SOCS5_dom.
IPR028420. SOCS5.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF71. PTHR24369:SF71. 2 hits.
PfamiPF00017. SH2. 1 hit.
PF12610. SOCS. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O54928-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKVGKMWNN LKYRCQNLFS HEGGSRNENV EMNPNRCPSV KEKSISLGEA
60 70 80 90 100
APQQESSPLR ENVALQLGLS PSKTFSRRNQ NCAAEIPQVV EISIEKDSDS
110 120 130 140 150
GATPGTRLAR RDSYSRHAPW GGKKKHSCST KTQSSLDTEK KFGRTRSGLQ
160 170 180 190 200
RRERRYGVSS MQDMDSVSSR AVGSRSLRQR LQDTVGLCFP MRTYSKQSKP
210 220 230 240 250
LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV SPHSTFFDTF
260 270 280 290 300
DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG
310 320 330 340 350
PKLAPGMTEI SGDGSAIPQT NCDSEEDSTT LCLQSRRQKQ RQVSGDSHAH
360 370 380 390 400
VSRQGAWKVH TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE
410 420 430 440 450
GTFLLRDSAQ EDYLFSVSFR RYNRSLHARI EQWNHNFSFD AHDPCVFHSS
460 470 480 490 500
TVTGLLEHYK DPSSCMFFEP LLTISLNRTF PFSLQYICRA VICRCTTYDG
510 520 530
IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK
Length:536
Mass (Da):61,086
Last modified:July 27, 2011 - v2
Checksum:iB63AD64BC8CEE254
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti171 – 1711A → T in AAB96648 (PubMed:9419338).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033187 mRNA. Translation: AAB96648.1.
AY902348 Genomic DNA. Translation: AAY21058.1.
CH466537 Genomic DNA. Translation: EDL38623.1.
BC053015 mRNA. Translation: AAH53015.1.
CCDSiCCDS29014.1.
RefSeqiNP_062628.2. NM_019654.2.
XP_006524734.1. XM_006524671.2.
XP_006524735.1. XM_006524672.2.
XP_006524737.1. XM_006524674.2.
XP_006524738.1. XM_006524675.2.
UniGeneiMm.126885.

Genome annotation databases

EnsembliENSMUST00000041369; ENSMUSP00000038591; ENSMUSG00000037104.
GeneIDi56468.
KEGGimmu:56468.
UCSCiuc008dup.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033187 mRNA. Translation: AAB96648.1.
AY902348 Genomic DNA. Translation: AAY21058.1.
CH466537 Genomic DNA. Translation: EDL38623.1.
BC053015 mRNA. Translation: AAH53015.1.
CCDSiCCDS29014.1.
RefSeqiNP_062628.2. NM_019654.2.
XP_006524734.1. XM_006524671.2.
XP_006524735.1. XM_006524672.2.
XP_006524737.1. XM_006524674.2.
XP_006524738.1. XM_006524675.2.
UniGeneiMm.126885.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N34NMR-A175-244[»]
ProteinModelPortaliO54928.
SMRiO54928. Positions 175-244, 369-524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208004. 9 interactions.
MINTiMINT-1323800.
STRINGi10090.ENSMUSP00000038591.

PTM databases

PhosphoSiteiO54928.

Proteomic databases

PaxDbiO54928.
PRIDEiO54928.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041369; ENSMUSP00000038591; ENSMUSG00000037104.
GeneIDi56468.
KEGGimmu:56468.
UCSCiuc008dup.2. mouse.

Organism-specific databases

CTDi9655.
MGIiMGI:2385459. Socs5.

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000027791.
HOVERGENiHBG054138.
InParanoidiO54928.
KOiK04698.
OMAiQVSGDSH.
OrthoDBiEOG7XH6QR.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi312726.
PROiO54928.
SOURCEiSearch...

Gene expression databases

BgeeiO54928.
CleanExiMM_SOCS5.
GenevisibleiO54928. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR022252. SOCS4/SOCS5_dom.
IPR028420. SOCS5.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF71. PTHR24369:SF71. 2 hits.
PfamiPF00017. SH2. 1 hit.
PF12610. SOCS. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Spleen.
  2. "Characterization of quantitative trait loci influencing growth and adiposity using congenic mouse strains."
    Farber C.R., Corva P.M., Medrano J.F.
    Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: CAST/EiJ.
    Tissue: Brain.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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].
    Strain: C57BL/6J.
    Tissue: Brain.
  5. "Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation."
    Seki Y., Hayashi K., Matsumoto A., Seki N., Tsukada J., Ransom J., Naka T., Kishimoto T., Yoshimura A., Kubo M.
    Proc. Natl. Acad. Sci. U.S.A. 99:13003-13008(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INHIBITION OF IL4 SIGNALING, TISSUE SPECIFICITY, INTERACTION WITH IL4RA.

Entry informationi

Entry nameiSOCS5_MOUSE
AccessioniPrimary (citable) accession number: O54928
Secondary accession number(s): Q7TSK1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.