SOCS5_MOUSE
ID SOCS5_MOUSE Reviewed; 536 AA.
AC O54928; Q7TSK1;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Suppressor of cytokine signaling 5;
DE Short=SOCS-5;
DE AltName: Full=Cytokine-inducible SH2-containing protein 5;
GN Name=Socs5; Synonyms=Cish5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=9419338; DOI=10.1073/pnas.95.1.114;
RA Hilton D.J., Richardson R.T., Alexander W.S., Viney E.M., Willson T.A.,
RA Sprigg N.S., Starr R., Nicholson S.E., Metcalf D., Nicola N.A.;
RT "Twenty proteins containing a C-terminal SOCS box form five structural
RT classes.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:114-119(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CAST/EiJ; TISSUE=Brain;
RA Farber C.R., Corva P.M., Medrano J.F.;
RT "Characterization of quantitative trait loci influencing growth and
RT adiposity using congenic mouse strains.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION IN INHIBITION OF IL4 SIGNALING, TISSUE SPECIFICITY, AND
RP INTERACTION WITH IL4RA.
RX PubMed=12242343; DOI=10.1073/pnas.202477099;
RA Seki Y., Hayashi K., Matsumoto A., Seki N., Tsukada J., Ransom J., Naka T.,
RA Kishimoto T., Yoshimura A., Kubo M.;
RT "Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively
RT regulates IL-4-dependent STAT6 activation and Th2 differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13003-13008(2002).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. May be a
CC substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-
CC SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates
CC the ubiquitination and subsequent proteasomal degradation of target
CC proteins. Inhibits for instance EGF signaling by mediating the
CC degradation of the EGF receptor/EGFR. Involved in the regulation of T-
CC helper cell differentiation by inhibiting of the IL4 signaling pathway
CC which promotes differentiation into the Th2 phenotype. Can also
CC partially inhibit IL6 and LIF signaling. {ECO:0000269|PubMed:12242343}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with EGFR. Interacts with ELOB and ELOC; mediates
CC EGFR ubiquitination and degradation (By similarity). Interacts with
CC IL4R; inhibits IL4 signaling. {ECO:0000250,
CC ECO:0000269|PubMed:12242343}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in TH1 but not TH2
CC cells. {ECO:0000269|PubMed:12242343}.
CC -!- DEVELOPMENTAL STAGE: During embryonic development, expressed from mid-
CC to-late gestation and in yolk sac.
CC -!- INDUCTION: By a subset of cytokines including IL6 and LIF.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Phosphorylation is induced by EGF (By similarity).
CC {ECO:0000250}.
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DR EMBL; AF033187; AAB96648.1; -; mRNA.
DR EMBL; AY902348; AAY21058.1; -; Genomic_DNA.
DR EMBL; CH466537; EDL38623.1; -; Genomic_DNA.
DR EMBL; BC053015; AAH53015.1; -; mRNA.
DR CCDS; CCDS29014.1; -.
DR RefSeq; NP_062628.2; NM_019654.2.
DR RefSeq; XP_006524734.1; XM_006524671.3.
DR RefSeq; XP_006524735.1; XM_006524672.3.
DR RefSeq; XP_006524737.1; XM_006524674.3.
DR RefSeq; XP_006524738.1; XM_006524675.3.
DR PDB; 2N34; NMR; -; A=175-244.
DR PDBsum; 2N34; -.
DR AlphaFoldDB; O54928; -.
DR BMRB; O54928; -.
DR SMR; O54928; -.
DR BioGRID; 208004; 9.
DR MINT; O54928; -.
DR STRING; 10090.ENSMUSP00000038591; -.
DR iPTMnet; O54928; -.
DR PhosphoSitePlus; O54928; -.
DR SwissPalm; O54928; -.
DR PaxDb; O54928; -.
DR PRIDE; O54928; -.
DR ProteomicsDB; 261547; -.
DR Antibodypedia; 15096; 203 antibodies from 35 providers.
DR DNASU; 56468; -.
DR Ensembl; ENSMUST00000041369; ENSMUSP00000038591; ENSMUSG00000037104.
DR GeneID; 56468; -.
DR KEGG; mmu:56468; -.
DR UCSC; uc008dup.2; mouse.
DR CTD; 9655; -.
DR MGI; MGI:2385459; Socs5.
DR VEuPathDB; HostDB:ENSMUSG00000037104; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000159000; -.
DR HOGENOM; CLU_035609_1_0_1; -.
DR InParanoid; O54928; -.
DR OMA; DSCVTTG; -.
DR OrthoDB; 722019at2759; -.
DR PhylomeDB; O54928; -.
DR TreeFam; TF321368; -.
DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-MMU-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 56468; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Socs5; mouse.
DR PRO; PR:O54928; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O54928; protein.
DR Bgee; ENSMUSG00000037104; Expressed in substantia nigra and 240 other tissues.
DR ExpressionAtlas; O54928; baseline and differential.
DR Genevisible; O54928; MM.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:MGI.
DR GO; GO:0019210; F:kinase inhibitor activity; NAS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IMP:BHF-UCL.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:1904988; P:negative regulation of endothelial cell activation; IC:BHF-UCL.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IMP:BHF-UCL.
DR GO; GO:0009968; P:negative regulation of signal transduction; NAS:UniProtKB.
DR GO; GO:0045629; P:negative regulation of T-helper 2 cell differentiation; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; TAS:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0097699; P:vascular endothelial cell response to fluid shear stress; IMP:BHF-UCL.
DR CDD; cd03739; SOCS_SOCS5; 1.
DR DisProt; DP01774; -.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR022252; SOCS4/SOCS5_dom.
DR InterPro; IPR028420; SOCS5.
DR InterPro; IPR037343; SOCS5_SOCS.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF15; PTHR10155:SF15; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF12610; SOCS; 1.
DR Pfam; PF07525; SOCS_box; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Growth regulation; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..536
FT /note="Suppressor of cytokine signaling 5"
FT /id="PRO_0000181250"
FT DOMAIN 381..476
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 471..520
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..50
FT /note="Required for interaction with IL4R"
FT REGION 22..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..159
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..175
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 171
FT /note="A -> T (in Ref. 1; AAB96648)"
FT /evidence="ECO:0000305"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:2N34"
SQ SEQUENCE 536 AA; 61086 MW; B63AD64BC8CEE254 CRC64;
MDKVGKMWNN LKYRCQNLFS HEGGSRNENV EMNPNRCPSV KEKSISLGEA APQQESSPLR
ENVALQLGLS PSKTFSRRNQ NCAAEIPQVV EISIEKDSDS GATPGTRLAR RDSYSRHAPW
GGKKKHSCST KTQSSLDTEK KFGRTRSGLQ RRERRYGVSS MQDMDSVSSR AVGSRSLRQR
LQDTVGLCFP MRTYSKQSKP LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV
SPHSTFFDTF DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG
PKLAPGMTEI SGDGSAIPQT NCDSEEDSTT LCLQSRRQKQ RQVSGDSHAH VSRQGAWKVH
TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE GTFLLRDSAQ EDYLFSVSFR
RYNRSLHARI EQWNHNFSFD AHDPCVFHSS TVTGLLEHYK DPSSCMFFEP LLTISLNRTF
PFSLQYICRA VICRCTTYDG IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK
