SOCS5_HUMAN
ID SOCS5_HUMAN Reviewed; 536 AA.
AC O75159; Q53SD4; Q8IYZ4;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Suppressor of cytokine signaling 5;
DE Short=SOCS-5;
DE AltName: Full=Cytokine-inducible SH2 protein 6;
DE Short=CIS-6;
DE AltName: Full=Cytokine-inducible SH2-containing protein 5;
GN Name=SOCS5; Synonyms=CIS6, CISH5, CISH6, KIAA0671;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=10773671; DOI=10.1159/000015490;
RA Magrangeas F., Apiou F., Denis S., Weidle U., Jacques Y., Minvielle S.;
RT "Cloning and expression of CIS6, chromosomal assignment to 3p22 and 2p21 by
RT in situ hybridization.";
RL Cytogenet. Cell Genet. 88:78-81(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [8]
RP FUNCTION IN EGFR DEGRADATION, INDUCTION BY EGF, PHOSPHORYLATION,
RP MUTAGENESIS OF ARG-406; LEU-484 AND CYS-488, AND INTERACTION WITH EGFR;
RP ELOB AND ELOC.
RX PubMed=15590694; DOI=10.1074/jbc.m408575200;
RA Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N.,
RA Rechavi G., Yarden Y.;
RT "Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor
RT receptor signaling.";
RL J. Biol. Chem. 280:7038-7048(2005).
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:15590694}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with IL4R; inhibits IL4 signaling (By similarity).
CC Interacts with EGFR. Interacts with ELOB and ELOC; mediates EGFR
CC ubiquitination and degradation. {ECO:0000250,
CC ECO:0000269|PubMed:15590694}.
CC -!- INTERACTION:
CC O75159; P08581: MET; NbExp=2; IntAct=EBI-970130, EBI-1039152;
CC -!- INDUCTION: Up-regulated by EGF (at protein level).
CC {ECO:0000269|PubMed:15590694}.
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.
CC -!- PTM: Phosphorylated. Phosphorylation is induced by EGF.
CC {ECO:0000269|PubMed:15590694}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31646.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF073958; AAD40484.1; -; mRNA.
DR EMBL; AB014571; BAA31646.2; ALT_INIT; mRNA.
DR EMBL; AL136896; CAB66830.1; -; mRNA.
DR EMBL; AK290194; BAF82883.1; -; mRNA.
DR EMBL; AC020604; AAY24289.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00236.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00237.1; -; Genomic_DNA.
DR EMBL; BC032862; AAH32862.1; -; mRNA.
DR CCDS; CCDS1830.1; -.
DR PIR; T46499; T46499.
DR RefSeq; NP_054730.1; NM_014011.4.
DR RefSeq; NP_659198.1; NM_144949.2.
DR AlphaFoldDB; O75159; -.
DR BMRB; O75159; -.
DR SMR; O75159; -.
DR BioGRID; 115013; 21.
DR IntAct; O75159; 8.
DR MINT; O75159; -.
DR STRING; 9606.ENSP00000305133; -.
DR iPTMnet; O75159; -.
DR PhosphoSitePlus; O75159; -.
DR BioMuta; SOCS5; -.
DR MassIVE; O75159; -.
DR PaxDb; O75159; -.
DR PeptideAtlas; O75159; -.
DR PRIDE; O75159; -.
DR ProteomicsDB; 49827; -.
DR Antibodypedia; 15096; 203 antibodies from 35 providers.
DR DNASU; 9655; -.
DR Ensembl; ENST00000306503.5; ENSP00000305133.5; ENSG00000171150.9.
DR Ensembl; ENST00000394861.3; ENSP00000378330.2; ENSG00000171150.9.
DR GeneID; 9655; -.
DR KEGG; hsa:9655; -.
DR MANE-Select; ENST00000394861.3; ENSP00000378330.2; NM_144949.3; NP_659198.1.
DR UCSC; uc002rvf.4; human.
DR CTD; 9655; -.
DR DisGeNET; 9655; -.
DR GeneCards; SOCS5; -.
DR HGNC; HGNC:16852; SOCS5.
DR HPA; ENSG00000171150; Low tissue specificity.
DR MIM; 607094; gene.
DR neXtProt; NX_O75159; -.
DR OpenTargets; ENSG00000171150; -.
DR PharmGKB; PA134884627; -.
DR VEuPathDB; HostDB:ENSG00000171150; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000159000; -.
DR HOGENOM; CLU_035609_1_0_1; -.
DR InParanoid; O75159; -.
DR OMA; DSCVTTG; -.
DR OrthoDB; 722019at2759; -.
DR PhylomeDB; O75159; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; O75159; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; O75159; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9655; 27 hits in 1084 CRISPR screens.
DR ChiTaRS; SOCS5; human.
DR GeneWiki; SOCS5; -.
DR GenomeRNAi; 9655; -.
DR Pharos; O75159; Tbio.
DR PRO; PR:O75159; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O75159; protein.
DR Bgee; ENSG00000171150; Expressed in sperm and 200 other tissues.
DR ExpressionAtlas; O75159; baseline and differential.
DR Genevisible; O75159; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
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; ISS: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; IMP:UniProtKB.
DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0097699; P:vascular endothelial cell response to fluid shear stress; IEA:Ensembl.
DR CDD; cd03739; SOCS_SOCS5; 1.
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 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_0000181249"
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 /evidence="ECO:0000250"
FT REGION 115..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..160
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 406
FT /note="R->K: Abrogates the ability to induce EGFR
FT degradation."
FT /evidence="ECO:0000269|PubMed:15590694"
FT MUTAGEN 484
FT /note="L->P: Abrogates the interaction with ELOB and ELOC
FT and the ability to suppress EGFR signaling; when associated
FT with F-488."
FT /evidence="ECO:0000269|PubMed:15590694"
FT MUTAGEN 488
FT /note="C->F: Abrogates the interaction with ELOB and ELOC
FT and the ability to suppress EGFR signaling; when associated
FT with P-484."
FT /evidence="ECO:0000269|PubMed:15590694"
FT CONFLICT 478
FT /note="R -> M (in Ref. 7; AAH32862)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 61246 MW; 0629CDCF2A97E9D8 CRC64;
MDKVGKMWNN FKYRCQNLFG HEGGSRSENV DMNSNRCLSV KEKNISIGDS TPQQQSSPLR
ENIALQLGLS PSKNSSRRNQ NCATEIPQIV EISIEKDNDS CVTPGTRLAR RDSYSRHAPW
GGKKKHSCST KTQSSLDADK KFGRTRSGLQ RRERRYGVSS VHDMDSVSSR TVGSRSLRQR
LQDTVGLCFP MRTYSKQSKP LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV
SPHSTFFDTF DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG
PKLAPGMTEI SGDSSAIPQA NCDSEEDTTT LCLQSRRQKQ RQISGDSHTH VSRQGAWKVH
TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE GTFLLRDSAQ EDYLFSVSFR
RYNRSLHARI EQWNHNFSFD AHDPCVFHSS TVTGLLEHYK DPSSCMFFEP LLTISLNRTF
PFSLQYICRA VICRCTTYDG IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK
