SOCS6_HUMAN
ID SOCS6_HUMAN Reviewed; 535 AA.
AC O14544; Q8WUM3;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Suppressor of cytokine signaling 6;
DE Short=SOCS-6;
DE AltName: Full=Cytokine-inducible SH2 protein 4;
DE Short=CIS-4;
DE AltName: Full=Suppressor of cytokine signaling 4;
DE Short=SOCS-4;
GN Name=SOCS6; Synonyms=CIS4, SOCS4;
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].
RX PubMed=9344848; DOI=10.1006/bbrc.1997.7484;
RA Masuhara M., Sakamoto H., Matsumoto A., Suzuki R., Yasukawa H., Mitsui K.,
RA Wakioka T., Tanimura S., Sasaki A., Misawa H., Yokouchi M., Ohtsubo M.,
RA Yoshimura A.;
RT "Cloning and characterization of novel CIS family genes.";
RL Biochem. Biophys. Res. Commun. 239:439-446(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [4]
RP REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 361-499 IN COMPLEX WITH KIT, AND
RP FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE FOR KIT.
RX PubMed=21030588; DOI=10.1074/jbc.m110.173526;
RA Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S.,
RA Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.;
RT "Structural basis for c-KIT inhibition by the suppressor of cytokine
RT signaling 6 (SOCS6) ubiquitin ligase.";
RL J. Biol. Chem. 286:480-490(2011).
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 (By similarity). Regulates KIT degradation by ubiquitination
CC of the tyrosine-phosphorylated receptor. {ECO:0000250,
CC ECO:0000269|PubMed:21030588}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with RBCK1. Interacts with phosphorylated IRS4 (By
CC similarity). Interacts with PIM3 (By similarity). Interacts with KIT
CC (phosphorylated). {ECO:0000250, ECO:0000269|PubMed:21030588}.
CC -!- INTERACTION:
CC O14544; P10275: AR; NbExp=4; IntAct=EBI-3929549, EBI-608057;
CC O14544; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-3929549, EBI-8643161;
CC O14544; O75460-2: ERN1; NbExp=3; IntAct=EBI-3929549, EBI-25852368;
CC O14544; P22607: FGFR3; NbExp=3; IntAct=EBI-3929549, EBI-348399;
CC O14544; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-3929549, EBI-10226858;
CC O14544; Q13480: GAB1; NbExp=9; IntAct=EBI-3929549, EBI-517684;
CC O14544; P06396: GSN; NbExp=3; IntAct=EBI-3929549, EBI-351506;
CC O14544; P54652: HSPA2; NbExp=3; IntAct=EBI-3929549, EBI-356991;
CC O14544; P10721: KIT; NbExp=12; IntAct=EBI-3929549, EBI-1379503;
CC O14544; P08581: MET; NbExp=4; IntAct=EBI-3929549, EBI-1039152;
CC O14544; O60260-5: PRKN; NbExp=3; IntAct=EBI-3929549, EBI-21251460;
CC O14544; P49591: SARS1; NbExp=3; IntAct=EBI-3929549, EBI-1053431;
CC O14544; Q13148: TARDBP; NbExp=3; IntAct=EBI-3929549, EBI-372899;
CC O14544; P42681: TXK; NbExp=3; IntAct=EBI-3929549, EBI-7877438;
CC O14544; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-3929549, EBI-741480;
CC O14544; P46937: YAP1; NbExp=2; IntAct=EBI-3929549, EBI-1044059;
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 ---------------------------------------------------------------------------
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; AB006968; BAA22538.1; -; mRNA.
DR EMBL; CH471117; EAW66522.1; -; Genomic_DNA.
DR EMBL; BC020082; AAH20082.1; -; mRNA.
DR CCDS; CCDS11998.1; -.
DR PIR; JC5762; JC5762.
DR RefSeq; NP_004223.2; NM_004232.3.
DR RefSeq; XP_005266840.1; XM_005266783.3.
DR RefSeq; XP_016881575.1; XM_017026086.1.
DR RefSeq; XP_016881576.1; XM_017026087.1.
DR PDB; 2VIF; X-ray; 1.45 A; A=361-499.
DR PDBsum; 2VIF; -.
DR AlphaFoldDB; O14544; -.
DR SMR; O14544; -.
DR BioGRID; 114719; 123.
DR IntAct; O14544; 42.
DR MINT; O14544; -.
DR STRING; 9606.ENSP00000381034; -.
DR GlyGen; O14544; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14544; -.
DR PhosphoSitePlus; O14544; -.
DR BioMuta; SOCS6; -.
DR EPD; O14544; -.
DR jPOST; O14544; -.
DR MassIVE; O14544; -.
DR MaxQB; O14544; -.
DR PaxDb; O14544; -.
DR PeptideAtlas; O14544; -.
DR PRIDE; O14544; -.
DR ProteomicsDB; 48079; -.
DR Antibodypedia; 4125; 206 antibodies from 31 providers.
DR DNASU; 9306; -.
DR Ensembl; ENST00000397942.4; ENSP00000381034.3; ENSG00000170677.6.
DR Ensembl; ENST00000582322.1; ENSP00000463395.1; ENSG00000170677.6.
DR GeneID; 9306; -.
DR KEGG; hsa:9306; -.
DR MANE-Select; ENST00000397942.4; ENSP00000381034.3; NM_004232.4; NP_004223.2.
DR UCSC; uc002lkr.2; human.
DR CTD; 9306; -.
DR DisGeNET; 9306; -.
DR GeneCards; SOCS6; -.
DR HGNC; HGNC:16833; SOCS6.
DR HPA; ENSG00000170677; Low tissue specificity.
DR MIM; 605118; gene.
DR neXtProt; NX_O14544; -.
DR OpenTargets; ENSG00000170677; -.
DR PharmGKB; PA134917653; -.
DR VEuPathDB; HostDB:ENSG00000170677; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000154847; -.
DR HOGENOM; CLU_038160_0_0_1; -.
DR InParanoid; O14544; -.
DR OMA; FHEEESQ; -.
DR OrthoDB; 924518at2759; -.
DR PhylomeDB; O14544; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; O14544; -.
DR Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9706369; Negative regulation of FLT3.
DR SignaLink; O14544; -.
DR SIGNOR; O14544; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9306; 8 hits in 1117 CRISPR screens.
DR ChiTaRS; SOCS6; human.
DR EvolutionaryTrace; O14544; -.
DR GeneWiki; SOCS6; -.
DR GenomeRNAi; 9306; -.
DR Pharos; O14544; Tbio.
DR PRO; PR:O14544; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O14544; protein.
DR Bgee; ENSG00000170677; Expressed in mucosa of paranasal sinus and 196 other tissues.
DR ExpressionAtlas; O14544; baseline and differential.
DR Genevisible; O14544; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001772; C:immunological synapse; IDA:MGI.
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:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR GO; GO:0050868; P:negative regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; TAS:ProtInc.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR CDD; cd10387; SH2_SOCS6; 1.
DR CDD; cd03740; SOCS_SOCS6; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028421; SOCS6.
DR InterPro; IPR035865; SOCS6_SH2.
DR InterPro; IPR037345; SOCS6_SOCS.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF17; PTHR10155:SF17; 1.
DR Pfam; PF00017; SH2; 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..535
FT /note="Suppressor of cytokine signaling 6"
FT /id="PRO_0000181251"
FT DOMAIN 384..491
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 486..535
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 80..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..105
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 74
FT /note="M -> I (in Ref. 1; BAA22538)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="S -> T (in Ref. 1; BAA22538)"
FT /evidence="ECO:0000305"
FT HELIX 372..382
FT /evidence="ECO:0007829|PDB:2VIF"
FT HELIX 391..397
FT /evidence="ECO:0007829|PDB:2VIF"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 406..410
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 417..424
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 427..436
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 439..442
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:2VIF"
FT HELIX 454..467
FT /evidence="ECO:0007829|PDB:2VIF"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:2VIF"
SQ SEQUENCE 535 AA; 59528 MW; AE513312A999B763 CRC64;
MKKISLKTLR KSFNLNKSKE ETDFMVVQQP SLASDFGKDD SLFGSCYGKD MASCDINGED
EKGGKNRSKS ESLMGTLKRR LSAKQKSKGK AGTPSGSSAD EDTFSSSSAP IVFKDVRAQR
PIRSTSLRSH HYSPAPWPLR PTNSEETCIK MEVRVKALVH SSSPSPALNG VRKDFHDLQS
ETTCQEQANS LKSSASHNGD LHLHLDEHVP VVIGLMPQDY IQYTVPLDEG MYPLEGSRSY
CLDSSSPMEV SAVPPQVGGR AFPEDESQVD QDLVVAPEIF VDQSVNGLLI GTTGVMLQSP
RAGHDDVPPL SPLLPPMQNN QIQRNFSGLT GTEAHVAESM RCHLNFDPNS APGVARVYDS
VQSSGPMVVT SLTEELKKLA KQGWYWGPIT RWEAEGKLAN VPDGSFLVRD SSDDRYLLSL
SFRSHGKTLH TRIEHSNGRF SFYEQPDVEG HTSIVDLIEH SIRDSENGAF CYSRSRLPGS
ATYPVRLTNP VSRFMQVRSL QYLCRFVIRQ YTRIDLIQKL PLPNKMKDYL QEKHY
