SOCS6_MOUSE
ID SOCS6_MOUSE Reviewed; 533 AA.
AC Q9JLY0; Q8VEN5; Q9D2A0;
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 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, Cish4, Socs4;
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=T-cell lymphoma;
RA Choi Y.B., Yun Y.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, Eye, Spleen, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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=Czech II, and FVB/N; TISSUE=Mammary tumor;
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 INTERACTION WITH IRS4.
RX PubMed=12052866; DOI=10.1128/mcb.22.13.4567-4578.2002;
RA Krebs D.L., Uren R.T., Metcalf D., Rakar S., Zhang J.-G., Starr R.,
RA De Souza D.P., Hanzinikolas K., Eyles J., Connolly L.M., Simpson R.J.,
RA Nicola N.A., Nicholson S.E., Baca M., Hilton D.J., Alexander W.S.;
RT "SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6
RT gene exhibit mild growth retardation.";
RL Mol. Cell. Biol. 22:4567-4578(2002).
RN [6]
RP FUNCTION AS E3 UBIQUITIN LIGASE, AND INTERACTION WITH RBCK1.
RX PubMed=16643902; DOI=10.1016/j.febslet.2006.03.093;
RA Bayle J., Lopez S., Iwai K., Dubreuil P., De Sepulveda P.;
RT "The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and
RT degradation of SOCS6 associated proteins.";
RL FEBS Lett. 580:2609-2614(2006).
RN [7]
RP INTERACTION WITH PIM3.
RX PubMed=21099329; DOI=10.4161/isl.2.5.13058;
RA Vlacich G., Nawijn M.C., Webb G.C., Steiner D.F.;
RT "Pim3 negatively regulates glucose-stimulated insulin secretion.";
RL Islets 2:308-317(2010).
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. Regulates KIT degradation by ubiquitination of the tyrosine-
CC phosphorylated receptor (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:16643902}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with KIT (phosphorylated) (By similarity). Interacts
CC with RBCK1. Interacts with phosphorylated IRS4. Interacts with PIM3.
CC {ECO:0000250, ECO:0000269|PubMed:12052866, ECO:0000269|PubMed:16643902,
CC ECO:0000269|PubMed:21099329}.
CC -!- INTERACTION:
CC Q9JLY0; Q9BYM8: RBCK1; Xeno; NbExp=5; IntAct=EBI-8500205, EBI-2340624;
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}.
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DR EMBL; AF121907; AAF28872.1; -; mRNA.
DR EMBL; AK019993; BAB31956.1; -; mRNA.
DR EMBL; AK028665; BAC26055.1; -; mRNA.
DR EMBL; AK028701; BAC26074.1; -; mRNA.
DR EMBL; AK031164; BAC27287.1; -; mRNA.
DR EMBL; AK044946; BAC32154.1; -; mRNA.
DR EMBL; AK142069; BAE24930.1; -; mRNA.
DR EMBL; AK156591; BAE33770.1; -; mRNA.
DR EMBL; CH466632; EDL00645.1; -; Genomic_DNA.
DR EMBL; CH466632; EDL00646.1; -; Genomic_DNA.
DR EMBL; BC017597; AAH17597.1; -; mRNA.
DR EMBL; BC094443; AAH94443.1; -; mRNA.
DR CCDS; CCDS29389.1; -.
DR RefSeq; NP_061291.2; NM_018821.4.
DR RefSeq; XP_006526576.1; XM_006526513.2.
DR RefSeq; XP_011245391.1; XM_011247089.1.
DR RefSeq; XP_011245392.1; XM_011247090.2.
DR AlphaFoldDB; Q9JLY0; -.
DR SMR; Q9JLY0; -.
DR BioGRID; 207682; 8.
DR IntAct; Q9JLY0; 3.
DR MINT; Q9JLY0; -.
DR STRING; 10090.ENSMUSP00000064929; -.
DR iPTMnet; Q9JLY0; -.
DR PhosphoSitePlus; Q9JLY0; -.
DR MaxQB; Q9JLY0; -.
DR PaxDb; Q9JLY0; -.
DR PeptideAtlas; Q9JLY0; -.
DR PRIDE; Q9JLY0; -.
DR ProteomicsDB; 261600; -.
DR Antibodypedia; 4125; 206 antibodies from 31 providers.
DR DNASU; 54607; -.
DR Ensembl; ENSMUST00000070116; ENSMUSP00000064929; ENSMUSG00000056153.
DR Ensembl; ENSMUST00000123826; ENSMUSP00000114993; ENSMUSG00000056153.
DR Ensembl; ENSMUST00000125362; ENSMUSP00000118764; ENSMUSG00000056153.
DR GeneID; 54607; -.
DR KEGG; mmu:54607; -.
DR UCSC; uc008fvf.1; mouse.
DR CTD; 9306; -.
DR MGI; MGI:1924885; Socs6.
DR VEuPathDB; HostDB:ENSMUSG00000056153; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000154847; -.
DR HOGENOM; CLU_038160_0_0_1; -.
DR InParanoid; Q9JLY0; -.
DR OMA; FHEEESQ; -.
DR OrthoDB; 924518at2759; -.
DR PhylomeDB; Q9JLY0; -.
DR TreeFam; TF321368; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54607; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Socs6; mouse.
DR PRO; PR:Q9JLY0; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9JLY0; protein.
DR Bgee; ENSMUSG00000056153; Expressed in ear vesicle and 256 other tissues.
DR ExpressionAtlas; Q9JLY0; baseline and differential.
DR Genevisible; Q9JLY0; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001772; C:immunological synapse; ISO: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: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; IDA:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0040008; P:regulation of growth; IMP:MGI.
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 Growth regulation; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..533
FT /note="Suppressor of cytokine signaling 6"
FT /id="PRO_0000181252"
FT DOMAIN 382..489
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 484..533
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 54..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..73
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 10
FT /note="R -> T (in Ref. 1; AAF28872)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="T -> S (in Ref. 1; AAF28872)"
FT /evidence="ECO:0000305"
FT CONFLICT 149..152
FT /note="MRVK -> IASE (in Ref. 1; AAF28872)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="L -> I (in Ref. 2; BAB31956)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 59077 MW; F779C6519DB0A17B CRC64;
MKKISLKTFR KSFNLSKSKD ETEFMVVQPQ SLAGDFVKDD SLFGSCYGKD MASCDIGSED
EKGKNRSKSE SLMGTLKRRL SAKQKTKGKG GTASTDEDTF SSASAPGGLK DVRAPRPIRS
TSLRSHHYSP TPWPLRPTSS EETCIKMEMR VKALVHAASP GPVNGVRKDL RELQPRELRD
LQPEPRPESR CSPSSPGDLS LHLEEHVPVV IGLMSQDYLQ YTVPLDDGMC PLEGPRSCCL
DTSSPMEVSA VPLPGASGAF SEDDSHVDQD LVVGPEILVD SSVNNLLIGT TGVMLQSPRG
GHDDAPPLSP LLPPMQNNPI QRNFSGLSGP DLHMAESVRC HLNFDPNSAP GVARVYDSVQ
SSGPMVVTSL TEELKKLAKQ GWYWGPITRW EAEGKLANVP DGSFLVRDSS DDRYLLSLSF
RSHGKTLHTR IEHSNGRFSF YEQPDVEGHT SIVDLIEHSI RDSENGAFCY SRSRLPGSAT
YPVRLTNPVS RFMQVRSLQY LCRFVIRQYT RIDLIQKLPL PNKMKDYLQE KHY
