ID SOCS3_MOUSE Reviewed; 225 AA.
AC O35718; P97803; Q3U7X5;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 200.
DE RecName: Full=Suppressor of cytokine signaling 3 {ECO:0000305};
DE Short=SOCS-3;
DE AltName: Full=Cytokine-inducible SH2 protein 3;
DE Short=CIS-3;
DE AltName: Full=Protein EF-10;
GN Name=Socs3 {ECO:0000312|MGI:MGI:1201791}; Synonyms=Cis3, Cish3;
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 TISSUE=Lung, and Thymus;
RX PubMed=9202125; DOI=10.1038/43206;
RA Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R.,
RA Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A.,
RA Hilton D.J.;
RT "A family of cytokine-inducible inhibitors of signaling.";
RL Nature 387:917-921(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Le Provost F., Henninghausen L.;
RT "Murine SOCS3 gene structure.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Cerebellum, and Spleen;
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 [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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
RC STRAIN=ICR X Swiss Webster;
RX PubMed=10359822; DOI=10.1073/pnas.96.12.6964;
RA Auernhammer C.J., Bousquet C., Melmed S.;
RT "Autoregulation of pituitary corticotroph SOCS-3 expression:
RT characterization of the murine SOCS-3 promoter.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6964-6969(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 221-225.
RC STRAIN=BALB/cJ;
RX PubMed=9032278; DOI=10.1128/mcb.17.3.1503;
RA Fu X., Kamps M.P.;
RT "E2a-Pbx1 induces aberrant expression of tissue-specific and
RT developmentally regulated genes when expressed in NIH 3T3 fibroblasts.";
RL Mol. Cell. Biol. 17:1503-1512(1997).
RN [7]
RP FUNCTION IN LIF AND IL6 SIGNALING.
RX PubMed=9889194; DOI=10.1093/emboj/18.2.375;
RA Nicholson S.E., Willson T.A., Farley A., Starr R., Zhang J.-G., Baca M.,
RA Alexander W.S., Metcalf D., Hilton D.J., Nicola N.A.;
RT "Mutational analyses of the SOCS proteins suggest a dual domain requirement
RT but distinct mechanisms for inhibition of LIF and IL-6 signal
RT transduction.";
RL EMBO J. 18:375-385(1999).
RN [8]
RP FUNCTION IN INHIBITION OF INSR KINASE ACTIVITY, AND INTERACTION WITH INSR.
RX PubMed=10821852; DOI=10.1074/jbc.275.21.15985;
RA Emanuelli B., Peraldi P., Filloux C., Sawka-Verhelle D., Hilton D.,
RA Van Obberghen E.;
RT "SOCS-3 is an insulin-induced negative regulator of insulin signaling.";
RL J. Biol. Chem. 275:15985-15991(2000).
RN [9]
RP INTERACTION WITH EPOR AND JAK2, AND MUTAGENESIS OF LEU-22; PHE-25; GLY-45
RP AND ARG-71.
RX PubMed=10882725; DOI=10.1074/jbc.m003456200;
RA Sasaki A., Yasukawa H., Shouda T., Kitamura T., Dikic I., Yoshimura A.;
RT "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO
RT receptor and JAK2.";
RL J. Biol. Chem. 275:29338-29347(2000).
RN [10]
RP TISSUE SPECIFICITY.
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).
RN [11]
RP FUNCTION IN ERYTHROPOIESIS.
RX PubMed=10490101; DOI=10.1016/s0092-8674(00)80049-5;
RA Marine J.-C., McKay C., Wang D., Topham D.J., Parganas E., Nakajima H.,
RA Pendeville H., Yasukawa H., Sasaki A., Yoshimura A., Ihle J.N.;
RT "SOCS3 is essential in the regulation of fetal liver erythropoiesis.";
RL Cell 98:617-627(1999).
RN [12]
RP ROLE IN IL-6 SIGNALING.
RX PubMed=12754505; DOI=10.1038/ni931;
RA Croker B.A., Krebs D.L., Zhang J.-G., Wormald S., Willson T.A.,
RA Stanley E.G., Robb L., Greenhalgh C.J., Foerster I., Clausen B.E.,
RA Nicola N.A., Metcalf D., Hilton D.J., Roberts A.W., Alexander W.S.;
RT "SOCS3 negatively regulates IL-6 signaling in vivo.";
RL Nat. Immunol. 4:540-545(2003).
RN [13]
RP ROLE IN ALLERGIC RESPONSE, AND INDUCTION BY IL-4.
RX PubMed=12847520; DOI=10.1038/nm896;
RA Seki Y., Inoue H., Nagata N., Hayashi K., Fukuyama S., Matsumoto K.,
RA Komine O., Hamano S., Himeno K., Inagaki-Ohara K., Cacalano N., O'Garra A.,
RA Oshida T., Saito H., Johnston J.A., Yoshimura A., Kubo M.;
RT "SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic
RT responses.";
RL Nat. Med. 9:1047-1054(2003).
RN [14]
RP INTERACTION WITH BCL10.
RX PubMed=15213237; DOI=10.1074/jbc.m400241200;
RA Liu Y., Dong W., Chen L., Xiang R., Xiao H., De G., Wang Z., Qi Y.;
RT "BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through
RT interaction with Pellino2.";
RL J. Biol. Chem. 279:37436-37444(2004).
RN [15]
RP INTERACTION WITH NOD2.
RX PubMed=23019338; DOI=10.1074/jbc.m112.410027;
RA Lee K.H., Biswas A., Liu Y.J., Kobayashi K.S.;
RT "Proteasomal degradation of Nod2 protein mediates tolerance to bacterial
RT cell wall components.";
RL J. Biol. Chem. 287:39800-39811(2012).
RN [16]
RP STRUCTURE BY NMR OF 22-185.
RX PubMed=16630890; DOI=10.1016/j.molcel.2006.03.024;
RA Babon J.J., McManus E.J., Yao S., DeSouza D.P., Mielke L.A., Sprigg N.S.,
RA Willson T.A., Hilton D.J., Nicola N.A., Baca M., Nicholson S.E.,
RA Norton R.S.;
RT "The structure of SOCS3 reveals the basis of the extended SH2 domain
RT function and identifies an unstructured insertion that regulates
RT stability.";
RL Mol. Cell 22:205-216(2006).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 15-185 IN COMPLEX WITH
RP PHOSPHORYLATED IL6ST.
RX PubMed=16905102; DOI=10.1016/j.str.2006.06.011;
RA Bergamin E., Wu J., Hubbard S.R.;
RT "Structural basis for phosphotyrosine recognition by suppressor of cytokine
RT signaling-3.";
RL Structure 14:1285-1292(2006).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. SOCS3 is
CC involved in negative regulation of cytokines that signal through the
CC JAK/STAT pathway. Inhibits cytokine signal transduction by binding to
CC tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin,
CC insulin, IL12, GCSF and leptin receptors (PubMed:10821852,
CC PubMed:12754505, PubMed:9889194). Binding to JAK2 inhibits its kinase
CC activity and regulates IL6 signaling (PubMed:12754505, PubMed:9889194).
CC Suppresses fetal liver erythropoiesis (PubMed:10490101). Regulates
CC onset and maintenance of allergic responses mediated by T-helper type 2
CC cells (PubMed:12847520). Probable substrate recognition component of a
CC SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein
CC ligase complex which mediates the ubiquitination and subsequent
CC proteasomal degradation of target proteins (By similarity).
CC {ECO:0000250|UniProtKB:O14543, ECO:0000269|PubMed:10490101,
CC ECO:0000269|PubMed:10821852, ECO:0000269|PubMed:12754505,
CC ECO:0000269|PubMed:12847520, ECO:0000269|PubMed:9889194}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including IGF1 receptor, insulin receptor and
CC JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a
CC phosphorylated tyrosine residue within the JAK2 JH1 domain (By
CC similarity). Binds specific activated tyrosine residues of the leptin,
CC EPO, IL12, GSCF and gp130 receptors (PubMed:10882725). Interaction with
CC CSNK1E stabilizes SOCS3 protein (By similarity). Component of the
CC probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains
CC CUL5, RNF7/RBX2, elongin BC complex and SOCS3 (By similarity).
CC Interacts with CUL5, RNF7, ELOB and ELOC (By similarity). Interacts
CC with FGFR3 (By similarity). Interacts with INSR (PubMed:10821852).
CC Interacts with BCL10; this interaction may interfere with BCL10-binding
CC with PELI2 (PubMed:15213237). Interacts with NOD2 (via CARD domain);
CC the interaction promotes NOD2 degradation (PubMed:23019338).
CC {ECO:0000250|UniProtKB:O14543, ECO:0000269|PubMed:10821852,
CC ECO:0000269|PubMed:10882725, ECO:0000269|PubMed:15213237,
CC ECO:0000269|PubMed:16905102, ECO:0000269|PubMed:23019338}.
CC -!- INTERACTION:
CC O35718; Q00560: Il6st; NbExp=6; IntAct=EBI-2659360, EBI-3862992;
CC -!- TISSUE SPECIFICITY: Low expression in lung, spleen and thymus.
CC Expressed in Th2 but not TH1 cells. {ECO:0000269|PubMed:12242343}.
CC -!- DEVELOPMENTAL STAGE: In the developing brain, expressed at low levels
CC from 10 dpc stages to young adulthood (P25) with peak levels from 14
CC dpc to P8. In the cortex, first expressed uniformly in all cells at 14
CC dpc. Not expressed in the retina. Highly expressed in fetal liver
CC progenitors at 12.5 dpc.
CC -!- INDUCTION: By a subset of cytokines including EPO, leptin, LIF, IL-2,
CC IL-3, IL-4, IGF1, growth hormone and prolactin.
CC {ECO:0000269|PubMed:12847520}.
CC -!- DOMAIN: The ESS and SH2 domains are required for JAK phosphotyrosine
CC binding. Further interaction with the KIR domain is necessary for
CC signal and kinase inhibition.
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 on tyrosine residues after stimulation by the
CC cytokines, IL-2, EPO or IGF1. {ECO:0000250}.
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DR EMBL; U88328; AAB62403.1; -; mRNA.
DR EMBL; AF314501; AAK60601.1; -; Genomic_DNA.
DR EMBL; AK047165; BAC32977.1; -; mRNA.
DR EMBL; AK139241; BAE23929.1; -; mRNA.
DR EMBL; AK152468; BAE31244.1; -; mRNA.
DR EMBL; AK152514; BAE31277.1; -; mRNA.
DR EMBL; AK157708; BAE34161.1; -; mRNA.
DR EMBL; AK159395; BAE35049.1; -; mRNA.
DR EMBL; AK170406; BAE41773.1; -; mRNA.
DR EMBL; AK172399; BAE42985.1; -; mRNA.
DR EMBL; BC052031; AAH52031.1; -; mRNA.
DR EMBL; AF117732; AAD18024.1; -; Genomic_DNA.
DR EMBL; U72673; AAB51035.1; ALT_SEQ; mRNA.
DR CCDS; CCDS25697.1; -.
DR RefSeq; NP_031733.1; NM_007707.3.
DR RefSeq; XP_011247009.1; XM_011248707.2.
DR PDB; 2BBU; NMR; -; A=22-185.
DR PDB; 2HMH; X-ray; 2.00 A; A=15-185.
DR PDB; 2JZ3; NMR; -; A=186-225.
DR PDB; 4GL9; X-ray; 3.90 A; E/F/G/H=22-128, E/F/G/H=163-185.
DR PDBsum; 2BBU; -.
DR PDBsum; 2HMH; -.
DR PDBsum; 2JZ3; -.
DR PDBsum; 4GL9; -.
DR AlphaFoldDB; O35718; -.
DR BMRB; O35718; -.
DR SMR; O35718; -.
DR BioGRID; 198718; 23.
DR DIP; DIP-29137N; -.
DR IntAct; O35718; 18.
DR MINT; O35718; -.
DR STRING; 10090.ENSMUSP00000059129; -.
DR iPTMnet; O35718; -.
DR PhosphoSitePlus; O35718; -.
DR PaxDb; 10090-ENSMUSP00000059129; -.
DR Antibodypedia; 3206; 958 antibodies from 44 providers.
DR DNASU; 12702; -.
DR Ensembl; ENSMUST00000054002.4; ENSMUSP00000059129.4; ENSMUSG00000053113.4.
DR GeneID; 12702; -.
DR KEGG; mmu:12702; -.
DR UCSC; uc007moi.2; mouse.
DR AGR; MGI:1201791; -.
DR CTD; 9021; -.
DR MGI; MGI:1201791; Socs3.
DR VEuPathDB; HostDB:ENSMUSG00000053113; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000159620; -.
DR HOGENOM; CLU_079452_3_0_1; -.
DR InParanoid; O35718; -.
DR OMA; KLVHYYM; -.
DR OrthoDB; 5362214at2759; -.
DR PhylomeDB; O35718; -.
DR TreeFam; TF321368; -.
DR Reactome; R-MMU-1059683; Interleukin-6 signaling.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-877312; Regulation of IFNG signaling.
DR Reactome; R-MMU-8849474; PTK6 Activates STAT3.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 12702; 8 hits in 80 CRISPR screens.
DR EvolutionaryTrace; O35718; -.
DR PRO; PR:O35718; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O35718; Protein.
DR Bgee; ENSMUSG00000053113; Expressed in cleaving embryo and 225 other cell types or tissues.
DR Genevisible; O35718; MM.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:MGI.
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:0035198; F:miRNA binding; IDA:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:CAFA.
DR GO; GO:0030292; F:protein tyrosine kinase inhibitor activity; ISO:MGI.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR GO; GO:0097398; P:cellular response to interleukin-17; IDA:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:MGI.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; IGI:MGI.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; IGI:MGI.
DR CDD; cd10384; SH2_SOCS3; 1.
DR CDD; cd03737; SOCS_SOCS3; 1.
DR DisProt; DP00446; -.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR Gene3D; 1.10.750.20; SOCS box; 1.
DR IDEAL; IID50193; -.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035863; SOCS3_SH2.
DR InterPro; IPR028414; SOCS3_SOCS_box.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155; PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT; 1.
DR PANTHER; PTHR10155:SF11; SUPPRESSOR OF CYTOKINE SIGNALING 3; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR SUPFAM; SSF158235; SOCS box-like; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Growth regulation; Phosphoprotein; Reference proteome;
KW SH2 domain; Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..225
FT /note="Suppressor of cytokine signaling 3"
FT /id="PRO_0000181244"
FT DOMAIN 46..142
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 177..224
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 22..33
FT /note="Kinase inhibitory region (KIR)"
FT REGION 34..45
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 131..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 22
FT /note="L->A: No effect on LIF-induced signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10882725"
FT MUTAGEN 22
FT /note="L->D: Abolishes binding to JAK2. No effect on
FT binding to EPOR."
FT /evidence="ECO:0000269|PubMed:10882725"
FT MUTAGEN 25
FT /note="F->A: Loss of LIF/EPO-induced signal transduction
FT suppression. Abolishes binding to JAK2 and to EPOR."
FT /evidence="ECO:0000269|PubMed:10882725"
FT MUTAGEN 30
FT /note="E->R: No effect on LIF-induced signal transduction
FT suppression."
FT MUTAGEN 45
FT /note="G->A: Abolishes binding to EPOR. No effect on
FT binding to JAK2."
FT /evidence="ECO:0000269|PubMed:10882725"
FT MUTAGEN 71
FT /note="R->K: Little effect on LIF-induced signal
FT transduction suppression. Loss of EPO-induced signal
FT transduction suppression. Abolishes binding to JAK2 and
FT EPOR."
FT /evidence="ECO:0000269|PubMed:10882725"
FT HELIX 32..43
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:2HMH"
FT HELIX 53..61
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 79..86
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:2HMH"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:2HMH"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:2BBU"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:2HMH"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:2HMH"
FT HELIX 189..199
FT /evidence="ECO:0007829|PDB:2JZ3"
SQ SEQUENCE 225 AA; 24776 MW; CD3859561D4CCDED CRC64;
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL
SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV
LKLVHHYMPP PGTPSFSLPP TEPSSEVPEQ PPAQALPGST PKRAYYIYSG GEKIPLVLSR
PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL
//
