SOCS1_MOUSE
ID SOCS1_MOUSE Reviewed; 212 AA.
AC O35716; A2RT46; O35960; Q3U3L0;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Suppressor of cytokine signaling 1 {ECO:0000305};
DE Short=SOCS-1 {ECO:0000305};
DE AltName: Full=JAK-binding protein;
DE Short=JAB;
DE AltName: Full=STAT-induced STAT inhibitor 1 {ECO:0000303|PubMed:9202125};
DE Short=SSI-1 {ECO:0000303|PubMed:9202125};
GN Name=Socs1 {ECO:0000312|MGI:MGI:1354910};
GN Synonyms=Cish1, Ssi1 {ECO:0000303|PubMed:9202125};
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], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=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 [MRNA].
RX PubMed=9202126; DOI=10.1038/43213;
RA Endo T.A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H., Mitsui K.,
RA Matsumoto A., Tanimura S., Ohtsubo M., Misawa H., Miyazaki T., Leonor N.,
RA Taniguchi T., Fujita T., Kanakura Y., Komiya S., Yoshimura A.;
RT "A new protein containing an SH2 domain that inhibits JAK kinases.";
RL Nature 387:921-924(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymus;
RX PubMed=9202127; DOI=10.1038/43219;
RA Naka T., Narazaki M., Hirata M., Matsumoto T., Minamoto S., Aono A.,
RA Nishimoto N., Kajita T., Taga T., Yoshizaki K., Akira S., Kishimoto T.;
RT "Structure and function of a new STAT-induced STAT inhibitor.";
RL Nature 387:924-929(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hematopoietic;
RX PubMed=10022833; DOI=10.1093/emboj/18.4.904;
RA De Sepulveda P., Okkenhaug K., La Rose J., Hawley R.G., Dubreuil P.,
RA Rottapel R.;
RT "SOCS-1 binds to multiple signaling proteins and suppresses Steel factor-
RT dependent proliferation.";
RL EMBO J. 18:904-915(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10764816; DOI=10.1074/jbc.m910087199;
RA Gregorieff A., Pyronnet S., Sonenberg N., Veillette A.;
RT "Regulation of SOCS-1 expression by translational repression.";
RL J. Biol. Chem. 275:21596-21604(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 INTERACTION WITH ELONGIN BC COMPLEX, AND MUTAGENESIS OF LEU-175 AND
RP CYS-179.
RX PubMed=9869640; DOI=10.1101/gad.12.24.3872;
RA Kamura T., Sato S., Haque D., Liu L., Kaelin W.G. Jr., Conaway R.C.,
RA Conaway J.W.;
RT "The Elongin BC complex interacts with the conserved SOCS-box motif present
RT in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families.";
RL Genes Dev. 12:3872-3881(1998).
RN [9]
RP INTERACTION WITH ELONGIN BC COMPLEX.
RX PubMed=10051596; DOI=10.1073/pnas.96.5.2071;
RA Zhang J.-G., Farley A., Nicholson S.E., Willson T.A., Zugaro L.M.,
RA Simpson R.J., Moritz R.L., Cary D., Richardson R., Hausmann G., Kile B.J.,
RA Kent S.B.H., Alexander W.S., Metcalf D., Hilton D.J., Nicola N.A., Baca M.;
RT "The conserved SOCS box motif in suppressors of cytokine signaling binds to
RT elongins B and C and may couple bound proteins to proteasomal
RT degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2071-2076(1999).
RN [10]
RP INTERACTION WITH TRIM8.
RX PubMed=12163497; DOI=10.1074/jbc.m205900200;
RA Toniato E., Chen X.P., Losman J., Flati V., Donahue L., Rothman P.;
RT "TRIM8/GERP RING finger protein interacts with SOCS-1.";
RL J. Biol. Chem. 277:37315-37322(2002).
RN [11]
RP MUTAGENESIS.
RX PubMed=9789053; DOI=10.1073/pnas.95.22.13130;
RA Narazaki M., Fujimoto M., Matsumoto T., Morita Y., Saito H., Kajita T.,
RA Yoshizaki K., Naka T., Kishimoto T.;
RT "Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its
RT suppression of interleukin 6 signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13130-13134(1998).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=9826711; DOI=10.1073/pnas.95.24.14395;
RA Starr R., Metcalf D., Elefanty A.G., Brysha M., Willson T.A., Nicola N.A.,
RA Hilton D.J., Alexander W.S.;
RT "Liver degeneration and lymphoid deficiencies in mice lacking suppressor of
RT cytokine signaling-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14395-14399(1998).
RN [13]
RP MUTAGENESIS.
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 [14]
RP FUNCTION IN INHIBITION OF JAK2 KINASE ACTIVITY, AND MUTAGENESIS OF HIS-55;
RP PHE-56; ARG-57; THR-58; PHE-59; ARG-60; SER-61; HIS-62; ASP-64; TYR-65 AND
RP ARG-105.
RX PubMed=10064597; DOI=10.1093/emboj/18.5.1309;
RA Yasukawa H., Misawa H., Sakamoto H., Masuhara M., Sasaki A., Wakioka T.,
RA Ohtsuka S., Imaizumi T., Matsuda T., Ihle J.N., Yoshimura A.;
RT "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity
RT through binding in the activation loop.";
RL EMBO J. 18:1309-1320(1999).
RN [15]
RP MUTAGENESIS OF PHE-59.
RX PubMed=11522790; DOI=10.1074/jbc.m106139200;
RA Hanada T., Yoshida T., Kinjyo I., Minoguchi S., Yasukawa H., Kato S.,
RA Mimata H., Nomura Y., Seki Y., Kubo M., Yoshimura A.;
RT "A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway
RT by accelerating degradation of wild-type JAB/CIS family proteins through
RT the SOCS-box.";
RL J. Biol. Chem. 276:40746-40754(2001).
RN [16]
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 [17]
RP FUNCTION IN INHIBITION OF INSR KINASE ACTIVITY, AND INTERACTION WITH INSR.
RX PubMed=15169905; DOI=10.1128/mcb.24.12.5434-5446.2004;
RA Ueki K., Kondo T., Kahn C.R.;
RT "Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin
RT resistance through inhibition of tyrosine phosphorylation of insulin
RT receptor substrate proteins by discrete mechanisms.";
RL Mol. Cell. Biol. 24:5434-5446(2004).
RN [18]
RP FUNCTION, AND INTERACTION WITH IFNGR1.
RX PubMed=15522878; DOI=10.1074/jbc.m409863200;
RA Qing Y., Costa-Pereira A.P., Watling D., Stark G.R.;
RT "Role of tyrosine 441 of interferon-gamma receptor subunit 1 in SOCS-1-
RT mediated attenuation of STAT1 activation.";
RL J. Biol. Chem. 280:1849-1853(2005).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24880459; DOI=10.1038/ni.2917;
RA Luckey M.A., Kimura M.Y., Waickman A.T., Feigenbaum L., Singer A.,
RA Park J.H.;
RT "The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage
RT fate by inducing the SOCS suppressors of cytokine signaling.";
RL Nat. Immunol. 15:638-645(2014).
CC -!- FUNCTION: Essential negative regulator of type I and type II interferon
CC (IFN) signaling, as well as that of other cytokines, including IL2,
CC IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:9202125,
CC PubMed:10064597, PubMed:15169905, PubMed:15522878). Downregulates
CC cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts
CC by binding to JAK proteins and to IFNGR1 and inhibiting their kinase
CC activity (PubMed:9202125, PubMed:10064597, PubMed:15522878). In vitro,
CC suppresses Tec protein-tyrosine activity (By similarity). Regulates
CC IFN-gamma (IFNG)-mediated sensory neuron survival. Probable substrate
CC recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3
CC ubiquitin ligase complex which mediates the ubiquitination and
CC subsequent proteasomal degradation of target proteins (By similarity).
CC {ECO:0000250|UniProtKB:O15524, ECO:0000269|PubMed:10064597,
CC ECO:0000269|PubMed:15169905, ECO:0000269|PubMed:15522878,
CC ECO:0000269|PubMed:9202125}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2
CC and VAV. Binding to JAKs is mediated through the KIR and SH2 domain to
CC a phosphorylated tyrosine residue within the JAK JH1 domain. Binds the
CC SH3 domain of GRB2 via diproline determinants in the N-terminus, and
CC the N-terminal regulatory domain of VAV. Interacts with the Elongin BC
CC complex (ELOB and ELOC). Component of an ECS CBC(SOCS1) E3 ubiquitin-
CC protein ligase complex which contains Elongin BC, CUL5, RBX1 and SOCS1.
CC Interacts (via SH2 domain and SOCS box) with TRIM8. Interacts with
CC CUL2. Interacts with AXL and FGFR3 (By similarity). Interacts with
CC INSR. Interacts with TRIM8 (By similarity). Interacts with DCUN1D1 (By
CC similarity). Interacts with IFNGR1 (PubMed:15522878).
CC {ECO:0000250|UniProtKB:O15524, ECO:0000269|PubMed:10051596,
CC ECO:0000269|PubMed:12163497, ECO:0000269|PubMed:15169905,
CC ECO:0000269|PubMed:9869640}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15524}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:O15524}. Note=Detected in
CC perinuclear cytoplasmic vesicles upon interaction with FGFR3.
CC {ECO:0000250|UniProtKB:O15524}.
CC -!- TISSUE SPECIFICITY: High expression in thymus. Lower expression in lung
CC and spleen (PubMed:9202125). Expressed in both Th1 and Th2 cells.
CC {ECO:0000269|PubMed:12242343, ECO:0000269|PubMed:9202125}.
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, expression first observed at 14 dpc uniformly
CC in all cells. Also expressed in the innermost layers of the developing
CC retina. Levels of expression remain unchanged from P8 until adulthood.
CC In the peripheral nervous system, high levels found in virtually all
CC neurons of the dorsal root ganglion.
CC -!- INDUCTION: By a subset of cytokines including those belonging to the
CC interferon, interleukin and colony-stimulating factor families.
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. The Elongin BC complex binding domain is also known as BC-
CC box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the
CC SOCS box.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit lymphocyte deficiency and
CC degeneration of the liver parenchyma. Animals die within 3 weeks of
CC age. Mutants show a much higher frequency of CD8 single positive
CC thymocytes (PubMed:24880459). {ECO:0000269|PubMed:24880459,
CC ECO:0000269|PubMed:9826711}.
CC -!- SIMILARITY: Belongs to the SOCS1 family. {ECO:0000305}.
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DR EMBL; U88325; AAB62400.1; -; mRNA.
DR EMBL; AB000677; BAA21538.1; -; mRNA.
DR EMBL; AB000710; BAA21539.1; -; mRNA.
DR EMBL; AF120490; AAD24777.1; -; mRNA.
DR EMBL; AF180302; AAD53324.1; -; mRNA.
DR EMBL; AK028632; BAC26040.1; -; mRNA.
DR EMBL; AK154706; BAE32775.1; -; mRNA.
DR EMBL; BC132366; AAI32367.1; -; mRNA.
DR EMBL; BC132368; AAI32369.1; -; mRNA.
DR CCDS; CCDS27952.1; -.
DR RefSeq; NP_001258532.1; NM_001271603.1.
DR RefSeq; NP_034026.1; NM_009896.2.
DR AlphaFoldDB; O35716; -.
DR SMR; O35716; -.
DR BioGRID; 198719; 32.
DR IntAct; O35716; 6.
DR MINT; O35716; -.
DR STRING; 10090.ENSMUSP00000038121; -.
DR iPTMnet; O35716; -.
DR PhosphoSitePlus; O35716; -.
DR EPD; O35716; -.
DR PaxDb; O35716; -.
DR PRIDE; O35716; -.
DR ProteomicsDB; 257284; -.
DR Antibodypedia; 4157; 643 antibodies from 44 providers.
DR DNASU; 12703; -.
DR Ensembl; ENSMUST00000038099; ENSMUSP00000038121; ENSMUSG00000038037.
DR Ensembl; ENSMUST00000229866; ENSMUSP00000155530; ENSMUSG00000038037.
DR GeneID; 12703; -.
DR KEGG; mmu:12703; -.
DR UCSC; uc007yed.1; mouse.
DR CTD; 8651; -.
DR MGI; MGI:1354910; Socs1.
DR VEuPathDB; HostDB:ENSMUSG00000038037; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000161164; -.
DR HOGENOM; CLU_079452_2_1_1; -.
DR InParanoid; O35716; -.
DR OMA; LERCGFY; -.
DR OrthoDB; 1135696at2759; -.
DR PhylomeDB; O35716; -.
DR TreeFam; TF321368; -.
DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-877312; Regulation of IFNG signaling.
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 SABIO-RK; O35716; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 12703; 20 hits in 76 CRISPR screens.
DR ChiTaRS; Socs1; mouse.
DR PRO; PR:O35716; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O35716; protein.
DR Bgee; ENSMUSG00000038037; Expressed in thymus and 78 other tissues.
DR Genevisible; O35716; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; 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:0005159; F:insulin-like growth factor receptor binding; ISO:MGI.
DR GO; GO:0019210; F:kinase inhibitor activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0030225; P:macrophage differentiation; ISO:MGI.
DR GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:1904898; P:negative regulation of hepatic stellate cell proliferation; ISO: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; IMP:MGI.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IDA:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; ISO:MGI.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:MGI.
DR GO; GO:0010533; P:regulation of activation of Janus kinase activity; IMP:MGI.
DR GO; GO:0001817; P:regulation of cytokine production; IMP:MGI.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IMP:MGI.
DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; IMP:MGI.
DR CDD; cd10382; SH2_SOCS1; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028411; SOCS1.
DR InterPro; IPR035861; SOCS1_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF4; PTHR10155:SF4; 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 Cytoplasmic vesicle; Growth regulation; Nucleus; Reference proteome;
KW SH2 domain; Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..212
FT /note="Suppressor of cytokine signaling 1"
FT /id="PRO_0000181236"
FT DOMAIN 80..175
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 162..211
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..67
FT /note="Kinase inhibitory region (KIR)"
FT REGION 68..79
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 174..183
FT /note="Interaction with Elongin BC complex"
FT COMPBIAS 21..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 51
FT /note="P->A: No effect on LIF signal transduction
FT suppression."
FT MUTAGEN 52
FT /note="G->A: No effect on LIF signal transduction
FT suppression."
FT MUTAGEN 53
FT /note="D->A,R: No effect on LIF signal transduction
FT suppression."
FT MUTAGEN 54
FT /note="T->A: No effect on LIF signal transduction
FT suppression."
FT MUTAGEN 55
FT /note="H->A,D: No effect on JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 56
FT /note="F->A,S,D: Loss of JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 56
FT /note="F->E,S: Reduced binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 56
FT /note="F->L: No effect on JAK signal transduction
FT inhibition nor on binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 57
FT /note="R->A,E: No effect on JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 58
FT /note="T->A: No effect on JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 59
FT /note="F->A,E: Loss of JAK signal transduction suppression.
FT Reduced binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597,
FT ECO:0000269|PubMed:11522790"
FT MUTAGEN 59
FT /note="F->D: Loss of JAK signal transduction suppression.
FT Destabilization of SOCS1."
FT /evidence="ECO:0000269|PubMed:10064597,
FT ECO:0000269|PubMed:11522790"
FT MUTAGEN 59
FT /note="F->L: No effect on JAK signal transduction
FT suppression nor on binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597,
FT ECO:0000269|PubMed:11522790"
FT MUTAGEN 60
FT /note="R->A: No effect on LIF signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 61
FT /note="S->E: No effect on JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 62
FT /note="H->E: No effect on JAK signal transduction
FT suppression."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 64
FT /note="D->R: Loss of JAK signal transduction suppression.
FT Reduced binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 65
FT /note="Y->A: Some loss of JAK signal transduction
FT signaling. Reduced binding to JH1."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 68
FT /note="I->E: Loss of binding to JH1/Y-1007 of JAK2 and loss
FT of signal transduction suppression."
FT MUTAGEN 70
FT /note="R->E: No effect on LIF signal transduction
FT suppression."
FT MUTAGEN 75
FT /note="L->E: Loss of binding to JH1/Y-1007 of JAK2 and loss
FT of signal transduction suppression."
FT MUTAGEN 105
FT /note="R->K: Loss of LIF signal transduction suppression.
FT Loss of binding to KIT. No effect on binding to VAV."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 105
FT /note="R->Q: Loss of IL-6 signal transduction suppression.
FT No effect on binding to TYK2."
FT /evidence="ECO:0000269|PubMed:10064597"
FT MUTAGEN 175
FT /note="L->P: Abolishes interaction with elongin BC complex;
FT when associated with F-179."
FT /evidence="ECO:0000269|PubMed:9869640"
FT MUTAGEN 179
FT /note="C->F: Abolishes interaction with elongin BC complex;
FT when associated with P-175."
FT /evidence="ECO:0000269|PubMed:9869640"
FT CONFLICT 141
FT /note="S -> N (in Ref. 2; BAA21538 and 3; BAA21539)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 212 AA; 23715 MW; 4621E05DC3D44C69 CRC64;
MVARNQVAAD NAISPAAEPR RRSEPSSSSS SSSPAAPVRP RPCPAVPAPA PGDTHFRTFR
SHSDYRRITR TSALLDACGF YWGPLSVHGA HERLRAEPVG TFLVRDSRQR NCFFALSVKM
ASGPTSIRVH FQAGRFHLDG SRETFDCLFE LLEHYVAAPR RMLGAPLRQR RVRPLQELCR
QRIVAAVGRE NLARIPLNPV LRDYLSSFPF QI
