SOCS2_MOUSE
ID SOCS2_MOUSE Reviewed; 198 AA.
AC O35717;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Suppressor of cytokine signaling 2;
DE Short=SOCS-2;
DE AltName: Full=Cytokine-inducible SH2 protein 2;
DE Short=CIS-2;
GN Name=Socs2; Synonyms=Cis2, Cish2;
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=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 DEVELOPMENTAL STAGE.
RX PubMed=10867663;
RX DOI=10.1002/1096-9861(20000724)423:2<348::aid-cne11>3.0.co;2-w;
RA Polizzotto M.N., Bartlett P.F., Turnley A.M.;
RT "Expression of 'suppressor of cytokine signaling' (SOCS) genes in the
RT developing and adult mouse nervous system.";
RL J. Comp. Neurol. 423:348-358(2000).
RN [3]
RP UBIQUITINATION AT LYS-173, PROTEASOMAL DEGRADATION, PHOSPHORYLATION AT
RP SER-52, AND INTERACTION WITH AREL1 AND PRKCA.
RX PubMed=31578312; DOI=10.1172/jci.insight.129110;
RA Lear T.B., McKelvey A.C., Evankovich J.W., Rajbhandari S., Coon T.A.,
RA Dunn S.R., Londino J.D., McVerry B.J., Zhang Y., Valenzi E., Burton C.L.,
RA Gordon R., Gingras S., Lockwood K.C., Jurczak M.J., Lafyatis R.,
RA Shlomchik M.J., Liu Y., Chen B.B.;
RT "KIAA0317 regulates pulmonary inflammation through SOCS2 degradation.";
RL JCI Insight 4:0-0(2019).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. SOCS2
CC appears to be a negative regulator in the growth hormone/IGF1 signaling
CC pathway. Probable substrate recognition component of a SCF-like ECS
CC (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which
CC mediates the ubiquitination and subsequent proteasomal degradation of
CC target proteins (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with IGF1R (By similarity). Associates with the
CC Elongin BC complex (By similarity). Interacts with AREL1 and PRKCA
CC (PubMed:31578312). Interacts with DCUN1D1 (By similarity).
CC {ECO:0000250|UniProtKB:O14508, ECO:0000269|PubMed:31578312}.
CC -!- TISSUE SPECIFICITY: Expressed primarily in the testis, some expression
CC in liver and lung.
CC -!- DEVELOPMENTAL STAGE: In the developing brain, expressed at relatively
CC high levels from 10 dpc stages to young adulthood (P25) with peak
CC levels from 14 dpc to P8. Levels of SOCS2 increase dramatically between
CC 10 dpc and 12 dpc. At 12 dpc, high expression found in the olfactory
CC epithelium with moderate expression in the neuroepithelium of the
CC neocortex, presumptive striatum, hippocampus and septum. Low expression
CC in the retina. At 14 dpc, in the cortical wall, levels increase in the
CC cortical plate and decrease in the intermediate zone. High expression
CC also in the hippocampus, fimbria, thalamic neuroepithelium and
CC innermost layer of the retina. At P8, high expression in the neurons of
CC the hippocampus. Lower levels found in the dentate gyrus. Levels of
CC expression decrease between P8 and P15 and remain constant until P25.
CC In adulthood, levels decrease. In the peripheral nervous system,
CC expression found at low levels at 14 dpc in a subpopulation of neurons
CC in the dorsal root ganglion. {ECO:0000269|PubMed:10867663}.
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: Ubiquitinated; mediated by AREL1 and leading to its subsequent
CC proteasomal degradation (PubMed:31578312). Ubiquitination is dependent
CC on phosphorylation at Ser-52, by PKC and is stimulated by LPS
CC (PubMed:31578312). {ECO:0000269|PubMed:31578312}.
CC -!- PTM: Phosphorylation at Ser-52 by PKC facilitates its ubiquitination
CC and proteosomal degradation. {ECO:0000269|PubMed:31578312}.
CC -!- MISCELLANEOUS: Mice deficient in SOCS2 exhibit considerable weight
CC increase (30-40% more than normal) after 3 weeks of age. This is
CC attributable to increase in visceral organ weight, carcass weight, long
CC bone length and body length. In addition there is a thickening of the
CC dermis due to excess collagen accumulation.
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DR EMBL; U88327; AAB62402.1; -; mRNA.
DR CCDS; CCDS24136.1; -.
DR RefSeq; NP_001162126.1; NM_001168655.1.
DR RefSeq; NP_001162127.1; NM_001168656.1.
DR RefSeq; NP_001162128.1; NM_001168657.1.
DR RefSeq; NP_031732.1; NM_007706.4.
DR RefSeq; XP_011241712.1; XM_011243410.2.
DR AlphaFoldDB; O35717; -.
DR SMR; O35717; -.
DR BioGRID; 229727; 13.
DR IntAct; O35717; 3.
DR MINT; O35717; -.
DR STRING; 10090.ENSMUSP00000020215; -.
DR PhosphoSitePlus; O35717; -.
DR EPD; O35717; -.
DR PaxDb; O35717; -.
DR PRIDE; O35717; -.
DR ProteomicsDB; 261315; -.
DR Antibodypedia; 4158; 297 antibodies from 37 providers.
DR DNASU; 216233; -.
DR Ensembl; ENSMUST00000020215; ENSMUSP00000020215; ENSMUSG00000020027.
DR Ensembl; ENSMUST00000119917; ENSMUSP00000113378; ENSMUSG00000020027.
DR Ensembl; ENSMUST00000170690; ENSMUSP00000129331; ENSMUSG00000020027.
DR Ensembl; ENSMUST00000172070; ENSMUSP00000131875; ENSMUSG00000020027.
DR GeneID; 216233; -.
DR KEGG; mmu:216233; -.
DR UCSC; uc007gwg.2; mouse.
DR CTD; 8835; -.
DR MGI; MGI:1201787; Socs2.
DR VEuPathDB; HostDB:ENSMUSG00000020027; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000157983; -.
DR HOGENOM; CLU_079452_4_0_1; -.
DR InParanoid; O35717; -.
DR OMA; AGWYWGN; -.
DR OrthoDB; 1135696at2759; -.
DR PhylomeDB; O35717; -.
DR TreeFam; TF321368; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 216233; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Socs2; mouse.
DR PRO; PR:O35717; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O35717; protein.
DR Bgee; ENSMUSG00000020027; Expressed in cumulus cell and 261 other tissues.
DR ExpressionAtlas; O35717; baseline and differential.
DR Genevisible; O35717; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
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:0005131; F:growth hormone receptor binding; IPI:MGI.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0008269; F:JAK pathway signal transduction adaptor activity; IEA:InterPro.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:MGI.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:MGI.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IGI:MGI.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IGI:MGI.
DR GO; GO:0001558; P:regulation of cell growth; IEA:InterPro.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0032355; P:response to estradiol; ISO:MGI.
DR CDD; cd10383; SH2_SOCS2; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028410; SOCS2.
DR InterPro; IPR035862; SOCS2_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF7; PTHR10155:SF7; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF07525; SOCS_box; 1.
DR PRINTS; PR00401; SH2DOMAIN.
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; Isopeptide bond; Phosphoprotein; Reference proteome;
KW SH2 domain; Signal transduction inhibitor; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..198
FT /note="Suppressor of cytokine signaling 2"
FT /id="PRO_0000181239"
FT DOMAIN 48..156
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 151..197
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..75
FT /note="Interaction with AREL1"
FT /evidence="ECO:0000250|UniProtKB:O14508"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14508"
FT MOD_RES 52
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:31578312"
FT CROSSLNK 173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O14508"
SQ SEQUENCE 198 AA; 22434 MW; C9051AE9C84BA7F5 CRC64;
MTLRCLEPSG NGADRTRSQW GTAGLPEEQS PEAARLAKAL RELSQTGWYW GSMTVNEAKE
KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ DGKFRLDSII CVKSKLKQFD
SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL YLTKPLYTSA PTLQHFCRLA INKCTGTIWG
LPLPTRLKDY LEEYKFQV
