ID   CISH_RAT                Reviewed;         256 AA.
AC   O70512; Q9ERQ1;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   25-MAY-2022, entry version 115.
DE   RecName: Full=Cytokine-inducible SH2-containing protein;
DE            Short=CIS;
DE   AltName: Full=CIS-1;
DE   AltName: Full=Suppressor of cytokine signaling;
DE            Short=SOCS;
DE   Flags: Fragment;
GN   Name=Cish;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=10579313; DOI=10.1210/endo.140.12.7212;
RA   Mao Y., Ling P.R., Fitzgibbons T.P., McCowen K.C., Frick G.P.,
RA   Bistrian B.R., Smith R.J.;
RT   "Endotoxin-induced inhibition of growth hormone receptor signaling in rat
RT   liver in vivo.";
RL   Endocrinology 140:5505-5515(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE OF 51-163.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RA   Siebenson L.N., Berry S.A.;
RT   "Cytokine inducible SH2-containing protein (CIS) from rat liver.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: SOCS family proteins form part of a classical negative
CC       feedback system that regulates cytokine signal transduction. CIS is
CC       involved in the negative regulation of cytokines that signal through
CC       the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin
CC       3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its
CC       tyrosine phosphorylation (By similarity). May be a substrate
CC       recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box
CC       protein) E3 ubiquitin-protein ligase complex which mediates the
CC       ubiquitination and subsequent proteasomal degradation of target
CC       proteins (By similarity). {ECO:0000250}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Stably associated with the tyrosine-phosphorylated IL3
CC       receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR).
CC       {ECO:0000250}.
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DR   EMBL; AF065161; AAC17502.1; -; mRNA.
DR   EMBL; AF294256; AAG29815.1; -; Genomic_DNA.
DR   AlphaFoldDB; O70512; -.
DR   SMR; O70512; -.
DR   STRING; 10116.ENSRNOP00000041734; -.
DR   iPTMnet; O70512; -.
DR   PhosphoSitePlus; O70512; -.
DR   PaxDb; O70512; -.
DR   UCSC; RGD:69261; rat.
DR   RGD; 69261; Cish.
DR   eggNOG; KOG4566; Eukaryota.
DR   InParanoid; O70512; -.
DR   Reactome; R-RNO-8951664; Neddylation.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IEP:RGD.
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:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR   GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR   CDD; cd10718; SH2_CIS; 1.
DR   Gene3D; 3.30.505.10; -; 1.
DR   InterPro; IPR028425; CIS.
DR   InterPro; IPR035887; CIS_SH2.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR001496; SOCS_box.
DR   InterPro; IPR036036; SOCS_box-like_dom_sf.
DR   PANTHER; PTHR10155:SF9; PTHR10155:SF9; 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   2: Evidence at transcript level;
KW   Growth regulation; Reference proteome; SH2 domain;
KW   Signal transduction inhibitor; Ubl conjugation pathway.
FT   CHAIN           <1..256
FT                   /note="Cytokine-inducible SH2-containing protein"
FT                   /id="PRO_0000181233"
FT   DOMAIN          81..162
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          207..255
FT                   /note="SOCS box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT   REGION          168..190
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   NON_TER         1
SQ   SEQUENCE   256 AA;  28399 MW;  1F6614A4EE9926B1 CRC64;
     VLCVQGSCPL LVVEQIGQRP LWAQSLELPG PAMQPLPTGA FPEEVTEETP VQSENEPKVL
     DPEGDLLCIA KTFSYLRESG WYWGSITASE ARQHLQKMPE GTFLVRDSTH PSYLFTLSVK
     TTRGPTNVRI EYADSSFRLD SNCLSRPRIL AFPDVVSLVQ HYVASCTADT RSDSPDPAPT
     PALPVSKPDA PGDPVLPIPV ATAVHLKLVQ PFVRRSSARS LQHLCRLVIN RLVTDVDCLP
     LPRRMADYLR QYPFQL