ID SOCS4_HUMAN Reviewed; 440 AA.
AC Q8WXH5;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 24-JAN-2024, entry version 171.
DE RecName: Full=Suppressor of cytokine signaling 4;
DE Short=SOCS-4;
DE AltName: Full=Suppressor of cytokine signaling 7;
DE Short=SOCS-7;
GN Name=SOCS4; Synonyms=SOCS7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hilton D.J., Alexander W.S., Nicola N.A.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP FUNCTION IN EGF SIGNALING, AND INDUCTION BY EGF.
RX PubMed=15590694; DOI=10.1074/jbc.m408575200;
RA Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N.,
RA Rechavi G., Yarden Y.;
RT "Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor
RT receptor signaling.";
RL J. Biol. Chem. 280:7038-7048(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 274-437 IN COMPLEX WITH ELONGINS
RP ELOB AND ELOC, FUNCTION, AND SUBUNIT.
RX PubMed=17997974; DOI=10.1016/j.str.2007.09.016;
RA Bullock A.N., Rodriguez M.C., Debreczeni J.E., Songyang Z., Knapp S.;
RT "Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box
RT interface and the molecular basis for SOCS-dependent EGFR degradation.";
RL Structure 15:1493-1504(2007).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. 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. Inhibits EGF signaling by mediating the degradation of the
CC Tyr-phosphorylated EGF receptor/EGFR. {ECO:0000269|PubMed:15590694,
CC ECO:0000269|PubMed:17997974}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- INTERACTION:
CC Q8WXH5; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-3942425, EBI-11532900;
CC Q8WXH5; G5E9A7: DMWD; NbExp=3; IntAct=EBI-3942425, EBI-10976677;
CC Q8WXH5; O43559: FRS3; NbExp=2; IntAct=EBI-3942425, EBI-725515;
CC Q8WXH5; P41250: GARS1; NbExp=3; IntAct=EBI-3942425, EBI-724143;
CC Q8WXH5; P62993: GRB2; NbExp=3; IntAct=EBI-3942425, EBI-401755;
CC Q8WXH5; O43464: HTRA2; NbExp=3; IntAct=EBI-3942425, EBI-517086;
CC Q8WXH5; P42858: HTT; NbExp=3; IntAct=EBI-3942425, EBI-466029;
CC Q8WXH5; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-3942425, EBI-1055254;
CC Q8WXH5; Q9BZ23-2: PANK2; NbExp=3; IntAct=EBI-3942425, EBI-25929070;
CC Q8WXH5; Q92569: PIK3R3; NbExp=3; IntAct=EBI-3942425, EBI-79893;
CC Q8WXH5; Q9BXM7: PINK1; NbExp=3; IntAct=EBI-3942425, EBI-2846068;
CC Q8WXH5; Q96R05: RBP7; NbExp=3; IntAct=EBI-3942425, EBI-2856326;
CC Q8WXH5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-3942425, EBI-5235340;
CC Q8WXH5; O15269-2: SPTLC1; NbExp=3; IntAct=EBI-3942425, EBI-25912901;
CC Q8WXH5; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-3942425, EBI-750487;
CC -!- INDUCTION: Up-regulated by EGF. {ECO:0000269|PubMed:15590694}.
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; AF424815; AAL60517.1; -; mRNA.
DR EMBL; BC060790; AAH60790.1; -; mRNA.
DR CCDS; CCDS9722.1; -.
DR RefSeq; NP_543143.1; NM_080867.2.
DR RefSeq; NP_955453.1; NM_199421.1.
DR RefSeq; XP_011534727.1; XM_011536425.1.
DR RefSeq; XP_011534728.1; XM_011536426.1.
DR PDB; 2IZV; X-ray; 2.55 A; A=274-437.
DR PDBsum; 2IZV; -.
DR AlphaFoldDB; Q8WXH5; -.
DR SMR; Q8WXH5; -.
DR BioGRID; 125796; 24.
DR DIP; DIP-29568N; -.
DR IntAct; Q8WXH5; 26.
DR MINT; Q8WXH5; -.
DR STRING; 9606.ENSP00000452522; -.
DR iPTMnet; Q8WXH5; -.
DR PhosphoSitePlus; Q8WXH5; -.
DR BioMuta; SOCS4; -.
DR DMDM; 20178106; -.
DR MassIVE; Q8WXH5; -.
DR MaxQB; Q8WXH5; -.
DR PaxDb; 9606-ENSP00000378855; -.
DR PeptideAtlas; Q8WXH5; -.
DR ProteomicsDB; 75057; -.
DR Antibodypedia; 4604; 314 antibodies from 34 providers.
DR DNASU; 122809; -.
DR Ensembl; ENST00000339298.2; ENSP00000341327.2; ENSG00000180008.9.
DR Ensembl; ENST00000395472.2; ENSP00000378855.2; ENSG00000180008.9.
DR Ensembl; ENST00000555846.2; ENSP00000452522.1; ENSG00000180008.9.
DR GeneID; 122809; -.
DR KEGG; hsa:122809; -.
DR MANE-Select; ENST00000555846.2; ENSP00000452522.1; NM_199421.2; NP_955453.1.
DR UCSC; uc001xbo.4; human.
DR AGR; HGNC:19392; -.
DR CTD; 122809; -.
DR DisGeNET; 122809; -.
DR GeneCards; SOCS4; -.
DR HGNC; HGNC:19392; SOCS4.
DR HPA; ENSG00000180008; Low tissue specificity.
DR MIM; 616337; gene.
DR neXtProt; NX_Q8WXH5; -.
DR OpenTargets; ENSG00000180008; -.
DR PharmGKB; PA164742477; -.
DR VEuPathDB; HostDB:ENSG00000180008; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000161456; -.
DR HOGENOM; CLU_035609_0_0_1; -.
DR InParanoid; Q8WXH5; -.
DR OMA; PSPMKLY; -.
DR OrthoDB; 5362214at2759; -.
DR PhylomeDB; Q8WXH5; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; Q8WXH5; -.
DR Reactome; R-HSA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR SignaLink; Q8WXH5; -.
DR SIGNOR; Q8WXH5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 122809; 11 hits in 1187 CRISPR screens.
DR ChiTaRS; SOCS4; human.
DR EvolutionaryTrace; Q8WXH5; -.
DR GenomeRNAi; 122809; -.
DR Pharos; Q8WXH5; Tbio.
DR PRO; PR:Q8WXH5; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8WXH5; Protein.
DR Bgee; ENSG00000180008; Expressed in epithelial cell of pancreas and 189 other cell types or tissues.
DR ExpressionAtlas; Q8WXH5; baseline and differential.
DR Genevisible; Q8WXH5; HS.
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:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR CDD; cd10385; SH2_SOCS4; 1.
DR CDD; cd03738; SOCS_SOCS4; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR022252; SOCS4/SOCS5_dom.
DR InterPro; IPR035864; SOCS4_SH2.
DR InterPro; IPR037342; SOCS4_SOCS.
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:SF21; SUPPRESSOR OF CYTOKINE SIGNALING 4; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF12610; SOCS; 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; 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; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..440
FT /note="Suppressor of cytokine signaling 4"
FT /id="PRO_0000181247"
FT DOMAIN 286..381
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 376..425
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 319..326
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 341..344
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 357..363
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 389..400
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 403..407
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:2IZV"
FT HELIX 413..419
FT /evidence="ECO:0007829|PDB:2IZV"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:2IZV"
SQ SEQUENCE 440 AA; 50623 MW; A4A747AB7F6FF08C CRC64;
MAENNENISK NVDVRPKTSR SRSADRKDGY VWSGKKLSWS KKSESYSDAE TVNGIEKTEV
SLRNQERKHS CSSIELDLDH SCGHRFLGRS LKQKLQDAVG QCFPIKNCSS RHSSGLPSKR
KIHISELMLD KCPFPPRSDL AFRWHFIKRH TAPINSKSDE WVSTDLSQTE LRDGQLKRRN
MEENINCFSH TNVQPCVITT DNALCREGPM TGSVMNLVSN NSIEDSDMDS DDEILTLCTS
SRKRNKPKWD LDDEILQLET PPKYHTQIDY VHCLVPDLLQ INNNPCYWGV MDKYAAEALL
EGKPEGTFLL RDSAQEDYLF SVSFRRYSRS LHARIEQWNH NFSFDAHDPC VFHSPDITGL
LEHYKDPSAC MFFEPLLSTP LIRTFPFSLQ HICRTVICNC TTYDGIDALP IPSSMKLYLK
EYHYKSKVRV LRIDAPEQQC
//
