WSB1_HUMAN
ID WSB1_HUMAN Reviewed; 421 AA.
AC Q9Y6I7; Q9NRB1; Q9UBH9; Q9UG25; Q9UNN6; Q9Y656;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=WD repeat and SOCS box-containing protein 1;
DE Short=WSB-1;
DE AltName: Full=SOCS box-containing WD protein SWiP-1;
GN Name=WSB1; Synonyms=SWIP1;
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] (ISOFORM 1).
RX PubMed=10354473; DOI=10.1016/s0925-4773(99)00014-3;
RA Vasiliauskas D., Hancock S., Stern C.D.;
RT "SWiP-1: novel SOCS box containing WD-protein regulated by signalling
RT centres and by Shh during development.";
RL Mech. Dev. 82:79-94(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Pituitary;
RA Peng Y., Song H., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human wsb-1 isoform gene.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Zhang J.W., Liu T.X., Shen Y., Chen S.J., Chen Z.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-16.
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-16.
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [9]
RP FUNCTION IN AN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND INTERACTION WITH CUL5; RNF7; ELOB AND ELOC.
RX PubMed=15601820; DOI=10.1101/gad.1252404;
RA Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C.,
RA Conaway J.W., Nakayama K.I.;
RT "VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1
RT and Cul5-Rbx2 modules of ubiquitin ligases.";
RL Genes Dev. 18:3055-3065(2004).
RN [10]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH DIO2.
RX PubMed=15965468; DOI=10.1038/ncb1272;
RA Dentice M., Bandyopadhyay A., Gereben B., Callebaut I.,
RA Christoffolete M.A., Kim B.W., Nissim S., Mornon J.P., Zavacki A.M.,
RA Zeold A., Capelo L.P., Curcio-Morelli C., Ribeiro R., Harney J.W.,
RA Tabin C.J., Bianco A.C.;
RT "The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid
RT hormone activation and PTHrP secretion in the developing growth plate.";
RL Nat. Cell Biol. 7:698-705(2005).
RN [11]
RP FUNCTION, AND INTERACTION WITH HIPK2.
RX PubMed=18093972; DOI=10.1074/jbc.m708873200;
RA Choi D.W., Seo Y.-M., Kim E.-A., Sung K.S., Ahn J.W., Park S.-J.,
RA Lee S.-R., Choi C.Y.;
RT "Ubiquitination and degradation of homeodomain-interacting protein kinase 2
RT by WD40 repeat/SOCS box protein WSB-1.";
RL J. Biol. Chem. 283:4682-4689(2008).
CC -!- FUNCTION: Probable substrate-recognition component of a SCF-like ECS
CC (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which
CC mediates the ubiquitination and subsequent proteasomal degradation of
CC target proteins. Recognizes type II iodothyronine deiodinase/DIO2.
CC Confers constitutive instability to HIPK2 through proteasomal
CC degradation. {ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:15965468,
CC ECO:0000269|PubMed:18093972}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with DIO2. Component of the probable ECS(WSB1) E3
CC ubiquitin ligase complex which contains CUL5, RNF7/RBX2, Elongin BC
CC complex and WSB1. Component of a probable ECS-like E3 ubiquitin-protein
CC ligase complex which contains CUL5, RBX1, Elongin BC complex and WSB1.
CC Interacts with CUL5, RNF7, ELOB and ELOC. Binds to HIPK2 through WD40
CC repeats. {ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:15965468,
CC ECO:0000269|PubMed:18093972}.
CC -!- INTERACTION:
CC Q9Y6I7; Q5S007: LRRK2; NbExp=5; IntAct=EBI-1171494, EBI-5323863;
CC Q9Y6I7; P40337-2: VHL; NbExp=3; IntAct=EBI-1171494, EBI-12157263;
CC Q9Y6I7; Q9QZR5: Hipk2; Xeno; NbExp=5; IntAct=EBI-1171494, EBI-366905;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9Y6I7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y6I7-2; Sequence=VSP_006792;
CC Name=3;
CC IsoId=Q9Y6I7-3; Sequence=VSP_039111, VSP_039112;
CC Name=4;
CC IsoId=Q9Y6I7-4; Sequence=VSP_053402, VSP_053403;
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; AF072880; AAD28808.1; -; mRNA.
DR EMBL; AF106684; AAD43037.1; -; mRNA.
DR EMBL; AF069313; AAD20954.2; -; mRNA.
DR EMBL; AF240696; AAF82746.1; -; mRNA.
DR EMBL; AL110243; CAB53693.1; -; mRNA.
DR EMBL; AF112205; AAF17193.1; -; mRNA.
DR EMBL; AF106683; AAD43036.1; -; mRNA.
DR EMBL; AL110269; CAB53708.2; -; mRNA.
DR EMBL; BC021110; AAH21110.1; -; mRNA.
DR CCDS; CCDS11220.1; -. [Q9Y6I7-1]
DR CCDS; CCDS11221.1; -. [Q9Y6I7-2]
DR PIR; T14773; T14773.
DR PIR; T14788; T14788.
DR RefSeq; NP_056441.6; NM_015626.9. [Q9Y6I7-1]
DR RefSeq; NP_599027.1; NM_134265.3. [Q9Y6I7-2]
DR RefSeq; XP_016879924.1; XM_017024435.1. [Q9Y6I7-4]
DR RefSeq; XP_016879925.1; XM_017024436.1. [Q9Y6I7-4]
DR AlphaFoldDB; Q9Y6I7; -.
DR SMR; Q9Y6I7; -.
DR BioGRID; 117560; 21.
DR CORUM; Q9Y6I7; -.
DR IntAct; Q9Y6I7; 9.
DR MINT; Q9Y6I7; -.
DR STRING; 9606.ENSP00000262394; -.
DR iPTMnet; Q9Y6I7; -.
DR PhosphoSitePlus; Q9Y6I7; -.
DR BioMuta; WSB1; -.
DR DMDM; 20532298; -.
DR EPD; Q9Y6I7; -.
DR MassIVE; Q9Y6I7; -.
DR MaxQB; Q9Y6I7; -.
DR PaxDb; Q9Y6I7; -.
DR PeptideAtlas; Q9Y6I7; -.
DR PRIDE; Q9Y6I7; -.
DR ProteomicsDB; 86693; -. [Q9Y6I7-1]
DR ProteomicsDB; 86694; -. [Q9Y6I7-2]
DR ProteomicsDB; 86695; -. [Q9Y6I7-3]
DR Antibodypedia; 1139; 156 antibodies from 23 providers.
DR DNASU; 26118; -.
DR Ensembl; ENST00000262394.7; ENSP00000262394.2; ENSG00000109046.15. [Q9Y6I7-1]
DR Ensembl; ENST00000348811.6; ENSP00000327055.2; ENSG00000109046.15. [Q9Y6I7-2]
DR GeneID; 26118; -.
DR KEGG; hsa:26118; -.
DR MANE-Select; ENST00000262394.7; ENSP00000262394.2; NM_015626.10; NP_056441.6.
DR UCSC; uc002gzd.2; human. [Q9Y6I7-1]
DR CTD; 26118; -.
DR DisGeNET; 26118; -.
DR GeneCards; WSB1; -.
DR HGNC; HGNC:19221; WSB1.
DR HPA; ENSG00000109046; Low tissue specificity.
DR MIM; 610091; gene.
DR neXtProt; NX_Q9Y6I7; -.
DR OpenTargets; ENSG00000109046; -.
DR PharmGKB; PA134867554; -.
DR VEuPathDB; HostDB:ENSG00000109046; -.
DR eggNOG; KOG0266; Eukaryota.
DR GeneTree; ENSGT00890000139406; -.
DR HOGENOM; CLU_056876_0_0_1; -.
DR InParanoid; Q9Y6I7; -.
DR OMA; YVWDPHT; -.
DR PhylomeDB; Q9Y6I7; -.
DR TreeFam; TF329216; -.
DR PathwayCommons; Q9Y6I7; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9Y6I7; -.
DR SIGNOR; Q9Y6I7; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 26118; 25 hits in 1118 CRISPR screens.
DR ChiTaRS; WSB1; human.
DR GeneWiki; WSB1; -.
DR GenomeRNAi; 26118; -.
DR Pharos; Q9Y6I7; Tbio.
DR PRO; PR:Q9Y6I7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y6I7; protein.
DR Bgee; ENSG00000109046; Expressed in corpus callosum and 205 other tissues.
DR ExpressionAtlas; Q9Y6I7; baseline and differential.
DR Genevisible; Q9Y6I7; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0140454; P:protein aggregate center assembly; IEA:Ensembl.
DR GO; GO:0044314; P:protein K27-linked ubiquitination; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 3.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF07525; SOCS_box; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50225; SOCS; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Reference proteome; Repeat; Ubl conjugation pathway;
KW WD repeat.
FT CHAIN 1..421
FT /note="WD repeat and SOCS box-containing protein 1"
FT /id="PRO_0000051457"
FT REPEAT 32..71
FT /note="WD 1"
FT REPEAT 124..165
FT /note="WD 2"
FT REPEAT 168..208
FT /note="WD 3"
FT REPEAT 212..251
FT /note="WD 4"
FT REPEAT 254..293
FT /note="WD 5"
FT REPEAT 309..346
FT /note="WD 6"
FT DOMAIN 372..421
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT VAR_SEQ 1..35
FT /note="MASFPPRVNEKEIVRLRTIGELLAPAAPFDKKCGR -> MLNIILIKFSSFS
FT IRCAILSSVCLNEAITFAFLLQ (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_053402"
FT VAR_SEQ 14..159
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_006792"
FT VAR_SEQ 36..237
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_053403"
FT VAR_SEQ 239..244
FT /note="FLWNMD -> VAAILV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_039111"
FT VAR_SEQ 245..421
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_039112"
FT VARIANT 16
FT /note="L -> S (in dbSNP:rs6561)"
FT /evidence="ECO:0000269|PubMed:10931946,
FT ECO:0000269|PubMed:11230166"
FT /id="VAR_024701"
FT CONFLICT 149
FT /note="N -> S (in Ref. 7; CAB53708)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="E -> G (in Ref. 7; CAB53708)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="F -> L (in Ref. 6; AAD43036)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="K -> R (in Ref. 7; CAB53708)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="S -> P (in Ref. 6; AAD43036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 47432 MW; 650D4942E97D4BED CRC64;
MASFPPRVNE KEIVRLRTIG ELLAPAAPFD KKCGRENWTV AFAPDGSYFA WSQGHRTVKL
VPWSQCLQNF LLHGTKNVTN SSSLRLPRQN SDGGQKNKPR EHIIDCGDIV WSLAFGSSVP
EKQSRCVNIE WHRFRFGQDQ LLLATGLNNG RIKIWDVYTG KLLLNLVDHT EVVRDLTFAP
DGSLILVSAS RDKTLRVWDL KDDGNMMKVL RGHQNWVYSC AFSPDSSMLC SVGASKAVFL
WNMDKYTMIR KLEGHHHDVV ACDFSPDGAL LATASYDTRV YIWDPHNGDI LMEFGHLFPP
PTPIFAGGAN DRWVRSVSFS HDGLHVASLA DDKMVRFWRI DEDYPVQVAP LSNGLCCAFS
TDGSVLAAGT HDGSVYFWAT PRQVPSLQHL CRMSIRRVMP TQEVQELPIP SKLLEFLSYR
I
