ID FBW12_HUMAN Reviewed; 464 AA. AC Q6X9E4; E9PG36; Q494Y9; Q494Z0; DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 10-JUN-2026, entry version 153. DE RecName: Full=F-box/WD repeat-containing protein 12; DE AltName: Full=F-box and WD-40 domain-containing protein 12; DE AltName: Full=F-box only protein 35; GN Name=FBXW12; Synonyms=FBW12, FBXO12, FBXO35; 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), TISSUE SPECIFICITY, AND VARIANT RP ASP-273. RC TISSUE=Brain; RX PubMed=15040455; DOI=10.1023/b:mole.0000013502.72069.19; RA Zeng L., Gu S., Li Y., Wang W., Huang Y., Ye X., Xu J., Zhao E., Ji C., RA Ying K., Xie Y., Mao Y.; RT "cDNA cloning and expression analysis of a novel human F-box domain RT containing gene."; RL Mol. Biol. Rep. 31:51-57(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT RP ASP-273. 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 [4] {ECO:0000305} RP FUNCTION, PATHWAY, AND INTERACTION WITH SKP1 AND IL22RA1. RX PubMed=26171402; DOI=10.1155/2015/912713; RA Franz J., Jerome J., Lear T., Gong Q., Weathington N.M.; RT "The Human IL-22 Receptor Is Regulated through the Action of the Novel E3 RT Ligase Subunit FBXW12, Which Functions as an Epithelial Growth RT Suppressor."; RL J. Immunol. Res. 2015:912713-912713(2015). CC -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box CC protein)-type E3 ubiquitin ligase complex (PubMed:26171402). Promotes CC degradation of interleukin-22 receptor subunit IL22RA1 in resting and CC IL22-stimulated conditions by facilitating its ubiquitination CC (PubMed:26171402). Functions as a cell growth suppressor CC (PubMed:26171402). {ECO:0000269|PubMed:26171402}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:26171402}. CC -!- SUBUNIT: Interacts with SKP1 (PubMed:26171402). Interacts with CUL1 (By CC similarity). Interacts with IL22RA1 (PubMed:26171402). CC {ECO:0000250|UniProtKB:Q9UKT8, ECO:0000269|PubMed:26171402}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6X9E4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6X9E4-2; Sequence=VSP_042911; CC Name=3; CC IsoId=Q6X9E4-3; Sequence=VSP_044601; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:15040455}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY247969; AAP75562.1; -; mRNA. DR EMBL; AC104448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC101304; AAI01305.1; -; mRNA. DR EMBL; BC101305; AAI01306.1; -; mRNA. DR CCDS; CCDS2764.1; -. [Q6X9E4-1] DR CCDS; CCDS54577.1; -. [Q6X9E4-3] DR CCDS; CCDS54578.1; -. [Q6X9E4-2] DR RefSeq; NP_001153399.1; NM_001159927.1. [Q6X9E4-2] DR RefSeq; NP_001153401.1; NM_001159929.1. [Q6X9E4-3] DR RefSeq; NP_996985.2; NM_207102.2. [Q6X9E4-1] DR AlphaFoldDB; Q6X9E4; -. DR BioGRID; 130052; 14. DR ComplexPortal; CPX-7822; SCF E3 ubiquitin ligase complex, FBXW12 variant. DR FunCoup; Q6X9E4; 21. DR IntAct; Q6X9E4; 6. DR STRING; 9606.ENSP00000296438; -. DR iPTMnet; Q6X9E4; -. DR PhosphoSitePlus; Q6X9E4; -. DR BioMuta; FBXW12; -. DR DMDM; 215273983; -. DR MassIVE; Q6X9E4; -. DR PaxDb; 9606-ENSP00000296438; -. DR PeptideAtlas; Q6X9E4; -. DR ProteomicsDB; 20236; -. DR ProteomicsDB; 67792; -. [Q6X9E4-1] DR ProteomicsDB; 67793; -. [Q6X9E4-2] DR Antibodypedia; 30045; 162 antibodies from 22 providers. DR DNASU; 285231; -. DR Ensembl; ENST00000296438.9; ENSP00000296438.5; ENSG00000164049.14. [Q6X9E4-1] DR Ensembl; ENST00000415155.5; ENSP00000414683.1; ENSG00000164049.14. [Q6X9E4-2] DR Ensembl; ENST00000445170.5; ENSP00000406139.1; ENSG00000164049.14. [Q6X9E4-3] DR GeneID; 285231; -. DR KEGG; hsa:285231; -. DR MANE-Select; ENST00000296438.9; ENSP00000296438.5; NM_207102.2; NP_996985.2. DR UCSC; uc003csr.3; human. [Q6X9E4-1] DR AGR; HGNC:20729; -. DR ClinPGx; PA134980842; -. DR CTD; 285231; -. DR DisGeNET; 285231; -. DR GeneCards; FBXW12; -. DR HGNC; HGNC:20729; FBXW12. DR HPA; ENSG00000164049; Tissue enriched (pancreas). DR MIM; 609075; gene. DR OpenTargets; ENSG00000164049; -. DR VEuPathDB; HostDB:ENSG00000164049; -. DR eggNOG; ENOG502QT73; Eukaryota. DR GeneTree; ENSGT00940000162557; -. DR HOGENOM; CLU_046549_1_0_1; -. DR InParanoid; Q6X9E4; -. DR OMA; LHLYMWE; -. DR OrthoDB; 63265at2759; -. DR PAN-GO; Q6X9E4; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q6X9E4; -. DR PathwayCommons; Q6X9E4; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SIGNOR; Q6X9E4; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000164049; -. DR BioGRID-ORCS; 285231; 14 hits in 1184 CRISPR screens. DR ChiTaRS; FBXW12; human. DR GenomeRNAi; 285231; -. DR Pharos; Q6X9E4; Tbio. DR PRO; PR:Q6X9E4; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q6X9E4; protein. DR Bgee; ENSG00000164049; Expressed in body of pancreas and 84 other cell types or tissues. DR ExpressionAtlas; Q6X9E4; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR CDD; cd22137; F-box_FBXW12; 1. DR FunFam; 1.20.1280.50:FF:000076; F-box/WD repeat-containing protein 12; 1. DR FunFam; 2.130.10.10:FF:002594; F-box/WD repeat-containing protein 12; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR052121; F-box_SCF_Substrate_Recog. DR InterPro; IPR011044; Quino_amine_DH_bsu. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR46550:SF2; EXPRESSED SEQUENCE C85627-RELATED; 1. DR PANTHER; PTHR46550; F-BOX ONLY PROTEIN 3; 1. DR Pfam; PF12937; F-box-like; 1. DR SMART; SM00256; FBOX; 1. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50969; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR PROSITE; PS50181; FBOX; 1. PE 1: Evidence at protein level; KW Alternative splicing; Proteomics identification; Reference proteome; KW Repeat; Ubl conjugation pathway; WD repeat. FT CHAIN 1..464 FT /note="F-box/WD repeat-containing protein 12" FT /id="PRO_0000051000" FT DOMAIN 1..45 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 89..132 FT /note="WD 1" FT REPEAT 136..174 FT /note="WD 2" FT REPEAT 178..217 FT /note="WD 3" FT REPEAT 222..263 FT /note="WD 4" FT REPEAT 270..315 FT /note="WD 5" FT REPEAT 320..367 FT /note="WD 6" FT REPEAT 370..407 FT /note="WD 7" FT REPEAT 416..461 FT /note="WD 8" FT VAR_SEQ 1..29 FT /note="MEIRLPDLALKRIFSFLDLFGLLQVSQVN -> MSPTHQIQDP (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044601" FT VAR_SEQ 136..205 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042911" FT VARIANT 6 FT /note="P -> L (in dbSNP:rs17080138)" FT /id="VAR_057601" FT VARIANT 166 FT /note="R -> W (in dbSNP:rs6442117)" FT /id="VAR_057602" FT VARIANT 273 FT /note="V -> D (in dbSNP:rs6784322)" FT /evidence="ECO:0000269|PubMed:15040455, FT ECO:0000269|PubMed:15489334" FT /id="VAR_057603" FT CONFLICT 278 FT /note="F -> L (in Ref. 3; AAI01306)" FT /evidence="ECO:0000305" FT CONFLICT 317 FT /note="T -> P (in Ref. 1; AAP75562)" FT /evidence="ECO:0000305" SQ SEQUENCE 464 AA; 53056 MW; DFF81F0D718CEF7B CRC64; MEIRLPDLAL KRIFSFLDLF GLLQVSQVNK HWNRIADSDY LWRSLSLQRW DCSNFTNQHL GTHTWKQFFL HQRRKELRLA LAQPHNFIYK VTKNIAFETE LAYLSGNRLT VDEQEKSIIC SVSPKQELCA WDVQEGTMIW SSPVQEFHFS NLVTLPQMHL AITMDRKKTI KVWNCQDRDA LAVLPMPQPC YCMEAYLTKD GPFLMVGDAA GDIYTFTLPG LRDVSKVTAF QYGIVLLHCS PDKKWVFACG TYSRTLPQVF LTESLLRPSE GSVPLSTFLP HKLCASACWT PKVKNRITLM SQSSTGKKTE FITFDLTTKK TGGQTVIQAY EIASFQVAAH LKCPIWMGAS DGYMIVFTSG PYLLLFSITG FLLQRFEDHQ AAINNFWVDP CYVLTTSENS VHVYMWEEGG RHPYLRSCCH LENTWHDHTT DSCISSVMCD NASIVLRVRK VSDSSILVMY SLNT //