FBXW4_HUMAN
ID FBXW4_HUMAN Reviewed; 412 AA.
AC P57775; Q5SVS1; Q96IM6;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=F-box/WD repeat-containing protein 4;
DE AltName: Full=Dactylin;
DE AltName: Full=F-box and WD-40 domain-containing protein 4;
GN Name=FBXW4; Synonyms=FBW4, SHFM3;
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], AND TISSUE SPECIFICITY.
RX PubMed=10405324; DOI=10.1006/bbrc.1999.0963;
RA Ianakiev P., Kilpatrick M.W., Dealy C., Kosher R., Korenberg J.R.,
RA Chen X.N., Tsipouras P.;
RT "A novel human gene encoding an F-box/WD40 containing protein maps in the
RT SHFM3 critical region on 10q24.";
RL Biochem. Biophys. Res. Commun. 261:64-70(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10945468; DOI=10.1006/geno.2000.6211;
RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.;
RT "cDNA cloning and expression analysis of new members of the mammalian F-box
RT protein family.";
RL Genomics 67:40-47(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [5]
RP INVOLVEMENT IN SHFM3.
RX PubMed=12913067; DOI=10.1093/hmg/ddg212;
RA de Mollerat X.J., Gurrieri F., Morgan C.T., Sangiorgi E., Everman D.B.,
RA Gaspari P., Amiel J., Bamshad M.J., Lyle R., Blouin J.-L., Allanson J.E.,
RA Le Marec B., Wilson M., Braverman N.E., Radhakrishna U.,
RA Delozier-Blanchet C., Abbott A., Elghouzzi V., Antonarakis S.E.,
RA Stevenson R.E., Munnich A., Neri G., Schwartz C.E.;
RT "A genomic rearrangement resulting in a tandem duplication is associated
RT with split hand-split foot malformation 3 (SHFM3) at 10q24.";
RL Hum. Mol. Genet. 12:1959-1971(2003).
CC -!- FUNCTION: Probably recognizes and binds to some phosphorylated proteins
CC and promotes their ubiquitination and degradation. Likely to be
CC involved in key signaling pathways crucial for normal limb development.
CC May participate in Wnt signaling.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex
CC (Probable). Interacts with POUF51 (By similarity).
CC {ECO:0000250|UniProtKB:Q9JMJ2, ECO:0000305}.
CC -!- INTERACTION:
CC P57775; O60260-5: PRKN; NbExp=3; IntAct=EBI-2372268, EBI-21251460;
CC P57775; P63208: SKP1; NbExp=2; IntAct=EBI-2372268, EBI-307486;
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, lung and liver.
CC {ECO:0000269|PubMed:10405324}.
CC -!- DISEASE: Split-hand/foot malformation 3 (SHFM3) [MIM:246560]: A limb
CC malformation involving the central rays of the autopod and presenting
CC with syndactyly, median clefts of the hands and feet, and aplasia
CC and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some
CC patients have been found to have intellectual disability, ectodermal
CC and craniofacial findings, and orofacial clefting.
CC {ECO:0000269|PubMed:12913067}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF281859; AAG22739.1; -; mRNA.
DR EMBL; AC010789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007380; AAH07380.2; -; mRNA.
DR EMBL; BC063415; AAH63415.1; -; mRNA.
DR RefSeq; NP_071322.1; NM_022039.3.
DR AlphaFoldDB; P57775; -.
DR SMR; P57775; -.
DR BioGRID; 112364; 57.
DR DIP; DIP-41762N; -.
DR IntAct; P57775; 22.
DR MINT; P57775; -.
DR STRING; 9606.ENSP00000359149; -.
DR iPTMnet; P57775; -.
DR MetOSite; P57775; -.
DR PhosphoSitePlus; P57775; -.
DR BioMuta; FBXW4; -.
DR DMDM; 13124191; -.
DR EPD; P57775; -.
DR jPOST; P57775; -.
DR MassIVE; P57775; -.
DR MaxQB; P57775; -.
DR PaxDb; P57775; -.
DR PeptideAtlas; P57775; -.
DR PRIDE; P57775; -.
DR ProteomicsDB; 57037; -.
DR Antibodypedia; 31311; 232 antibodies from 27 providers.
DR DNASU; 6468; -.
DR Ensembl; ENST00000664783.1; ENSP00000499522.1; ENSG00000107829.15.
DR GeneID; 6468; -.
DR KEGG; hsa:6468; -.
DR UCSC; uc001kto.4; human.
DR CTD; 6468; -.
DR DisGeNET; 6468; -.
DR GeneCards; FBXW4; -.
DR HGNC; HGNC:10847; FBXW4.
DR HPA; ENSG00000107829; Low tissue specificity.
DR MIM; 246560; phenotype.
DR MIM; 608071; gene.
DR neXtProt; NX_P57775; -.
DR OpenTargets; ENSG00000107829; -.
DR PharmGKB; PA35751; -.
DR VEuPathDB; HostDB:ENSG00000107829; -.
DR eggNOG; ENOG502QV15; Eukaryota.
DR GeneTree; ENSGT00390000005029; -.
DR HOGENOM; CLU_034660_0_0_1; -.
DR InParanoid; P57775; -.
DR OrthoDB; 730077at2759; -.
DR PhylomeDB; P57775; -.
DR TreeFam; TF325020; -.
DR PathwayCommons; P57775; -.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P57775; -.
DR BioGRID-ORCS; 6468; 10 hits in 1116 CRISPR screens.
DR ChiTaRS; FBXW4; human.
DR GeneWiki; FBXW4; -.
DR GenomeRNAi; 6468; -.
DR Pharos; P57775; Tbio.
DR PRO; PR:P57775; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P57775; protein.
DR Bgee; ENSG00000107829; Expressed in C1 segment of cervical spinal cord and 197 other tissues.
DR ExpressionAtlas; P57775; baseline and differential.
DR Genevisible; P57775; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0030326; P:embryonic limb morphogenesis; NAS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; NAS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Reference proteome; Repeat; Ubl conjugation pathway;
KW WD repeat; Wnt signaling pathway.
FT CHAIN 1..412
FT /note="F-box/WD repeat-containing protein 4"
FT /id="PRO_0000050990"
FT DOMAIN 25..71
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 154..190
FT /note="WD 1"
FT REPEAT 193..229
FT /note="WD 2"
FT REPEAT 236..277
FT /note="WD 3"
FT REPEAT 283..321
FT /note="WD 4"
FT REPEAT 327..366
FT /note="WD 5"
FT REPEAT 373..409
FT /note="WD 6"
FT CONFLICT 363
FT /note="L -> P (in Ref. 4; AAH07380)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 46337 MW; 36C175FDE30D283B CRC64;
MAAAAGEEEE EEEAARESAA RPAAGPALWR LPEELLLLIC SYLDMRALGR LAQVCRWLRR
FTSCDLLWRR IARASLNSGF TRLGTDLMTS VPVKERVKVS QNWRLGRCRE GILLKWRCSQ
MPWMQLEDDS LYISQANFIL AYQFRPDGAS LNRRPLGVFA GHDEDVCHFV LANSHIVSAG
GDGKIGIHKI HSTFTVKYSA HEQEVNCVDC KGGIIVSGSR DRTAKVWPLA SGRLGQCLHT
IQTEDRVWSI AISPLLSSFV TGTACCGHFS PLRIWDLNSG QLMTHLGSDF PPGAGVLDVM
YESPFTLLSC GYDTYVRYWD LRTSVRKCVM EWEEPHDSTL YCLQTDGNHL LATGSSYYGV
VRLWDRRQRA CLHAFPLTST PLSSPVYCLR LTTKHLYAAL SYNLHVLDFQ NP
