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   10-JUN-2026, entry version 208.
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=3; 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_071322.2; NM_022039.4.
DR   AlphaFoldDB; P57775; -.
DR   SMR; P57775; -.
DR   BioGRID; 112364; 60.
DR   ComplexPortal; CPX-7761; SCF E3 ubiquitin ligase complex, FBXW4 variant.
DR   DIP; DIP-41762N; -.
DR   FunCoup; P57775; 170.
DR   IntAct; P57775; 27.
DR   MINT; P57775; -.
DR   STRING; 9606.ENSP00000499522; -.
DR   GlyGen; P57775; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P57775; -.
DR   MetOSite; P57775; -.
DR   PhosphoSitePlus; P57775; -.
DR   BioMuta; FBXW4; -.
DR   DMDM; 13124191; -.
DR   jPOST; P57775; -.
DR   MassIVE; P57775; -.
DR   PaxDb; 9606-ENSP00000499522; -.
DR   PeptideAtlas; P57775; -.
DR   ProteomicsDB; 57037; -.
DR   Pumba; P57775; -.
DR   Antibodypedia; 31311; 231 antibodies from 27 providers.
DR   DNASU; 6468; -.
DR   Ensembl; ENST00000664783.1; ENSP00000499522.1; ENSG00000107829.16.
DR   GeneID; 6468; -.
DR   KEGG; hsa:6468; -.
DR   UCSC; uc001kto.4; human.
DR   AGR; HGNC:10847; -.
DR   ClinPGx; PA35751; -.
DR   CTD; 6468; -.
DR   DisGeNET; 6468; -.
DR   GeneCards; FBXW4; -.
DR   HGNC; HGNC:10847; FBXW4.
DR   HPA; ENSG00000107829; Low tissue specificity.
DR   MalaCards; FBXW4; -.
DR   MIM; 246560; phenotype.
DR   MIM; 608071; gene.
DR   OpenTargets; ENSG00000107829; -.
DR   Orphanet; 2440; Isolated split hand-split foot malformation.
DR   VEuPathDB; HostDB:ENSG00000107829; -.
DR   eggNOG; ENOG502QV15; Eukaryota.
DR   GeneTree; ENSGT00390000005029; -.
DR   HOGENOM; CLU_034660_0_0_1; -.
DR   InParanoid; P57775; -.
DR   OrthoDB; 435188at2759; -.
DR   PAN-GO; P57775; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; P57775; -.
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   Agora; ENSG00000107829; -.
DR   BioGRID-ORCS; 6468; 12 hits in 1194 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 199 other cell types or tissues.
DR   ExpressionAtlas; P57775; baseline and differential.
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:0060173; P:limb development; NAS:ComplexPortal.
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   CDD; cd20090; F-box_FBXW4; 1.
DR   FunFam; 2.130.10.10:FF:000376; F-box and WD repeat domain containing 4; 1.
DR   FunFam; 1.20.1280.50:FF:000031; F-box/WD repeat-containing protein 4 isoform X1; 1.
DR   FunFam; 2.130.10.10:FF:000327; F-box/WD repeat-containing protein 4 isoform X1; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR052301; SCF_F-box/WD-repeat.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   InterPro; IPR001680; WD40_rpt.
DR   PANTHER; PTHR14381; DACTYLIN; 1.
DR   PANTHER; PTHR14381:SF1; F-BOX_WD REPEAT-CONTAINING PROTEIN 4; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   Pfam; PF00400; WD40; 2.
DR   SMART; SM00320; WD40; 5.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF50978; WD40 repeat-like; 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; Proteomics identification; Reference proteome;
KW   Repeat; Ubl conjugation pathway; 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
//