Human Gene FBXW4 (uc001kto.3) Description and Page Index
  Description: Homo sapiens F-box and WD repeat domain containing 4 (FBXW4), mRNA.
RefSeq Summary (NM_022039): This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22. [provided by RefSeq, Jul 2008]. CCDS Note: The coding region has been updated to extend the N-terminus and this extension is supported by conservation data. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF281859.1, SRR1163655.35849.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000331272.9/ ENSP00000359149.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr10:103,370,421-103,454,743 Size: 84,323 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr10:103,371,048-103,454,397 Size: 83,350 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr10:103,370,421-103,454,743)mRNA (may differ from genome)Protein (412 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=F-box/WD repeat-containing protein 4; AltName: Full=Dactylin; AltName: Full=F-box and WD-40 domain-containing protein 4;
FUNCTION: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. Likely to be involved in key signaling pathways crucial for normal limb development. May participate in Wnt signaling.
SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex (By similarity).
TISSUE SPECIFICITY: Expressed in brain, kidney, lung and liver.
DISEASE: Defects in FBXW4 are a cause of split-hand/foot malformation type 3 (SHFM3) [MIM:246560]. SHFM3 is an autosomal dominant disorder characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits.
SIMILARITY: Contains 1 F-box domain.
SIMILARITY: Contains 4 WD repeats.
WEB RESOURCE: Name=GeneReviews; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: FBXW4
Diseases sorted by gene-association score: split-hand/foot malformation 3* (141), split hand (29), split hand-foot malformation (28), split foot (17), split hand-split foot malformation (11), split hand-foot malformation 2 (10), split-hand/foot malformation 5 (8), split-hand/foot malformation 4 (8), chromosome 2q35 duplication syndrome (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 34.12 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 908.28 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -104.90346-0.303 Picture PostScript Text
3' UTR -251.80627-0.402 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001810 - F-box_dom_cyclin-like
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00400 - WD domain, G-beta repeat
PF00646 - F-box domain
PF12937 - F-box-like

SCOP Domains:
81383 - F-box domain
50952 - Soluble quinoprotein glucose dehydrogenase
50960 - TolB, C-terminal domain
63829 - Calcium-dependent phosphotriesterase
69304 - Tricorn protease N-terminal domain
101898 - NHL repeat
50965 - Galactose oxidase, central domain
75011 - 3-carboxy-cis,cis-mucoante lactonizing enzyme
101908 - Putative isomerase YbhE
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50974 - Nitrous oxide reductase, N-terminal domain
50978 - WD40 repeat-like
50993 - Prolyl oligopeptidase, N-terminal domain
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
82171 - Dipeptidyl peptidase IV/CD26, N-terminal domain

ModBase Predicted Comparative 3D Structure on P57775
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details  Gene Details  
Gene Sorter  Gene Sorter  
  Protein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003674 molecular_function
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding

Biological Process:
GO:0000209 protein polyubiquitination
GO:0002053 positive regulation of mesenchymal cell proliferation
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0007275 multicellular organism development
GO:0016055 Wnt signaling pathway
GO:0030326 embryonic limb morphogenesis
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0042733 embryonic digit morphogenesis
GO:0043687 post-translational protein modification
GO:0051216 cartilage development
GO:0060173 limb development

Cellular Component:
GO:0000151 ubiquitin ligase complex
GO:0005829 cytosol
GO:0019005 SCF ubiquitin ligase complex

-  Descriptions from all associated GenBank mRNAs
  BC063415 - Homo sapiens F-box and WD repeat domain containing 4, mRNA (cDNA clone MGC:74486 IMAGE:5223794), complete cds.
GQ900968 - Homo sapiens clone HEL-T-80 epididymis secretory sperm binding protein mRNA, complete cds.
BC007380 - Homo sapiens F-box and WD repeat domain containing 4, mRNA (cDNA clone IMAGE:3641604), partial cds.
AF281859 - Homo sapiens dactylin mRNA, complete cds.
AK314735 - Homo sapiens cDNA, FLJ95597, highly similar to Homo sapiens split hand/foot malformation (ectrodactyly) type 3(SHFM3), mRNA.
KJ901737 - Synthetic construct Homo sapiens clone ccsbBroadEn_11131 FBXW4 gene, encodes complete protein.
AK123173 - Homo sapiens cDNA FLJ41178 fis, clone BRACE2042873, highly similar to Homo sapiens dactylin mRNA.
AK056917 - Homo sapiens cDNA FLJ32355 fis, clone PROST2007956, highly similar to Homo sapiens dactylin mRNA.
JD387268 - Sequence 368292 from Patent EP1572962.
JD184860 - Sequence 165884 from Patent EP1572962.
JD064744 - Sequence 45768 from Patent EP1572962.
JD043608 - Sequence 24632 from Patent EP1572962.
JD418691 - Sequence 399715 from Patent EP1572962.
JD415404 - Sequence 396428 from Patent EP1572962.
JD393895 - Sequence 374919 from Patent EP1572962.
JD217275 - Sequence 198299 from Patent EP1572962.
JD272701 - Sequence 253725 from Patent EP1572962.
JD375227 - Sequence 356251 from Patent EP1572962.
JD167508 - Sequence 148532 from Patent EP1572962.
JD507544 - Sequence 488568 from Patent EP1572962.
JD292514 - Sequence 273538 from Patent EP1572962.
JD123497 - Sequence 104521 from Patent EP1572962.
JD270656 - Sequence 251680 from Patent EP1572962.
JD413841 - Sequence 394865 from Patent EP1572962.
JD473104 - Sequence 454128 from Patent EP1572962.
JD175032 - Sequence 156056 from Patent EP1572962.
JD324549 - Sequence 305573 from Patent EP1572962.
JD337207 - Sequence 318231 from Patent EP1572962.
JD117517 - Sequence 98541 from Patent EP1572962.
JD384009 - Sequence 365033 from Patent EP1572962.
DQ578758 - Homo sapiens piRNA piR-46870, complete sequence.
JD355810 - Sequence 336834 from Patent EP1572962.
JD180400 - Sequence 161424 from Patent EP1572962.
JD361683 - Sequence 342707 from Patent EP1572962.
JD044467 - Sequence 25491 from Patent EP1572962.
JD068131 - Sequence 49155 from Patent EP1572962.
JD362138 - Sequence 343162 from Patent EP1572962.
JD381086 - Sequence 362110 from Patent EP1572962.
JD121052 - Sequence 102076 from Patent EP1572962.
JD378099 - Sequence 359123 from Patent EP1572962.
JD475730 - Sequence 456754 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P57775 (Reactome details) participates in the following event(s):

R-HSA-390470 Association of CCT/TriC with other substrates during biosynthesis (unknown chaperone)
R-HSA-8952620 NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
R-HSA-8956200 MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases
R-HSA-8952618 AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-390466 Chaperonin-mediated protein folding
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-391251 Protein folding
R-HSA-597592 Post-translational protein modification
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-392499 Metabolism of proteins
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: FBW4, FBXW4_HUMAN, NM_022039, NP_071322, P57775, Q5SVS1, Q96IM6, SHFM3
UCSC ID: uc001kto.3
RefSeq Accession: NM_022039
Protein: P57775 (aka FBXW4_HUMAN or FBW4_HUMAN)
CCDS: CCDS31271.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_022039.3
exon count: 9CDS single in 3' UTR: no RNA size: 2303
ORF size: 1239CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2443.00frame shift in genome: no % Coverage: 96.05
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.