DUX4

Double homeobox, 4 also known as DUX4 is a protein which in humans is encoded by the DUX4 gene.[3]

DUX4
Identifiers
Aliases	DUX4, DUX4L, double homeobox 4
External IDs	OMIM: 606009 GeneCards: DUX4
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q35.2 Start 190,173,774 bp[1] End 190,185,942 bp[1]
Gene ontology Molecular function • DNA binding • transcription regulatory region sequence-specific DNA binding • GO:0001948 protein binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • sequence-specific double-stranded DNA binding Cellular component • nuclear membrane • cell nucleus • nucleoplasm • nucleolus • cytosol • Golgi apparatus Biological process • negative regulation of G0 to G1 transition • regulation of transcription, DNA-templated • transcription, DNA-templated • negative regulation of cell proliferation • positive regulation of transcription from RNA polymerase II promoter • apoptotic process • transcription from RNA polymerase II promoter • multicellular organism development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	100288687	n/a
Ensembl	ENSG00000260596 ENSG00000283949	n/a
UniProt	Q9UBX2	n/a
RefSeq (mRNA)	NM_001205218 NM_001278056 NM_001293798 NM_001306068 NM_001363820	n/a
RefSeq (protein)	NP_001280727 NP_001292997 NP_001350749	n/a
Location (UCSC)	Chr 4: 190.17 – 190.19 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

Gene

This gene is located within a D4Z4 repeat array in the subtelomeric region of chromosome 4q35. The D4Z4 repeat is polymorphic in length; a similar D4Z4 repeat array has been identified on chromosome 10. Each D4Z4 repeat unit has an open reading frame (named DUX4) that contains two homeoboxes; the repeat-array and ORF is conserved in other mammals. There was no evidence for transcription from standard cDNA libraries however RTPCR and in-vitro expression experiments indicate that the ORF is transcribed.[4]

Function

The encoded protein has been reported to function as a transcriptional activator of paired-like homeodomain transcription factor 1 (PITX1).[4]

Clinical significance

DUX is normally expressed in the testes and cleavage-stage embryos.[5]

Inappropriate expression of DUX4 in muscle cells is the cause of facioscapulohumeral muscular dystrophy.[6][7]

Overexpression of DUX4 due to translocations can cause B cell leukemia.[5]

See also

• Homeobox
• PITX1

References

1. ENSG00000283949 GRCh38: Ensembl release 89: ENSG00000260596, ENSG00000283949 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Gabriëls J, Beckers MC, Ding H, De Vriese A, Plaisance S, van der Maarel SM, et al. (August 1999). "Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element". Gene. 236 (1): 25–32. doi:10.1016/S0378-1119(99)00267-X. PMID 10433963.
4. "Entrez Gene: DUX4 Double homeobox, 4".
5. Lee JK, Bosnakovski D, Toso EA, Dinh T, Banerjee S, Bohl TE, et al. (December 2018). "Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA". Cell Reports. 25 (11): 2955–2962.e3. doi:10.1016/j.celrep.2018.11.060. PMC 6463520. PMID 30540931.
6. Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, et al. (September 2010). "A unifying genetic model for facioscapulohumeral muscular dystrophy". Science. 329 (5999): 1650–3. Bibcode:2010Sci...329.1650L. doi:10.1126/science.1189044. PMC 4677822. PMID 20724583.
7. Jones TI, Chen JC, Rahimov F, Homma S, Arashiro P, Beermann ML, et al. (October 2012). "Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: evidence for disease modifiers and a quantitative model of pathogenesis". Human Molecular Genetics. 21 (20): 4419–30. doi:10.1093/hmg/dds284. PMC 3459465. PMID 22798623.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.