DUX4
entrez
100288687
canonical
uniprot
Q9UBX2
canonical
ensembl
ENSG00000260596
resolver
ensembl
ENSG00000283363
resolver
ensembl
ENSG00000283767
resolver
ensembl
ENSG00000283820
resolver
ensembl
ENSG00000283878
resolver
ensembl
ENSG00000283884
resolver
ensembl
ENSG00000283949
resolver
ensembl
ENSG00000283955
resolver
ensembl
ENSG00000284025
resolver
ensembl
ENSG00000284181
resolver
ensembl
ENSG00000284210
resolver
ensembl
ENSG00000284262
resolver
ensembl
ENSG00000284383
resolver
ensembl
ENSG00000284496
resolver
ensp
ENSP00000455112
resolver
ensp
ENSP00000456539
resolver
ensp
ENSP00000458065
resolver
genesymbol
DUX4
resolver
genesymbol_syn
DUX10
resolver
genesymbol_syn
DUX4L
resolver
hgnc
HGNC:50800
resolver
uniprot
C3U3A0
resolver
uniprot
E2JJS1
resolver
uniprot_entry
C3U3A0_HUMAN
resolver
uniprot_entry
DUX4_HUMAN
resolver
uniprot_sec
E2JJS1
resolver
amino_acid_sequence
MALPTPSDSTLPAEARGRGRRRRLVWTPSQSEALRACFERNPYPGIATRERLAQAIGIPEPRVQIWFQNERSRQLRQHRRESRPWPGRRGPPEGRRKRTAVTGSQTALLLRAFEKDRFPGIAAREELARETGLPESRIQIWFQNRRARHPGQGGRAPAQAGGLCSAAPGGGHPAPSWVAFAHTGAWGTGLPAPHVPCAPGALPQGAFVSQAARAAPALQPSQAAPAEGISQPAPARGDFAYAAPAPPDGALSHPQAPRWPPHPGKSREDRDPQRDGLPGPCAVAQPGPAQAGPQGQGVLAPPTSQGSPWWGWGRGPQVAGAAWEPQAGAAPPPQPAPPDASASARQGQMQGIPAPSQALQEPAPWSALPCGLLLDELLASPEFLQQAQPLLETEAPGELEASEEAASLEAPLSEEEYRALLEEL
uniprot
proteins
disease_involvement
DISEASE: Facioscapulohumeral muscular dystrophy 1 (FSHD1) [MIM:158900]: A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. {ECO:0000269|PubMed:10433963, ECO:0000269|PubMed:19320656}. Note=The gene represented in this entry is involved in disease pathogenesis. The disease is caused by deletion of an integral number of units of a 3.3-kb tandem repeats, termed D4Z4 macrosatellite, located on chromosome 4q35. In unaffected subjects, the D4Z4 array consists of 11-150 repeats, while in FSHD1 patients, the array is reduced to 1-10 repeats (PubMed:19320656). DUX4 is located in D4Z4 macrosatellite which is epigenetically repressed in somatic tissues. D4Z4 chromatin relaxation in FSHD1 results in inefficient epigenetic repression of DUX4 and a variegated pattern of DUX4 protein expression in a subset of skeletal muscle nuclei. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death. {ECO:0000269|PubMed:19320656}.
uniprot
proteins
function
FUNCTION: [Isoform 1]: Transcription factor that is selectively and transiently expressed in cleavage-stage embryos (PubMed:28459457). Binds to double-stranded DNA elements with the consensus sequence 5'-TAATCTAATCA-3' (PubMed:28459454, PubMed:28459457, PubMed:29572508, PubMed:30315230, PubMed:30540931). Binds to chromatin containing histone H3 acetylated at 'Lys-27' (H3K27ac) and promotes deacetylation of H3K27ac. In parallel, binds to chromatin that lacks histone H3 acetylation at 'Lys-27' (H3K27ac) and recruits EP300 and CREBBP to promote acetylation of histone H3 at 'Lys-27' at new sites (PubMed:26951377). Involved in transcriptional regulation of numerous genes, primarily as transcriptional activator, but also mediates repression of a set of target genes (PubMed:17984056, PubMed:26951377, PubMed:27378237, PubMed:28459454, PubMed:28459457, PubMed:29572508, PubMed:29618456, PubMed:30540931). Promotes expression of ZSCAN4 and KDM4E, two proteins with essential roles during early embryogenesis (PubMed:26951377, PubMed:27378237, PubMed:28459457, PubMed:29618456). Promotes nuclear translocation of CTNNB1/beta-catenin and its subsequent activation of target genes (PubMed:36158201). Heterologous expression in cultured embryonic stem cells mediates transcription of HERVL retrotransposons and transcripts derived from ACRO1 and HSATII satellite repeats (PubMed:28459457). May activate expression of PITX1 (PubMed:17984056). May regulate microRNA (miRNA) expression (PubMed:24145033). Inappropriate expression can inhibit myogenesis and promote apoptosis (PubMed:26951377, PubMed:28935672, PubMed:29618456). {ECO:0000269|PubMed:17984056, ECO:0000269|PubMed:24145033, ECO:0000269|PubMed:26951377, ECO:0000269|PubMed:27378237, ECO:0000269|PubMed:28459454, ECO:0000269|PubMed:28459457, ECO:0000269|PubMed:28935672, ECO:0000269|PubMed:29572508, ECO:0000269|PubMed:29618456, ECO:0000269|PubMed:30315230, ECO:0000269|PubMed:30540931, ECO:0000269|PubMed:36158201}.; FUNCTION: [Isoform 2]: Probably inactive as a transcriptional activator, due to the absence of the C-terminal region that is important for transcriptional activation. Can inhibit transcriptional activation mediated by isoform 1. Heterologous expression of isoform 2 has no deleterious effect on cell survival. {ECO:0000269|PubMed:29618456}.
uniprot
proteins
mass_dalton
44940
uniprot
proteins
mutagenesis
MUTAGEN 20; /note="R->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 23; /note="R->A: Mildly decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 26; /note="W->A: No effect on DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 69; /note="N->A: Mildly decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 95; /note="R->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 95; /note="R->A: No effect on DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 96; /note="R->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 97; /note="K->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 98; /note="R->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508, ECO:0000269|PubMed:30322619"; MUTAGEN 143; /note="Q->E: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 144; /note="N->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 144; /note="N->E: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 145; /note="R->E: Altered sequence specificity, with increased affinity for the DNA sequence 5'-TAATCTAATTA-3'."; /evidence="ECO:0000269|PubMed:30540931"; MUTAGEN 147; /note="A->S: Altered sequence specificity, with increased affinity for the DNA sequence 5'-TAATCTAATTA-3'."; /evidence="ECO:0000269|PubMed:30540931"; MUTAGEN 148; /note="R->A: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:30322619"; MUTAGEN 148; /note="R->E: Decreased DNA binding affinity."; /evidence="ECO:0000269|PubMed:29572508"; MUTAGEN 159..371; /note="Missing: Decreased activity as transcriptional activator."; /evidence="ECO:0000269|PubMed:26951377"; MUTAGEN 159..326; /note="Missing: No effect on activity as transcriptional activator."; /evidence="ECO:0000269|PubMed:26951377"; MUTAGEN 160..342; /note="Missing: No effect on activity as transcriptional activator."; /evidence="ECO:0000269|PubMed:29618456"; MUTAGEN 327..424; /note="Missing: Loss of interaction with EP300 and CREBBP."; /evidence="ECO:0000269|PubMed:26951377"; MUTAGEN 374..424; /note="Missing: Abolishes activity as transcriptional activator."; /evidence="ECO:0000269|PubMed:29618456"; MUTAGEN 405..424; /note="Missing: Reduced activity as transcriptional activator."; /evidence="ECO:0000269|PubMed:29618456
uniprot
proteins
protein_family
Paired homeobox family
uniprot
proteins
pubmed
10433963
uniprot
proteins
pubmed
15709750
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17984056
uniprot
proteins
pubmed
19320656
uniprot
proteins
pubmed
21060811
uniprot
proteins
pubmed
24145033
uniprot
proteins
pubmed
26816005
uniprot
proteins
pubmed
26951377
uniprot
proteins
pubmed
27378237
uniprot
proteins
pubmed
28459454
uniprot
proteins
pubmed
28459457
uniprot
proteins
pubmed
28935672
uniprot
proteins
pubmed
29572508
uniprot
proteins
pubmed
29618456
uniprot
proteins
pubmed
30054554
uniprot
proteins
pubmed
30315230
uniprot
proteins
pubmed
30322619
uniprot
proteins
pubmed
30540931
uniprot
proteins
pubmed
36158201
uniprot
proteins
sequence_length
424
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, ECO:0000269|PubMed:15709750, ECO:0000269|PubMed:17984056, ECO:0000269|PubMed:21060811, ECO:0000269|PubMed:26816005, ECO:0000269|PubMed:26951377, ECO:0000269|PubMed:27378237, ECO:0000269|PubMed:28459457, ECO:0000269|PubMed:29618456}. Cytoplasm {ECO:0000269|PubMed:26816005}. Note=Actively transported through the nuclear pore complex (NPC). {ECO:0000305|PubMed:15709750}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:29618456, ECO:0000305|PubMed:15709750}.
uniprot
proteins