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Protein

Double homeobox protein 4

Gene

DUX4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in transcriptional regulation. May regulate microRNA (miRNA) expression.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi19 – 7860Homeobox 1PROSITE-ProRule annotationAdd
BLAST
DNA bindingi94 – 15360Homeobox 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. transcription regulatory region sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. negative regulation of cell proliferation Source: UniProtKB
  3. negative regulation of G0 to G1 transition Source: UniProtKB
  4. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  5. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Double homeobox protein 4Imported
Alternative name(s):
Double homeobox protein 10Imported
Gene namesi
Name:DUX4Imported
Synonyms:DUX10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:50800. DUX4.

Subcellular locationi

Nucleus PROSITE-ProRule annotation2 Publications
Note: Actively transported through the nuclear pore complex (NPC).

GO - Cellular componenti

  1. nuclear membrane Source: UniProtKB
  2. nucleoplasm Source: UniProtKB
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Facioscapulohumeral muscular dystrophy 1 (FSHD1)2 Publications

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.

Disease descriptionA 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.

See also OMIM:158900

Organism-specific databases

MIMi158900. phenotype.
Orphaneti269. Facioscapulohumeral dystrophy.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 424424Double homeobox protein 4PRO_0000252413Add
BLAST

Proteomic databases

PaxDbiQ9UBX2.
PRIDEiQ9UBX2.

PTM databases

PhosphoSiteiQ9UBX2.

Expressioni

Tissue specificityi

Does not seem to be expressed in normal muscle, but is detected in muscle of individuals with FSHD, and also in testis (at protein level) (PubMed:21060811). Does not seem to be expressed in normal muscle, but in muscle of individuals with FSHD, where it may be toxic to cells.2 Publications

Gene expression databases

CleanExiHS_DUX4.
ExpressionAtlasiQ9UBX2. baseline.
GenevestigatoriQ9UBX2.

Interactioni

Subunit structurei

May exist as a monomer or a dimer.

Protein-protein interaction databases

STRINGi9606.ENSP00000414381.

Structurei

3D structure databases

ProteinModelPortaliQ9UBX2.
SMRiQ9UBX2. Positions 20-77, 95-148.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi16 – 9883Arg-richAdd
BLAST
Compositional biasi156 – 24590Ala-richAdd
BLAST

Domaini

Both homeobox domains confer nuclear targeting.

Sequence similaritiesi

Belongs to the paired homeobox family.Curated
Contains 2 homeobox DNA-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox, Repeat

Phylogenomic databases

eggNOGiNOG323819.
GeneTreeiENSGT00610000085975.
HOVERGENiHBG063255.
InParanoidiQ9UBX2.
PhylomeDBiQ9UBX2.

Family and domain databases

Gene3Di1.10.10.60. 2 hits.
InterProiIPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamiPF00046. Homeobox. 2 hits.
[Graphical view]
PRINTSiPR00031. HTHREPRESSR.
SMARTiSM00389. HOX. 2 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 2 hits.
PROSITEiPS50071. HOMEOBOX_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UBX2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALPTPSDST LPAEARGRGR RRRLVWTPSQ SEALRACFER NPYPGIATRE
60 70 80 90 100
RLAQAIGIPE PRVQIWFQNE RSRQLRQHRR ESRPWPGRRG PPEGRRKRTA
110 120 130 140 150
VTGSQTALLL RAFEKDRFPG IAAREELARE TGLPESRIQI WFQNRRARHP
160 170 180 190 200
GQGGRAPAQA GGLCSAAPGG GHPAPSWVAF AHTGAWGTGL PAPHVPCAPG
210 220 230 240 250
ALPQGAFVSQ AARAAPALQP SQAAPAEGIS QPAPARGDFA YAAPAPPDGA
260 270 280 290 300
LSHPQAPRWP PHPGKSREDR DPQRDGLPGP CAVAQPGPAQ AGPQGQGVLA
310 320 330 340 350
PPTSQGSPWW GWGRGPQVAG AAWEPQAGAA PPPQPAPPDA SASARQGQMQ
360 370 380 390 400
GIPAPSQALQ EPAPWSALPC GLLLDELLAS PEFLQQAQPL LETEAPGELE
410 420
ASEEAASLEA PLSEEEYRAL LEEL
Length:424
Mass (Da):44,940
Last modified:October 1, 2001 - v2
Checksum:iC51E9EE25C6661B8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF117653 Genomic DNA. Translation: AAD54067.2.
AF117653 Genomic DNA. Translation: AAD54068.2.
AY044051 Genomic DNA. Translation: AAK91509.1.
AC215524 Genomic DNA. No translation available.
RefSeqiNP_001280727.1. NM_001293798.1.
UniGeneiHs.728749.

Genome annotation databases

EnsembliENST00000565211; ENSP00000458065; ENSG00000260596.
ENST00000569241; ENSP00000456539; ENSG00000260596.
ENST00000616166; ENSP00000483555; ENSG00000260596.
GeneIDi100288687.
KEGGihsa:100288687.

Polymorphism databases

DMDMi74720085.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF117653 Genomic DNA. Translation: AAD54067.2.
AF117653 Genomic DNA. Translation: AAD54068.2.
AY044051 Genomic DNA. Translation: AAK91509.1.
AC215524 Genomic DNA. No translation available.
RefSeqiNP_001280727.1. NM_001293798.1.
UniGeneiHs.728749.

3D structure databases

ProteinModelPortaliQ9UBX2.
SMRiQ9UBX2. Positions 20-77, 95-148.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000414381.

PTM databases

PhosphoSiteiQ9UBX2.

Polymorphism databases

DMDMi74720085.

Proteomic databases

PaxDbiQ9UBX2.
PRIDEiQ9UBX2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000565211; ENSP00000458065; ENSG00000260596.
ENST00000569241; ENSP00000456539; ENSG00000260596.
ENST00000616166; ENSP00000483555; ENSG00000260596.
GeneIDi100288687.
KEGGihsa:100288687.

Organism-specific databases

CTDi100288687.
GeneCardsiGC04P191005.
GeneReviewsiDUX4.
HGNCiHGNC:50800. DUX4.
MIMi158900. phenotype.
606009. gene.
neXtProtiNX_Q9UBX2.
Orphaneti269. Facioscapulohumeral dystrophy.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG323819.
GeneTreeiENSGT00610000085975.
HOVERGENiHBG063255.
InParanoidiQ9UBX2.
PhylomeDBiQ9UBX2.

Miscellaneous databases

PROiQ9UBX2.
SOURCEiSearch...

Gene expression databases

CleanExiHS_DUX4.
ExpressionAtlasiQ9UBX2. baseline.
GenevestigatoriQ9UBX2.

Family and domain databases

Gene3Di1.10.10.60. 2 hits.
InterProiIPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamiPF00046. Homeobox. 2 hits.
[Graphical view]
PRINTSiPR00031. HTHREPRESSR.
SMARTiSM00389. HOX. 2 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 2 hits.
PROSITEiPS50071. HOMEOBOX_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element."
    Gabrieels J., Beckers M.-C., Ding H., De Vriese A., Plaisance S., van der Maarel S.M., Padberg G.W., Frants R.R., Hewitt J.E., Collen D., Belayew A.
    Gene 236:25-32(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN FSHD1.
  2. "A subtelomeric exchange between chromosomes 4q35 and 10q26 observed in a patient with FSHD maintains a double homeobox (DUX) gene within the 3.3 kb repeats of the D4Z4 locus."
    Leclercq I., Matteotti C., Deneubourg G., Leo O., Van der Maarel S.M., Frants R.R., Padberg G.W., Coppee F., Belayew A.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Intracellular trafficking and dynamics of double homeodomain proteins."
    Oestlund C., Garcia-Carrasquillo R.M., Belayew A., Worman H.J.
    Biochemistry 44:2378-2384(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  5. "Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample."
    Mostacciuolo M.L., Pastorello E., Vazza G., Miorin M., Angelini C., Tomelleri G., Galluzzi G., Trevisan C.P.
    Clin. Genet. 75:550-555(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN FSHD1.
  6. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. Cited for: FUNCTION.

Entry informationi

Entry nameiDUX4_HUMAN
AccessioniPrimary (citable) accession number: Q9UBX2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 1, 2001
Last modified: February 4, 2015
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

DUX genes are present in 3.3-kilobase elements, a tandem repeat family scattered in the genome found on the short arms of all acrocentric chromosomes as well as on several other chromosomes.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.