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Q9UBX2 (DUX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Double homeobox protein 4
Alternative name(s):
Double homeobox protein 10
Double homeobox protein 4/10
Gene names
Name:DUX4
Synonyms:DUX10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length424 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Involved in transcriptional regulation. May regulate microRNA (miRNA) expression. Ref.1 Ref.5

Subunit structure

May exist as a monomer or a dimer.

Subcellular location

Nucleus. Note: Actively transported through the nuclear pore complex (NPC). Ref.3

Tissue specificity

Does not seem to be expressed in normal muscle, but in muscle of individuals with FSHD, where it may be toxic to cells. Ref.1

Domain

Both homeobox domains confer nuclear targeting.

Involvement in 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.
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 (Ref.4). 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. Ref.1 Ref.4

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.

Sequence similarities

Belongs to the paired homeobox family.

Contains 2 homeobox DNA-binding domains.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 424424Double homeobox protein 4
PRO_0000252413

Regions

DNA binding19 – 7860Homeobox 1
DNA binding94 – 15360Homeobox 2
Compositional bias16 – 9883Arg-rich
Compositional bias156 – 24590Ala-rich

Sequences

Sequence LengthMass (Da)Tools
Q9UBX2 [UniParc].

Last modified October 1, 2001. Version 2.
Checksum: C51E9EE25C6661B8

FASTA42444,940
        10         20         30         40         50         60 
MALPTPSDST LPAEARGRGR RRRLVWTPSQ SEALRACFER NPYPGIATRE RLAQAIGIPE 

        70         80         90        100        110        120 
PRVQIWFQNE RSRQLRQHRR ESRPWPGRRG PPEGRRKRTA VTGSQTALLL RAFEKDRFPG 

       130        140        150        160        170        180 
IAAREELARE TGLPESRIQI WFQNRRARHP GQGGRAPAQA GGLCSAAPGG GHPAPSWVAF 

       190        200        210        220        230        240 
AHTGAWGTGL PAPHVPCAPG ALPQGAFVSQ AARAAPALQP SQAAPAEGIS QPAPARGDFA 

       250        260        270        280        290        300 
YAAPAPPDGA LSHPQAPRWP PHPGKSREDR DPQRDGLPGP CAVAQPGPAQ AGPQGQGVLA 

       310        320        330        340        350        360 
PPTSQGSPWW GWGRGPQVAG AAWEPQAGAA PPPQPAPPDA SASARQGQMQ GIPAPSQALQ 

       370        380        390        400        410        420 
EPAPWSALPC GLLLDELLAS PEFLQQAQPL LETEAPGELE ASEEAASLEA PLSEEEYRAL 


LEEL 

« Hide

References

[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(1999) [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 (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Intracellular trafficking and dynamics of double homeodomain proteins."
Oestlund C., Garcia-Carrasquillo R.M., Belayew A., Worman H.J.
Biochemistry 44:2378-2384(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[4]"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(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FSHD1.
[5]"Defective regulation of microRNA target genes in myoblasts from facioscapulohumeral dystrophy patients."
Dmitriev P., Stankevicins L., Ansseau E., Petrov A., Barat A., Dessen P., Robert T., Turki A., Lazar V., Labourer E., Belayew A., Carnac G., Laoudj-Chenivesse D., Lipinski M., Vassetzky Y.S.
J. Biol. Chem. 288:34989-35002(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF117653 Genomic DNA. Translation: AAD54067.2.
AF117653 Genomic DNA. Translation: AAD54068.2.
AY044051 Genomic DNA. Translation: AAK91509.1.
CCDSCCDS54828.2.

3D structure databases

ProteinModelPortalQ9UBX2.
SMRQ9UBX2. Positions 20-77, 95-148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000414381.

PTM databases

PhosphoSiteQ9UBX2.

Polymorphism databases

DMDM74720085.

Proteomic databases

PaxDbQ9UBX2.
PRIDEQ9UBX2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000565211; ENSP00000458065; ENSG00000260596.
ENST00000569241; ENSP00000456539; ENSG00000260596.
KEGGhsa:100288289.
hsa:100288325.
hsa:100288355.
hsa:100288398.
hsa:100288433.
hsa:100288466.
hsa:100288494.
hsa:100288523.
hsa:100288557.
hsa:100288593.
hsa:100288627.
hsa:100288657.
hsa:100653046.

Organism-specific databases

CTD22947.
GeneCardsGC04P191005.
GeneReviewsDUX4.
HGNCHGNC:3082. DUX4.
MIM158900. phenotype.
606009. gene.
neXtProtNX_Q9UBX2.
Orphanet269. Facioscapulohumeral dystrophy.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG323819.
HOVERGENHBG063255.
InParanoidQ9UBX2.
PhylomeDBQ9UBX2.

Gene expression databases

CleanExHS_DUX4.
GenevestigatorQ9UBX2.

Family and domain databases

Gene3D1.10.10.60. 2 hits.
InterProIPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamPF00046. Homeobox. 2 hits.
[Graphical view]
PRINTSPR00031. HTHREPRESSR.
SMARTSM00389. HOX. 2 hits.
[Graphical view]
SUPFAMSSF46689. SSF46689. 2 hits.
PROSITEPS50071. HOMEOBOX_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

PROQ9UBX2.
SOURCESearch...

Entry information

Entry nameDUX4_HUMAN
AccessionPrimary (citable) accession number: Q9UBX2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 1, 2001
Last modified: July 9, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM