Q9UBX2 (DUX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Double homeobox protein 4

Alternative name(s):
Double homeobox protein 10
Double homeobox protein 4/10

Gene names

Name:	DUX4
Synonyms:	DUX10

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Involved in transcriptional regulation. Ref.1
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 homebox 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

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Homeobox Repeat
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transcription regulatory region sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 424	424	Double homeobox protein 4		PRO_0000252413
Regions
	DNA binding	19 – 78	60	Homeobox 1
	DNA binding	94 – 153	60	Homeobox 2
	Compositional bias	16 – 98	83	Arg-rich
	Compositional bias	156 – 245	90	Ala-rich

Sequences

	Sequence		Length	Mass (Da)
	Q9UBX2 [UniParc]. Last modified October 1, 2001. Version 2. Checksum: C51E9EE25C6661B8	FASTA	424	44,940
	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

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.
+	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.
IPI	IPI00965468.
UniGene	Hs.553518. Hs.714687. Hs.723089.
3D structure databases
HSSP	HSSP built from PDB template 1FJL based on UniProtKB P06601.
ProteinModelPortal	Q9UBX2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000414381.
PTM databases
PhosphoSite	Q9UBX2.
Polymorphism databases
DMDM	74720085.
Proteomic databases
PaxDb	Q9UBX2.
PRIDE	Q9UBX2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000565211; ENSP00000458065; ENSG00000260596. ENST00000569241; ENSP00000456539; ENSG00000260596.
Organism-specific databases
GeneCards	GC04P191005.
HGNC	HGNC:3082. DUX4.
MIM	158900. phenotype. 606009. gene.
neXtProt	NX_Q9UBX2.
Orphanet	269. Facioscapulohumeral dystrophy.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG323819.
HOVERGEN	HBG063255.
InParanoid	Q9UBX2.
Gene expression databases
CleanEx	HS_DUX4.
Genevestigator	Q9UBX2.
GermOnline	ENSG00000075705. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 2 hits.
InterPro	IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR000047. HTH_motif. [Graphical view]
Pfam	PF00046. Homeobox. 2 hits. [Graphical view]
PRINTS	PR00031. HTHREPRESSR.
SMART	SM00389. HOX. 2 hits. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 2 hits.
PROSITE	PS00027. HOMEOBOX_1. False negative. PS50071. HOMEOBOX_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

DUX4_HUMAN

Accession

Primary (citable) accession number: Q9UBX2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 1, 2001
Last modified:	May 1, 2013
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.