Reviewed, UniProtKB/Swiss-Prot Q15475 (SIX1_HUMAN)

Names and origin

Protein names

Recommended name:
    Homeobox protein SIX1
Alternative name(s):
    Sine oculis homeobox homolog 1

Gene names

Name:

SIX1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	284 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May be involved in limb tendon and ligament development By similarity.
Subcellular location	Nucleus.
Tissue specificity	Specifically expressed in skeletal muscle.
Involvement in disease	Defects in SIX1 are the cause of autosomal dominant deafness type 23 (DFNA23) [MIM:605192]. Ref.4 Defects in SIX1 are the cause of branchiootic syndrome type 3 (BOS3) [MIM:608389]. Urinary tract malformations constitute the most frequent cause of chronic renal failure in the first two decades of life. Branchio-oto-renal syndrome (BOR) is an autosomal dominant developmental disorder of kidney and urinary tract malformations with hearing loss. The major feature of BOR is hearing loss (93% of patients), which can be conductive, sensorineural, or both and varies in age of onset. Ref.4
Sequence similarities	Belongs to the SIX/Sine oculis homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	branching involved in ureteric bud morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB induction of an organ Inferred from sequence or structural similarity. Source: UniProtKB inner ear morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB myoblast migration Inferred from sequence or structural similarity. Source: UniProtKB pattern specification process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.4 Inferred from direct assay. Source: UniProtKB protein localization in nucleus Inferred from direct assay. Source: UniProtKB thymus development Inferred from sequence or structural similarity. Source: UniProtKB thyroid gland development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA
Molecular function	promoter binding Inferred from direct assay. Source: UniProtKB protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDFI	Q99750	1	EBI-743675,EBI-724076

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Homeobox protein SIX1		PRO_0000049295
Regions
	DNA binding	124 – 183	60	Homeobox
Natural variations
	Natural variant	110	1	R → W in BOS3; crucial for EYA1-SIX1 interaction. Ref.4		VAR_031024
	Natural variant	129	1	Y → C in BOS3; crucial for EYA1-SIX1 interaction; crucial for SIX1-DNA protein-DNA binding. Ref.4		VAR_031025
	Natural variant	133	1	Missing in DFNA23; crucial for EYA1-SIX1 interaction; crucial for SIX1-DNA protein-DNA binding.		VAR_031026
Experimental info
	Sequence conflict	99	1	R → C in AAH08874. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q15475-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A4195376CFB9E3EA	FASTA	284	32,210
	10 20 30 40 50 60 MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR 70 80 90 100 110 120 GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT 130 140 150 160 170 180 IWDGEETSYC FKEKSRGVLR EWYAHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR 190 200 210 220 230 240 AAEAKERENT ENNNSSSNKQ NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQGNMGH 250 260 270 280 ARSSNYSLPG LTASQPSHGL QTHQHQLQDS LLGPLTSSLV DLGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human SIX1 gene and its assignment to chromosome 14." Boucher C.A., Carey N., Edwards Y.H., Siciliano M.J., Johnson K.J. Genomics 33:140-142(1996) [PubMed: 8617500] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Muscle.
[2]	"Partial genomic sequence of human SIX1." Gallardo M.E., Rodriguez de Cordoba S. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[4]	"SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes." Ruf R.G., Xu P.-X., Silvius D., Otto E.A., Beekmann F., Muerb U.T., Kumar S., Neuhaus T.J., Kemper M.J., Raymond R.M. Jr., Brophy P.D., Berkman J., Gattas M., Hyland V., Ruf E.-M., Schwartz C., Chang E.H., Smith R.J.H. , Stratakis C.A., Weil D., Petit C., Hildebrandt F. Proc. Natl. Acad. Sci. U.S.A. 101:8090-8095(2004) [PubMed: 15141091] [Abstract] Cited for: VARIANTS BOS3 TRP-110 AND CYS-129, VARIANT DFNA23 GLU-133 DEL, CHARACTERIZATION OF VARIANTS BOS3 TRP-110 AND CYS-129, CHARACTERIZATION OF VARIANT DFNA23 GLU-133 DEL.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91868 mRNA. Translation: CAA62974.1. AF323497 Genomic DNA. Translation: AAK06772.1. BC008874 mRNA. Translation: AAH08874.1.
IPI	IPI00017506.
RefSeq	NP_005973.1.
3D structure databases
SMR	Q15475. Positions 52-181.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15475. 2 interactions.
STRING	Q15475.
Proteomic databases
PRIDE	Q15475.
Genome annotation databases
Ensembl	ENST00000247182; ENSP00000247182; ENSG00000126778; Homo sapiens. [Genome view]
GeneID	6495.
KEGG	hsa:6495.
UCSC	uc001xfb.2. human.
Organism-specific databases
CTD	6495.
GeneCards	GC14M060182.
HGNC	HGNC:10887. SIX1.
HPA	HPA001893.
MIM	601205. gene. 605192. phenotype. 608389. phenotype.
Orphanet	107. BOR syndrome. 52429. Branchio-otic syndrome.
PharmGKB	PA35787.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15385.
HOGENOM	HBG443955.
HOVERGEN	Q15475.
InParanoid	Q15475.
OMA	NTSSNKQ.
OrthoDB	EOG9HX7KZ.
PhylomeDB	Q15475.
Gene expression databases
ArrayExpress	Q15475.
Bgee	Q15475.
CleanEx	HS_SIX1.
Genevestigator	Q15475.
GermOnline	ENSG00000126778. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	25247.
SOURCE	Search...

Entry information

Entry name

SIX1_HUMAN

Accession

Primary (citable) accession number: Q15475
Secondary accession number(s): Q96H64

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.