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Reviewed, UniProtKB/Swiss-Prot Q15475 (SIX1_HUMAN)

Last modified February 9, 2010. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Homeobox protein SIX1
Alternative name(s):
    Sine oculis homeobox homolog 1
Gene names
Name: SIX1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentNucleus
   DiseaseDeafness
Disease mutation
Non-syndromic deafness
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processbranching 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 componentcytoplasm

Inferred from direct assay. Source: HPA

nucleolus

Inferred from direct assay. Source: HPA

   Molecular functionpromoter 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

MDFIQ997501EBI-743675,EBI-724076

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Homeobox protein SIX1
PRO_0000049295

Regions

DNA binding124 – 18360Homeobox

Natural variations

Natural variant1101R → W in BOS3; crucial for EYA1-SIX1 interaction. Ref.4
VAR_031024
Natural variant1291Y → C in BOS3; crucial for EYA1-SIX1 interaction; crucial for SIX1-DNA protein-DNA binding. Ref.4
VAR_031025
Natural variant1331Missing in DFNA23; crucial for EYA1-SIX1 interaction; crucial for SIX1-DNA protein-DNA binding.
VAR_031026

Experimental info

Sequence conflict991R → C in AAH08874. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q15475-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: A4195376CFB9E3EA

FASTA28432,210
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X91868 mRNA. Translation: CAA62974.1.
AF323497 Genomic DNA. Translation: AAK06772.1.
BC008874 mRNA. Translation: AAH08874.1.
IPIIPI00017506.
RefSeqNP_005973.1.

3D structure databases

SMRQ15475. Positions 52-181.
ModBaseSearch...

Protein-protein interaction databases

IntActQ15475. 2 interactions.
STRINGQ15475.

Proteomic databases

PRIDEQ15475.

Genome annotation databases

EnsemblENST00000247182; ENSP00000247182; ENSG00000126778; Homo sapiens. [Genome view]
GeneID6495.
KEGGhsa:6495.
UCSCuc001xfb.2. human.

Organism-specific databases

CTD6495.
GeneCardsGC14M060182.
HGNCHGNC:10887. SIX1.
HPAHPA001893.
MIM601205. gene.
605192. phenotype.
608389. phenotype.
Orphanet107. BOR syndrome.
52429. Branchio-otic syndrome.
PharmGKBPA35787.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG15385.
HOGENOMHBG443955.
HOVERGENQ15475.
InParanoidQ15475.
OMANTSSNKQ.
OrthoDBEOG9HX7KZ.
PhylomeDBQ15475.

Gene expression databases

ArrayExpressQ15475.
BgeeQ15475.
CleanExHS_SIX1.
GenevestigatorQ15475.
GermOnlineENSG00000126778. Homo sapiens.

Family and domain databases

InterProIPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR009057. Homeodomain-like.
IPR012287. Homeodomain-rel.
[Graphical view]
Gene3DG3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio25247.
SOURCESearch...

Entry information

Entry nameSIX1_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents