Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8N196 (SIX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein SIX5
Alternative name(s):
DM locus-associated homeodomain protein
Sine oculis homeobox homolog 5
Gene names
Name:SIX5
Synonyms:DMAHP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length739 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter By similarity. Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 By similarity.

Subunit structure

Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2 By similarity.

Subcellular location

Cytoplasm. Nucleus Ref.7.

Tissue specificity

Expressed in adult but not in fetal eyes. Found in corneal epithelium and endothelium, lens epithelium, ciliary body epithelia, cellular layers of the retina and the sclera. Ref.5

Developmental stage

At the begin of fourth week of development detected in cytoplasm of somite cells, and at the end of fourth week is accumulated in the nucleus. Between the sixth and eighth week of development detected in the nucleus of limb bud cells. Ref.7

Involvement in disease

Branchiootorenal syndrome 2 (BOR2) [MIM:610896]: A syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the SIX/Sine oculis homeobox family.

Contains 1 homeobox DNA-binding domain.

Sequence caution

The sequence AAH33204.1 differs from that shown. Reason: Aberrant splicing.

The sequence AK074826 differs from that shown. Reason: Erroneous termination at position 721. Translated as Glu.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATXN1P542534EBI-946167,EBI-930964

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 739739Homeobox protein SIX5
PRO_0000049305

Regions

DNA binding201 – 26060Homeobox Ref.6

Natural variations

Natural variant1581A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. Ref.8
VAR_032941
Natural variant2961A → T in BOR2. Ref.8
VAR_032942
Natural variant3651G → R in BOR2. Ref.8
VAR_032943
Natural variant5521T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. Ref.8
Corresponds to variant rs80356464 [ dbSNP | Ensembl ].
VAR_032944
Natural variant5561L → V.
Corresponds to variant rs2014377 [ dbSNP | Ensembl ].
VAR_032945
Natural variant6351P → S.
Corresponds to variant rs2014576 [ dbSNP | Ensembl ].
VAR_032946
Natural variant6931V → M.
Corresponds to variant rs2341097 [ dbSNP | Ensembl ].
VAR_032947

Sequences

Sequence LengthMass (Da)Tools
Q8N196 [UniParc].

Last modified June 26, 2007. Version 3.
Checksum: D8A2E8DBBBA263A2

FASTA73974,562
        10         20         30         40         50         60 
MATLPAEPSA GPAAGGEAVA AAAATEEEEE EARQLLQTLQ AAEGEAAAAA GAGAGAAAAG 

        70         80         90        100        110        120 
AEGPGSPGVP GSPPEAASEP PTGLRFSPEQ VACVCEALLQ AGHAGRLSRF LGALPPAERL 

       130        140        150        160        170        180 
RGSDPVLRAR ALVAFQRGEY AELYRLLESR PFPAAHHAFL QDLYLRARYH EAERARGRAL 

       190        200        210        220        230        240 
GAVDKYRLRK KFPLPKTIWD GEETVYCFKE RSRAALKACY RGNRYPTPDE KRRLATLTGL 

       250        260        270        280        290        300 
SLTQVSNWFK NRRQRDRTGA GGGAPCKSES DGNPTTEDES SRSPEDLERG AAPVSAEAAA 

       310        320        330        340        350        360 
QGSIFLAGTG PPAPCPASSS ILVNGSFLAA SGSPAVLLNG GPVIINGLAL GEASSLGPLL 

       370        380        390        400        410        420 
LTGGGGAPPP QPSPQGASET KTSLVLDPQT GEVRLEEAQS EAPETKGAQV AAPGPALGEE 

       430        440        450        460        470        480 
VLGPLAQVVP GPPTAATFPL PPGPVPAVAA PQVVPLSPPP GYPTGLSPTS PLLNLPQVVP 

       490        500        510        520        530        540 
TSQVVTLPQA VGPLQLLAAG PGSPVKVAAA AGPANVHLIN SGVGVTALQL PSATAPGNFL 

       550        560        570        580        590        600 
LANPVSGSPI VTGVALQQGK IILTATFPTS MLVSQVLPPA PGLALPLKPE TAISVPEGGL 

       610        620        630        640        650        660 
PVAPSPALPE AHALGTLSAQ QPPPAAATTS STSLPFSPDS PGLLPNFPAP PPEGLMLSPA 

       670        680        690        700        710        720 
AVPVWSAGLE LSAGTEGLLE AEKGLGTQAP HTVLRLPDPD PEGLLLGATA GGEVDEGLEA 

       730 
EAKVLTQLQS VPVEEPLEL 

« Hide

References

« Hide 'large scale' references
[1]"A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat."
Boucher C.A., King S.K., Carey N., Krahe R., Winchester C.L., Rahman S., Creavin T., Meghji P., Bailey M.E., Chartier F.L., Brown S.D., Sicilliano M.J., Johnson K.J.
Hum. Mol. Genet. 4:1919-1925(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-739.
[5]"Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy."
Winchester C.L., Ferrier R.K., Sermoni A., Clark B.J., Johnson K.J.
Hum. Mol. Genet. 8:481-492(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Functional analysis of the homeodomain protein SIX5."
Harris S.E., Winchester C.L., Johnson K.J.
Nucleic Acids Res. 28:1871-1878(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING.
[7]"Six and Eya expression during human somitogenesis and MyoD gene family activation."
Fougerousse F., Durand M., Lopez S., Suel L., Demignon J., Thornton C., Ozaki H., Kawakami K., Barbet P., Beckmann J.S., Maire P.
J. Muscle Res. Cell Motil. 23:255-264(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[8]"Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome."
Hoskins B.E., Cramer C.H., Silvius D., Zou D., Raymond R.M., Orten D.J., Kimberling W.J., Smith R.J.H., Weil D., Petit C., Otto E.A., Xu P.-X., Hildebrandt F.
Am. J. Hum. Genet. 80:800-804(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BOR2 THR-158; THR-296; ARG-365 AND MET-552, CHARACTERIZATION OF VARIANTS BOR2 THR-158 AND MET-552.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X84813 Genomic DNA. No translation available.
AC074212 Genomic DNA. No translation available.
BC033204 mRNA. Translation: AAH33204.1. Sequence problems.
BU859227 mRNA. No translation available.
AK074826 mRNA. No translation available.
RefSeqNP_787071.2. NM_175875.4.
UniGeneHs.43314.

3D structure databases

ProteinModelPortalQ8N196.
SMRQ8N196. Positions 86-259.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127096. 4 interactions.
IntActQ8N196. 4 interactions.
MINTMINT-2855964.
STRING9606.ENSP00000316842.

PTM databases

PhosphoSiteQ8N196.

Polymorphism databases

DMDM150421671.

Proteomic databases

PaxDbQ8N196.
PRIDEQ8N196.

Protocols and materials databases

DNASU147912.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317578; ENSP00000316842; ENSG00000177045.
GeneID147912.
KEGGhsa:147912.
UCSCuc002pdb.3. human.

Organism-specific databases

CTD147912.
GeneCardsGC19M046268.
H-InvDBHIX0202857.
HGNCHGNC:10891. SIX5.
HPAHPA042068.
MIM600963. gene.
610896. phenotype.
neXtProtNX_Q8N196.
Orphanet107. BOR syndrome.
PharmGKBPA35791.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG244874.
HOGENOMHOG000154329.
HOVERGENHBG050139.
InParanoidQ8N196.
OMAAFQRGEY.
OrthoDBEOG7C5M8Z.
PhylomeDBQ8N196.
TreeFamTF315545.

Gene expression databases

ArrayExpressQ8N196.
BgeeQ8N196.
CleanExHS_SIX5.
GenevestigatorQ8N196.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSIX5.
GenomeRNAi147912.
NextBio85758.
PROQ8N196.
SOURCESearch...

Entry information

Entry nameSIX5_HUMAN
AccessionPrimary (citable) accession number: Q8N196
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: June 26, 2007
Last modified: April 16, 2014
This is version 108 of the entry and version 3 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM