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O95343 (SIX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein SIX3
Alternative name(s):
Sine oculis homeobox homolog 3
Gene names
Name:SIX3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length332 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in visual system development.

Subcellular location

Nucleus.

Involvement in disease

Holoprosencephaly 2 (HPE2) [MIM:157170]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9

Sequence similarities

Belongs to the SIX/Sine oculis homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Cellular componentNucleus
   DiseaseDisease mutation
Holoprosencephaly
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Traceable author statement Ref.7. Source: ProtInc

circadian behavior

Inferred from electronic annotation. Source: Ensembl

diencephalon development

Inferred from electronic annotation. Source: Ensembl

forebrain anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

lens induction in camera-type eye

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

telencephalon development

Inferred from electronic annotation. Source: Ensembl

visual perception

Traceable author statement Ref.7. Source: ProtInc

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 332332Homeobox protein SIX3
PRO_0000049299

Regions

DNA binding206 – 26560Homeobox
Compositional bias33 – 6937Poly-Gly
Compositional bias263 – 2664Poly-Ala

Natural variations

Natural variant691G → D in HPE2. Ref.9
VAR_038418
Natural variant921V → G in HPE2. Ref.8
VAR_023797
Natural variant1051I → V in HPE2. Ref.8
VAR_023798
Natural variant1731H → P in HPE2. Ref.8
VAR_023799
Natural variant2021T → I in HPE2. Ref.8
VAR_023800
Natural variant2261L → V in HPE2. Ref.7
VAR_003771
Natural variant2311P → R in HPE2. Ref.8
VAR_023801
Natural variant2501V → A in HPE2. Ref.7
VAR_003772
Natural variant2571R → P in HPE2. Ref.7
VAR_003773
Natural variant2571R → W in HPE2. Ref.8
VAR_023802

Sequences

Sequence LengthMass (Da)Tools
O95343 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 21EA07F6A2DD978F

FASTA33235,487
        10         20         30         40         50         60 
MVFRSPLDLY SSHFLLPNFA DSHHRSILLA SSGGGNGAGG GGGAGGGSGG GNGAGGGGAG 

        70         80         90        100        110        120 
GAGGGGGGGS RAPPEELSMF QLPTLNFSPE QVASVCETLE ETGDIERLGR FLWSLPVAPG 

       130        140        150        160        170        180 
ACEAINKHES ILRARAVVAF HTGNFRDLYH ILENHKFTKE SHGKLQAMWL EAHYQEAEKL 

       190        200        210        220        230        240 
RGRPLGPVDK YRVRKKFPLP RTIWDGEQKT HCFKERTRSL LREWYLQDPY PNPSKKRELA 

       250        260        270        280        290        300 
QATGLTPTQV GNWFKNRRQR DRAAAAKNRL QHQAIGPSGM RSLAEPGCPT HGSAESPSTA 

       310        320        330 
ASPTTSVSSL TERADTGTSI LSVTSSDSEC DV 

« Hide

References

« Hide 'large scale' references
[1]"Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene."
Granadino B., Gallardo M.E., Lopez-Rios J., Sanz R., Ramos C., Ayuso C., Bovolenta P., Rodriguez de Cordoba S.
Genomics 55:100-105(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Sequence and location of SIX3, a homeobox gene expressed in the human eye."
Leppert G.S., Yang J.-M., Sundin O.H.
Ophthalmic Genet. 20:7-21(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"SIX3, a member of the Sine oculis/Six family of transcription factors, is expressed in the developing and adult human eye."
Clark B.J., Hanson I.M., Brown A.G., Ferrier R.K., Prosser J., van Heyningen V.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Retina.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly."
Wallis D.E., Roessler E., Hehr U., Nanni L., Wiltshire T., Richieri-Costa A., Gillessen-Kaesbach G., Zackai E.H., Rommens J., Muenke M.
Nat. Genet. 22:196-198(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE2 VAL-226; ALA-250 AND PRO-257.
[8]"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations."
Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F., Durou M.-R., Odent S., David V.
Hum. Mutat. 24:43-51(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE2 GLY-92; VAL-105; PRO-173; ILE-202; ARG-231 AND TRP-257.
[9]"SIX3 mutations with holoprosencephaly."
Ribeiro L.A., El-Jaick K.B., Muenke M., Richieri-Costa A.
Am. J. Med. Genet. A 140:2577-2583(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPE2 ASP-69.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF092047 Genomic DNA. Translation: AAD11939.1.
AF049339 Genomic DNA. Translation: AAD15753.1.
AF083891 Genomic DNA. Translation: AAD51091.1.
AJ012611 mRNA. Translation: CAB42539.1.
AC012354 Genomic DNA. Translation: AAX93283.1.
CH471053 Genomic DNA. Translation: EAX00267.1.
CH471053 Genomic DNA. Translation: EAX00268.1.
CCDSCCDS1821.1.
RefSeqNP_005404.1. NM_005413.3.
UniGeneHs.567336.

3D structure databases

ProteinModelPortalO95343.
SMRO95343. Positions 79-267.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112387. 5 interactions.
STRING9606.ENSP00000260653.

PTM databases

PhosphoSiteO95343.

Proteomic databases

PaxDbO95343.
PRIDEO95343.

Protocols and materials databases

DNASU6496.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260653; ENSP00000260653; ENSG00000138083.
GeneID6496.
KEGGhsa:6496.
UCSCuc002run.2. human.

Organism-specific databases

CTD6496.
GeneCardsGC02P045168.
GeneReviewsSIX3.
H-InvDBHIX0161628.
HGNCHGNC:10889. SIX3.
MIM157170. phenotype.
603714. gene.
neXtProtNX_O95343.
Orphanet93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
799. Schizencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBPA35789.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG244436.
HOGENOMHOG000261680.
HOVERGENHBG003609.
InParanoidO95343.
OMASSMTERV.
OrthoDBEOG7C5M8Z.
PhylomeDBO95343.
TreeFamTF315545.

Gene expression databases

ArrayExpressO95343.
BgeeO95343.
CleanExHS_SIX3.
GenevestigatorO95343.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSIX3.
GenomeRNAi6496.
NextBio25251.
PROO95343.
SOURCESearch...

Entry information

Entry nameSIX3_HUMAN
AccessionPrimary (citable) accession number: O95343
Secondary accession number(s): D6W5A5, Q53T42
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 123 of the entry and version 1 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 2

Human chromosome 2: entries, gene names and cross-references to MIM