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O95343

- SIX3_HUMAN

UniProt

O95343 - SIX3_HUMAN

Protein

Homeobox protein SIX3

Gene

SIX3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    Functioni

    Transcriptional repressor essential for eye and forebrain development. Involved in the development of the forebrain by negatively regulating the expression of WNT1. Plays an important role during retina development and lens morphogenesis in an AES and TLE4-dependent manner By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi206 – 26560HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
    2. sequence-specific DNA binding Source: Ensembl

    GO - Biological processi

    1. brain development Source: ProtInc
    2. circadian behavior Source: Ensembl
    3. diencephalon development Source: Ensembl
    4. forebrain anterior/posterior pattern specification Source: Ensembl
    5. lens induction in camera-type eye Source: Ensembl
    6. negative regulation of transcription, DNA-templated Source: Ensembl
    7. negative regulation of Wnt signaling pathway Source: Ensembl
    8. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    9. protein import into nucleus Source: Ensembl
    10. telencephalon development Source: Ensembl
    11. visual perception Source: ProtInc

    Keywords - Molecular functioni

    Developmental protein, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homeobox protein SIX3
    Alternative name(s):
    Sine oculis homeobox homolog 3
    Gene namesi
    Name:SIX3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:10889. SIX3.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti69 – 691G → D in HPE2. 1 Publication
    VAR_038418
    Natural varianti92 – 921V → G in HPE2. 1 Publication
    VAR_023797
    Natural varianti105 – 1051I → V in HPE2. 1 Publication
    VAR_023798
    Natural varianti173 – 1731H → P in HPE2. 1 Publication
    VAR_023799
    Natural varianti202 – 2021T → I in HPE2. 1 Publication
    VAR_023800
    Natural varianti226 – 2261L → V in HPE2. 1 Publication
    VAR_003771
    Natural varianti231 – 2311P → R in HPE2. 1 Publication
    VAR_023801
    Natural varianti250 – 2501V → A in HPE2. 1 Publication
    VAR_003772
    Natural varianti257 – 2571R → P in HPE2. 1 Publication
    VAR_003773
    Natural varianti257 – 2571R → W in HPE2. 1 Publication
    VAR_023802

    Keywords - Diseasei

    Disease mutation, Holoprosencephaly

    Organism-specific databases

    MIMi157170. phenotype.
    Orphaneti93925. Alobar holoprosencephaly.
    93924. Lobar holoprosencephaly.
    280200. Microform holoprosencephaly.
    93926. Midline interhemispheric variant of holoprosencephaly.
    799. Schizencephaly.
    220386. Semilobar holoprosencephaly.
    280195. Septopreoptic holoprosencephaly.
    PharmGKBiPA35789.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 332332Homeobox protein SIX3PRO_0000049299Add
    BLAST

    Proteomic databases

    PaxDbiO95343.
    PRIDEiO95343.

    PTM databases

    PhosphoSiteiO95343.

    Expressioni

    Gene expression databases

    ArrayExpressiO95343.
    BgeeiO95343.
    CleanExiHS_SIX3.
    GenevestigatoriO95343.

    Interactioni

    Subunit structurei

    Interacts with TLE4 and AES (via Q domain) By similarity. Interacts with MTA1.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi112387. 5 interactions.
    STRINGi9606.ENSP00000260653.

    Structurei

    3D structure databases

    ProteinModelPortaliO95343.
    SMRiO95343. Positions 79-267.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni72 – 11948Interaction with AESBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi33 – 6937Poly-GlyAdd
    BLAST
    Compositional biasi263 – 2664Poly-Ala

    Sequence similaritiesi

    Belongs to the SIX/Sine oculis homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG244436.
    HOGENOMiHOG000261680.
    HOVERGENiHBG003609.
    InParanoidiO95343.
    OMAiSSMTERV.
    OrthoDBiEOG7C5M8Z.
    PhylomeDBiO95343.
    TreeFamiTF315545.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    [Graphical view]
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O95343-1 [UniParc]FASTAAdd to Basket

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    MVFRSPLDLY SSHFLLPNFA DSHHRSILLA SSGGGNGAGG GGGAGGGSGG    50
    GNGAGGGGAG GAGGGGGGGS RAPPEELSMF QLPTLNFSPE QVASVCETLE 100
    ETGDIERLGR FLWSLPVAPG ACEAINKHES ILRARAVVAF HTGNFRDLYH 150
    ILENHKFTKE SHGKLQAMWL EAHYQEAEKL RGRPLGPVDK YRVRKKFPLP 200
    RTIWDGEQKT HCFKERTRSL LREWYLQDPY PNPSKKRELA QATGLTPTQV 250
    GNWFKNRRQR DRAAAAKNRL QHQAIGPSGM RSLAEPGCPT HGSAESPSTA 300
    ASPTTSVSSL TERADTGTSI LSVTSSDSEC DV 332
    Length:332
    Mass (Da):35,487
    Last modified:May 1, 1999 - v1
    Checksum:i21EA07F6A2DD978F
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti69 – 691G → D in HPE2. 1 Publication
    VAR_038418
    Natural varianti92 – 921V → G in HPE2. 1 Publication
    VAR_023797
    Natural varianti105 – 1051I → V in HPE2. 1 Publication
    VAR_023798
    Natural varianti173 – 1731H → P in HPE2. 1 Publication
    VAR_023799
    Natural varianti202 – 2021T → I in HPE2. 1 Publication
    VAR_023800
    Natural varianti226 – 2261L → V in HPE2. 1 Publication
    VAR_003771
    Natural varianti231 – 2311P → R in HPE2. 1 Publication
    VAR_023801
    Natural varianti250 – 2501V → A in HPE2. 1 Publication
    VAR_003772
    Natural varianti257 – 2571R → P in HPE2. 1 Publication
    VAR_003773
    Natural varianti257 – 2571R → W in HPE2. 1 Publication
    VAR_023802

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS1821.1.
    RefSeqiNP_005404.1. NM_005413.3.
    UniGeneiHs.567336.

    Genome annotation databases

    EnsembliENST00000260653; ENSP00000260653; ENSG00000138083.
    GeneIDi6496.
    KEGGihsa:6496.
    UCSCiuc002run.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS1821.1.
    RefSeqi NP_005404.1. NM_005413.3.
    UniGenei Hs.567336.

    3D structure databases

    ProteinModelPortali O95343.
    SMRi O95343. Positions 79-267.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112387. 5 interactions.
    STRINGi 9606.ENSP00000260653.

    PTM databases

    PhosphoSitei O95343.

    Proteomic databases

    PaxDbi O95343.
    PRIDEi O95343.

    Protocols and materials databases

    DNASUi 6496.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260653 ; ENSP00000260653 ; ENSG00000138083 .
    GeneIDi 6496.
    KEGGi hsa:6496.
    UCSCi uc002run.2. human.

    Organism-specific databases

    CTDi 6496.
    GeneCardsi GC02P045168.
    GeneReviewsi SIX3.
    H-InvDB HIX0161628.
    HGNCi HGNC:10889. SIX3.
    MIMi 157170. phenotype.
    603714. gene.
    neXtProti NX_O95343.
    Orphaneti 93925. Alobar holoprosencephaly.
    93924. Lobar holoprosencephaly.
    280200. Microform holoprosencephaly.
    93926. Midline interhemispheric variant of holoprosencephaly.
    799. Schizencephaly.
    220386. Semilobar holoprosencephaly.
    280195. Septopreoptic holoprosencephaly.
    PharmGKBi PA35789.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG244436.
    HOGENOMi HOG000261680.
    HOVERGENi HBG003609.
    InParanoidi O95343.
    OMAi SSMTERV.
    OrthoDBi EOG7C5M8Z.
    PhylomeDBi O95343.
    TreeFami TF315545.

    Miscellaneous databases

    GeneWikii SIX3.
    GenomeRNAii 6496.
    NextBioi 25251.
    PROi O95343.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95343.
    Bgeei O95343.
    CleanExi HS_SIX3.
    Genevestigatori O95343.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    [Graphical view ]
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "Metastasis-associated protein 1 and its short form variant stimulates Wnt1 transcription through promoting its derepression from Six3 corepressor."
      Kumar R., Balasenthil S., Manavathi B., Rayala S.K., Pakala S.B.
      Cancer Res. 70:6649-6658(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MTA1.
    8. Cited for: VARIANTS HPE2 VAL-226; ALA-250 AND PRO-257.
    9. "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.
    10. Cited for: VARIANT HPE2 ASP-69.

    Entry informationi

    Entry nameiSIX3_HUMAN
    AccessioniPrimary (citable) accession number: O95343
    Secondary accession number(s): D6W5A5, Q53T42
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: May 1, 1999
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3