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Q62233

- SIX3_MOUSE

UniProt

Q62233 - SIX3_MOUSE

Protein

Homeobox protein SIX3

Gene

Six3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 2 (15 Dec 1998)
      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.3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi207 – 26660HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. protein binding Source: IntAct
    3. RNA polymerase II distal enhancer sequence-specific DNA binding Source: NTNU_SB
    4. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
    5. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    6. sequence-specific DNA binding Source: MGI

    GO - Biological processi

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

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:102764. Six3.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Embryos die at birth and lack most head structures anterior to the midbrain, including the eyes and nose.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi88 – 881F → E: Loss of interaction with AES and TLE4. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 333333Homeobox protein SIX3PRO_0000049300Add
    BLAST

    Proteomic databases

    PRIDEiQ62233.

    PTM databases

    PhosphoSiteiQ62233.

    Expressioni

    Developmental stagei

    Expressed in the developing retina (at protein level). First expressed at E6.5 of embryo development around the anterior border. At E8.5, expression is found over the anterior neural plate. At E9.5, in the diencephalic part of the ventral forebrain, optic vesicles, olfactory placodes and Rathke pouch. In later stages, present in hypothalamus, eyes and pituitary.

    Inductioni

    Represses its own transcription in a TLE4-dependent manner.1 Publication

    Gene expression databases

    ArrayExpressiQ62233.
    BgeeiQ62233.
    GenevestigatoriQ62233.

    Interactioni

    Subunit structurei

    Interacts with MTA1, TLE4 and AES (via Q domain).2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AesP630025EBI-2297327,EBI-646888
    groP163712EBI-2297327,EBI-153866From a different organism.
    Tle4Q624412EBI-2297327,EBI-2297871

    Protein-protein interaction databases

    BioGridi203261. 4 interactions.
    DIPiDIP-46499N.
    IntActiQ62233. 3 interactions.
    STRINGi10090.ENSMUSP00000039867.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62233.
    SMRiQ62233. Positions 80-268.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni73 – 12048Interaction with AESAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi33 – 7038Gly-richAdd
    BLAST
    Compositional biasi264 – 2674Poly-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.
    GeneTreeiENSGT00540000070251.
    HOVERGENiHBG003609.
    InParanoidiQ4QQQ3.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform SIX3B (identifier: Q62233-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MVFRSPLDLY SSHFLLPNFA DSHHCSLLLA SSGGGSGASG GGGGAGGGGG    50
    GNRAGGGGAG GAGGGSGGGG SRAPPEELSM FQLPTLNFSP EQVASVCETL 100
    EETGDIERLG RFLWSLPVAP GACEAINKHE SILRARAVVA FHTGNFRDLY 150
    HILENHKFTK ESHGKLQAMW LEAHYQEAEK LRGRPLGPVD KYRVRKKFPL 200
    PRTIWDGEQK THCFKERTRS LLREWYLQDP YPNPSKKREL AQATGLTPTQ 250
    VGNWFKNRRQ RDRAAAAKNR LQHQAIGPSG MRSLAEPGCP THGSAESPST 300
    AASPTTSVSS LTERADTGTS ILSVTSSDSE CDV 333
    Length:333
    Mass (Da):35,593
    Last modified:December 15, 1998 - v2
    Checksum:i1AD7D3C4388043B9
    GO
    Isoform SIX3A (identifier: Q62233-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         271-286: LQHQAIGPSGMRSLAE → SVAGTAARPPQA
         287-333: Missing.

    Show »
    Length:282
    Mass (Da):30,456
    Checksum:iA549F11FB9A48237
    GO

    Sequence cautioni

    The sequence CAA62379.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti44 – 441G → GG in CAA62379. (PubMed:8575305)Curated
    Sequence conflicti118 – 1192VA → WP in CAA62379. (PubMed:8575305)Curated
    Sequence conflicti278 – 33356PSGMR…SECDV → ERDALPGRARLPHARLSRVT VHGGQPDHQCVQPDGARGHR HFDPLGNLQRLGM in CAA62379. (PubMed:8575305)CuratedAdd
    BLAST

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei271 – 28616LQHQA…RSLAE → SVAGTAARPPQA in isoform SIX3A. CuratedVSP_002291Add
    BLAST
    Alternative sequencei287 – 33347Missing in isoform SIX3A. CuratedVSP_002292Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X90871 mRNA. Translation: CAA62379.1. Different initiation.
    D83144 mRNA. Translation: BAA11822.1.
    D83145 mRNA. Translation: BAA11823.1.
    BC098096 mRNA. Translation: AAH98096.1.
    CCDSiCCDS50203.1. [Q62233-1]
    PIRiS74255.
    RefSeqiNP_035511.2. NM_011381.4. [Q62233-1]
    UniGeneiMm.370208.
    Mm.391586.

    Genome annotation databases

    EnsembliENSMUST00000175898; ENSMUSP00000135677; ENSMUSG00000038805. [Q62233-1]
    ENSMUST00000176081; ENSMUSP00000135312; ENSMUSG00000038805. [Q62233-1]
    GeneIDi20473.
    KEGGimmu:20473.
    UCSCiuc008dtz.2. mouse. [Q62233-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X90871 mRNA. Translation: CAA62379.1 . Different initiation.
    D83144 mRNA. Translation: BAA11822.1 .
    D83145 mRNA. Translation: BAA11823.1 .
    BC098096 mRNA. Translation: AAH98096.1 .
    CCDSi CCDS50203.1. [Q62233-1 ]
    PIRi S74255.
    RefSeqi NP_035511.2. NM_011381.4. [Q62233-1 ]
    UniGenei Mm.370208.
    Mm.391586.

    3D structure databases

    ProteinModelPortali Q62233.
    SMRi Q62233. Positions 80-268.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203261. 4 interactions.
    DIPi DIP-46499N.
    IntActi Q62233. 3 interactions.
    STRINGi 10090.ENSMUSP00000039867.

    PTM databases

    PhosphoSitei Q62233.

    Proteomic databases

    PRIDEi Q62233.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000175898 ; ENSMUSP00000135677 ; ENSMUSG00000038805 . [Q62233-1 ]
    ENSMUST00000176081 ; ENSMUSP00000135312 ; ENSMUSG00000038805 . [Q62233-1 ]
    GeneIDi 20473.
    KEGGi mmu:20473.
    UCSCi uc008dtz.2. mouse. [Q62233-1 ]

    Organism-specific databases

    CTDi 6496.
    MGIi MGI:102764. Six3.

    Phylogenomic databases

    eggNOGi NOG244436.
    GeneTreei ENSGT00540000070251.
    HOVERGENi HBG003609.
    InParanoidi Q4QQQ3.
    TreeFami TF315545.

    Miscellaneous databases

    NextBioi 298587.
    PROi Q62233.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q62233.
    Bgeei Q62233.
    Genevestigatori Q62233.

    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. "Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development."
      Oliver G., Mailhos A., Wehr R., Copeland N.G., Jenkins N.A., Gruss P.
      Development 121:4045-4055(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Embryonic brain.
    2. "Identification and expression of Six family genes in mouse retina."
      Kawakami K., Ohto H., Takizawa T., Saito T.
      FEBS Lett. 393:259-263(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
    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] (ISOFORM SIX3B).
      Strain: C57BL/6.
      Tissue: Brain.
    4. "Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors."
      Zhu C.C., Dyer M.A., Uchikawa M., Kondoh H., Lagutin O.V., Oliver G.
      Development 129:2835-2849(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH AES AND TLE4, MUTAGENESIS OF PHE-88.
    5. "Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development."
      Lagutin O.V., Zhu C.C., Kobayashi D., Topczewski J., Shimamura K., Puelles L., Russell H.R., McKinnon P.J., Solnica-Krezel L., Oliver G.
      Genes Dev. 17:368-379(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    6. "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: FUNCTION, INTERACTION WITH MTA1.

    Entry informationi

    Entry nameiSIX3_MOUSE
    AccessioniPrimary (citable) accession number: Q62233
    Secondary accession number(s): P70176, P70177, Q4QQQ3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 125 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3