SIX3_ORYLA
ID SIX3_ORYLA Reviewed; 272 AA.
AC O73916;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 25-MAY-2022, entry version 118.
DE RecName: Full=Homeobox protein SIX3;
DE AltName: Full=Sine oculis homeobox homolog 3;
GN Name=six3;
OS Oryzias latipes (Japanese rice fish) (Japanese killifish).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Ovalentaria; Atherinomorphae; Beloniformes; Adrianichthyidae; Oryziinae;
OC Oryzias.
OX NCBI_TaxID=8090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Carolina Biological;
RX PubMed=9651515; DOI=10.1016/s0925-4773(98)00055-0;
RA Loosli F., Koester R.W., Carl M., Krone A., Wittbrodt J.;
RT "Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is
RT expressed in the anterior embryonic shield and the developing eye.";
RL Mech. Dev. 74:159-164(1998).
RN [2]
RP INTERACTION WITH GMNN.
RX PubMed=14973488; DOI=10.1038/nature02292;
RA Del Bene F., Tessmar-Raible K., Wittbrodt J.;
RT "Direct interaction of geminin and Six3 in eye development.";
RL Nature 427:745-749(2004).
CC -!- FUNCTION: Transcriptional regulator which can act as both a
CC transcriptional repressor and activator by binding a ATTA homeodomain
CC core recognition sequence on these target genes. During forebrain
CC development represses WNT1 expression allowing zona limitans
CC intrathalamica formation and thereby ensuring proper anterio-posterior
CC patterning of the diencephalon and formation of the rostral
CC diencephalon. Acts as a direct upstream activator of SHH expression in
CC the rostral diencephalon ventral midline and that in turn SHH maintains
CC its expression. In addition, Six3 activity is required for the
CC formation of the telencephalon. During postnatal stages of brain
CC development is necessary for ependymal cell maturation by promoting the
CC maturation of radial glia into ependymal cells through regulation of
CC neuroblast proliferation and migration. Acts on the proliferation and
CC differentiation of neural progenitor cells through activating
CC transcription of CCND1 AND CCND2. During early lens formation plays a
CC role in lens induction and specification by activating directly PAX6 in
CC the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in
CC activation of PDGFRA and CCND1 promoting cell proliferation. Also is
CC required for the neuroretina development by directly suppressing WNT8B
CC expression in the anterior neural plate territory. Its action during
CC retina development and lens morphogenesis is AES and TLE4-dependent
CC manner. Furthermore, during eye development regulates several genes
CC expression. Before and during early lens development represses the
CC CRYGF promoter by binding a SIX repressor element. Directly activates
CC RHO transcription, or cooperates with CRX or NRL. Six3 functions also
CC in the formation of the proximodistal axis of the optic cup, and
CC promotes the formation of optic vesicles-like structures. During
CC pituitary development, acts in parallel or alternatively with HESX1 to
CC control cell proliferation through Wnt/beta-catenin pathway. Plays a
CC role in eye development by suppressing WNT1 expression and in dorsal-
CC ventral patterning by repressing BMP signaling pathway.
CC {ECO:0000250|UniProtKB:O42406, ECO:0000250|UniProtKB:O95343,
CC ECO:0000250|UniProtKB:Q62233}.
CC -!- SUBUNIT: Interacts with GMNN. {ECO:0000269|PubMed:14973488}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q62233,
CC ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
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DR EMBL; AJ000937; CAA04394.1; -; mRNA.
DR RefSeq; NP_001098230.1; NM_001104760.1.
DR AlphaFoldDB; O73916; -.
DR SMR; O73916; -.
DR STRING; 8090.ENSORLP00000012924; -.
DR GeneID; 100049355; -.
DR KEGG; ola:100049355; -.
DR CTD; 30636; -.
DR eggNOG; KOG0775; Eukaryota.
DR InParanoid; O73916; -.
DR OrthoDB; 1197104at2759; -.
DR Proteomes; UP000001038; Unplaced.
DR Proteomes; UP000265180; Chromosome 9.
DR Proteomes; UP000265200; Chromosome 9.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; ISS:UniProtKB.
DR GO; GO:0021846; P:cell proliferation in forebrain; ISS:UniProtKB.
DR GO; GO:0002070; P:epithelial cell maturation; ISS:UniProtKB.
DR GO; GO:0001654; P:eye development; ISS:UniProtKB.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; ISS:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; ISS:UniProtKB.
DR GO; GO:1990086; P:lens fiber cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0070306; P:lens fiber cell differentiation; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0014016; P:neuroblast differentiation; ISS:UniProtKB.
DR GO; GO:0097402; P:neuroblast migration; ISS:UniProtKB.
DR GO; GO:0003404; P:optic vesicle morphogenesis; ISS:UniProtKB.
DR GO; GO:0021983; P:pituitary gland development; ISS:UniProtKB.
DR GO; GO:0009946; P:proximal/distal axis specification; ISS:UniProtKB.
DR GO; GO:1901987; P:regulation of cell cycle phase transition; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0061074; P:regulation of neural retina development; ISS:UniProtKB.
DR GO; GO:1902692; P:regulation of neuroblast proliferation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021537; P:telencephalon development; ISS:UniProtKB.
DR GO; GO:0021978; P:telencephalon regionalization; ISS:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR031701; SIX1_SD.
DR InterPro; IPR032949; SIX3/SIX6.
DR PANTHER; PTHR10390:SF67; PTHR10390:SF67; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF16878; SIX1_SD; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..272
FT /note="Homeobox protein SIX3"
FT /id="PRO_0000049302"
FT DNA_BIND 169..228
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 244..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 272 AA; 30946 MW; CDDE939EB8C0AB22 CRC64;
MVFRAPLDFI SASRLLLPHF ADAPPVLSRS RSPEHPPAGF LSLALPGLCF SATQIASVCE
TLEETGDIER LARFLWSLPV NTDGRDSISE HESVQRARAV VAFHTGCYRE LYRILETHRF
TRASHSKLQA MWLEAHYREA EKLRGRPLGP VDKYRVRKKF PLPRTIWDGE QKTHCFKERT
RGLLREWYLQ DPYPNPGKKR ELAHATGLTP TQVGNWFKNR RQRDRAAAAK NRLQHHRICP
DSACTLSGGD SSERADGDTF LSVTDSDSDL DV
