SIX3_CHICK
ID SIX3_CHICK Reviewed; 314 AA.
AC O42406; Q53Z11;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Homeobox protein SIX3;
DE AltName: Full=CSIX3;
DE AltName: Full=Sine oculis homeobox homolog 3;
GN Name=SIX3;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9510037; DOI=10.1016/s0925-4773(97)00183-4;
RA Bovolenta P., Mallamaci A., Puelles L., Boncinelli E.;
RT "Expression pattern of cSix3, a member of the Six/sine oculis family of
RT transcription factors.";
RL Mech. Dev. 70:201-203(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen A., Cepko C.L.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=12050133; DOI=10.1242/dev.129.12.2835;
RA Zhu C.C., Dyer M.A., Uchikawa M., Kondoh H., Lagutin O.V., Oliver G.;
RT "Six3-mediated auto repression and eye development requires its interaction
RT with members of the Groucho-related family of co-repressors.";
RL Development 129:2835-2849(2002).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=12167403; DOI=10.1006/dbio.2002.0732;
RA Hsieh Y.W., Zhang X.M., Lin E., Oliver G., Yang X.J.;
RT "The homeobox gene Six3 is a potential regulator of anterior segment
RT formation in the chick eye.";
RL Dev. Biol. 248:265-280(2002).
RN [5]
RP FUNCTION.
RX PubMed=12569128; DOI=10.1101/gad.1059403;
RA Lagutin O.V., Zhu C.C., Kobayashi D., Topczewski J., Shimamura K.,
RA Puelles L., Russell H.R., McKinnon P.J., Solnica-Krezel L., Oliver G.;
RT "Six3 repression of Wnt signaling in the anterior neuroectoderm is
RT essential for vertebrate forebrain development.";
RL Genes Dev. 17:368-379(2003).
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 (PubMed:12569128). Acts as a direct upstream activator of
CC SHH expression in the rostral diencephalon ventral midline and that in
CC turn SHH maintains its expression. In addition, Six3 activity is
CC required for the formation of the telencephalon. During postnatal
CC stages of brain development is necessary for ependymal cell maturation
CC by promoting the maturation of radial glia into ependymal cells through
CC regulation of neuroblast proliferation and migration. Acts on the
CC proliferation and differentiation of neural progenitor cells through
CC activating transcription of CCND1 AND CCND2. During early lens
CC formation plays a role in lens induction and specification by
CC activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6
CC activates SIX3 resulting in activation of PDGFRA and CCND1 promoting
CC cell proliferation. Also is required for the neuroretina development by
CC directly suppressing WNT8B expression in the anterior neural plate
CC territory. Its action during retina development and lens morphogenesis
CC is AES and TLE4-dependent manner (PubMed:12050133). Furthermore, during
CC eye development regulates several genes expression. Before and during
CC early lens development represses the CRYGF promoter by binding a SIX
CC repressor element. Directly activates RHO transcription, or cooperates
CC with CRX or NRL. Six3 functions also in the formation of the
CC proximodistal axis of the optic cup, and promotes the formation of
CC optic vesicles-like structures. During pituitary development, acts in
CC parallel or alternatively with HESX1 to control cell proliferation
CC through Wnt/beta-catenin pathway. Plays a role in eye development by
CC suppressing WNT1 expression and in dorsal-ventral patterning by
CC repressing BMP signaling pathway (By similarity).
CC {ECO:0000250|UniProtKB:O95343, ECO:0000250|UniProtKB:Q62233,
CC ECO:0000269|PubMed:12050133, ECO:0000269|PubMed:12569128}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q62233,
CC ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DEVELOPMENTAL STAGE: First detected in the corneal epithelium and lens
CC epithelium at E6.5 and E12. At E12 is present in the corneal
CC endothelium and the limbal region. After E16 and at hatching (H1),
CC expression persisted in multiple anterior segment tissues, including
CC the lens epithelium, the corneal endothelium, the iris, and the
CC trabecular meshwork (at protein level). {ECO:0000269|PubMed:12167403}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
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DR EMBL; Y15106; CAA75380.1; -; mRNA.
DR EMBL; AY373324; AAQ76043.1; -; mRNA.
DR RefSeq; NP_989695.1; NM_204364.1.
DR AlphaFoldDB; O42406; -.
DR BMRB; O42406; -.
DR SMR; O42406; -.
DR Ensembl; ENSGALT00000046696; ENSGALP00000058342; ENSGALG00000032259.
DR GeneID; 378786; -.
DR KEGG; gga:378786; -.
DR CTD; 6496; -.
DR VEuPathDB; HostDB:geneid_378786; -.
DR GeneTree; ENSGT00940000160346; -.
DR InParanoid; O42406; -.
DR OMA; PGCPTHN; -.
DR PhylomeDB; O42406; -.
DR PRO; PR:O42406; -.
DR Proteomes; UP000000539; Chromosome 3.
DR Bgee; ENSGALG00000032259; Expressed in brain.
DR ExpressionAtlas; O42406; baseline and differential.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; ISS:AgBase.
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; ISS:AgBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1902742; P:apoptotic process involved in development; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:AgBase.
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:0030178; P:negative regulation of Wnt signaling pathway; ISS:AgBase.
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:SF31; PTHR10390:SF31; 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..314
FT /note="Homeobox protein SIX3"
FT /id="PRO_0000049301"
FT DNA_BIND 188..247
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 214..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 314 AA; 34677 MW; D9A04530185BA75F CRC64;
MVFRSPLELY PTHFFLPNFA ADPHHRSLLL ASGGSGSGSG CSPGAGGGGG SSRAPHEELS
MFQLPTLNFS PEQVASVCET LEETGDIERL GRFLWSLPVA PGACEAINKH ESILRARAVV
AFHTGNFRDL YHILENHKFT KESHGKLQAM WLEAHYQEAE KLRGRPLGPV DKYRVRKKFP
LPRTIWDGEQ KTHCFKERTR SLLREWYLQD PYPNPSKKRE LAQATGLTPT QVGNWFKNRR
QRDRAAAAKN RLQHQAIGQS GMRSLAEPGC PTHSSAESPS TAASPTTSVS SLTERAETGT
SILSVTSSDS ECDV
