SIX3_MOUSE
ID SIX3_MOUSE Reviewed; 333 AA.
AC Q62233; P70176; P70177; Q4QQQ3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Homeobox protein SIX3;
DE AltName: Full=Sine oculis homeobox homolog 3;
GN Name=Six3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SIX3B).
RC STRAIN=BALB/cJ; TISSUE=Embryonic brain;
RX PubMed=8575305; DOI=10.1242/dev.121.12.4045;
RA Oliver G., Mailhos A., Wehr R., Copeland N.G., Jenkins N.A., Gruss P.;
RT "Six3, a murine homologue of the sine oculis gene, demarcates the most
RT anterior border of the developing neural plate and is expressed during eye
RT development.";
RL Development 121:4045-4055(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SIX3A), AND NUCLEOTIDE SEQUENCE [MRNA]
RP OF 4-333 (ISOFORM SIX3B).
RC STRAIN=BALB/cJ;
RX PubMed=8814301; DOI=10.1016/0014-5793(96)00899-x;
RA Kawakami K., Ohto H., Takizawa T., Saito T.;
RT "Identification and expression of Six family genes in mouse retina.";
RL FEBS Lett. 393:259-263(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SIX3B).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION IN OPTIC VESICLE MORPHOGENESIS, AND DEVELOPMENTAL STAGE.
RX PubMed=11458394; DOI=10.1002/dvdy.1148;
RA Lagutin O., Zhu C.C., Furuta Y., Rowitch D.H., McMahon A.P., Oliver G.;
RT "Six3 promotes the formation of ectopic optic vesicle-like structures in
RT mouse embryos.";
RL Dev. Dyn. 221:342-349(2001).
RN [5]
RP FUNCTION IN LENS DEVELOPMENT.
RX PubMed=11139622; DOI=10.1093/nar/29.2.515;
RA Lengler J., Krausz E., Tomarev S., Prescott A., Quinlan R.A., Graw J.;
RT "Antagonistic action of Six3 and Prox1 at the gamma-crystallin promoter.";
RL Nucleic Acids Res. 29:515-526(2001).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH TLE5 AND TLE4,
RP AND MUTAGENESIS OF PHE-88.
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 [7]
RP FUNCTION IN PROXIMAL/DISTAL AXIS SPECIFICATION.
RX PubMed=12163408; DOI=10.1242/dev.129.17.4057;
RA Carl M., Loosli F., Wittbrodt J.;
RT "Six3 inactivation reveals its essential role for the formation and
RT patterning of the vertebrate eye.";
RL Development 129:4057-4063(2002).
RN [8]
RP FUNCTION IN LENS DEVELOPMENT, AND INDUCTION.
RX PubMed=12072567; DOI=10.1073/pnas.132195699;
RA Goudreau G., Petrou P., Reneker L.W., Graw J., Loster J., Gruss P.;
RT "Mutually regulated expression of Pax6 and Six3 and its implications for
RT the Pax6 haploinsufficient lens phenotype.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8719-8724(2002).
RN [9]
RP FUNCTION IN FOREBRAIN DEVELOPMENT, AND DISRUPTION PHENOTYPE.
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).
RN [10]
RP INTERACTION WITH EYA1, AND DEVELOPMENTAL STAGE.
RX PubMed=16024294; DOI=10.1016/j.modgep.2005.04.010;
RA Purcell P., Oliver G., Mardon G., Donner A.L., Maas R.L.;
RT "Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal
RT placode induction.";
RL Gene Expr. Patterns 6:110-118(2005).
RN [11]
RP FUNCTION IN LENS INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17066077; DOI=10.1038/sj.emboj.7601398;
RA Liu W., Lagutin O.V., Mende M., Streit A., Oliver G.;
RT "Six3 activation of Pax6 expression is essential for mammalian lens
RT induction and specification.";
RL EMBO J. 25:5383-5395(2006).
RN [12]
RP FUNCTION, INTERACTION WITH HDAC2 AND MTA1, AND MUTAGENESIS OF
RP 233-ASN--SER-235.
RX PubMed=17666527; DOI=10.1073/pnas.0705878104;
RA Manavathi B., Peng S., Rayala S.K., Talukder A.H., Wang M.H., Wang R.A.,
RA Balasenthil S., Agarwal N., Frishman L.J., Kumar R.;
RT "Repression of Six3 by a corepressor regulates rhodopsin expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13128-13133(2007).
RN [13]
RP FUNCTION IN PROLIFERATION OF NEURAL PROGENITOR CELLS.
RX PubMed=17576749; DOI=10.1093/cercor/bhm092;
RA Appolloni I., Calzolari F., Corte G., Perris R., Malatesta P.;
RT "Six3 controls the neural progenitor status in the murine CNS.";
RL Cereb. Cortex 18:553-562(2008).
RN [14]
RP FUNCTION IN FOREBRAIN DEVELOPMENT, AND DISRUPTION PHENOTYPE.
RX PubMed=18094027; DOI=10.1242/dev.010082;
RA Lavado A., Lagutin O.V., Oliver G.;
RT "Six3 inactivation causes progressive caudalization and aberrant patterning
RT of the mammalian diencephalon.";
RL Development 135:441-450(2008).
RN [15]
RP FUNCTION IN PITUITARY DEVELOPMENT, AND DISRUPTION PHENOTYPE.
RX PubMed=18775421; DOI=10.1016/j.ydbio.2008.08.008;
RA Gaston-Massuet C., Andoniadou C.L., Signore M., Sajedi E., Bird S.,
RA Turner J.M., Martinez-Barbera J.P.;
RT "Genetic interaction between the homeobox transcription factors HESX1 and
RT SIX3 is required for normal pituitary development.";
RL Dev. Biol. 324:322-333(2008).
RN [16]
RP FUNCTION IN FOREBRAIN DEVELOPMENT, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18694563; DOI=10.1016/j.devcel.2008.07.003;
RA Geng X., Speirs C., Lagutin O., Inbal A., Liu W., Solnica-Krezel L.,
RA Jeong Y., Epstein D.J., Oliver G.;
RT "Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in
RT the ventral forebrain and causes holoprosencephaly.";
RL Dev. Cell 15:236-247(2008).
RN [17]
RP INTERACTION WITH EYA4.
RX PubMed=19606496; DOI=10.1002/humu.21094;
RA Abe Y., Oka A., Mizuguchi M., Igarashi T., Ishikawa S., Aburatani H.,
RA Yokoyama S., Asahara H., Nagao K., Yamada M., Miyashita T.;
RT "EYA4, deleted in a case with middle interhemispheric variant of
RT holoprosencephaly, interacts with SIX3 both physically and functionally.";
RL Hum. Mutat. 30:E946-E955(2009).
RN [18]
RP FUNCTION.
RX PubMed=20682799; DOI=10.1158/0008-5472.can-10-0909;
RA Kumar R., Balasenthil S., Manavathi B., Rayala S.K., Pakala S.B.;
RT "Metastasis-associated protein 1 and its short form variant stimulates Wnt1
RT transcription through promoting its derepression from Six3 corepressor.";
RL Cancer Res. 70:6649-6658(2010).
RN [19]
RP FUNCTION IN NEURAL RETINA DEVELOPMENT.
RX PubMed=20890044; DOI=10.1172/jci43219;
RA Liu W., Lagutin O., Swindell E., Jamrich M., Oliver G.;
RT "Neuroretina specification in mouse embryos requires Six3-mediated
RT suppression of Wnt8b in the anterior neural plate.";
RL J. Clin. Invest. 120:3568-3577(2010).
RN [20]
RP FUNCTION IN CELL MATURATION, AND TISSUE SPECIFICITY.
RX PubMed=22071110; DOI=10.1242/dev.067470;
RA Lavado A., Oliver G.;
RT "Six3 is required for ependymal cell maturation.";
RL Development 138:5291-5300(2011).
RN [21]
RP INDUCTION.
RX PubMed=23792023; DOI=10.1016/j.ydbio.2013.06.016;
RA Lee B., Song H., Rizzoti K., Son Y., Yoon J., Baek K., Jeong Y.;
RT "Genomic code for Sox2 binding uncovers its regulatory role in Six3
RT activation in the forebrain.";
RL Dev. Biol. 381:491-501(2013).
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:18094027). 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 (PubMed:18775421). In addition, Six3
CC activity is required for the formation of the telencephalon. During
CC postnatal stages of brain development is necessary for ependymal cell
CC maturation by promoting the maturation of radial glia into ependymal
CC cells through regulation of neuroblast proliferation and migration
CC (PubMed:22071110). Acts on the proliferation and differentiation of
CC neural progenitor cells through activating transcription of CCND1 AND
CC CCND2 (PubMed:17576749). During early lens formation plays a role in
CC lens induction and specification by activating directly PAX6 in the
CC presumptive lens ectoderm (PubMed:17066077). In turn PAX6 activates
CC SIX3 resulting in activation of PDGFRA and CCND1 promoting cell
CC proliferation (PubMed:12072567). Also is required for the neuroretina
CC development by directly suppressing WNT8B expression in the anterior
CC neural plate territory (PubMed:20890044). Its action during retina
CC development and lens morphogenesis is TLE5 and TLE4-dependent manner.
CC Furthermore, during eye development regulates several genes expression.
CC Before and during early lens development represses the CRYGF promoter
CC by binding a SIX repressor element (PubMed:11139622). Directly
CC activates RHO transcription, or cooperates with CRX or NRL
CC (PubMed:17666527). Six3 functions also in the formation of the
CC proximodistal axis of the optic cup (PubMed:12163408), and promotes the
CC formation of optic vesicles-like structures (PubMed:11458394). During
CC pituitary development, acts in parallel or alternatively with HESX1 to
CC control cell proliferation through Wnt/beta-catenin pathway
CC (PubMed:18694563). Plays a role in eye development by suppressing WNT1
CC expression and in dorsal-ventral patterning by repressing BMP signaling
CC pathway (By similarity). {ECO:0000250|UniProtKB:O95343,
CC ECO:0000269|PubMed:11139622, ECO:0000269|PubMed:11458394,
CC ECO:0000269|PubMed:12050133, ECO:0000269|PubMed:12072567,
CC ECO:0000269|PubMed:12163408, ECO:0000269|PubMed:12569128,
CC ECO:0000269|PubMed:17066077, ECO:0000269|PubMed:17576749,
CC ECO:0000269|PubMed:17666527, ECO:0000269|PubMed:18094027,
CC ECO:0000269|PubMed:18694563, ECO:0000269|PubMed:18775421,
CC ECO:0000269|PubMed:20682799, ECO:0000269|PubMed:20890044,
CC ECO:0000269|PubMed:22071110}.
CC -!- SUBUNIT: Interacts with EYA4; translocates EYA4 from the cytoplasm to
CC the nucleus and promotes activation of their target genes. Interacts
CC with MTA1 and HDAC2; represses its own transcription. Interacts with
CC MTA1; facilitates the binding of SIX3 to the core DNA motif of SIX3
CC promoter. Interacts with EYA1; promotes EYA1 translocation to the
CC nucleus. Interacts with TLE1 and TLE5 (via Q domain); can act in
CC combination with either TLE1 and/or TLE5 leading to transcriptional
CC repression or activation, respectively (By similarity). Interacts (via
CC homeobox) with NR4A3; differentially regulates the transcriptional
CC activities NR4A3 (By similarity). Interacts with GMNN (By similarity).
CC Interacts with TLE4. {ECO:0000250|UniProtKB:O95343,
CC ECO:0000269|PubMed:12050133, ECO:0000269|PubMed:16024294,
CC ECO:0000269|PubMed:17666527, ECO:0000269|PubMed:19606496}.
CC -!- INTERACTION:
CC Q62233; P70288: Hdac2; NbExp=2; IntAct=EBI-2297327, EBI-302251;
CC Q62233; Q8K4B0: Mta1; NbExp=2; IntAct=EBI-2297327, EBI-1216353;
CC Q62233; Q62441: Tle4; NbExp=2; IntAct=EBI-2297327, EBI-2297871;
CC Q62233; P63002: Tle5; NbExp=5; IntAct=EBI-2297327, EBI-646888;
CC Q62233; P16371: gro; Xeno; NbExp=2; IntAct=EBI-2297327, EBI-153866;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:12050133}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=SIX3B {ECO:0000303|PubMed:8814301};
CC IsoId=Q62233-1; Sequence=Displayed;
CC Name=SIX3A {ECO:0000303|PubMed:8814301};
CC IsoId=Q62233-2; Sequence=VSP_002291, VSP_002292;
CC -!- TISSUE SPECIFICITY: Expressed in ependymal cells during the formation
CC of the lateral wall. {ECO:0000269|PubMed:22071110}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing retina (at protein
CC level). First expressed at 6.5 dpc of embryo development around the
CC anterior border. At 8.5 dpc, expression is found over the anterior
CC neural plate. At 9.5 dpc, in the diencephalic part of the ventral
CC forebrain, optic vesicles, olfactory placodes and Rathke pouch. In
CC later stages, present in hypothalamus, eyes and pituitary. Expression
CC at around 7.5 dpc to 8 dpc is high in the anterior neural ectoderm.
CC Weaker expression is detected in the prechordal plate. At the 5 somite
CC stage (8.0 dpc), expression is maintained in the anterior neural
CC ectoderm. Around the 8 somite stage (8.0 dpc), expression is already
CC restricted to the ventral forebrain and eye field. At the 12 somite
CC stage (8.5 dpc), expression is maintained in the ventral forebrain
CC (PubMed:18694563). At 9.5 dpc strongly expressed throughout the
CC prospective nasal ectoderm. At 10.5 dpc remains expressed throughout
CC the nasal ectoderm (PubMed:16024294). At 7.5 dpc expression is found in
CC the developing anterior neuroectoderm. At 9.0 dpc expression is found
CC in the region of the presumptive lens ectoderm and developing optic
CC vesicle. At 9.5 dpc expression is found in the lens placode, optic
CC vesicles, and ventral forebrain (PubMed:11458394).
CC {ECO:0000269|PubMed:11458394, ECO:0000269|PubMed:16024294,
CC ECO:0000269|PubMed:18694563}.
CC -!- INDUCTION: Represses its own transcription in a TLE4-dependent manner.
CC Induces in lens by PAX6 in a dosage-dependent manner. Activated by SOX2
CC during forebrain development. Inhibited by MTA1 in mammary glands.
CC {ECO:0000269|PubMed:12050133, ECO:0000269|PubMed:12072567,
CC ECO:0000269|PubMed:23792023}.
CC -!- DISRUPTION PHENOTYPE: Embryos die at birth and lack most head
CC structures anterior to the midbrain, including the eyes and nose
CC (PubMed:12569128). Embryonic SHH and SIX3 double heterozygous mice
CC exhibit a semilobar holoprosencephaly-like phenotype and a dorsoventral
CC patterning defects in telencephalon (PubMed:18694563). Embryonic WNT1
CC and SIX3 double homozygous mice lack cerebellum and colliculus and have
CC a severely reduced midbrain (PubMed:18094027). Conditional knockout in
CC eye exhibit drastically reduced lens size, cataracts, or absence of the
CC lens (PubMed:17066077). Embryo of SIX3 and HESX1 heterozygous mice
CC exhibit severe growth retardation after weaning, with additional
CC gonadal and thyroid gland defects, resulting in a lethal phenotype
CC (PubMed:18775421). {ECO:0000269|PubMed:12569128,
CC ECO:0000269|PubMed:17066077, ECO:0000269|PubMed:18094027,
CC ECO:0000269|PubMed:18694563, ECO:0000269|PubMed:18775421}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA62379.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA62379.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X90871; CAA62379.1; ALT_SEQ; mRNA.
DR EMBL; D83144; BAA11822.1; -; mRNA.
DR EMBL; D83145; BAA11823.1; -; mRNA.
DR EMBL; BC098096; AAH98096.1; -; mRNA.
DR CCDS; CCDS50203.1; -. [Q62233-1]
DR PIR; S74255; S74255.
DR RefSeq; NP_035511.2; NM_011381.4. [Q62233-1]
DR AlphaFoldDB; Q62233; -.
DR BMRB; Q62233; -.
DR SMR; Q62233; -.
DR BioGRID; 203261; 4.
DR DIP; DIP-46499N; -.
DR IntAct; Q62233; 5.
DR STRING; 10090.ENSMUSP00000135312; -.
DR iPTMnet; Q62233; -.
DR PhosphoSitePlus; Q62233; -.
DR MaxQB; Q62233; -.
DR PaxDb; Q62233; -.
DR PRIDE; Q62233; -.
DR ProteomicsDB; 261243; -. [Q62233-1]
DR ProteomicsDB; 261244; -. [Q62233-2]
DR Antibodypedia; 29931; 272 antibodies from 29 providers.
DR DNASU; 20473; -.
DR Ensembl; ENSMUST00000175898; ENSMUSP00000135677; ENSMUSG00000038805. [Q62233-1]
DR Ensembl; ENSMUST00000176081; ENSMUSP00000135312; ENSMUSG00000038805. [Q62233-1]
DR GeneID; 20473; -.
DR KEGG; mmu:20473; -.
DR UCSC; uc008dub.2; mouse. [Q62233-1]
DR CTD; 6496; -.
DR MGI; MGI:102764; Six3.
DR VEuPathDB; HostDB:ENSMUSG00000038805; -.
DR eggNOG; KOG0775; Eukaryota.
DR GeneTree; ENSGT00940000160346; -.
DR HOGENOM; CLU_046914_0_0_1; -.
DR InParanoid; Q62233; -.
DR OMA; PGCPTHN; -.
DR OrthoDB; 1197104at2759; -.
DR TreeFam; TF315545; -.
DR BioGRID-ORCS; 20473; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Six3; mouse.
DR PRO; PR:Q62233; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q62233; protein.
DR Bgee; ENSMUSG00000038805; Expressed in optic fissure and 116 other tissues.
DR ExpressionAtlas; Q62233; baseline and differential.
DR Genevisible; Q62233; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0043010; P:camera-type eye development; IGI:MGI.
DR GO; GO:0021846; P:cell proliferation in forebrain; IMP:UniProtKB.
DR GO; GO:0048512; P:circadian behavior; IMP:MGI.
DR GO; GO:0021536; P:diencephalon development; IGI:MGI.
DR GO; GO:0002070; P:epithelial cell maturation; IMP:UniProtKB.
DR GO; GO:0001654; P:eye development; IDA:MGI.
DR GO; GO:0021797; P:forebrain anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; ISS:UniProtKB.
DR GO; GO:0008406; P:gonad development; IGI:MGI.
DR GO; GO:0002088; P:lens development in camera-type eye; IDA:UniProtKB.
DR GO; GO:1990086; P:lens fiber cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0070306; P:lens fiber cell differentiation; IDA:UniProtKB.
DR GO; GO:0060235; P:lens induction in camera-type eye; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:MGI.
DR GO; GO:0014016; P:neuroblast differentiation; IMP:UniProtKB.
DR GO; GO:0097402; P:neuroblast migration; IMP:UniProtKB.
DR GO; GO:0003404; P:optic vesicle morphogenesis; IDA:UniProtKB.
DR GO; GO:0021983; P:pituitary gland development; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0009946; P:proximal/distal axis specification; IDA:UniProtKB.
DR GO; GO:1901987; P:regulation of cell cycle phase transition; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IDA:UniProtKB.
DR GO; GO:0061074; P:regulation of neural retina development; IMP:UniProtKB.
DR GO; GO:1902692; P:regulation of neuroblast proliferation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021537; P:telencephalon development; IMP:UniProtKB.
DR GO; GO:0021978; P:telencephalon regionalization; IMP:UniProtKB.
DR GO; GO:0030878; P:thyroid gland development; IGI:MGI.
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 Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..333
FT /note="Homeobox protein SIX3"
FT /id="PRO_0000049300"
FT DNA_BIND 207..266
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 57..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 73..120
FT /note="Interaction with TLE5"
FT /evidence="ECO:0000269|PubMed:12050133"
FT REGION 233..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..235
FT /note="Bind to RHO promoter"
FT /evidence="ECO:0000269|PubMed:17666527"
FT REGION 259..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 271..284
FT /note="LQHQAIGPSGMRSL -> SVAGTAARPPQAPG (in isoform SIX3A)"
FT /evidence="ECO:0000305"
FT /id="VSP_002291"
FT VAR_SEQ 285..333
FT /note="Missing (in isoform SIX3A)"
FT /evidence="ECO:0000305"
FT /id="VSP_002292"
FT MUTAGEN 88
FT /note="F->E: Loss of interaction with TLE5 and TLE4."
FT /evidence="ECO:0000269|PubMed:12050133"
FT MUTAGEN 233..235
FT /note="Missing: Suppression of SIX3-binding to rhodopsin
FT promoter. Impairs the ability of Six3 to stimulate RHO
FT transcription."
FT /evidence="ECO:0000269|PubMed:17666527"
FT CONFLICT 44
FT /note="G -> GG (in Ref. 1; CAA62379)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="S -> C (in Ref. 1; CAA62379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 333 AA; 35593 MW; 1AD7D3C4388043B9 CRC64;
MVFRSPLDLY SSHFLLPNFA DSHHCSLLLA SSGGGSGASG GGGGAGGGGG GNRAGGGGAG
GAGGGSGGGG SRAPPEELSM FQLPTLNFSP EQVASVCETL EETGDIERLG RFLWSLPVAP
GACEAINKHE SILRARAVVA FHTGNFRDLY HILENHKFTK ESHGKLQAMW LEAHYQEAEK
LRGRPLGPVD KYRVRKKFPL PRTIWDGEQK THCFKERTRS LLREWYLQDP YPNPSKKREL
AQATGLTPTQ VGNWFKNRRQ RDRAAAAKNR LQHQAIGPSG MRSLAEPGCP THGSAESPST
AASPTTSVSS LTERADTGTS ILSVTSSDSE CDV
