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 24-JAN-2024, entry version 176. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000135312; -. DR ProteomicsDB; 261243; -. [Q62233-1] DR ProteomicsDB; 261244; -. [Q62233-2] DR Antibodypedia; 29931; 286 antibodies from 29 providers. DR DNASU; 20473; -. DR Ensembl; ENSMUST00000175898.4; ENSMUSP00000135677.2; ENSMUSG00000038805.11. [Q62233-1] DR Ensembl; ENSMUST00000176081.3; ENSMUSP00000135312.3; ENSMUSG00000038805.11. [Q62233-1] DR GeneID; 20473; -. DR KEGG; mmu:20473; -. DR UCSC; uc008dub.2; mouse. [Q62233-1] DR AGR; MGI:102764; -. 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; 602349at2759; -. DR TreeFam; TF315545; -. DR BioGRID-ORCS; 20473; 1 hit in 79 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 118 other cell types or tissues. DR ExpressionAtlas; Q62233; baseline and differential. 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:0005102; F:signaling receptor 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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045665; P:negative regulation of neuron differentiation; 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 Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR031701; SIX1_SD. DR PANTHER; PTHR10390; HOMEOBOX PROTEIN SIX; 1. DR PANTHER; PTHR10390:SF31; HOMEOBOX PROTEIN SIX3; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF16878; SIX1_SD; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR Genevisible; Q62233; MM. 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 //