ID PAX6_HUMAN Reviewed; 422 AA. AC P26367; Q6N006; Q99413; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 27-MAR-2024, entry version 253. DE RecName: Full=Paired box protein Pax-6; DE AltName: Full=Aniridia type II protein; DE AltName: Full=Oculorhombin; GN Name=PAX6; Synonyms=AN2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal eye; RX PubMed=1684738; DOI=10.1016/0092-8674(91)90284-6; RA Ton C.C.T., Hirvonen H., Miwa H., Weil M.M., Monaghan P., Jordan T., RA van Heyningen V., Hastie N.D., Meijers-Heijboer H., Drechsler M., RA Royer-Pokora B., Collins F.S., Swaroop A., Strong L.C., Saunders G.F.; RT "Positional cloning and characterization of a paired box- and homeobox- RT containing gene from the aniridia region."; RL Cell 67:1059-1074(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1345175; DOI=10.1038/ng1192-232; RA Glaser T., Walton D.S., Maas R.L.; RT "Genomic structure, evolutionary conservation and aniridia mutations in the RT human PAX6 gene."; RL Nat. Genet. 2:232-239(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Liu J., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5A). RC TISSUE=Cerebellum; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [7] RP ALTERNATIVE SPLICING, DNA-BINDING, AND TISSUE SPECIFICITY. RX PubMed=7958875; DOI=10.1101/gad.8.17.2022; RA Epstein J.A., Glaser T., Cai J., Jepeal L., Walton D.S., Maas R.L.; RT "Two independent and interactive DNA-binding subdomains of the Pax6 paired RT domain are regulated by alternative splicing."; RL Genes Dev. 8:2022-2034(1994). RN [8] RP INVOLVEMENT IN KERH. RX PubMed=7668281; RA Mirzayans F., Pearce W.G., MacDonald I.M., Walter M.A.; RT "Mutation of the PAX6 gene in patients with autosomal dominant keratitis."; RL Am. J. Hum. Genet. 57:539-548(1995). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP DEVELOPMENTAL STAGE. RX PubMed=19414065; DOI=10.1016/j.ijdevneu.2009.04.004; RA Larsen K.B., Lutterodt M., Rath M.F., Moeller M.; RT "Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human RT fetal retina."; RL Int. J. Dev. Neurosci. 27:485-492(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP INVOLVEMENT IN AN2. RX PubMed=24290376; DOI=10.1016/j.ajhg.2013.10.028; RA Bhatia S., Bengani H., Fish M., Brown A., Divizia M.T., de Marco R., RA Damante G., Grainger R., van Heyningen V., Kleinjan D.A.; RT "Disruption of autoregulatory feedback by a mutation in a remote, RT ultraconserved PAX6 enhancer causes aniridia."; RL Am. J. Hum. Genet. 93:1126-1134(2013). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 4-136. RX PubMed=10346815; DOI=10.1101/gad.13.10.1263; RA Xu H.E., Rould M.A., Xu W., Epstein J.A., Maas R.L., Pabo C.O.; RT "Crystal structure of the human Pax-6 paired domain-DNA complex reveals RT specific roles for the linker region and carboxyl-terminal subdomain in DNA RT binding."; RL Genes Dev. 13:1263-1275(1999). RN [14] RP REVIEW ON VARIANTS. RX PubMed=9482572; RX DOI=10.1002/(sici)1098-1004(1998)11:2<93::aid-humu1>3.0.co;2-m; RA Prosser J., van Heyningen V.; RT "PAX6 mutations reviewed."; RL Hum. Mutat. 11:93-108(1998). RN [15] RP STRUCTURE BY NMR OF 211-277. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the homeobox domain of the human paired box protein RT PAX-6."; RL Submitted (NOV-2005) to the PDB data bank. RN [16] RP VARIANT AN1 TRP-208. RX PubMed=8364574; DOI=10.1093/hmg/2.7.915; RA Hanson I.M., Seawright A., Hardman K., Hodgson S., Zaletayev D., Fekete G., RA van Heyningen V.; RT "PAX6 mutations in aniridia."; RL Hum. Mol. Genet. 2:915-920(1993). RN [17] RP VARIANT ASGD5 GLY-26. RX PubMed=8162071; DOI=10.1038/ng0294-168; RA Hanson I.M., Fletcher J.M., Jordan T., Brown A., Taylor D., Adams R.J., RA Punnet H.H., van Heyningen V.; RT "Mutations at the PAX6 locus are found in heterogeneous anterior segment RT malformations including Peters' anomaly."; RL Nat. Genet. 6:168-173(1994). RN [18] RP VARIANTS FVH1 CYS-125 AND CYS-128. RX PubMed=8640214; DOI=10.1038/ng0696-141; RA Azuma N., Nishina S., Yanagisawa H., Okuyama T., Yamada M.; RT "PAX6 missense mutation in isolated foveal hypoplasia."; RL Nat. Genet. 13:141-142(1996). RN [19] RP VARIANT AN1 ARG-87, AND VARIANT GLY-26. RX PubMed=9147640; DOI=10.1093/hmg/6.3.381; RA Tang H.K., Chao L.-Y., Saunders G.F.; RT "Functional analysis of paired box missense mutations in the PAX6 gene."; RL Hum. Mol. Genet. 6:381-386(1997). RN [20] RP VARIANT AN1 22-PRO--ARG-26 DEL. RX PubMed=9281415; DOI=10.1006/mcpr.1997.0117; RA Axton R., Hanson I.M., Love J., Seawright A., Prosser J., van Heyningen V.; RT "Combined SSCP/heteroduplex analysis in the screening for PAX6 mutations."; RL Mol. Cell. Probes 11:287-292(1997). RN [21] RP VARIANT AN1 TRP-18. RX PubMed=9792406; RX DOI=10.1002/(sici)1098-1004(1998)12:5<304::aid-humu3>3.0.co;2-d; RA Wolf M.T.F., Lorenz B., Winterpacht A., Drechsler M., Schumacher V., RA Royer-Pokora B., Blankenagel A., Zabel B., Wildhardt G.; RT "Ten novel mutations found in Aniridia."; RL Hum. Mutat. 12:304-313(1998). RN [22] RP VARIANT EYE MALFORMATIONS ARG-422. RX PubMed=9538891; RA Azuma N., Yamada M.; RT "Missense mutation at the C-terminus of the PAX6 gene in ocular anterior RT segment anomalies."; RL Invest. Ophthalmol. Vis. Sci. 39:828-830(1998). RN [23] RP VARIANTS AN1 SER-17; VAL-29; GLN-44 AND HIS-178. RX PubMed=9856761; RA Azuma N., Hotta Y., Tanaka H., Yamada M.; RT "Missense mutations in the PAX6 gene in aniridia."; RL Invest. Ophthalmol. Vis. Sci. 39:2524-2528(1998). RN [24] RP VARIANT ASGD5 ASP-53. RX PubMed=10441571; DOI=10.1086/302529; RA Azuma N., Yamaguchi Y., Handa H., Hayakawa M., Kanai A., Yamada M.; RT "Missense mutation in the alternative splice region of the PAX6 gene in eye RT anomalies."; RL Am. J. Hum. Genet. 65:656-663(1999). RN [25] RP ALTERNATIVE SPLICING, AND VARIANTS AN1 SER-42; LEU-53; PRO-63; GLU-79 AND RP GLN-208. RX PubMed=10234503; DOI=10.1038/sj.ejhg.5200308; RA Groenskov K., Rosenberg T., Sand A., Broendum-Nielsen K.; RT "Mutational analysis of PAX6: 16 novel mutations including 5 missense RT mutations with a mild aniridia phenotype."; RL Eur. J. Hum. Genet. 7:274-286(1999). RN [26] RP VARIANTS AN1 PRO-33; PRO-43 AND ASP-126, AND VARIANT FVH1 VAL-64. RX PubMed=9931324; DOI=10.1093/hmg/8.2.165; RA Hanson I.M., Churchill A., Love J., Axton R., Moore T., Clarke M., RA Meire F., van Heyningen V.; RT "Missense mutations in the most ancient residues of the PAX6 paired domain RT underlie a spectrum of human congenital eye malformations."; RL Hum. Mol. Genet. 8:165-172(1999). RN [27] RP VARIANTS AN1 SER-29; ARG-119 AND ALA-353. RA Wildhardt G.; RL Unpublished observations (APR-1999). RN [28] RP VARIANT AN1 37-ALA--PRO-39 DEL. RA Saunders G.F.; RL Unpublished observations (AUG-1999). RN [29] RP VARIANT NYSTAGMUS ARG-118. RX PubMed=10955655; DOI=10.1007/s004170000124; RA Sonoda S., Isashiki Y., Tabata Y., Kimura K., Kakiuchi T., Ohba N.; RT "A novel PAX6 gene mutation (P118R) in a family with congenital nystagmus RT associated with a variant form of aniridia."; RL Graefes Arch. Clin. Exp. Ophthalmol. 238:552-558(2000). RN [30] RP VARIANT AN1 37-ARG--PRO-39 DEL, AND VARIANT ASP-387. RX PubMed=10737978; RX DOI=10.1002/(sici)1098-1004(200004)15:4<332::aid-humu5>3.0.co;2-1; RA Chao L.-Y., Huff V., Strong L.C., Saunders G.F.; RT "Mutation in the PAX6 gene in twenty patients with aniridia."; RL Hum. Mutat. 15:332-339(2000). RN [31] RP VARIANT AN1 ARG-119. RX PubMed=11553050; DOI=10.1034/j.1399-0004.2001.600210.x; RA Malandrini A., Mari F., Palmeri S., Gambelli S., Berti G., Bruttini M., RA Bardelli A.M., Williamson K., van Heyningen V., Renieri A.; RT "PAX6 mutation in a family with aniridia, congenital ptosis, and mental RT retardation."; RL Clin. Genet. 60:151-154(2001). RN [32] RP VARIANTS AN1 GLN-375 AND ARG-422. RX PubMed=11309364; DOI=10.1093/hmg/10.9.911; RA Singh S., Chao L.-Y., Mishra R., Davies J., Saunders G.F.; RT "Missense mutation at the C-terminus of PAX6 negatively modulates RT homeodomain function."; RL Hum. Mol. Genet. 10:911-918(2001). RN [33] RP VARIANT AN1 THR-242. RX PubMed=11826019; DOI=10.1136/jmg.39.1.16; RA Morrison D., FitzPatrick D., Hanson I., Williamson K., van Heyningen V., RA Fleck B., Jones I., Chalmers J., Campbell H.; RT "National study of microphthalmia, anophthalmia, and coloboma (MAC) in RT Scotland: investigation of genetic aetiology."; RL J. Med. Genet. 39:16-22(2002). RN [34] RP INVOLVEMENT IN OPTIC-NERVE MALFORMATIONS, VARIANT MORNING GLORY DISK RP ANOMALY SER-68, VARIANT COLON SER-258, VARIANT COAD SER-258, VARIANT ASGD5 RP PRO-363, AND VARIANTS BONH ILE-292; ARG-378; VAL-381 AND ALA-391. RX PubMed=12721955; DOI=10.1086/375555; RA Azuma N., Yamaguchi Y., Handa H., Tadokoro K., Asaka A., Kawase E., RA Yamada M.; RT "Mutations of the PAX6 gene detected in patients with a variety of optic- RT nerve malformations."; RL Am. J. Hum. Genet. 72:1565-1570(2003). RN [35] RP VARIANTS AN1 PRO-19 AND 22-PRO--ARG-26 DEL. RX PubMed=12634864; DOI=10.1038/sj.ejhg.5200940; RA Vincent M.-C., Pujo A.-L., Olivier D., Calvas P.; RT "Screening for PAX6 gene mutations is consistent with haploinsufficiency as RT the main mechanism leading to various ocular defects."; RL Eur. J. Hum. Genet. 11:163-169(2003). RN [36] RP VARIANTS AN1 ARG-46; ARG-52; THR-56; ASP-73 AND LYS-87, VARIANT THR-321, RP CHARACTERIZATION OF VARIANTS AN1 ARG-46; ARG-52; LEU-53; THR-56 AND ASP-73, RP AND CHARACTERIZATION OF VARIANT THR-321. RX PubMed=12552561; DOI=10.1002/humu.10163; RA Chao L.-Y., Mishra R., Strong L.C., Saunders G.F.; RT "Missense mutations in the DNA-binding region and termination codon in RT PAX6."; RL Hum. Mutat. 21:138-145(2003). RN [37] RP CHARACTERIZATION OF VARIANT AN1 THR-242. RX PubMed=16493447; DOI=10.1038/sj.ejhg.5201579; RA D'Elia A.V., Puppin C., Pellizzari L., Pianta A., Bregant E., Lonigro R., RA Tell G., Fogolari F., van Heyningen V., Damante G.; RT "Molecular analysis of a human PAX6 homeobox mutant."; RL Eur. J. Hum. Genet. 14:744-751(2006). RN [38] RP INVOLVEMENT IN AN1. RX PubMed=17595013; DOI=10.1002/ajmg.a.31808; RA Graziano C., D'Elia A.V., Mazzanti L., Moscano F., Guidelli Guidi S., RA Scarano E., Turchetti D., Franzoni E., Romeo G., Damante G., Seri M.; RT "A de novo nonsense mutation of PAX6 gene in a patient with aniridia, RT ataxia, and mental retardation."; RL Am. J. Med. Genet. A 143:1802-1805(2007). RN [39] RP VARIANT AN1 ARG-395. RX PubMed=21850189; RA Zhang X., Wang P., Li S., Xiao X., Guo X., Zhang Q.; RT "Mutation spectrum of PAX6 in Chinese patients with aniridia."; RL Mol. Vis. 17:2139-2147(2011). RN [40] RP VARIANT AN1 PRO-19. RX PubMed=24033328; DOI=10.1111/cge.12275; RA Chassaing N., Causse A., Vigouroux A., Delahaye A., Alessandri J.L., RA Boespflug-Tanguy O., Boute-Benejean O., Dollfus H., Duban-Bedu B., RA Gilbert-Dussardier B., Giuliano F., Gonzales M., Holder-Espinasse M., RA Isidor B., Jacquemont M.L., Lacombe D., Martin-Coignard D., RA Mathieu-Dramard M., Odent S., Picone O., Pinson L., Quelin C., Sigaudy S., RA Toutain A., Thauvin-Robinet C., Kaplan J., Calvas P.; RT "Molecular findings and clinical data in a cohort of 150 patients with RT anophthalmia/microphthalmia."; RL Clin. Genet. 86:326-334(2014). RN [41] RP VARIANT FVH1 GLN-38. RX PubMed=29914532; DOI=10.1186/s13023-018-0828-0; RA Li J., Leng Y., Han S., Yan L., Lu C., Luo Y., Zhang X., Cao L.; RT "Clinical and genetic characteristics of Chinese patients with familial or RT sporadic pediatric cataract."; RL Orphanet J. Rare Dis. 13:94-94(2018). CC -!- FUNCTION: Transcription factor with important functions in the CC development of the eye, nose, central nervous system and pancreas. CC Required for the differentiation of pancreatic islet alpha cells (By CC similarity). Competes with PAX4 in binding to a common element in the CC glucagon, insulin and somatostatin promoters. Regulates specification CC of the ventral neuron subtypes by establishing the correct progenitor CC domains (By similarity). Acts as a transcriptional repressor of NFATC1- CC mediated gene expression (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P63015}. CC -!- SUBUNIT: Interacts with MAF and MAFB (By similarity). Interacts with CC TRIM11; this interaction leads to ubiquitination and proteasomal CC degradation, as well as inhibition of transactivation, possibly in part CC by preventing PAX6 binding to consensus DNA sequences (By similarity). CC Interacts with TLE6/GRG6 (By similarity). CC {ECO:0000250|UniProtKB:P63015}. CC -!- INTERACTION: CC P26367; Q8WYK0: ACOT12; NbExp=3; IntAct=EBI-747278, EBI-11954993; CC P26367; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-747278, EBI-8643161; CC P26367; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-747278, EBI-541426; CC P26367; O95376: ARIH2; NbExp=3; IntAct=EBI-747278, EBI-711158; CC P26367; Q8N8Y2: ATP6V0D2; NbExp=3; IntAct=EBI-747278, EBI-3923949; CC P26367; Q8NEY4-2: ATP6V1C2; NbExp=3; IntAct=EBI-747278, EBI-10270867; CC P26367; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-747278, EBI-11524452; CC P26367; Q5TBC7: BCL2L15; NbExp=3; IntAct=EBI-747278, EBI-10247136; CC P26367; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-747278, EBI-739879; CC P26367; Q8IW40: CCDC103; NbExp=3; IntAct=EBI-747278, EBI-10261970; CC P26367; Q16204: CCDC6; NbExp=3; IntAct=EBI-747278, EBI-1045350; CC P26367; Q9Y258: CCL26; NbExp=3; IntAct=EBI-747278, EBI-7783416; CC P26367; Q00526: CDK3; NbExp=3; IntAct=EBI-747278, EBI-1245761; CC P26367; Q9UFW8: CGGBP1; NbExp=3; IntAct=EBI-747278, EBI-723153; CC P26367; Q13111: CHAF1A; NbExp=3; IntAct=EBI-747278, EBI-1020839; CC P26367; Q96Q77: CIB3; NbExp=3; IntAct=EBI-747278, EBI-10292696; CC P26367; Q9BW66: CINP; NbExp=3; IntAct=EBI-747278, EBI-739784; CC P26367; P61024: CKS1B; NbExp=3; IntAct=EBI-747278, EBI-456371; CC P26367; P68400: CSNK2A1; NbExp=5; IntAct=EBI-747278, EBI-347804; CC P26367; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-747278, EBI-11962928; CC P26367; Q8TB03: CXorf38; NbExp=3; IntAct=EBI-747278, EBI-12024320; CC P26367; P49366: DHPS; NbExp=3; IntAct=EBI-747278, EBI-741925; CC P26367; Q96JC9: EAF1; NbExp=3; IntAct=EBI-747278, EBI-769261; CC P26367; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-747278, EBI-743105; CC P26367; Q8N9N8: EIF1AD; NbExp=3; IntAct=EBI-747278, EBI-750700; CC P26367; P62508-3: ESRRG; NbExp=3; IntAct=EBI-747278, EBI-12001340; CC P26367; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-747278, EBI-742802; CC P26367; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-747278, EBI-7960826; CC P26367; O75603: GCM2; NbExp=3; IntAct=EBI-747278, EBI-10188645; CC P26367; O14893: GEMIN2; NbExp=3; IntAct=EBI-747278, EBI-443648; CC P26367; O95872: GPANK1; NbExp=3; IntAct=EBI-747278, EBI-751540; CC P26367; Q6ISB3: GRHL2; NbExp=3; IntAct=EBI-747278, EBI-10219092; CC P26367; O14964: HGS; NbExp=3; IntAct=EBI-747278, EBI-740220; CC P26367; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-747278, EBI-2549423; CC P26367; O15347: HMGB3; NbExp=3; IntAct=EBI-747278, EBI-2214136; CC P26367; P07910: HNRNPC; NbExp=3; IntAct=EBI-747278, EBI-357966; CC P26367; Q9NSC5: HOMER3; NbExp=6; IntAct=EBI-747278, EBI-748420; CC P26367; P49639: HOXA1; NbExp=3; IntAct=EBI-747278, EBI-740785; CC P26367; P31273: HOXC8; NbExp=3; IntAct=EBI-747278, EBI-1752118; CC P26367; P31274: HOXC9; NbExp=3; IntAct=EBI-747278, EBI-1779423; CC P26367; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-747278, EBI-2556193; CC P26367; Q96MP8-2: KCTD7; NbExp=3; IntAct=EBI-747278, EBI-11954971; CC P26367; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-747278, EBI-1043191; CC P26367; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-747278, EBI-11958364; CC P26367; Q6P4E2: LARP4; NbExp=3; IntAct=EBI-747278, EBI-12079790; CC P26367; Q9C0E8-2: LNPK; NbExp=3; IntAct=EBI-747278, EBI-11024283; CC P26367; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-747278, EBI-2341787; CC P26367; Q9BS40: LXN; NbExp=3; IntAct=EBI-747278, EBI-1044504; CC P26367; Q96S90: LYSMD1; NbExp=3; IntAct=EBI-747278, EBI-10293291; CC P26367; Q15691: MAPRE1; NbExp=3; IntAct=EBI-747278, EBI-1004115; CC P26367; P55081: MFAP1; NbExp=3; IntAct=EBI-747278, EBI-1048159; CC P26367; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-747278, EBI-2548751; CC P26367; Q8IVT2: MISP; NbExp=3; IntAct=EBI-747278, EBI-2555085; CC P26367; Q6PF18: MORN3; NbExp=3; IntAct=EBI-747278, EBI-9675802; CC P26367; Q96EL3: MRPL53; NbExp=3; IntAct=EBI-747278, EBI-2513715; CC P26367; Q9UBB6: NCDN; NbExp=3; IntAct=EBI-747278, EBI-1053490; CC P26367; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-747278, EBI-10271199; CC P26367; Q13952-2: NFYC; NbExp=3; IntAct=EBI-747278, EBI-11956831; CC P26367; Q96IV0: NGLY1; NbExp=3; IntAct=EBI-747278, EBI-6165879; CC P26367; Q08493-2: PDE4C; NbExp=3; IntAct=EBI-747278, EBI-12169289; CC P26367; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-747278, EBI-79165; CC P26367; Q13526: PIN1; NbExp=3; IntAct=EBI-747278, EBI-714158; CC P26367; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-747278, EBI-5452779; CC P26367; Q9BT43: POLR3GL; NbExp=3; IntAct=EBI-747278, EBI-2855862; CC P26367; Q8WUA2: PPIL4; NbExp=3; IntAct=EBI-747278, EBI-2513119; CC P26367; P54619: PRKAG1; NbExp=3; IntAct=EBI-747278, EBI-1181439; CC P26367; Q9UIG4: PSORS1C2; NbExp=3; IntAct=EBI-747278, EBI-11974061; CC P26367; Q2TAL8: QRICH1; NbExp=3; IntAct=EBI-747278, EBI-2798044; CC P26367; Q9UBE0: SAE1; NbExp=3; IntAct=EBI-747278, EBI-743154; CC P26367; Q9UDX3: SEC14L4; NbExp=3; IntAct=EBI-747278, EBI-10320311; CC P26367; Q01105-2: SET; NbExp=3; IntAct=EBI-747278, EBI-7481343; CC P26367; O43699-3: SIGLEC6; NbExp=3; IntAct=EBI-747278, EBI-12161783; CC P26367; A0AV02: SLC12A8; NbExp=3; IntAct=EBI-747278, EBI-11737524; CC P26367; Q5MJ68: SPDYC; NbExp=3; IntAct=EBI-747278, EBI-12162209; CC P26367; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-747278, EBI-742688; CC P26367; Q05519-2: SRSF11; NbExp=3; IntAct=EBI-747278, EBI-11975029; CC P26367; Q99469: STAC; NbExp=3; IntAct=EBI-747278, EBI-2652799; CC P26367; Q9NUJ3: TCP11L1; NbExp=3; IntAct=EBI-747278, EBI-2555179; CC P26367; Q96FV9: THOC1; NbExp=3; IntAct=EBI-747278, EBI-1765605; CC P26367; Q9UKI8: TLK1; NbExp=3; IntAct=EBI-747278, EBI-740492; CC P26367; Q86UE8: TLK2; NbExp=3; IntAct=EBI-747278, EBI-1047967; CC P26367; O75865-2: TRAPPC6A; NbExp=3; IntAct=EBI-747278, EBI-8451480; CC P26367; Q15642-2: TRIP10; NbExp=3; IntAct=EBI-747278, EBI-6550597; CC P26367; Q969M7: UBE2F; NbExp=3; IntAct=EBI-747278, EBI-1056876; CC P26367; P61086: UBE2K; NbExp=3; IntAct=EBI-747278, EBI-473850; CC P26367; Q14CS0: UBXN2B; NbExp=3; IntAct=EBI-747278, EBI-1993619; CC P26367; O94888: UBXN7; NbExp=3; IntAct=EBI-747278, EBI-1993627; CC P26367; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-747278, EBI-739895; CC P26367; Q3SXR9: VCX2; NbExp=3; IntAct=EBI-747278, EBI-11983741; CC P26367; Q9Y3C0: WASHC3; NbExp=3; IntAct=EBI-747278, EBI-712969; CC P26367; O96006: ZBED1; NbExp=3; IntAct=EBI-747278, EBI-740037; CC P26367; Q15973: ZNF124; NbExp=3; IntAct=EBI-747278, EBI-2555767; CC P26367; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-747278, EBI-11741890; CC P26367; A0A384ME25; NbExp=3; IntAct=EBI-747278, EBI-10211777; CC P26367; P63168: Dynll1; Xeno; NbExp=3; IntAct=EBI-747278, EBI-349121; CC P26367-1; P63166: Sumo1; Xeno; NbExp=2; IntAct=EBI-15892945, EBI-80152; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P63015}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus CC {ECO:0000250|UniProtKB:P63016}. CC -!- SUBCELLULAR LOCATION: [Isoform 5a]: Nucleus CC {ECO:0000250|UniProtKB:P63016}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P26367-1; Sequence=Displayed; CC Name=5a; Synonyms=Pax6-5a; CC IsoId=P26367-2; Sequence=VSP_002366; CC Name=3; Synonyms=Pax6-5A,6*; CC IsoId=P26367-3; Sequence=Not described; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in lymphoblasts. CC {ECO:0000269|PubMed:7958875}. CC -!- TISSUE SPECIFICITY: [Isoform 5a]: Weakly expressed in lymphoblasts. CC {ECO:0000269|PubMed:7958875}. CC -!- DEVELOPMENTAL STAGE: Expressed in the developing eye and brain. CC Expression in the retina peaks at fetal days 51-60. At 6-week old, in CC the retina, is predominantly detected in the neural layer (at protein CC level). At 8- and 10-week old, in the retina, the expression is CC strongest in the inner and middle layer of the neural part (at protein CC level). {ECO:0000269|PubMed:19414065}. CC -!- PTM: Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal CC degradation. {ECO:0000250}. CC -!- DISEASE: Aniridia 1 (AN1) [MIM:106210]: A congenital, bilateral, CC panocular disorder characterized by complete absence of the iris or CC extreme iris hypoplasia. Aniridia is not just an isolated defect in CC iris development but it is associated with macular and optic nerve CC hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is CC generally low but is unrelated to the degree of iris hypoplasia. CC Glaucoma is a secondary problem causing additional visual loss over CC time. {ECO:0000269|PubMed:10234503, ECO:0000269|PubMed:10737978, CC ECO:0000269|PubMed:11309364, ECO:0000269|PubMed:11553050, CC ECO:0000269|PubMed:11826019, ECO:0000269|PubMed:12552561, CC ECO:0000269|PubMed:12634864, ECO:0000269|PubMed:16493447, CC ECO:0000269|PubMed:17595013, ECO:0000269|PubMed:21850189, CC ECO:0000269|PubMed:24033328, ECO:0000269|PubMed:8364574, CC ECO:0000269|PubMed:9147640, ECO:0000269|PubMed:9281415, CC ECO:0000269|PubMed:9792406, ECO:0000269|PubMed:9856761, CC ECO:0000269|PubMed:9931324, ECO:0000269|Ref.27, ECO:0000269|Ref.28}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Anterior segment dysgenesis 5 (ASGD5) [MIM:604229]: A form of CC anterior segment dysgenesis, a group of defects affecting anterior CC structures of the eye including cornea, iris, lens, trabecular CC meshwork, and Schlemm canal. Anterior segment dysgeneses result from CC abnormal migration or differentiation of the neural crest derived CC mesenchymal cells that give rise to components of the anterior chamber CC during eye development. Different anterior segment anomalies may exist CC alone or in combination, including iris hypoplasia, enlarged or reduced CC corneal diameter, corneal vascularization and opacity, posterior CC embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, CC ectopia lentis, and anterior synechiae between the iris and posterior CC corneal surface. Clinical conditions falling within the phenotypic CC spectrum of anterior segment dysgeneses include aniridia, Axenfeld CC anomaly, Reiger anomaly/syndrome, Peters anomaly, and CC iridogoniodysgenesis. {ECO:0000269|PubMed:10441571, CC ECO:0000269|PubMed:12721955, ECO:0000269|PubMed:8162071}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Foveal hypoplasia 1 (FVH1) [MIM:136520]: An isolated form of CC foveal hypoplasia, a developmental defect of the eye defined as the CC lack of foveal depression with continuity of all neurosensory retinal CC layers in the presumed foveal area. Clinical features include absence CC of foveal pit on optical coherence tomography, absence of foveal CC hyperpigmentation, absence of foveal avascularity, absence of foveal CC and macular reflexes, decreased visual acuity, and nystagmus. Anterior CC segment anomalies and cataract are observed in some FVH1 patients. CC {ECO:0000269|PubMed:29914532, ECO:0000269|PubMed:8640214, CC ECO:0000269|PubMed:9931324}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Keratitis hereditary (KERH) [MIM:148190]: An ocular disorder CC characterized by corneal opacification, recurrent stromal keratitis and CC vascularization. {ECO:0000269|PubMed:7668281}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Coloboma, ocular, autosomal dominant (COAD) [MIM:120200]: A CC set of malformations resulting from abnormal morphogenesis of the optic CC cup and stalk, and the fusion of the fetal fissure (optic fissure). The CC clinical presentation is variable. Some individuals may present with CC minimal defects in the anterior iris leaf without other ocular defects. CC More complex malformations create a combination of iris, uveoretinal CC and/or optic nerve defects without or with microphthalmia or even CC anophthalmia. {ECO:0000269|PubMed:12721955}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Coloboma of optic nerve (COLON) [MIM:120430]: An ocular defect CC that is due to malclosure of the fetal intraocular fissure affecting CC the optic nerve head. In some affected individuals, it appears as CC enlargement of the physiologic cup with severely affected eyes showing CC huge cavities at the site of the disk. {ECO:0000269|PubMed:12721955}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Bilateral optic nerve hypoplasia (BONH) [MIM:165550]: A CC congenital anomaly in which the optic disk appears abnormally small. It CC may be an isolated finding or part of a spectrum of anatomic and CC functional abnormalities that includes partial or complete agenesis of CC the septum pellucidum, other midline brain defects, cerebral anomalies, CC pituitary dysfunction, and structural abnormalities of the pituitary. CC {ECO:0000269|PubMed:12721955}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Aniridia 2 (AN2) [MIM:617141]: A form of aniridia, a CC congenital, bilateral, panocular disorder characterized by complete CC absence of the iris or extreme iris hypoplasia. Aniridia is not just an CC isolated defect in iris development but it is associated with macular CC and optic nerve hypoplasia, cataract, corneal changes, nystagmus. CC Visual acuity is generally low but is unrelated to the degree of iris CC hypoplasia. Glaucoma is a secondary problem causing additional visual CC loss over time. {ECO:0000269|PubMed:24290376}. Note=The gene CC represented in this entry is involved in disease pathogenesis. A CC mutation in a PAX6 long-range cis-regulatory element, known as SIMO, CC affects PAX6 expression in the developing eye and has pathological CC consequences. The mutation is located in ELP4 intron 9, 150 kb CC downstream of PAX6. {ECO:0000269|PubMed:24290376}. CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Human PAX6 allelic variant database web site; CC URL="http://pax6.hgu.mrc.ac.uk/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/211/PAX6"; 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; M77844; AAA59962.1; -; mRNA. DR EMBL; M93650; AAA36416.1; -; mRNA. DR EMBL; AY047583; AAK95849.1; -; mRNA. DR EMBL; BX640762; CAE45868.1; -; mRNA. DR EMBL; Z83307; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z95332; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC011953; AAH11953.1; -; mRNA. DR CCDS; CCDS31451.1; -. [P26367-1] DR CCDS; CCDS31452.1; -. [P26367-2] DR PIR; A56674; A56674. DR RefSeq; NP_000271.1; NM_000280.4. [P26367-1] DR RefSeq; NP_001121084.1; NM_001127612.1. [P26367-1] DR RefSeq; NP_001245393.1; NM_001258464.1. [P26367-1] DR RefSeq; NP_001245394.1; NM_001258465.1. [P26367-1] DR RefSeq; NP_001297088.1; NM_001310159.1. DR RefSeq; NP_001297090.1; NM_001310161.1. DR RefSeq; NP_001595.2; NM_001604.5. [P26367-2] DR PDB; 2CUE; NMR; -; A=211-277. DR PDB; 6PAX; X-ray; 2.50 A; A=4-136. DR PDBsum; 2CUE; -. DR PDBsum; 6PAX; -. DR AlphaFoldDB; P26367; -. DR BMRB; P26367; -. DR SMR; P26367; -. DR BioGRID; 111114; 332. DR CORUM; P26367; -. DR DIP; DIP-37436N; -. DR IntAct; P26367; 325. DR MINT; P26367; -. DR STRING; 9606.ENSP00000492024; -. DR GlyGen; P26367; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P26367; -. DR PhosphoSitePlus; P26367; -. DR BioMuta; PAX6; -. DR DMDM; 6174889; -. DR jPOST; P26367; -. DR MassIVE; P26367; -. DR PaxDb; 9606-ENSP00000404100; -. DR PeptideAtlas; P26367; -. DR ProteomicsDB; 54323; -. [P26367-1] DR ProteomicsDB; 54324; -. [P26367-2] DR Pumba; P26367; -. DR Antibodypedia; 12821; 1083 antibodies from 49 providers. DR DNASU; 5080; -. DR Ensembl; ENST00000241001.13; ENSP00000241001.8; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000379107.7; ENSP00000368401.2; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000379109.7; ENSP00000368403.2; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000379129.7; ENSP00000368424.2; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000379132.8; ENSP00000368427.2; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000419022.6; ENSP00000404100.1; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000606377.7; ENSP00000480026.1; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000638914.3; ENSP00000492315.2; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000639409.1; ENSP00000492476.1; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000639916.1; ENSP00000490963.1; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000640287.1; ENSP00000492822.1; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000640368.2; ENSP00000492024.1; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000640610.1; ENSP00000491295.1; ENSG00000007372.25. [P26367-1] DR Ensembl; ENST00000640975.1; ENSP00000491872.1; ENSG00000007372.25. [P26367-2] DR Ensembl; ENST00000643871.1; ENSP00000495109.1; ENSG00000007372.25. [P26367-1] DR GeneID; 5080; -. DR KEGG; hsa:5080; -. DR MANE-Select; ENST00000640368.2; ENSP00000492024.1; NM_001368894.2; NP_001355823.1. [P26367-2] DR UCSC; uc001mtg.6; human. [P26367-1] DR AGR; HGNC:8620; -. DR DisGeNET; 5080; -. DR GeneCards; PAX6; -. DR GeneReviews; PAX6; -. DR HGNC; HGNC:8620; PAX6. DR HPA; ENSG00000007372; Group enriched (brain, retina). DR MalaCards; PAX6; -. DR MIM; 106210; phenotype. DR MIM; 120200; phenotype. DR MIM; 120430; phenotype. DR MIM; 136520; phenotype. DR MIM; 148190; phenotype. DR MIM; 165550; phenotype. DR MIM; 604229; phenotype. DR MIM; 607108; gene. DR MIM; 617141; phenotype. DR neXtProt; NX_P26367; -. DR OpenTargets; ENSG00000007372; -. DR Orphanet; 1065; Aniridia-cerebellar ataxia-intellectual disability syndrome. DR Orphanet; 2334; Autosomal dominant keratitis. DR Orphanet; 98942; Coloboma of choroid and retina. DR Orphanet; 98943; Coloboma of eye lens. DR Orphanet; 98946; Coloboma of eyelid. DR Orphanet; 98944; Coloboma of iris. DR Orphanet; 98945; Coloboma of macula. DR Orphanet; 98947; Coloboma of optic disc. DR Orphanet; 2253; Foveal hypoplasia-presenile cataract syndrome. DR Orphanet; 250923; Isolated aniridia. DR Orphanet; 35737; Morning glory disc anomaly. DR Orphanet; 708; Peters anomaly. DR Orphanet; 893; WAGR syndrome. DR PharmGKB; PA32960; -. DR VEuPathDB; HostDB:ENSG00000007372; -. DR eggNOG; KOG0849; Eukaryota. DR GeneTree; ENSGT00940000155391; -. DR HOGENOM; CLU_019281_1_0_1; -. DR InParanoid; P26367; -. DR OMA; PYWPRIQ; -. DR OrthoDB; 5398393at2759; -. DR PhylomeDB; P26367; -. DR TreeFam; TF320146; -. DR PathwayCommons; P26367; -. DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells. DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1). DR Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP). DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis. DR Reactome; R-HSA-9823739; Formation of the anterior neural plate. DR SignaLink; P26367; -. DR SIGNOR; P26367; -. DR BioGRID-ORCS; 5080; 15 hits in 1165 CRISPR screens. DR ChiTaRS; PAX6; human. DR EvolutionaryTrace; P26367; -. DR GeneWiki; PAX6; -. DR GenomeRNAi; 5080; -. DR Pharos; P26367; Tbio. DR PRO; PR:P26367; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P26367; Protein. DR Bgee; ENSG00000007372; Expressed in palpebral conjunctiva and 148 other cell types or tissues. DR ExpressionAtlas; P26367; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0070410; F:co-SMAD binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl. DR GO; GO:0035035; F:histone acetyltransferase binding; ISS:BHF-UCL. DR GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl. DR GO; GO:0003680; F:minor groove of adenine-thymine-rich DNA binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; ISS:BHF-UCL. DR GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL. DR GO; GO:0003723; F:RNA binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB. DR GO; GO:0001221; F:transcription coregulator binding; ISS:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc. DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl. DR GO; GO:0007411; P:axon guidance; IEA:Ensembl. DR GO; GO:0001568; P:blood vessel development; IMP:DFLAT. DR GO; GO:0001709; P:cell fate determination; IEA:Ensembl. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0021796; P:cerebral cortex regionalization; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IEA:Ensembl. DR GO; GO:0021902; P:commitment of neuronal cell to specific neuron type in forebrain; IEA:Ensembl. DR GO; GO:0061303; P:cornea development in camera-type eye; IMP:DFLAT. DR GO; GO:0080111; P:DNA demethylation; IEA:Ensembl. DR GO; GO:0006306; P:DNA methylation; IEA:Ensembl. DR GO; GO:0009950; P:dorsal/ventral axis specification; IEA:Ensembl. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IEA:Ensembl. DR GO; GO:0001654; P:eye development; TAS:ProtInc. DR GO; GO:0042462; P:eye photoreceptor cell development; IEA:Ensembl. DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl. DR GO; GO:0021905; P:forebrain-midbrain boundary formation; IEA:Ensembl. DR GO; GO:0042593; P:glucose homeostasis; IMP:DFLAT. DR GO; GO:0021986; P:habenula development; IEA:Ensembl. DR GO; GO:1901142; P:insulin metabolic process; IEA:Ensembl. DR GO; GO:0022027; P:interkinetic nuclear migration; IEA:Ensembl. DR GO; GO:0061072; P:iris morphogenesis; IMP:DFLAT. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0032808; P:lacrimal gland development; IEA:Ensembl. DR GO; GO:0098598; P:learned vocalization behavior or vocal learning; IEA:Ensembl. DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IMP:BHF-UCL. DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0048663; P:neuron fate commitment; NAS:UniProtKB. DR GO; GO:0061034; P:olfactory bulb mitral cell layer development; IEA:Ensembl. DR GO; GO:0021778; P:oligodendrocyte cell fate specification; IEA:Ensembl. DR GO; GO:0003322; P:pancreatic A cell development; IMP:BHF-UCL. DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl. DR GO; GO:0042660; P:positive regulation of cell fate specification; IEA:Ensembl. DR GO; GO:1904798; P:positive regulation of core promoter binding; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0120008; P:positive regulation of glutamatergic neuron differentiation; IEA:Ensembl. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:2001224; P:positive regulation of neuron migration; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0033365; P:protein localization to organelle; IEA:Ensembl. DR GO; GO:0009786; P:regulation of asymmetric cell division; IEA:Ensembl. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0048505; P:regulation of timing of cell differentiation; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IEP:UniProtKB. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0021593; P:rhombomere morphogenesis; IEA:Ensembl. DR GO; GO:0007435; P:salivary gland morphogenesis; IEA:Ensembl. DR GO; GO:1904937; P:sensory neuron migration; IEA:Ensembl. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl. DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0003309; P:type B pancreatic cell differentiation; IEA:Ensembl. DR GO; GO:0021517; P:ventral spinal cord development; ISS:UniProtKB. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR CDD; cd00086; homeodomain; 1. DR CDD; cd00131; PAX; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2. DR IDEAL; IID00197; -. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR043182; PAIRED_DNA-bd_dom. DR InterPro; IPR001523; Paired_dom. DR InterPro; IPR043565; PAX_fam. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR PANTHER; PTHR45636:SF21; PAIRED BOX PROTEIN PAX-6; 1. DR PANTHER; PTHR45636; PAIRED BOX PROTEIN PAX-6-RELATED-RELATED; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF00292; PAX; 1. DR PRINTS; PR00027; PAIREDBOX. DR SMART; SM00389; HOX; 1. DR SMART; SM00351; PAX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 2. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS00034; PAIRED_1; 1. DR PROSITE; PS51057; PAIRED_2; 1. DR Genevisible; P26367; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Developmental protein; Differentiation; KW Disease variant; DNA-binding; Homeobox; Nucleus; Paired box; KW Peters anomaly; Reference proteome; Repressor; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..422 FT /note="Paired box protein Pax-6" FT /id="PRO_0000050185" FT DNA_BIND 4..130 FT /note="Paired" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT DNA_BIND 210..269 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 7..63 FT /note="PAI subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT REGION 82..130 FT /note="RED subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT REGION 162..201 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 269..311 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 345..422 FT /note="Required for suppression of NFATC1-mediated FT transcription" FT /evidence="ECO:0000250|UniProtKB:P63015" FT COMPBIAS 167..199 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 276..311 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 47 FT /note="Q -> QTHADAKVQVLDNQN (in isoform 5a)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_002366" FT VARIANT 17 FT /note="N -> S (in AN1)" FT /evidence="ECO:0000269|PubMed:9856761" FT /id="VAR_003808" FT VARIANT 18 FT /note="G -> W (in AN1)" FT /evidence="ECO:0000269|PubMed:9792406" FT /id="VAR_003809" FT VARIANT 19 FT /note="R -> P (in AN1)" FT /evidence="ECO:0000269|PubMed:12634864, FT ECO:0000269|PubMed:24033328" FT /id="VAR_047860" FT VARIANT 22..26 FT /note="Missing (in AN1)" FT /evidence="ECO:0000269|PubMed:12634864, FT ECO:0000269|PubMed:9281415" FT /id="VAR_008693" FT VARIANT 26 FT /note="R -> G (in ASGD5; dbSNP:rs121907913)" FT /evidence="ECO:0000269|PubMed:8162071, FT ECO:0000269|PubMed:9147640" FT /id="VAR_003810" FT VARIANT 29 FT /note="I -> S (in AN1)" FT /evidence="ECO:0000269|Ref.27" FT /id="VAR_008694" FT VARIANT 29 FT /note="I -> V (in AN1)" FT /evidence="ECO:0000269|PubMed:9856761" FT /id="VAR_003811" FT VARIANT 33 FT /note="A -> P (in AN1)" FT /evidence="ECO:0000269|PubMed:9931324" FT /id="VAR_008695" FT VARIANT 37..39 FT /note="Missing (in AN1)" FT /evidence="ECO:0000269|Ref.28" FT /id="VAR_008696" FT VARIANT 38 FT /note="R -> Q (in FVH1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29914532" FT /id="VAR_084825" FT VARIANT 42 FT /note="I -> S (in AN1; mild)" FT /evidence="ECO:0000269|PubMed:10234503" FT /id="VAR_008697" FT VARIANT 43 FT /note="S -> P (in AN1)" FT /evidence="ECO:0000269|PubMed:9931324" FT /id="VAR_008698" FT VARIANT 44 FT /note="R -> Q (in AN1)" FT /evidence="ECO:0000269|PubMed:9856761" FT /id="VAR_003812" FT VARIANT 46 FT /note="L -> R (in AN1; shows almost no binding efficiency; FT transcriptional activation ability is about 50% lower than FT that of the wild-type protein)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047861" FT VARIANT 52 FT /note="C -> R (in AN1; shows almost no binding efficiency; FT transcriptional activation ability is about 50% lower than FT that of the wild-type protein)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047862" FT VARIANT 53 FT /note="V -> D (in ASGD5; also found in patients with FT congenital cataract and foveal hypoplasia)" FT /evidence="ECO:0000269|PubMed:10441571" FT /id="VAR_008700" FT VARIANT 53 FT /note="V -> L (in AN1; mild; shows 50% lower DNA-binding FT and transactivation ability than the wild-type protein)" FT /evidence="ECO:0000269|PubMed:10234503, FT ECO:0000269|PubMed:12552561" FT /id="VAR_008699" FT VARIANT 56 FT /note="I -> T (in AN1; shows only one-quarter to one-third FT the binding ability of the normal wild-type protein; FT exhibits normal transactivation)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047863" FT VARIANT 63 FT /note="T -> P (in AN1; mild)" FT /evidence="ECO:0000269|PubMed:10234503" FT /id="VAR_008701" FT VARIANT 64 FT /note="G -> V (in foveal hypoplasia; associated with FT presenile cataract syndrome; dbSNP:rs121907920)" FT /evidence="ECO:0000269|PubMed:9931324" FT /id="VAR_008702" FT VARIANT 68 FT /note="P -> S (in morning glory disk anomaly; significant FT impairment of transcriptional activation ability; FT dbSNP:rs121907923)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017540" FT VARIANT 73 FT /note="G -> D (in AN1; shows almost no binding efficiency; FT transcriptional activation ability is about 80% of that of FT the wild-type protein)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047864" FT VARIANT 79 FT /note="A -> E (in AN1; mild)" FT /evidence="ECO:0000269|PubMed:10234503" FT /id="VAR_008703" FT VARIANT 87 FT /note="I -> K (in AN1)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047865" FT VARIANT 87 FT /note="I -> R (in AN1; loss of activity)" FT /evidence="ECO:0000269|PubMed:9147640" FT /id="VAR_003813" FT VARIANT 118 FT /note="P -> R (in a family with nystagmus associated with a FT variant form of aniridia)" FT /evidence="ECO:0000269|PubMed:10955655" FT /id="VAR_015065" FT VARIANT 119 FT /note="S -> R (in AN1; dbSNP:rs121907928)" FT /evidence="ECO:0000269|PubMed:11553050, ECO:0000269|Ref.27" FT /id="VAR_008704" FT VARIANT 125 FT /note="R -> C (in FVH1; isolated)" FT /evidence="ECO:0000269|PubMed:8640214" FT /id="VAR_017541" FT VARIANT 126 FT /note="V -> D (in AN1; atypical form; dbSNP:rs121907919)" FT /evidence="ECO:0000269|PubMed:9931324" FT /id="VAR_008705" FT VARIANT 128 FT /note="R -> C (in FVH1; isolated; dbSNP:rs121907918)" FT /evidence="ECO:0000269|PubMed:8640214" FT /id="VAR_003814" FT VARIANT 178 FT /note="Q -> H (in AN1)" FT /evidence="ECO:0000269|PubMed:9856761" FT /id="VAR_003815" FT VARIANT 208 FT /note="R -> Q (in AN1; mild; dbSNP:rs749244084)" FT /evidence="ECO:0000269|PubMed:10234503" FT /id="VAR_008706" FT VARIANT 208 FT /note="R -> W (in AN1; dbSNP:rs757259413)" FT /evidence="ECO:0000269|PubMed:8364574" FT /id="VAR_003816" FT VARIANT 242 FT /note="R -> T (in AN1; the mutant homeodomain binds DNA as FT well as the wild-type homeodomain; the mutant does not FT modify the DNA-binding properties of the paired domain; the FT steady-state levels of the full-length mutant protein are FT higher than those of the wild-type one; a responsive FT promoter is activated to a higher extent by the mutant FT protein than by the wild-type protein; the presence of the FT mutation reduces sensitivity to trypsin digestion; FT dbSNP:rs121907927)" FT /evidence="ECO:0000269|PubMed:11826019, FT ECO:0000269|PubMed:16493447" FT /id="VAR_047866" FT VARIANT 258 FT /note="F -> S (in COAD and COLON; significant impairment of FT transcriptional activation ability; dbSNP:rs121907925)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017542" FT VARIANT 292 FT /note="S -> I (in BONH; significant impairment of ability FT to activate transcription)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017543" FT VARIANT 321 FT /note="A -> T (shows about two-fold higher binding FT efficiency than the normal wild-type protein; FT transcriptional activation ability is about 89% of that of FT the wild-type protein)" FT /evidence="ECO:0000269|PubMed:12552561" FT /id="VAR_047867" FT VARIANT 353 FT /note="S -> A (in AN1; dbSNP:rs373661718)" FT /evidence="ECO:0000269|Ref.27" FT /id="VAR_008707" FT VARIANT 363 FT /note="S -> P (in ASGD5)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017544" FT VARIANT 375 FT /note="P -> Q (in AN1; reduced DNA binding ability; FT dbSNP:rs200015827)" FT /evidence="ECO:0000269|PubMed:11309364" FT /id="VAR_015066" FT VARIANT 378 FT /note="Q -> R (in optic nerve aplasia)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017545" FT VARIANT 381 FT /note="M -> V (in BONH)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017546" FT VARIANT 387 FT /note="G -> D (in dbSNP:rs1392343463)" FT /evidence="ECO:0000269|PubMed:10737978" FT /id="VAR_047868" FT VARIANT 391 FT /note="T -> A (in BONH; dbSNP:rs121907926)" FT /evidence="ECO:0000269|PubMed:12721955" FT /id="VAR_017547" FT VARIANT 395 FT /note="G -> R (in AN1)" FT /evidence="ECO:0000269|PubMed:21850189" FT /id="VAR_067698" FT VARIANT 422 FT /note="Q -> R (in AN1 and ocular anterior segment FT anomalies; loss of DNA binding ability; dbSNP:rs780356070)" FT /evidence="ECO:0000269|PubMed:11309364, FT ECO:0000269|PubMed:9538891" FT /id="VAR_008708" FT CONFLICT 317 FT /note="R -> L (in Ref. 1; AAA59962)" FT /evidence="ECO:0000305" FT CONFLICT 369 FT /note="Y -> C (in Ref. 4; CAE45868)" FT /evidence="ECO:0000305" FT STRAND 6..8 FT /evidence="ECO:0007829|PDB:6PAX" FT STRAND 14..16 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 23..34 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 39..46 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 50..63 FT /evidence="ECO:0007829|PDB:6PAX" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 81..93 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 99..108 FT /evidence="ECO:0007829|PDB:6PAX" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 120..133 FT /evidence="ECO:0007829|PDB:6PAX" FT HELIX 219..229 FT /evidence="ECO:0007829|PDB:2CUE" FT HELIX 237..246 FT /evidence="ECO:0007829|PDB:2CUE" FT HELIX 251..275 FT /evidence="ECO:0007829|PDB:2CUE" SQ SEQUENCE 422 AA; 46683 MW; C33CDD2C1B13C397 CRC64; MQNSHSGVNQ LGGVFVNGRP LPDSTRQKIV ELAHSGARPC DISRILQVSN GCVSKILGRY YETGSIRPRA IGGSKPRVAT PEVVSKIAQY KRECPSIFAW EIRDRLLSEG VCTNDNIPSV SSINRVLRNL ASEKQQMGAD GMYDKLRMLN GQTGSWGTRP GWYPGTSVPG QPTQDGCQQQ EGGGENTNSI SSNGEDSDEA QMRLQLKRKL QRNRTSFTQE QIEALEKEFE RTHYPDVFAR ERLAAKIDLP EARIQVWFSN RRAKWRREEK LRNQRRQASN TPSHIPISSS FSTSVYQPIP QPTTPVSSFT SGSMLGRTDT ALTNTYSALP PMPSFTMANN LPMQPPVPSQ TSSYSCMLPT SPSVNGRSYD TYTPPHMQTH MNSQPMGTSG TTSTGLISPG VSVPVQVPGS EPDMSQYWPR LQ //