PAX6_HUMAN
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 03-AUG-2022, entry version 244.
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; 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; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-747278, EBI-8643161;
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="http://atlasgeneticsoncology.org/Genes/PAX6ID211ch11p13.html";
CC ---------------------------------------------------------------------------
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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; 330.
DR CORUM; P26367; -.
DR DIP; DIP-37436N; -.
DR IntAct; P26367; 309.
DR MINT; P26367; -.
DR STRING; 9606.ENSP00000404100; -.
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; P26367; -.
DR PeptideAtlas; P26367; -.
DR PRIDE; P26367; -.
DR ProteomicsDB; 54323; -. [P26367-1]
DR ProteomicsDB; 54324; -. [P26367-2]
DR Antibodypedia; 12821; 935 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 CTD; 5080; -.
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; 137902; Isolated optic nerve hypoplasia/aplasia.
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; WYPSGAG; -.
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 SignaLink; P26367; -.
DR SIGNOR; P26367; -.
DR BioGRID-ORCS; 5080; 15 hits in 1093 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 146 other tissues.
DR ExpressionAtlas; P26367; baseline and differential.
DR Genevisible; P26367; HS.
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; IEA:Ensembl.
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: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:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
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:0016573; P:histone acetylation; 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: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:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0048663; P:neuron fate commitment; NAS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; 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:1904798; P:positive regulation of core promoter binding; 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:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0033365; P:protein localization to organelle; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0009786; P:regulation of asymmetric cell division; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; 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:0009611; P:response to wounding; IEP:UniProtKB.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007435; P:salivary gland morphogenesis; 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 DisProt; DP01518; -.
DR Gene3D; 1.10.10.10; -; 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; PTHR45636; 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; SSF46689; 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.
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; unknown pathological 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
