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CSC8312 -- Bioinformatics Theory and Applications

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   23-SEP-2008, entry version 108.
DE   RecName: Full=Paired box protein Pax-6;
DE   AltName: Full=Oculorhombin;
DE   AltName: Full=Aniridia type II protein;
GN   Name=PAX6; Synonyms=AN2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=92103673; 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
RT   homeobox-containing gene from the aniridia region.";
RL   Cell 67:1059-1074(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=94258210; PubMed=1345175; DOI=10.1038/ng1192-232;
RA   Glaser T., Walton D.S., Maas R.L.;
RT   "Genomic structure, evolutionary conservation and aniridia mutations
RT   in the human PAX6 gene.";
RL   Nat. Genet. 2:232-239(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE (ISOFORM PAX6).
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;
RG   The German cDNA consortium;
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 5A).
RA   Wilkinson J.;
RL   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   ALTERNATIVE SPLICING, AND DNA-BINDING.
RX   MEDLINE=95047352; PubMed=7958875;
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
RT   paired domain are regulated by alternative splicing.";
RL   Genes Dev. 8:2022-2034(1994).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 4-136.
RX   PubMed=10346815;
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
RT   reveals specific roles for the linker region and carboxyl-terminal
RT   subdomain in DNA binding.";
RL   Genes Dev. 13:1263-1275(1999).
RN   [9]
RP   REVIEW ON VARIANTS.
RX   MEDLINE=98141676; PubMed=9482572;
RX   DOI=10.1002/(SICI)1098-1004(1998)11:2<93::AID-HUMU1>3.3.CO;2-J;
RA   Prosser J., van Heyningen V.;
RT   "PAX6 mutations reviewed.";
RL   Hum. Mutat. 11:93-108(1998).
RN   [10]
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
RT   protein PAX-6.";
RL   Submitted (NOV-2005) to the PDB data bank.
RN   [11]
RP   VARIANT AN2 TRP-208.
RX   MEDLINE=93372853; PubMed=8364574; DOI=10.1093/hmg/2.7.915;
RA   Hanson I.M., Seawright A., Hardman K., Hodgson S., Zaletayev D.,
RA   Fekete G., van Heyningen V.;
RT   "PAX6 mutations in aniridia.";
RL   Hum. Mol. Genet. 2:915-920(1993).
RN   [12]
RP   VARIANT PETERS ANOMALY GLY-26.
RX   MEDLINE=94214497; PubMed=8162071; DOI=10.1038/ng0294-168;
RA   Hanson I.M., Fletcher J.M., Jordan T., Brown A., Taylor D.,
RA   Adams R.J., Punnet H.H., van Heyningen V.;
RT   "Mutations at the PAX6 locus are found in heterogeneous anterior
RT   segment malformations including Peters' anomaly.";
RL   Nat. Genet. 6:168-173(1994).
RN   [13]
RP   VARIANTS FOVEAL HYPOPLASIA CYS-125 AND CYS-128.
RX   MEDLINE=96225435; 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   [14]
RP   VARIANT AN2 ARG-87, AND VARIANT GLY-26.
RX   MEDLINE=97227282; 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
RT   gene.";
RL   Hum. Mol. Genet. 6:381-386(1997).
RN   [15]
RP   VARIANT AN2 22-PRO--ARG-26 DEL.
RX   MEDLINE=97428347; PubMed=9281415; DOI=10.1006/mcpr.1997.0117;
RA   Axton R., Hanson I.M., Love J., Seawright A., Prosser J.,
RA   van Heyningen V.;
RT   "Combined SSCP/heteroduplex analysis in the screening for PAX6
RT   mutations.";
RL   Mol. Cell. Probes 11:287-292(1997).
RN   [16]
RP   VARIANT AN2 TRP-18.
RX   MEDLINE=99006892; PubMed=9792406;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:5<304::AID-HUMU3>3.3.CO;2-Y;
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   [17]
RP   VARIANT EYE MALFORMATIONS ARG-422.
RX   MEDLINE=98199717; PubMed=9538891;
RA   Azuma N., Yamada M.;
RT   "Missense mutation at the C-terminus of the PAX6 gene in ocular
RT   anterior segment anomalies.";
RL   Invest. Ophthalmol. Vis. Sci. 39:828-830(1998).
RN   [18]
RP   VARIANTS AN2 SER-17; VAL-29; GLN-44 AND HIS-178.
RX   MEDLINE=99072581; 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   [19]
RP   VARIANT EYE MALFORMATIONS ASP-53.
RX   MEDLINE=99375017; 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
RT   in eye anomalies.";
RL   Am. J. Hum. Genet. 65:656-663(1999).
RN   [20]
RP   ALTERNATIVE SPLICING, AND VARIANTS AN2 SER-42; LEU-53; PRO-63; GLU-79
RP   AND GLN-208.
RX   MEDLINE=99250762; 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   [21]
RP   VARIANTS AN2 PRO-33 AND PRO-43, VARIANT FOVEAL HYPOPLASIA VAL-64, AND
RP   VARIANT ECTOPIA PUPILLAE ASP-126.
RX   MEDLINE=99135896; 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
RT   domain underlie a spectrum of human congenital eye malformations.";
RL   Hum. Mol. Genet. 8:165-172(1999).
RN   [22]
RP   VARIANTS AN2 SER-29; ARG-119 AND ALA-353.
RA   Wildhardt G.;
RL   Unpublished observations (APR-1999).
RN   [23]
RP   VARIANT AN2 37-ALA--PRO-39 DEL.
RA   Saunders G.F.;
RL   Unpublished observations (AUG-1999).
RN   [24]
RP   VARIANT NYSTAGMUS ARG-118.
RX   MEDLINE=20410622; 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
RT   nystagmus associated with a variant form of aniridia.";
RL   Graefes Arch. Clin. Exp. Ophthalmol. 238:552-558(2000).
RN   [25]
RP   VARIANTS AN2 GLN-375 AND ARG-422.
RX   MEDLINE=21205761; 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   [26]
RP   VARIANT MORNING GLORY DISK ANOMALY SER-68, VARIANT OCULAR COLOBOMA
RP   SER-258, VARIANT PETERS ANOMALY PRO-363, AND VARIANTS OPTIC NERVE
RP   HYPOPLASIA/APLASIA ILE-292; ARG-378; VAL-381 AND ALA-391.
RX   MEDLINE=22633032; 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
RT   optic-nerve malformations.";
RL   Am. J. Hum. Genet. 72:1565-1570(2003).
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
CC       (By similarity). Competes with PAX4 in binding to a common element
CC       in the glucagon, insulin and somatostatin promoters. Regulates
CC       specification of the ventral neuron subtypes by establishing the
CC       correct progenitor domains (By similarity). Isoform 5a appears to
CC       function as a molecular switch that specifies target genes.
CC   -!- INTERACTION:
CC       P63168:Dynll1 (xeno); NbExp=2; IntAct=EBI-747278, EBI-349121;
CC       Q9NSC5:HOMER3; NbExp=2; IntAct=EBI-747278, EBI-748420;
CC       Q96F44:TRIM11; NbExp=2; IntAct=EBI-747278, EBI-851809;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
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: Fetal eye, brain, spinal cord and olfactory
CC       epithelium. Isoform 5a is less abundant than the PAX6 shorter
CC       form.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the developing eye and brain.
CC   -!- DISEASE: Defects in PAX6 are the cause of aniridia type II (AN2)
CC       [MIM:106210]. AN2 is a bilateral panocular disorder characterized
CC       by complete or partial absence of the iris, absence of the fovea
CC       and malformations of the lens and anterior chamber. Severe age-
CC       related corneal degeneration is a frequent complication which
CC       contributes to a poor visual prognostis in aniridia. About one
CC       third of the cases are sporadic, and two thirds are familial, with
CC       autosomal dominant inheritance and high penetrance. Nearly one
CC       third of sporadic AN patients develop Wilms tumor in association
CC       with genitourinary anomalies and mental retardation (WAGR
CC       syndrome) as a consequence of heterozygous (sub)microscopic
CC       deletions of chromosome 11p13.
CC   -!- DISEASE: Defects in PAX6 are a cause of Peters anomaly
CC       [MIM:604229]. Peters anomaly consists of a central corneal
CC       leukoma, absence of the posterior corneal stroma and Descemet
CC       membrane, and a variable degree of iris and lenticular attachments
CC       to the central aspect of the posterior cornea.
CC   -!- DISEASE: Defects in PAX6 are a cause of ectopia pupillae
CC       [MIM:129750]. It is a congenital eye malformation in which the
CC       pupils are displaced from their normal central position.
CC   -!- DISEASE: Defects in PAX6 are a cause of foveal hypoplasia
CC       [MIM:136520]. Foveal hypoplasia can be isolated or associated with
CC       presenile cataract. Inheritance is autosomal dominant.
CC   -!- DISEASE: Defects in PAX6 are a cause of autosomal dominant
CC       keratitis [MIM:148190]. It is an eye disorder characterized by
CC       corneal opacification and vascularization, and by foveal
CC       hypoplasia.
CC   -!- DISEASE: Defects in PAX6 are a cause of ocular coloboma
CC       [MIM:120200]; also known as uveoretinal coloboma or coloboma of
CC       iris, choroid and retina. Ocular colobomas are a set of
CC       malformations resulting from abnormal morphogenesis of the optic
CC       cup and stalk, and the fusion of the fetal fissure (optic
CC       fissure). Severe colobomatous malformations may cause as much as
CC       10% of the childhood blindness. The clinical presentation of
CC       ocular coloboma is variable. Some individuals may present with
CC       minimal defects in the anterior iris leaf without other ocular
CC       defects. More complex malformations create a combination of iris,
CC       uveoretinal and/or optic nerve defects without or with
CC       microphthalmia or even anophthalmia.
CC   -!- DISEASE: Defects in PAX6 are a cause of coloboma of optic nerve
CC       [MIM:120430].
CC   -!- DISEASE: Defects in PAX6 are a cause of bilateral optic nerve
CC       hypoplasia [MIM:165550]; also known as bilateral optic nerve
CC       aplasia. Inheritance is autosomal dominant.
CC   -!- SIMILARITY: Belongs to the paired homeobox family.
CC   -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC   -!- SIMILARITY: Contains 1 paired domain.
CC   -!- WEB RESOURCE: Name=Human PAX6 allelic variant database web site;
CC       URL="http://pax6.hgu.mrc.ac.uk/";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.genetests.org/query?gene=PAX6";
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DR   EMBL; M77844; AAA59963.1; -; mRNA.
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; Z95332; CAG38363.1; -; Genomic_DNA.
DR   EMBL; Z83307; CAG38363.1; JOINED; Genomic_DNA.
DR   EMBL; Z83307; CAG38087.1; -; Genomic_DNA.
DR   EMBL; Z95332; CAG38087.1; JOINED; Genomic_DNA.
DR   EMBL; BC011953; AAH11953.1; -; mRNA.
DR   PIR; A56674; A56674.
DR   RefSeq; NP_000271.1; -.
DR   RefSeq; NP_001121084.1; -.
DR   RefSeq; NP_001595.2; -.
DR   UniGene; Hs.591993; -.
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   IntAct; P26367; -.
DR   PhosphoSite; P26367; -.
DR   Ensembl; ENSG00000007372; Homo sapiens.
DR   GeneID; 5080; -.
DR   KEGG; hsa:5080; -.
DR   H-InvDB; HIX0009529; -.
DR   HGNC; HGNC:8620; PAX6.
DR   MIM; 106210; phenotype.
DR   MIM; 120200; phenotype.
DR   MIM; 120430; phenotype.
DR   MIM; 129750; phenotype.
DR   MIM; 136520; phenotype.
DR   MIM; 148190; phenotype.
DR   MIM; 165550; phenotype.
DR   MIM; 604229; phenotype.
DR   MIM; 607108; gene.
DR   Orphanet; 77; Aniridia.
DR   Orphanet; 194; Coloboma, ocular.
DR   Orphanet; 2253; Foveal hypoplasia presenile cataract.
DR   Orphanet; 2334; Keratitis, hereditary.
DR   Orphanet; 708; Peters anomaly.
DR   PharmGKB; PA32960; -.
DR   HOVERGEN; P26367; -.
DR   ArrayExpress; P26367; -.
DR   CleanEx; HS_PAX6; -.
DR   GermOnline; ENSG00000007372; Homo sapiens.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0003700; F:transcription factor activity; TAS:ProtInc.
DR   GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR   GO; GO:0001654; P:eye development; TAS:ProtInc.
DR   GO; GO:0009887; P:organ morphogenesis; TAS:ProtInc.
DR   GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR   InterPro; IPR001356; Homeobox.
DR   InterPro; IPR012287; Homeodomain-rel.
DR   InterPro; IPR001523; Paired_box_N.
DR   InterPro; IPR011991; Wing_hlx_DNA_bd.
DR   Gene3D; G3DSA:1.10.10.60; Homeodomain-rel; 1.
DR   Gene3D; G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 2.
DR   Pfam; PF00046; Homeobox; 1.
DR   Pfam; PF00292; PAX; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   PRINTS; PR00027; PAIREDBOX.
DR   ProDom; PD000010; Homeobox; 1.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00351; PAX; 1.
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;
KW   Differentiation; Disease mutation; DNA-binding; Homeobox; Nucleus;
KW   Paired box; Repressor; Transcription; Transcription regulation.
FT   CHAIN         1    422       Paired box protein Pax-6.
FT                                /FTId=PRO_0000050185.
FT   DOMAIN        4    130       Paired.
FT   DNA_BIND    210    269       Homeobox.
FT   COMPBIAS    131    209       Gln/Gly-rich.
FT   COMPBIAS    279    422       Pro/Ser/Thr-rich.
FT   VAR_SEQ      47     47       Q -> QTHADAKVQVLDNQN (in isoform 5a).
FT                                /FTId=VSP_002366.
FT   VARIANT      17     17       N -> S (in AN2).
FT                                /FTId=VAR_003808.
FT   VARIANT      18     18       G -> W (in AN2 and Peters anomaly).
FT                                /FTId=VAR_003809.
FT   VARIANT      22     26       Missing (in AN2; sporadic form).
FT                                /FTId=VAR_008693.
FT   VARIANT      26     26       R -> G (in Peters anomaly).
FT                                /FTId=VAR_003810.
FT   VARIANT      29     29       I -> S (in AN2; sporadic form).
FT                                /FTId=VAR_008694.
FT   VARIANT      29     29       I -> V (in AN2).
FT                                /FTId=VAR_003811.
FT   VARIANT      33     33       A -> P (in AN2; sporadic form).
FT                                /FTId=VAR_008695.
FT   VARIANT      37     39       Missing (in AN2; sporadic form).
FT                                /FTId=VAR_008696.
FT   VARIANT      42     42       I -> S (in AN2; mild).
FT                                /FTId=VAR_008697.
FT   VARIANT      43     43       S -> P (in AN2; sporadic form).
FT                                /FTId=VAR_008698.
FT   VARIANT      44     44       R -> Q (in AN2).
FT                                /FTId=VAR_003812.
FT   VARIANT      53     53       V -> D (in Peters anomaly, congenital
FT                                cataract and foveal hypoplasia; Japanese
FT                                pedigrees).
FT                                /FTId=VAR_008700.
FT   VARIANT      53     53       V -> L (in AN2; mild).
FT                                /FTId=VAR_008699.
FT   VARIANT      63     63       T -> P (in AN2; mild).
FT                                /FTId=VAR_008701.
FT   VARIANT      64     64       G -> V (in foveal hypoplasia; associated
FT                                with presenile cataract syndrome).
FT                                /FTId=VAR_008702.
FT   VARIANT      68     68       P -> S (in morning glory disk anomaly;
FT                                significant impairment of transcriptional
FT                                activation ability).
FT                                /FTId=VAR_017540.
FT   VARIANT      79     79       A -> E (in AN2; mild).
FT                                /FTId=VAR_008703.
FT   VARIANT      87     87       I -> R (in AN2; loss of activity).
FT                                /FTId=VAR_003813.
FT   VARIANT     118    118       P -> R (in nystagmus associated with a
FT                                variant form of aniridia).
FT                                /FTId=VAR_015065.
FT   VARIANT     119    119       S -> R (in AN2; sporadic form).
FT                                /FTId=VAR_008704.
FT   VARIANT     125    125       R -> C (in foveal hypoplasia; isolated).
FT                                /FTId=VAR_017541.
FT   VARIANT     126    126       V -> D (in ectopia pupillae).
FT                                /FTId=VAR_008705.
FT   VARIANT     128    128       R -> C (in foveal hypoplasia; isolated).
FT                                /FTId=VAR_003814.
FT   VARIANT     178    178       Q -> H (in AN2).
FT                                /FTId=VAR_003815.
FT   VARIANT     208    208       R -> Q (in AN2; mild).
FT                                /FTId=VAR_008706.
FT   VARIANT     208    208       R -> W (in AN2).
FT                                /FTId=VAR_003816.
FT   VARIANT     258    258       F -> S (in ocular coloboma; significant
FT                                impairment of transcriptional activation
FT                                ability).
FT                                /FTId=VAR_017542.
FT   VARIANT     292    292       S -> I (in bilateral optic nerve
FT                                hypoplasia; significant impairment of
FT                                transcriptional activation ability).
FT                                /FTId=VAR_017543.
FT   VARIANT     353    353       S -> A (in AN2; familial form).
FT                                /FTId=VAR_008707.
FT   VARIANT     363    363       S -> P (in Peters anomaly).
FT                                /FTId=VAR_017544.
FT   VARIANT     375    375       P -> Q (in AN2; reduced DNA binding
FT                                ability).
FT                                /FTId=VAR_015066.
FT   VARIANT     378    378       Q -> R (in optic nerve aplasia).
FT                                /FTId=VAR_017545.
FT   VARIANT     381    381       M -> V (in bilateral optic nerve
FT                                hypoplasia).
FT                                /FTId=VAR_017546.
FT   VARIANT     391    391       T -> A (in bilateral optic nerve
FT                                aplasia).
FT                                /FTId=VAR_017547.
FT   VARIANT     422    422       Q -> R (in AN2 and ocular anterior
FT                                segment anomalies; loss of DNA binding
FT                                ability).
FT                                /FTId=VAR_008708.
FT   CONFLICT    317    317       R -> L (in Ref. 1; AAA59963/AAA59962).
FT   CONFLICT    369    369       Y -> C (in Ref. 4; CAE45868).
FT   STRAND        6      8
FT   STRAND       14     16
FT   HELIX        23     34
FT   HELIX        39     46
FT   HELIX        50     63
FT   STRAND       77     79
FT   HELIX        81     93
FT   HELIX        99    108
FT   TURN        114    116
FT   HELIX       120    133
FT   HELIX       219    229
FT   HELIX       237    246
FT   HELIX       251    275
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
//

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