MGP Database

MGP002204

UniProt Annotations

Entry Information

Gene Name	paired box 6
Protein Entry	PAX6_HUMAN
UniProt ID	P26367
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P26367-1; Sequence=Displayed; Name=5a; Synonyms=Pax6-5a; IsoId=P26367-2; Sequence=VSP_002366; Name=3; Synonyms=Pax6-5A,6*; IsoId=P26367-3; Sequence=Not described;
Developmental Stage	Expressed in the developing eye and brain. Expression in the retina peaks at fetal days 51-60. At 6-week old, in the retina, is predominantly detected in the neural layer (at protein level). At 8- and 10-week old, in the retina, the expression is strongest in the inner and middle layer of the neural part (at protein level). {ECO:0000269\|PubMed:19414065}.
Disease	Aniridia (AN) [MIM:106210]: A congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time. {ECO:0000269\|PubMed:10234503, ECO:0000269\|PubMed:10737978, ECO:0000269\|PubMed:11309364, ECO:0000269\|PubMed:11553050, ECO:0000269\|PubMed:11826019, ECO:0000269\|PubMed:12552561, ECO:0000269\|PubMed:12634864, ECO:0000269\|PubMed:21850189, ECO:0000269\|PubMed:8364574, ECO:0000269\|PubMed:9147640, ECO:0000269\|PubMed:9281415, ECO:0000269\|PubMed:9792406, ECO:0000269\|PubMed:9856761, ECO:0000269\|PubMed:9931324, ECO:0000269\|Ref.25, ECO:0000269\|Ref.26}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Aniridia, cerebellar ataxia and mental deficiency (ACAMD) [MIM:206700]: A rare condition consisting of partial rudimentary iris, cerebellar impairment of the ability to perform coordinated voluntary movements, and mental retardation. {ECO:0000269\|PubMed:17595013}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Bilateral optic nerve hypoplasia (BONH) [MIM:165550]: A congenital anomaly in which the optic disk appears abnormally small. It may be an isolated finding or part of a spectrum of anatomic and functional abnormalities that includes partial or complete agenesis of the septum pellucidum, other midline brain defects, cerebral anomalies, pituitary dysfunction, and structural abnormalities of the pituitary. {ECO:0000269\|PubMed:12721955}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Coloboma, ocular, autosomal dominant (COAD) [MIM:120200]: A set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia. {ECO:0000269\|PubMed:12721955}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Coloboma of optic nerve (COLON) [MIM:120430]: An ocular defect that is due to malclosure of the fetal intraocular fissure affecting the optic nerve head. In some affected individuals, it appears as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disk. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Foveal hypoplasia 1 (FVH1) [MIM:136520]: An isolated form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus. Anterior segment anomalies and cataract are observed in some FVH1 patients. {ECO:0000269\|PubMed:8640214, ECO:0000269\|PubMed:9931324}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Keratitis hereditary (KERH) [MIM:148190]: An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Peters anomaly (PETAN) [MIM:604229]: Consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea. {ECO:0000269\|PubMed:10441571, ECO:0000269\|PubMed:12721955, ECO:0000269\|PubMed:8162071}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Function	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Isoform 5a appears to function as a molecular switch that specifies target genes. {ECO:0000250}.
Interaction	P63168:Dynll1 (xeno); NbExp=3; IntAct=EBI-747278, EBI-349121; Q9NSC5:HOMER3; NbExp=3; IntAct=EBI-747278, EBI-748420;
Ptm	Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation. {ECO:0000250}.
Similarity	Belongs to the paired homeobox family. {ECO:0000305}.
Similarity	Contains 1 homeobox DNA-binding domain. {ECO:0000255\|PROSITE-ProRule:PRU00108}.
Similarity	Contains 1 paired domain. {ECO:0000255\|PROSITE- ProRule:PRU00381}.
Subcellular Location	Nucleus.
Subunit	Interacts with MAF and MAFB. Interacts with TRIM11; this interaction leads to ubiquitination and proteasomal degradation, as well as inhibition of transactivation, possibly in part by preventing PAX6 binding to consensus DNA sequences. {ECO:0000250}.
Tissue Specificity	Fetal eye, brain, spinal cord and olfactory epithelium. Isoform 5a is less abundant than the PAX6 shorter form.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PAX6ID211ch11p13.html";
Web Resource	Name=Human PAX6 allelic variant database web site; URL="http://pax6.hgu.mrc.ac.uk/";