ID:PAX6_HUMAN DESCRIPTION: RecName: Full=Paired box protein Pax-6; AltName: Full=Aniridia type II protein; AltName: Full=Oculorhombin; 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. SUBUNIT: Interacts with MAF and MAFB (By similarity). 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 (By similarity). INTERACTION: P63168:Dynll1 (xeno); NbExp=3; IntAct=EBI-747278, EBI-349121; Q9NSC5:HOMER3; NbExp=3; IntAct=EBI-747278, EBI-748420; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Fetal eye, brain, spinal cord and olfactory epithelium. Isoform 5a is less abundant than the PAX6 shorter form. DEVELOPMENTAL STAGE: Expressed in the developing eye and brain. PTM: Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation (By similarity). DISEASE: Defects in PAX6 are the cause of 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. DISEASE: Defects in PAX6 are a cause of Peters anomaly (PAN) [MIM:604229]. Peters anomaly 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. DISEASE: Defects in PAX6 are a cause of foveal hypoplasia (FOVHYP) [MIM:136520]. Foveal hypoplasia can be isolated or associated with presenile cataract. Inheritance is autosomal dominant. DISEASE: Defects in PAX6 are a cause of keratitis hereditary (KERH) [MIM:148190]. An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization. DISEASE: Defects in PAX6 are a cause of coloboma of iris choroid and retina (COI) [MIM:120200]; also known as uveoretinal coloboma. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Severe colobomatous malformations may cause as much as 10% of the childhood blindness. The clinical presentation of ocular coloboma 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. DISEASE: Defects in PAX6 are a cause of coloboma of optic nerve (COLON) [MIM:120430]. DISEASE: Defects in PAX6 are a cause of bilateral optic nerve hypoplasia (BONH) [MIM:165550]; also known as bilateral optic nerve aplasia. A congenital anomaly in which the optic disc 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. DISEASE: Defects in PAX6 are a cause of aniridia cerebellar ataxia and mental deficiency (ACAMD) [MIM:206700]; also known as Gillespie syndrome. A rare condition consisting of partial rudimentary iris, cerebellar impairment of the ability to perform coordinated voluntary movements, and mental retardation. SIMILARITY: Belongs to the paired homeobox family. SIMILARITY: Contains 1 homeobox DNA-binding domain. SIMILARITY: Contains 1 paired domain. WEB RESOURCE: Name=Human PAX6 allelic variant database web site; URL="http://pax6.hgu.mrc.ac.uk/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PAX6";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P26367
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0008134 transcription factor binding GO:0019901 protein kinase binding GO:0031625 ubiquitin protein ligase binding GO:0035035 histone acetyltransferase binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0070410 co-SMAD binding GO:0070412 R-SMAD binding GO:0071837 HMG box domain binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000132 establishment of mitotic spindle orientation GO:0001568 blood vessel development GO:0001654 eye development GO:0001709 cell fate determination GO:0001764 neuron migration GO:0001933 negative regulation of protein phosphorylation GO:0002052 positive regulation of neuroblast proliferation GO:0002088 lens development in camera-type eye GO:0003002 regionalization GO:0003309 type B pancreatic cell differentiation GO:0003322 pancreatic A cell development GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0007224 smoothened signaling pathway GO:0007275 multicellular organism development GO:0007409 axonogenesis GO:0007411 axon guidance GO:0007417 central nervous system development GO:0007420 brain development GO:0007435 salivary gland morphogenesis GO:0007601 visual perception GO:0008285 negative regulation of cell proliferation GO:0009611 response to wounding GO:0009786 regulation of asymmetric cell division GO:0009887 animal organ morphogenesis GO:0009950 dorsal/ventral axis specification GO:0009952 anterior/posterior pattern specification GO:0009953 dorsal/ventral pattern formation GO:0010468 regulation of gene expression GO:0010628 positive regulation of gene expression GO:0016567 protein ubiquitination GO:0021543 pallium development GO:0021778 oligodendrocyte cell fate specification GO:0021796 cerebral cortex regionalization GO:0021798 forebrain dorsal/ventral pattern formation GO:0021902 commitment of neuronal cell to specific neuron type in forebrain GO:0021905 forebrain-midbrain boundary formation GO:0021912 regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification GO:0021913 regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification GO:0021918 regulation of transcription from RNA polymerase II promoter involved in somatic motor neuron fate commitment GO:0021978 telencephalon regionalization GO:0021983 pituitary gland development GO:0021986 habenula development GO:0023019 signal transduction involved in regulation of gene expression GO:0030154 cell differentiation GO:0030216 keratinocyte differentiation GO:0030334 regulation of cell migration GO:0030858 positive regulation of epithelial cell differentiation GO:0030900 forebrain development GO:0032808 lacrimal gland development GO:0033365 protein localization to organelle GO:0042462 eye photoreceptor cell development GO:0042593 glucose homeostasis GO:0043010 camera-type eye development GO:0045165 cell fate commitment GO:0045665 negative regulation of neuron differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048505 regulation of timing of cell differentiation GO:0048596 embryonic camera-type eye morphogenesis GO:0048663 neuron fate commitment GO:0048708 astrocyte differentiation GO:0050680 negative regulation of epithelial cell proliferation GO:0050767 regulation of neurogenesis GO:0050768 negative regulation of neurogenesis GO:0060041 retina development in camera-type eye GO:0061072 iris morphogenesis GO:0061303 cornea development in camera-type eye GO:1990830 cellular response to leukemia inhibitory factor GO:2000178 negative regulation of neural precursor cell proliferation
AB593092 - Homo sapiens PAX6 mRNA for paired box protein Pax-6, complete cds, clone: HP06376-ARe92D06. AB593093 - Homo sapiens PAX6 mRNA for paired box protein Pax-6, complete cds, clone: HP06376-ARh11B12. AB593094 - Homo sapiens PAX6 mRNA for paired box protein Pax-6, complete cds, clone: HP06376-ARi61A11. M77844 - Homo sapiens oculorhombin (PAX6) mRNA, complete cds, alternatively spliced. M93650 - Human paired box gene (PAX6) homologue, complete cds. BC011953 - Homo sapiens paired box 6, mRNA (cDNA clone MGC:17209 IMAGE:3880468), complete cds. BX640762 - Homo sapiens mRNA; cDNA DKFZp686B14266 (from clone DKFZp686B14266). AY707088 - Homo sapiens paired box gene 6 isoform a mRNA, complete cds. AY047583 - Homo sapiens paired box protein PAX6 (PAX6) mRNA, complete cds. AK314470 - Homo sapiens cDNA, FLJ95274. DQ891436 - Synthetic construct clone IMAGE:100004066; FLH176929.01X; RZPDo839B01124D paired box gene 6 (aniridia, keratitis) (PAX6) gene, encodes complete protein. AK094172 - Homo sapiens cDNA FLJ36853 fis, clone ASTRO2014498, highly similar to PAIRED BOX PROTEIN PAX-6. AK094249 - Homo sapiens cDNA FLJ36930 fis, clone BRACE2005251, highly similar to PAIRED BOX PROTEIN PAX-6. DQ894612 - Synthetic construct Homo sapiens clone IMAGE:100009072; FLH176926.01L; RZPDo839B01123D paired box gene 6 (aniridia, keratitis) (PAX6) gene, encodes complete protein. AK074881 - Homo sapiens cDNA FLJ90400 fis, clone NT2RP2005941, highly similar to Paired box protein Pax-6. AB209177 - Homo sapiens mRNA for paired box gene 6 isoform a variant protein. AB528383 - Synthetic construct DNA, clone: pF1KB7983, Homo sapiens PAX6 gene for paired box 6, without stop codon, in Flexi system. GQ141695 - Homo sapiens paired box protein 6 isoform c (PAX6) mRNA, complete cds, alternatively spliced. CU680128 - Synthetic construct Homo sapiens gateway clone IMAGE:100017234 5' read PAX6 mRNA. KP255960 - UNVERIFIED: Homo sapiens paired box 6-like mRNA, complete sequence. JD242206 - Sequence 223230 from Patent EP1572962. JD037394 - Sequence 18418 from Patent EP1572962. JD493110 - Sequence 474134 from Patent EP1572962. JD053733 - Sequence 34757 from Patent EP1572962. JD503363 - Sequence 484387 from Patent EP1572962. JD128343 - Sequence 109367 from Patent EP1572962. JD406008 - Sequence 387032 from Patent EP1572962. JD478179 - Sequence 459203 from Patent EP1572962. KM609512 - Homo sapiens clone S3 paired box protein Pax-6 (PAX6) mRNA, partial cds.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P26367 (Reactome details) participates in the following event(s):
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-5619507 Activation of HOX genes during differentiation R-HSA-1266738 Developmental Biology
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
