Paired box protein Pax-6

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). Acts as a transcriptional repressor of NFATC1-mediated gene expression (By similarity).

Classification

Family (Pfam)

PF00046 Homeodomain, PF00292 PAX

InterPro

HD, Homeobox_CS, Homeodomain-like_sf, PAIRED_DNA-bd_dom, Paired_dom, PAX_fam, WH-like_DNA-bd_sf

Functional cluster

RNA-Polymerase II Transcription Factors

Experimental structures · PDB · 2

• 2CUE NMR
• 6PAX X-ray 2.50A

A predicted model is available from AlphaFold.

Gene Ontology · 50

• GO:0000785 chromatin
• GO:0005737 cytoplasm
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0031490 chromatin DNA binding
• GO:0070410 co-SMAD binding
• GO:0003677 DNA binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
• GO:0035035 histone acetyltransferase binding
• GO:0071837 HMG box domain binding
• GO:0019901 protein kinase binding
• GO:0070412 R-SMAD binding
• GO:0003723 RNA binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
• GO:1990837 sequence-specific double-stranded DNA binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0001221 transcription coregulator binding
• GO:0031625 ubiquitin protein ligase binding
• GO:0009887 animal organ morphogenesis
• GO:0001568 blood vessel development
• GO:0007420 brain development
• GO:0007417 central nervous system development
• GO:0021987 cerebral cortex development
• GO:0006338 chromatin remodeling
• GO:0061303 cornea development in camera-type eye
• GO:0006351 DNA-templated transcription
• GO:0001654 eye development
• GO:0030900 forebrain development
• GO:0042593 glucose homeostasis
• GO:0061072 iris morphogenesis
• GO:0050768 negative regulation of neurogenesis
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0007399 nervous system development
• GO:0048663 neuron fate commitment
• GO:0003322 pancreatic A cell development
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0010628 positive regulation of gene expression
• GO:1902895 positive regulation of miRNA transcription
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0009611 response to wounding
• GO:0060041 retina development in camera-type eye
• GO:0007423 sensory organ development
• GO:0003309 type B pancreatic cell differentiation
• GO:0021517 ventral spinal cord development
• GO:0007601 visual perception

Disease associations

• aniridia 1 MONDO:0024507
• coloboma, ocular, autosomal dominant MONDO:0007350
• coloboma of optic nerve MONDO:0007354
• foveal hypoplasia 1 MONDO:0007628
• autosomal dominant keratitis MONDO:0007848
• isolated optic nerve hypoplasia MONDO:0008136
• Peters anomaly MONDO:0011414
• aniridia 2 MONDO:0014937

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Paired box protein Pax-6 1.00
• Paired box protein Pax-6 1.00
• Paired box protein Pax-6 1.00
• Paired box protein Pax-6 0.99
• Paired box protein Pax-6 0.99
• Paired box protein Pax-6 0.99
• Paired box protein Pax-3 0.91
• Paired box protein Pax-3 0.91
• Paired box protein Pax-6 0.89
• Paired box protein 6 homolog 0.89
• Paired box protein Pax-3-B 0.89
• Paired box protein Pax-7 0.89

Co-cited proteins · studied together in the literature

• Elongator complex protein 4 1 shared papers
• Homeobox protein OTX1 1 shared papers
• Homeobox protein OTX2 1 shared papers
• Retinal homeobox protein Rx 1 shared papers
• Visual system homeobox 2 1 shared papers
• Growth/differentiation factor 6 1 shared papers
• Isoleucine--tRNA ligase, mitochondrial 1 shared papers
• Transcription factor SOX-2 1 shared papers
• Phakinin 1 shared papers
• Beta-crystallin B1 1 shared papers
• Lens fiber major intrinsic protein 1 shared papers
• N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase 1 shared papers

Literature · 37 cited papers

• Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract. Orphanet J. Rare Dis. · 2018
• Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia. Am. J. Hum. Genet. · 2013
• Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. Clin. Genet. · 2014
• Mutation spectrum of PAX6 in Chinese patients with aniridia. Mol. Vis. · 2011
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina. Int. J. Dev. Neurosci. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
• A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation. Am. J. Med. Genet. A · 2007
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• Molecular analysis of a human PAX6 homeobox mutant. Eur. J. Hum. Genet. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 25 more in the literature graph