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Identification
HMDB Protein ID HMDBP13589
Secondary Accession Numbers None
Name Paired box protein Pax-6
Synonyms
  1. Aniridia type II protein
  2. Oculorhombin
Gene Name PAX6
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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).
Pathways
  • Maturity onset diabetes of the young
  • Signaling pathways regulating pluripotency of stem cells
Reactions Not Available
GO Classification
Biological Process
organ morphogenesis
response to wounding
anatomical structure development
cornea development in camera-type eye
iris morphogenesis
pancreatic A cell development
positive regulation of core promoter binding
ventral spinal cord development
regulation of transcription from RNA polymerase II promoter
glucose homeostasis
positive regulation of transcription, DNA-dependent
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
eye development
neuron fate commitment
visual perception
blood vessel development
positive regulation of gene expression
negative regulation of neurogenesis
central nervous system development
Cellular Component
cytosol
cytoplasm
nucleus
nucleoplasm
chromatin
Molecular Function
protein kinase binding
sequence-specific DNA binding transcription factor activity
histone acetyltransferase binding
R-SMAD binding
transcription factor binding
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II core promoter proximal region sequence-specific DNA binding
sequence-specific double-stranded DNA binding
transcription regulatory region sequence-specific DNA binding
DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 422
Molecular Weight 46683.075
Theoretical pI 9.364
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P26367
UniProtKB/Swiss-Prot Entry Name PAX6_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  4. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811 ]
  5. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231 ]
  6. Ton CC, Hirvonen H, Miwa H, Weil MM, Monaghan P, Jordan T, van Heyningen V, Hastie ND, Meijers-Heijboer H, Drechsler M, et al.: Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell. 1991 Dec 20;67(6):1059-74. doi: 10.1016/0092-8674(91)90284-6. [PubMed:1684738 ]
  7. Glaser T, Walton DS, Maas RL: Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet. 1992 Nov;2(3):232-9. doi: 10.1038/ng1192-232. [PubMed:1345175 ]
  8. Epstein JA, Glaser T, Cai J, Jepeal L, Walton DS, Maas RL: Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. Genes Dev. 1994 Sep 1;8(17):2022-34. doi: 10.1101/gad.8.17.2022. [PubMed:7958875 ]
  9. Mirzayans F, Pearce WG, MacDonald IM, Walter MA: Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet. 1995 Sep;57(3):539-48. [PubMed:7668281 ]
  10. Larsen KB, Lutterodt M, Rath MF, Moller M: Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina. Int J Dev Neurosci. 2009 Aug;27(5):485-92. doi: 10.1016/j.ijdevneu.2009.04.004. Epub 2009 May 3. [PubMed:19414065 ]
  11. Bhatia S, Bengani H, Fish M, Brown A, Divizia MT, de Marco R, Damante G, Grainger R, van Heyningen V, Kleinjan DA: Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved PAX6 enhancer causes aniridia. Am J Hum Genet. 2013 Dec 5;93(6):1126-34. doi: 10.1016/j.ajhg.2013.10.028. Epub 2013 Nov 27. [PubMed:24290376 ]
  12. Xu HE, Rould MA, Xu W, Epstein JA, Maas RL, Pabo CO: Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev. 1999 May 15;13(10):1263-75. doi: 10.1101/gad.13.10.1263. [PubMed:10346815 ]
  13. Hanson IM, Seawright A, Hardman K, Hodgson S, Zaletayev D, Fekete G, van Heyningen V: PAX6 mutations in aniridia. Hum Mol Genet. 1993 Jul;2(7):915-20. doi: 10.1093/hmg/2.7.915. [PubMed:8364574 ]
  14. Hanson IM, Fletcher JM, Jordan T, Brown A, Taylor D, Adams RJ, Punnett HH, van Heyningen V: Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat Genet. 1994 Feb;6(2):168-73. doi: 10.1038/ng0294-168. [PubMed:8162071 ]
  15. Azuma N, Nishina S, Yanagisawa H, Okuyama T, Yamada M: PAX6 missense mutation in isolated foveal hypoplasia. Nat Genet. 1996 Jun;13(2):141-2. doi: 10.1038/ng0696-141. [PubMed:8640214 ]
  16. Tang HK, Chao LY, Saunders GF: Functional analysis of paired box missense mutations in the PAX6 gene. Hum Mol Genet. 1997 Mar;6(3):381-6. doi: 10.1093/hmg/6.3.381. [PubMed:9147640 ]
  17. Wolf MT, Lorenz B, Winterpacht A, Drechsler M, Schumacher V, Royer-Pokora B, Blankenagel A, Zabel B, Wildhardt G: Ten novel mutations found in Aniridia. Hum Mutat. 1998;12(5):304-13. doi: 10.1002/(SICI)1098-1004(1998)12:5<304::AID-HUMU3>3.0.CO;2-D. [PubMed:9792406 ]
  18. Azuma N, Yamada M: Missense mutation at the C terminus of the PAX6 gene in ocular anterior segment anomalies. Invest Ophthalmol Vis Sci. 1998 Apr;39(5):828-30. [PubMed:9538891 ]
  19. Azuma N, Hotta Y, Tanaka H, Yamada M: Missense mutations in the PAX6 gene in aniridia. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2524-8. [PubMed:9856761 ]
  20. Gronskov K, Rosenberg T, Sand A, Brondum-Nielsen K: Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. Eur J Hum Genet. 1999 Apr;7(3):274-86. doi: 10.1038/sj.ejhg.5200308. [PubMed:10234503 ]
  21. Hanson I, Churchill A, Love J, Axton R, Moore T, Clarke M, Meire F, van Heyningen V: Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations. Hum Mol Genet. 1999 Feb;8(2):165-72. doi: 10.1093/hmg/8.2.165. [PubMed:9931324 ]
  22. Sonoda S, Isashiki Y, Tabata Y, Kimura K, Kakiuchi T, Ohba N: A novel PAX6 gene mutation (P118R) in a family with congenital nystagmus associated with a variant form of aniridia. Graefes Arch Clin Exp Ophthalmol. 2000 Jul;238(7):552-8. doi: 10.1007/s004170000124. [PubMed:10955655 ]
  23. Chao LY, Huff V, Strong LC, Saunders GF: Mutation in the PAX6 gene in twenty patients with aniridia. Hum Mutat. 2000;15(4):332-9. doi: 10.1002/(SICI)1098-1004(200004)15:4<332::AID-HUMU5>3.0.CO;2-1. [PubMed:10737978 ]
  24. Malandrini A, Mari F, Palmeri S, Gambelli S, Berti G, Bruttini M, Bardelli AM, Williamson K, van Heyningen V, Renieri A: PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation. Clin Genet. 2001 Aug;60(2):151-4. doi: 10.1034/j.1399-0004.2001.600210.x. [PubMed:11553050 ]
  25. Singh S, Chao LY, Mishra R, Davies J, Saunders GF: Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Hum Mol Genet. 2001 Apr 15;10(9):911-8. doi: 10.1093/hmg/10.9.911. [PubMed:11309364 ]
  26. Morrison D, FitzPatrick D, Hanson I, Williamson K, van Heyningen V, Fleck B, Jones I, Chalmers J, Campbell H: National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology. J Med Genet. 2002 Jan;39(1):16-22. doi: 10.1136/jmg.39.1.16. [PubMed:11826019 ]
  27. Azuma N, Yamaguchi Y, Handa H, Tadokoro K, Asaka A, Kawase E, Yamada M: Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am J Hum Genet. 2003 Jun;72(6):1565-70. doi: 10.1086/375555. Epub 2003 Apr 29. [PubMed:12721955 ]
  28. Vincent MC, Pujo AL, Olivier D, Calvas P: Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects. Eur J Hum Genet. 2003 Feb;11(2):163-9. doi: 10.1038/sj.ejhg.5200940. [PubMed:12634864 ]
  29. D'Elia AV, Puppin C, Pellizzari L, Pianta A, Bregant E, Lonigro R, Tell G, Fogolari F, van Heyningen V, Damante G: Molecular analysis of a human PAX6 homeobox mutant. Eur J Hum Genet. 2006 Jun;14(6):744-51. doi: 10.1038/sj.ejhg.5201579. [PubMed:16493447 ]
  30. Graziano C, D'Elia AV, Mazzanti L, Moscano F, Guidelli Guidi S, Scarano E, Turchetti D, Franzoni E, Romeo G, Damante G, Seri M: A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation. Am J Med Genet A. 2007 Aug 1;143A(15):1802-5. doi: 10.1002/ajmg.a.31808. [PubMed:17595013 ]
  31. Zhang X, Wang P, Li S, Xiao X, Guo X, Zhang Q: Mutation spectrum of PAX6 in Chinese patients with aniridia. Mol Vis. 2011;17:2139-47. Epub 2011 Aug 11. [PubMed:21850189 ]
  32. Chassaing N, Causse A, Vigouroux A, Delahaye A, Alessandri JL, Boespflug-Tanguy O, Boute-Benejean O, Dollfus H, Duban-Bedu B, Gilbert-Dussardier B, Giuliano F, Gonzales M, Holder-Espinasse M, Isidor B, Jacquemont ML, Lacombe D, Martin-Coignard D, Mathieu-Dramard M, Odent S, Picone O, Pinson L, Quelin C, Sigaudy S, Toutain A, Thauvin-Robinet C, Kaplan J, Calvas P: Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. Clin Genet. 2014 Oct;86(4):326-34. doi: 10.1111/cge.12275. Epub 2013 Oct 7. [PubMed:24033328 ]