Paired box protein Pax-6

NamePaired box protein Pax-6
Synonyms
  • AN2
  • Aniridia type II protein
  • Oculorhombin
Gene NamePAX6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009255|Paired box protein Pax-6
MQNSHSGVNQLGGVFVNGRPLPDSTRQKIVELAHSGARPCDISRILQVSNGCVSKILGRY
YETGSIRPRAIGGSKPRVATPEVVSKIAQYKRECPSIFAWEIRDRLLSEGVCTNDNIPSV
SSINRVLRNLASEKQQMGADGMYDKLRMLNGQTGSWGTRPGWYPGTSVPGQPTQDGCQQQ
EGGGENTNSISSNGEDSDEAQMRLQLKRKLQRNRTSFTQEQIEALEKEFERTHYPDVFAR
ERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRRQASNTPSHIPISSSFSTSVYQPIP
QPTTPVSSFTSGSMLGRTDTALTNTYSALPPMPSFTMANNLPMQPPVPSQTSSYSCMLPT
SPSVNGRSYDTYTPPHMQTHMNSQPMGTSGTTSTGLISPGVSVPVQVPGSEPDMSQYWPR
LQ
Number of residues422
Molecular Weight46683.075
Theoretical pINot Available
GO Classification
Functions
  • protein kinase binding
  • transcription factor activity, sequence-specific DNA binding
  • DNA binding
  • transcription factor binding
  • R-SMAD binding
  • ubiquitin-protein transferase activity
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding
  • RNA polymerase II core promoter sequence-specific DNA binding
  • histone acetyltransferase binding
Processes
  • iris morphogenesis
  • positive regulation of transcription, DNA-templated
  • neuron fate commitment
  • positive regulation of transcription from RNA polymerase II promoter
  • cornea development in camera-type eye
  • response to wounding
  • pancreatic A cell development
  • positive regulation of gene expression
  • organ morphogenesis
  • eye development
  • central nervous system development
  • protein ubiquitination
  • visual perception
  • transcription from RNA polymerase II promoter
  • glucose homeostasis
  • negative regulation of neurogenesis
  • blood vessel development
Components
  • nuclear chromatin
  • cytoplasm
  • nucleus
  • nucleoplasm
General FunctionUbiquitin-protein transferase activity
Specific FunctionTranscription 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP26367
UniProtKB Entry NamePAX6_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0021735|Paired box protein Pax-6 (PAX6)
ATGCAGAACAGTCACAGCGGAGTGAATCAGCTCGGTGGTGTCTTTGTCAACGGGCGGCCA
CTGCCGGACTCCACCCGGCAGAAGATTGTAGAGCTAGCTCACAGCGGGGCCCGGCCGTGC
GACATTTCCCGAATTCTGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTAT
TACGAGACTGGCTCCATCAGACCCAGGGCAATCGGTGGTAGTAAACCGAGAGTAGCGACT
CCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGG
GAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTG
TCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGAC
GGCATGTATGATAAACTAAGGATGTTGAACGGGCAGACCGGAAGCTGGGGCACCCGCCCT
GGTTGGTATCCGGGGACTTCGGTGCCAGGGCAACCTACGCAAGATGGCTGCCAGCAACAG
GAAGGAGGGGGAGAGAATACCAACTCCATCAGTTCCAACGGAGAAGATTCAGATGAGGCT
CAAATGCGACTTCAGCTGAAGCGGAAGCTGCAAAGAAATAGAACATCCTTTACCCAAGAG
CAAATTGAGGCCCTGGAGAAAGAGTTTGAGAGAACCCATTATCCAGATGTGTTTGCCCGA
GAAAGACTAGCAGCCAAAATAGATCTACCTGAAGCAAGAATACAGGTATGGTTTTCTAAT
CGAAGGGCCAAATGGAGAAGAGAAGAAAAACTGAGGAATCAGAGAAGACAGGCCAGCAAC
ACACCTAGTCATATTCCTATCAGCAGTAGTTTCAGCACCAGTGTCTACCAACCAATTCCA
CAACCCACCACACCGGTTTCCTCCTTCACATCTGGCTCCATGTTGGGCCGAACAGACACA
GCCCTCACAAACACCTACAGCGCTCTGCCGCCTATGCCCAGCTTCACCATGGCAAATAAC
CTGCCTATGCAACCCCCAGTCCCCAGCCAGACCTCCTCATACTCCTGCATGCTGCCCACC
AGCCCTTCGGTGAATGGGCGGAGTTATGATACCTACACCCCCCCACATATGCAGACACAC
ATGAACAGTCAGCCAATGGGCACCTCGGGCACCACTTCAACAGGACTCATTTCCCCTGGT
GTGTCAGTTCCAGTTCAAGTTCCCGGAAGTGAACCTGATATGTCTCAATACTGGCCAAGA
TTACAGTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:8620
Chromosome Location11
LocusNot Available
References
  1. 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. 1684738
  2. 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. 1345175
  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. 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. 16554811
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. 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. 7958875
  7. 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. 7668281
  8. 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. 18669648
  9. 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. 19414065
  10. 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. 20068231
  11. 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. 10346815
  12. Prosser J, van Heyningen V: PAX6 mutations reviewed. Hum Mutat. 1998;11(2):93-108. 9482572
  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. 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. 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. 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. 9147640
  17. Axton RA, Hanson IM, Love J, Seawright A, Prosser J, van Heyningen V: Combined SSCP/heteroduplex analysis in the screening for PAX6 mutations. Mol Cell Probes. 1997 Aug;11(4):287-92. 9281415
  18. 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. 9792406
  19. 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. 9538891
  20. 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. 9856761
  21. Azuma N, Yamaguchi Y, Handa H, Hayakawa M, Kanai A, Yamada M: Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. Am J Hum Genet. 1999 Sep;65(3):656-63. 10441571
  22. 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. 10234503
  23. 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. 9931324
  24. 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. 10955655
  25. 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. 10737978
  26. 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. 11553050
  27. 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. 11309364
  28. 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. 11826019
  29. 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. Epub 2003 Apr 29. 12721955
  30. 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. 12634864
  31. Chao LY, Mishra R, Strong LC, Saunders GF: Missense mutations in the DNA-binding region and termination codon in PAX6. Hum Mutat. 2003 Feb;21(2):138-45. 12552561
  32. 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. 16493447
  33. 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. 17595013
  34. 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. 21850189