In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members (PAX3, PAX4, PAX6 and PAX7),[1] a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present.[2] Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.
Within the mammalian family, there are four well defined groups of Pax genes.
Pax group 1 (Pax 1 and 9),
Pax group 2 (Pax 2, 5 and 8),
Pax group 3 (Pax 3 and 7) and
Pax group 4 (Pax 4 and 6).
Two more families, Pox-neuro and Pax-α/β, exist in basal bilaterian species.[5][6] Orthologous genes exist throughout the Metazoa, including extensive study of the ectopic expression in Drosophila using murine Pax6.[7] The two rounds of whole-genome duplications in vertebrate evolution is responsible for the creation of as many as 4 paralogs for each Pax protein.[8]
Membersedit
PAX1 has been identified in mice with the development of vertebrate and embryo segmentation, and some evidence this is also true in humans. It transcribes a 440 amino acid protein from 4 exons and 1,323bps in humans. In the mouse Pax1 mutation has been linked to undulated mutant suffering from skeletal malformations.[9]
PAX2 has been identified with kidney and optic nerve development. It transcribes a 417 amino acid protein from 11 exons and 4,261 bps in humans. Mutation of PAX2 in humans has been associated with renal-coloboma syndrome as well as oligomeganephronia.[10]
PAX3 has been identified with ear, eye and facial development. It transcribes a 479 amino acid protein in humans. Mutations in it can cause Waardenburg syndrome. PAX3 is frequently expressed in melanomas[11] and contributes to tumor cell survival.[12]
PAX4 has been identified with pancreatic islet beta cells. It transcribes a 350 amino acid protein from 9 exons and 2,010 bps in humans. Knockout mice lacking Pax4 expression fail to develop insulin-producing cells.[13] Pax4 undergoes mutual reciprocal interaction with the transcription factor Arx to endow pancreatic endocrine cells with insulin and glucagon cells respectively[14]
PAX5 has been identified with neural and spermatogenesis development and b-cell differentiation. It transcribes a 391 amino acid protein from 10 exons and 3,644bps in humans.
PAX6 (eyeless) is the most researched and appears throughout the literature as a "master control" gene for the development of eyes and sensory organs, certain neural and epidermal tissues as well as other homologous structures, usually derived from ectodermal tissues.[15]
PAX7 has been possibly associated with myogenesis. It transcribes a protein of 520 amino acids from 8 exons and 2,260bps in humans. PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not for the specification.[16]
PAX8 has been associated with thyroid specific expression. It transcribes a protein of 451 amino acids from 11 exons and 2,526bps in humans. Pax8 loss-of-function mutant mice lack follicular cells of the thyroid gland.[17]
PAX9 has found to be associated with a number of organ and other skeletal developments, particularly teeth. It transcribes a protein of 341 amino acids from 4 exons and 1,644bps in humans.
^Chi, N; Epstein, JA (January 2002). "Getting your Pax straight: Pax proteins in development and disease". Trends in Genetics. 18 (1): 41–7. doi:10.1016/s0168-9525(01)02594-x. PMID 11750700.
^Eberhard, D; Jiménez, G; Heavey, B; Busslinger, M (15 May 2000). "Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family". The EMBO Journal. 19 (10): 2292–303. doi:10.1093/emboj/19.10.2292. PMC384353. PMID 10811620.
^Bopp, D; Burri, M; Baumgartner, S; Frigerio, G; Noll, M (26 December 1986). "Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila". Cell. 47 (6): 1033–40. doi:10.1016/0092-8674(86)90818-4. PMID 2877747. S2CID 21943167.
^Baumgartner, S; Bopp, D; Burri, M; Noll, M (December 1987). "Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis". Genes & Development. 1 (10): 1247–67. doi:10.1101/gad.1.10.1247. PMID 3123319.
^Navet, S; Buresi, A; Baratte, S; Andouche, A; Bonnaud-Ponticelli, L; Bassaglia, Y (2017). "The Pax gene family: Highlights from cephalopods". PLOS ONE. 12 (3): e0172719. Bibcode:2017PLoSO..1272719N. doi:10.1371/journal.pone.0172719. PMC5333810. PMID 28253300.
^Franke, FA; Schumann, I; Hering, L; Mayer, G (2015). "Phylogenetic analysis and expression patterns of Pax genes in the onychophoran Euperipatoides rowelli reveal a novel bilaterian Pax subfamily". Evolution & Development. 17 (1): 3–20. doi:10.1111/ede.12110. PMID 25627710. S2CID 205095304.
^Gehring WJ, Ikeo K (September 1999). "Pax 6: mastering eye morphogenesis and eye evolution". Trends in Genetics. 15 (9): 371–7. doi:10.1016/S0168-9525(99)01776-X. PMID 10461206.
^Ravi V, Bhatia S, Gautier P, Loosli F, Tay BH, Tay A, Murdoch E, Coutinho P, van Heyningen V, Brenner S, Venkatesh B, Kleinjan DA (2013). "Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences". PLOS Genetics. 9 (1): e1003177. doi:10.1371/journal.pgen.1003177. PMC3554528. PMID 23359656.
^Medic S, Ziman M (April 2010). Soyer, H. Peter (ed.). "PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas)". PLOS ONE. 5 (4): e9977. Bibcode:2010PLoSO...5.9977M. doi:10.1371/journal.pone.0009977. PMC2858648. PMID 20421967.
^Scholl FA, Kamarashev J, Murmann OV, Geertsen R, Dummer R, Schäfer BW (Feb 2001). "PAX3 is expressed in human melanomas and contributes to tumor cell survival". Cancer Res. 61 (3): 823–6. PMID 11221862.
^Oustanina, S; et al. (2004). "PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification". The EMBO Journal. 23 (16): 3430–3439. doi:10.1038/sj.emboj.7600346. PMC514519. PMID 15282552.
Zuker, Charles S. (August 1994). "On the evolution of eyes: would you like it simple or compound?". Science. 265 (5173): 742–3. Bibcode:1994Sci...265..742Z. doi:10.1126/science.8047881. PMID 8047881.
Quiring, Rebecca; Walldorf, Uwe; Kloter U; Gehring WJ (August 1994). "Homology of the eyeless gene of Drosophila to the small eye gene in mice and Aniridia in humans". Science. 265 (5173): 785–9. Bibcode:1994Sci...265..785Q. doi:10.1126/science.7914031. PMID 7914031.
genes, evolutionary, developmental, biology, paired, genes, family, genes, coding, tissue, specific, transcription, factors, containing, terminal, paired, domain, usually, partial, case, four, family, members, pax3, pax4, pax6, pax7, complete, homeodomain, ter. In evolutionary developmental biology Paired box Pax genes are a family of genes coding for tissue specific transcription factors containing an N terminal paired domain and usually a partial or in the case of four family members PAX3 PAX4 PAX6 and PAX7 1 a complete homeodomain to the C terminus An octapeptide as well as a Pro Ser Thr rich C terminus may also be present 2 Pax proteins are important in early animal development for the specification of specific tissues as well as during epimorphic limb regeneration in animals capable of such Paired domainPAX5 bound to DNA PDB 1mdm IdentifiersSymbolPAXPfamPF00292InterProIPR001523PROSITEPDOC00034CATH1pdnSCOP21pdn SCOPe SUPFAMCDDcd00131Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary The paired domain was initially described in 1987 as the paired box in the Drosophila protein paired prd P06601 3 4 Contents 1 Groups 2 Members 3 See also 4 References 5 External linksGroups editWithin the mammalian family there are four well defined groups of Pax genes Pax group 1 Pax 1 and 9 Pax group 2 Pax 2 5 and 8 Pax group 3 Pax 3 and 7 and Pax group 4 Pax 4 and 6 Two more families Pox neuro and Pax a b exist in basal bilaterian species 5 6 Orthologous genes exist throughout the Metazoa including extensive study of the ectopic expression in Drosophila using murine Pax6 7 The two rounds of whole genome duplications in vertebrate evolution is responsible for the creation of as many as 4 paralogs for each Pax protein 8 Members editPAX1 has been identified in mice with the development of vertebrate and embryo segmentation and some evidence this is also true in humans It transcribes a 440 amino acid protein from 4 exons and 1 323bps in humans In the mouse Pax1 mutation has been linked to undulated mutant suffering from skeletal malformations 9 PAX2 has been identified with kidney and optic nerve development It transcribes a 417 amino acid protein from 11 exons and 4 261 bps in humans Mutation of PAX2 in humans has been associated with renal coloboma syndrome as well as oligomeganephronia 10 PAX3 has been identified with ear eye and facial development It transcribes a 479 amino acid protein in humans Mutations in it can cause Waardenburg syndrome PAX3 is frequently expressed in melanomas 11 and contributes to tumor cell survival 12 PAX4 has been identified with pancreatic islet beta cells It transcribes a 350 amino acid protein from 9 exons and 2 010 bps in humans Knockout mice lacking Pax4 expression fail to develop insulin producing cells 13 Pax4 undergoes mutual reciprocal interaction with the transcription factor Arx to endow pancreatic endocrine cells with insulin and glucagon cells respectively 14 PAX5 has been identified with neural and spermatogenesis development and b cell differentiation It transcribes a 391 amino acid protein from 10 exons and 3 644bps in humans PAX6 eyeless is the most researched and appears throughout the literature as a master control gene for the development of eyes and sensory organs certain neural and epidermal tissues as well as other homologous structures usually derived from ectodermal tissues 15 PAX7 has been possibly associated with myogenesis It transcribes a protein of 520 amino acids from 8 exons and 2 260bps in humans PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not for the specification 16 PAX8 has been associated with thyroid specific expression It transcribes a protein of 451 amino acids from 11 exons and 2 526bps in humans Pax8 loss of function mutant mice lack follicular cells of the thyroid gland 17 PAX9 has found to be associated with a number of organ and other skeletal developments particularly teeth It transcribes a protein of 341 amino acids from 4 exons and 1 644bps in humans See also editHomeobox Evolutionary developmental biology Body plan SOX genesReferences edit Chi N Epstein JA January 2002 Getting your Pax straight Pax proteins in development and disease Trends in Genetics 18 1 41 7 doi 10 1016 s0168 9525 01 02594 x PMID 11750700 Eberhard D Jimenez G Heavey B Busslinger M 15 May 2000 Transcriptional repression by Pax5 BSAP through interaction with corepressors of the Groucho family The EMBO Journal 19 10 2292 303 doi 10 1093 emboj 19 10 2292 PMC 384353 PMID 10811620 Bopp D Burri M Baumgartner S Frigerio G Noll M 26 December 1986 Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila Cell 47 6 1033 40 doi 10 1016 0092 8674 86 90818 4 PMID 2877747 S2CID 21943167 Baumgartner S Bopp D Burri M Noll M December 1987 Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis Genes amp Development 1 10 1247 67 doi 10 1101 gad 1 10 1247 PMID 3123319 Navet S Buresi A Baratte S Andouche A Bonnaud Ponticelli L Bassaglia Y 2017 The Pax gene family Highlights from cephalopods PLOS ONE 12 3 e0172719 Bibcode 2017PLoSO 1272719N doi 10 1371 journal pone 0172719 PMC 5333810 PMID 28253300 Franke FA Schumann I Hering L Mayer G 2015 Phylogenetic analysis and expression patterns of Pax genes in the onychophoran Euperipatoides rowelli reveal a novel bilaterian Pax subfamily Evolution amp Development 17 1 3 20 doi 10 1111 ede 12110 PMID 25627710 S2CID 205095304 Gehring WJ Ikeo K September 1999 Pax 6 mastering eye morphogenesis and eye evolution Trends in Genetics 15 9 371 7 doi 10 1016 S0168 9525 99 01776 X PMID 10461206 Ravi V Bhatia S Gautier P Loosli F Tay BH Tay A Murdoch E Coutinho P van Heyningen V Brenner S Venkatesh B Kleinjan DA 2013 Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes forged by ancient duplications and divergences PLOS Genetics 9 1 e1003177 doi 10 1371 journal pgen 1003177 PMC 3554528 PMID 23359656 Balling et al 1988 Online Mendelian Inheritance in Man OMIM 167409 Medic S Ziman M April 2010 Soyer H Peter ed PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions Naevi and Melanomas PLOS ONE 5 4 e9977 Bibcode 2010PLoSO 5 9977M doi 10 1371 journal pone 0009977 PMC 2858648 PMID 20421967 Scholl FA Kamarashev J Murmann OV Geertsen R Dummer R Schafer BW Feb 2001 PAX3 is expressed in human melanomas and contributes to tumor cell survival Cancer Res 61 3 823 6 PMID 11221862 Sosa Pineda et al 1997 Collombat et al 2003 Walter and Gruss 1991 Oustanina S et al 2004 PAX7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification The EMBO Journal 23 16 3430 3439 doi 10 1038 sj emboj 7600346 PMC 514519 PMID 15282552 Mansouri et al 1998 1 Further reading Zuker Charles S August 1994 On the evolution of eyes would you like it simple or compound Science 265 5173 742 3 Bibcode 1994Sci 265 742Z doi 10 1126 science 8047881 PMID 8047881 Quiring Rebecca Walldorf Uwe Kloter U Gehring WJ August 1994 Homology of the eyeless gene of Drosophila to the small eye gene in mice and Aniridia in humans Science 265 5173 785 9 Bibcode 1994Sci 265 785Q doi 10 1126 science 7914031 PMID 7914031 External links editA Review of the Highly Conserved PAX6 Gene in Eye Development Regulation Paired domain permanent dead link in PROSITE Pax Transcription Factors at the U S National Library of Medicine Medical Subject Headings MeSH This article incorporates text from the public domain Pfam and InterPro IPR001523 Mansouri A et al 1996 Retrieved from https en wikipedia org w index php title Pax genes amp oldid 1212886625, wikipedia, wiki, book, books, library,
