Pax Genes: Evolution and Function


The transcription factors of the Pax protein family have been conserved throughout metazoan evolution and play essential roles in brain development and organogenesis. Loss‐of‐function and gain‐of‐function mutations in PAX genes cause inherited disease syndromes and tumor formation respectively.

Keywords: Pax; transcription factor; paired domain; gene duplications; brain development; organogenesis; haploinsufficiency; inherited disease; tumorigenesis

Figure 1.

Structure and classification of mammalian Pax proteins. The different domains of Pax proteins are indicated. The consensus sequence of the conserved octapeptide (OP) is (Y/H)SI(N/D/S)GILG. PD: paired domain; HD: homeodomain; TAD: transactivation domain; PST: prolineserinethreonine.

Figure 2.

Structure and evolution of the paired domain. (a) Sequence conservation of the paired domain, the structure of which indicates the positions of α helices and β sheets. The paired domain sequences are shown without the additional amino acids that can be inserted by alternative splicing to modify the DNA‐binding function of Pax proteins. GenBank protein accession numbers: human (hu) Pax1 (P15863), Pax2 (Q02962), Pax3 (14250714), Pax4 (O43316), Pax5 (Q02548), Pax6 (383296), Pax7 (P23759), Pax8 (Q06710), Pax9 (AAH01159); amphioxus (am) Branchiostoma floridae Pax19 (644847), Pax258 (3025752), Pax37 (9621907), Pax46 (3204114); cnidarian (cn) Acropora millepora PaxA (AAC15713), PaxB (AAF64460), PaxC (AAC15711), PaxD (AAF64461), and Caenorhabditis elegans (ce) Tc1 transposase (17510681). The cephalochordate amphioxus is considered to be at the phylogenetic base of vertebrates. (b) Phylogenetic tree based on the sequence alignment shown in (a). (c) The consensus recognition sequence of the Pax6 paired domain is shown together with the three‐dimensional structure of the Pax6 paired domain–DNA complex (Xu et al., ).



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Further Reading

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Web Links

forkhead box O1A (rhabdomyosarcoma)(FOXO1A); LocusID: 2308. LocusLink:

forkhead box O1A (rhabdomyosarcoma)(FOXO1A); MIM number: 136533. OMIM:‐post/Omim/dispmim?136533

paired box gene 6 (aniridia, keratitis)(PAX6); LocusID: 5080. LocusLink:

paired box gene 6 (aniridia, keratitis)(PAX6); MIM number: 106210. OMIM:‐post/Omim/dispmim?106210

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Bouchard, Maxime, Schleiffer, Alexander, Eisenhaber, Frank, and Busslinger, Meinrad(Apr 2008) Pax Genes: Evolution and Function. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005114.pub2]