PHOX2A explained

Paired mesoderm homeobox protein 2A is a protein that in humans is encoded by the PHOX2A gene.^{[1] [2] [3]}

Function

The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. This protein is expressed specifically in noradrenergic cell types. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of noradrenergic phenotype. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles (CFEOM2).

Interactions

PHOX2A has been shown to interact with HAND2.^[4]

Further reading

• Brunet JF, Pattyn A . Phox2 genes - from patterning to connectivity . Curr. Opin. Genet. Dev. . 12 . 4 . 435–40 . 2002 . 12100889 . 10.1016/S0959-437X(02)00322-2 .
• Merscher S, Bekri S, de Leeuw B, Pedeutour F, Grosgeorge J, Shows TB, Müllenbach R, Le Paslier D, Nowak NJ, Gaudray P . A 5.5-Mb high-resolution integrated map of distal 11q13 . Genomics . 39 . 3 . 340–7 . 1997 . 9119371 . 10.1006/geno.1996.4460 .
• Swanson DJ, Zellmer E, Lewis EJ . The homeodomain protein Arix interacts synergistically with cyclic AMP to regulate expression of neurotransmitter biosynthetic genes . J. Biol. Chem. . 272 . 43 . 27382–92 . 1997 . 9341190 . 10.1074/jbc.272.43.27382 . free .
• Wang SM, Zwaan J, Mullaney PB, Jabak MH, Al-Awad A, Beggs AH, Engle EC . Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13 . Am. J. Hum. Genet. . 63 . 2 . 517–25 . 1998 . 9683611 . 1377321 . 10.1086/301980 .
• Swanson DJ, Adachi M, Lewis EJ . The homeodomain protein Arix promotes protein kinase A-dependent activation of the dopamine beta-hydroxylase promoter through multiple elements and interaction with the coactivator cAMP-response element-binding protein-binding protein . J. Biol. Chem. . 275 . 4 . 2911–23 . 2000 . 10644760 . 10.1074/jbc.275.4.2911 . free .
• Flora A, Lucchetti H, Benfante R, Goridis C, Clementi F, Fornasari D . Sp proteins and Phox2b regulate the expression of the human Phox2a gene . J. Neurosci. . 21 . 18 . 7037–45 . 2001 . 11549713 . 10.1523/jneurosci.21-18-07037.2001 . 6763013.
• Strømme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis SM, Bruyere H, Lütcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints SG, Fryns JP, Sutherland GR, Mulley JC, Gécz J . Grant Robert Sutherland . Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy . Nat. Genet. . 30 . 4 . 441–5 . 2002 . 11889467 . 10.1038/ng862 . 12822090 .
• Adachi M, Lewis EJ . The paired-like homeodomain protein, Arix, mediates protein kinase A-stimulated dopamine beta-hydroxylase gene transcription through its phosphorylation status . J. Biol. Chem. . 277 . 25 . 22915–24 . 2002 . 11943777 . 10.1074/jbc.M201695200 . free .
• Rychlik JL, Gerbasi V, Lewis EJ . The interaction between dHAND and Arix at the dopamine beta-hydroxylase promoter region is independent of direct dHAND binding to DNA . J. Biol. Chem. . 278 . 49 . 49652–60 . 2003 . 14506227 . 10.1074/jbc.M308577200 . free .
• Sasaki A, Kanai M, Kijima K, Akaba K, Hashimoto M, Hasegawa H, Otaki S, Koizumi T, Kusuda S, Ogawa Y, Tuchiya K, Yamamoto W, Nakamura T, Hayasaka K . Molecular analysis of congenital central hypoventilation syndrome . Hum. Genet. . 114 . 1 . 22–6 . 2003 . 14566559 . 10.1007/s00439-003-1036-z . 24588298 .
• Yazdani A, Chung DC, Abbaszadegan MR, Al-Khayer K, Chan WM, Yazdani M, Ghodsi K, Engle EC, Traboulsi EI . A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2) . Am. J. Ophthalmol. . 136 . 5 . 861–5 . 2003 . 14597037 . 10.1016/S0002-9394(03)00891-2 .
• Jiang Y, Matsuo T, Fujiwara H, Hasebe S, Ohtsuki H, Yasuda T . ARIX and PHOX2B polymorphisms in patients with congenital superior oblique muscle palsy . Acta Med. Okayama . 59 . 2 . 55–62 . 2005 . 16049556 .
• Bachetti T, Borghini S, Ravazzolo R, Ceccherini I . An in vitro approach to test the possible role of candidate factors in the transcriptional regulation of the RET proto-oncogene . Gene Expr. . 12 . 3 . 137–49 . 2005 . 16127999 . 10.3727/000000005783992106 . 6009117 .
• Hsieh MM, Lupas G, Rychlik J, Dziennis S, Habecker BA, Lewis EJ . ERK1/2 is a negative regulator of homeodomain protein Arix/Phox2a . J. Neurochem. . 94 . 6 . 1719–27 . 2005 . 16156742 . 10.1111/j.1471-4159.2005.03333.x . 2985635 . free .
• Rychlik JL, Hsieh M, Eiden LE, Lewis EJ . Phox2 and dHAND transcription factors select shared and unique target genes in the noradrenergic cell type . J. Mol. Neurosci. . 27 . 3 . 281–92 . 2005 . 16280598 . 10.1385/JMN:27:3:281 . 1021814 .

External links

• Engle Laboratory CFEOM page
• GeneReviews/NCBI/NIH/UW entry on Congenital Fibrosis of the Extraocular Muscles
• OMIM entries on Congenital Fibrosis of the Extraocular Muscles

Notes and References

1. Johnson KR, Smith L, Johnson DK, Rhodes J, Rinchik EM, Thayer M, Lewis EJ . Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human chromosome 11q13 . Genomics . 33 . 3 . 527–31 . Sep 1996 . 8661014 . 10.1006/geno.1996.0230 .
2. Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH, Zwaan J, Mullaney PB, Bosley TM, Engle EC . Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2 . Nat. Genet. . 29 . 3 . 315–20 . Nov 2001 . 11600883 . 10.1038/ng744 . 25403574 .
3. Web site: Entrez Gene: PHOX2A paired-like (aristaless) homeobox 2a.
4. Rychlik JL, Gerbasi V, Lewis EJ . The interaction between dHAND and Arix at the dopamine beta-hydroxylase promoter region is independent of direct dHAND binding to DNA . J. Biol. Chem. . 278 . 49 . 49652–60 . Dec 2003 . 14506227 . 10.1074/jbc.M308577200 . free .