PAX3

Paired box 3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3CMY​
Identifiers
Symbols	PAX3 ; CDHS; HUP2; WS1; WS3
External IDs	OMIM: 606597 MGI: 97487 HomoloGene: 22494 GeneCards: PAX3 Gene
Gene ontology Molecular function • chromatin binding • sequence-specific DNA binding transcription factor activity • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity • protein binding • sequence-specific DNA binding • HMG box domain binding Cellular component • nucleoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • neural crest cell migration • neural tube closure • chromatin organization • transcription from RNA polymerase II promoter • apoptotic process • heart development • sensory perception of sound • cell proliferation • positive regulation of cell proliferation • organ morphogenesis • regulation of somitogenesis • spinal cord association neuron differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • developmental pigmentation • neuron fate commitment • skeletal muscle organ development • mammary gland specification Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5077	18505
Ensembl	ENSG00000135903	ENSMUSG00000004872
UniProt	P23760	P24610
RefSeq (mRNA)	NM_000438	NM_001159520
RefSeq (protein)	NP_000429	NP_001152992
Location (UCSC)	Chr 2: 222.2 – 222.3 Mb	Chr 1: 78.1 – 78.2 Mb
PubMed search

PAX3 is a gene that belongs to the paired box (PAX) family of transcription factors.^[1] This gene was formerly known as splotch.^[2] PAX3 has been identified with ear, eye and facial development.^[3] Mutations in it can cause Waardenburg syndrome types 1 and 3 . It is expressed in early embryonic phases in dermatomyotome of paraxial mesoderm which it helps to demarcate. In that way PAX3 contributes to early striated muscle development since all myoblasts are derived from dermatomyotome of paraxial mesoderm.

Alternative splicing results in transcripts encoding isoforms with different C-termini.^[1]

Role in rhabdomyosarcoma

A PAX3/FKHR fusion gene is often associated with the alveolar type of rhabdomyosarcoma,^[4] a kind of cancer arisen from striated muscle cells. Translocation between chromosomes 2 & 13 produce fusion protein PAX3/FKHR which serves as a tumor marker in this type of RMS.Also in ARMS expressing PAX3/FKHR increased risk of metastasis to bone marrow and hence increased rate of failure and death were seen.

Interactions

PAX3 has been shown to interact with MEOX1,^[5] MEOX2^[5] and SOX10^[6][7] as well as phosphatidylcholine transfer protein (PCTP).^[8] PAX3 has an important relationship with c-met in myogenesis; if PAX3 is mutated, c-met expression may be inhibited or prevented altogether resulting in a lack of lateral migration.

References

1. "Entrez Gene: PAX3 paired box 3 [Homo sapiens]".
2. "Entrez Gene: Pax3 paired box gene 3 [Mus musculus]".
3. http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002932
4. Begum S, Emami N, Emani N, et al. (March 2005). "Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR". Oncogene 24 (11): 1860–72. doi:10.1038/sj.onc.1208315. PMID 15688035.
5. Stamataki D, Kastrinaki M, Mankoo BS, Pachnis V, Karagogeos D (June 2001). "Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors". FEBS Lett. 499 (3): 274–8. doi:10.1016/S0014-5793(01)02556-X. PMID 11423130.
6. Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID 12668617.
7. Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID 10942418.
8. Kanno K, Wu MK, Agate DA, Fanelli BK, Wagle N, Scapa EF, Ukomadu C, Cohen DE (October 2007). "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2.". J. Biol. Chem. 282 (42): 30728–36. doi:10.1074/jbc.M703745200. PMID 17704541.

Further reading

• Moase CE, Trasler DG (1992). "Splotch locus mouse mutants: models for neural tube defects and Waardenburg syndrome type I in humans.". J. Med. Genet. 29 (3): 145–51. doi:10.1136/jmg.29.3.145. PMC 1015886. PMID 1552554.
• Baldwin CT, Hoth CF, Macina RA, Milunsky A (1996). "Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.". Am. J. Med. Genet. 58 (2): 115–22. doi:10.1002/ajmg.1320580205. PMID 8533800.
• Blake J, Ziman MR (2003). "Aberrant PAX3 and PAX7 expression. A link to the metastatic potential of embryonal rhabdomyosarcoma and cutaneous malignant melanoma?". Histol. Histopathol. 18 (2): 529–39. PMID 12647804.
• Reddi KK (1976). "Human granulocyte ribonuclease.". Biochem. Biophys. Res. Commun. 68 (4): 1119–25. doi:10.1016/0006-291X(76)90312-0. PMID 5077.
• Morell R, Friedman TB, Moeljopawiro S, et al. (1993). "A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.". Hum. Mol. Genet. 1 (4): 243–7. doi:10.1093/hmg/1.4.243. PMID 1303193.
• Carezani-Gavin M, Clarren SK, Steege T (1993). "Waardenburg syndrome associated with meningomyelocele.". Am. J. Med. Genet. 42 (1): 135–6. doi:10.1002/ajmg.1320420127. PMID 1308353.
• Tassabehji M, Read AP, Newton VE, et al. (1992). "Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene.". Nature 355 (6361): 635–6. doi:10.1038/355635a0. PMID 1347148.
• Baldwin CT, Hoth CF, Amos JA, et al. (1992). "An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.". Nature 355 (6361): 637–8. doi:10.1038/355637a0. PMID 1347149.
• Farrer LA, Grundfast KM, Amos J, et al. (1992). "Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium.". Am. J. Hum. Genet. 50 (5): 902–13. PMC 1682585. PMID 1349198.
• Sheffer R, Zlotogora J (1992). "Autosomal dominant inheritance of Klein-Waardenburg syndrome.". Am. J. Med. Genet. 42 (3): 320–2. doi:10.1002/ajmg.1320420312. PMID 1536170.
• Burri M, Tromvoukis Y, Bopp D, et al. (1989). "Conservation of the paired domain in metazoans and its structure in three isolated human genes.". EMBO J. 8 (4): 1183–90. PMC 400932. PMID 2501086.
• Newton VE (1990). "Waardenburg's syndrome: a comparison of biometric indices used to diagnose lateral displacement of the inner canthi.". Scandinavian audiology 18 (4): 221–3. doi:10.3109/01050398909042198. PMID 2609099.
• Newton CR, Graham A, Heptinstall LE, et al. (1989). "Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS).". Nucleic Acids Res. 17 (7): 2503–16. doi:10.1093/nar/17.7.2503. PMC 317639. PMID 2785681.
• Sommer A, Young-Wee T, Frye T (1983). "Previously undescribed syndrome of craniofacial, hand anomalies, and sensorineural deafness.". Am. J. Med. Genet. 15 (1): 71–7. doi:10.1002/ajmg.1320150109. PMID 6859126.
• Goodman RM, Lewithal I, Solomon A, Klein D (1982). "Upper limb involvement in the Klein-Waardenburg syndrome.". Am. J. Med. Genet. 11 (4): 425–33. doi:10.1002/ajmg.1320110407. PMID 7091186.
• Tsukamoto K, Nakamura Y, Niikawa N (1994). "Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues.". Hum. Genet. 93 (3): 270–4. doi:10.1007/BF00212021. PMID 7545913.
• Zlotogora J, Lerer I, Bar-David S, et al. (1995). "Homozygosity for Waardenburg syndrome.". Am. J. Hum. Genet. 56 (5): 1173–8. PMC 1801439. PMID 7726174.
• Macina RA, Barr FG, Galili N, Riethman HC (1995). "Genomic organization of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma.". Genomics 26 (1): 1–8. doi:10.1016/0888-7543(95)80076-X. PMID 7782066.
• Lalwani AK, Brister JR, Fex J, et al. (1995). "Further elucidation of the genomic structure of PAX3, and identification of two different point mutations within the PAX3 homeobox that cause Waardenburg syndrome type 1 in two families.". Am. J. Hum. Genet. 56 (1): 75–83. PMC 1801294. PMID 7825605.

External links

• GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I
• PAX3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)