PURA
Template:PBB Transcriptional activator protein Pur-alpha is a protein that in humans is encoded by the PURA gene.[1]
Gene
PURA is located on chromosome 5 at 5q31.2 and is encoded by a single exon that encodes a highly conserved multifunctional protein, Purα (Pur-alpha). PURA is expressed ubiquitously, including the brain, muscle, heart, and blood.
Function
Transcriptional activator protein Pur-alpha is a sequence-specific, single-stranded DNA-binding protein. It binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. Thus, it is implicated in the control of both DNA replication and transcription.[2]
The Pur-alpha protein is very highly conserved, with regulatory roles in DNA replication, gene transcription and RNA transport.[3][4] It is involved in neuronal proliferation, dendrite maturation, and the transport of mRNA to translation sites during neuronal development.[5]
Structure
Purα is a member of the Pur family of nucleic acid binding proteins which consist of a glycine-rich flexible amino terminus, a central core region and a potential carboxy-terminal protein binding region. Other family member include PURB and PURG. All human Pur proteins have three sequence-specific repeats, Pur repeats I–III.
Clinical significance
Deletion of the PURA gene has been associated with myelodysplastic syndrome and acute myelogenous leukemia.[2] Mutations in PURA may alter normal brain development and impair neuronal function, causing a condition being known as PURA Syndrome.
PURA is a candidate gene responsible for the developmental phenotype in the 5q31.3 microdeletion syndrome. However recently, a separate condition called PURA Syndrome has been identified. De novo mutations in PURA have been reported in 21 individuals.[3][5][6] Patients were identified by clinical whole-exome sequencing (WES). All mutations are heterozygous, with a similar phenotype of hypotonia, developmental delay, movement disorder and seizures / seizure like movements.
Protein interactions
PURA has been shown to interact with E2F1.[7]
References
- ^ Bergemann AD, Ma ZW, Johnson EM (Dec 1992). "Sequence of cDNA comprising the human pur gene and sequence-specific single-stranded-DNA-binding properties of the encoded protein". Molecular and Cellular Biology. 12 (12): 5673–82. doi:10.1128/mcb.12.12.5673. PMC 360507. PMID 1448097.
- ^ a b "Entrez Gene: PURA purine-rich element binding protein A".
- ^ a b Hunt D, Leventer RJ, Simons C, Taft R, Swoboda KJ, Gawne-Cain M, et al. (Dec 2014). "Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability". Journal of Medical Genetics. 51 (12): 806–13. doi:10.1136/jmedgenet-2014-102798. PMC 4251168. PMID 25342064.
- ^ "Pura Syndrome - PURA gene". PURA Medical Advisory Group.
- ^ a b Hunt D, Leventer RJ, Simons C, Taft R, Swoboda KJ, Gawne-Cain M, et al. (Dec 2014). "Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability". Journal of Medical Genetics. 51 (12): 806–13. doi:10.1136/jmedgenet-2014-102798. PMC 4251168. PMID 25342064.
- ^ Lalani SR, Zhang J, Schaaf CP, Brown CW, Magoulas P, Tsai AC, et al. (Nov 2014). "Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome". American Journal of Human Genetics. 95 (5): 579–83. doi:10.1016/j.ajhg.2014.09.014. PMC 4225583. PMID 25439098.
- ^ Darbinian N, Gallia GL, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K (Nov 1999). "Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1". Oncogene. 18 (46): 6398–402. doi:10.1038/sj.onc.1203011. PMID 10597240.
Further reading
- Gallia GL, Johnson EM, Khalili K (Sep 2000). "Puralpha: a multifunctional single-stranded DNA- and RNA-binding protein". Nucleic Acids Research. 28 (17): 3197–205. doi:10.1093/nar/28.17.3197. PMC 110688. PMID 10954586.
- Peruzzi F, Gordon J, Darbinian N, Amini S (Dec 2002). "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". Journal of Neurovirology. 8 Suppl 2 (2): 91–6. doi:10.1080/13550280290167885. PMID 12491158.
- Bergemann AD, Johnson EM (Mar 1992). "The HeLa Pur factor binds single-stranded DNA at a specific element conserved in gene flanking regions and origins of DNA replication". Molecular and Cellular Biology. 12 (3): 1257–65. doi:10.1128/mcb.12.3.1257. PMC 369558. PMID 1545807.
- Johnson EM, Chen PL, Krachmarov CP, Barr SM, Kanovsky M, Ma ZW, Lee WH (Oct 1995). "Association of human Pur alpha with the retinoblastoma protein, Rb, regulates binding to the single-stranded DNA Pur alpha recognition element". The Journal of Biological Chemistry. 270 (41): 24352–60. doi:10.1074/jbc.270.41.24352. PMID 7592647.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - Ma ZW, Pejovic T, Najfeld V, Ward DC, Johnson EM (1995). "Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding protein Pur alpha, to chromosome band 5q31". Cytogenetics and Cell Genetics. 71 (1): 64–7. doi:10.1159/000134065. PMID 7606931.
- Jurk M, Weissinger F, Lottspeich F, Schwarz U, Winnacker EL (Jul 1996). "Characterization of the single-strand-specific BPV-1 origin binding protein, SPSF I, as the HeLa Pur alpha factor". Nucleic Acids Research. 24 (14): 2799–806. doi:10.1093/nar/24.14.2799. PMC 146002. PMID 8759014.
- Krachmarov CP, Chepenik LG, Barr-Vagell S, Khalili K, Johnson EM (Nov 1996). "Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Pur alpha". Proceedings of the National Academy of Sciences of the United States of America. 93 (24): 14112–7. doi:10.1073/pnas.93.24.14112. PMC 34556. PMID 8943069.
- Kelm RJ, Elder PK, Strauch AR, Getz MJ (Oct 1997). "Sequence of cDNAs encoding components of vascular actin single-stranded DNA-binding factor 2 establish identity to Puralpha and Purbeta". The Journal of Biological Chemistry. 272 (42): 26727–33. doi:10.1074/jbc.272.42.26727. PMID 9334258.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - Thatikunta P, Sawaya BE, Denisova L, Cole C, Yusibova G, Johnson EM, Khalili K, Amini S (Dec 1997). "Identification of a cellular protein that binds to Tat-responsive element of TGF beta-1 promoter in glial cells". Journal of Cellular Biochemistry. 67 (4): 466–77. doi:10.1002/(SICI)1097-4644(19971215)67:4<466::AID-JCB5>3.0.CO;2-Q. PMID 9383706.
- Itoh H, Wortman MJ, Kanovsky M, Uson RR, Gordon RE, Alfano N, Johnson EM (Aug 1998). "Alterations in Pur(alpha) levels and intracellular localization in the CV-1 cell cycle". Cell Growth & Differentiation. 9 (8): 651–65. PMID 9716182.
- Gallia GL, Safak M, Khalili K (Dec 1998). "Interaction of the single-stranded DNA-binding protein Puralpha with the human polyomavirus JC virus early protein T-antigen". The Journal of Biological Chemistry. 273 (49): 32662–9. doi:10.1074/jbc.273.49.32662. PMID 9830007.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - Safak M, Gallia GL, Khalili K (Apr 1999). "Reciprocal interaction between two cellular proteins, Puralpha and YB-1, modulates transcriptional activity of JCVCY in glial cells". Molecular and Cellular Biology. 19 (4): 2712–23. doi:10.1128/mcb.19.4.2712. PMC 84064. PMID 10082537.
- Kelm RJ, Cogan JG, Elder PK, Strauch AR, Getz MJ (May 1999). "Molecular interactions between single-stranded DNA-binding proteins associated with an essential MCAT element in the mouse smooth muscle alpha-actin promoter". The Journal of Biological Chemistry. 274 (20): 14238–45. doi:10.1074/jbc.274.20.14238. PMID 10318844.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - Gallia GL, Darbinian N, Johnson EM, Khalili K (Sep 1999). "Self-association of Puralpha is mediated by RNA". Journal of Cellular Biochemistry. 74 (3): 334–48. doi:10.1002/(SICI)1097-4644(19990901)74:3<334::AID-JCB3>3.0.CO;2-O. PMID 10412036.
- Tretiakova A, Steplewski A, Johnson EM, Khalili K, Amini S (Oct 1999). "Regulation of myelin basic protein gene transcription by Sp1 and Puralpha: evidence for association of Sp1 and Puralpha in brain". Journal of Cellular Physiology. 181 (1): 160–8. doi:10.1002/(SICI)1097-4652(199910)181:1<160::AID-JCP17>3.0.CO;2-H. PMID 10457364.
- Gallia GL, Darbinian N, Tretiakova A, Ansari SA, Rappaport J, Brady J, Wortman MJ, Johnson EM, Khalili K (Sep 1999). "Association of HIV-1 Tat with the cellular protein, Puralpha, is mediated by RNA". Proceedings of the National Academy of Sciences of the United States of America. 96 (20): 11572–7. doi:10.1073/pnas.96.20.11572. PMC 18075. PMID 10500218.
- Darbinian N, Gallia GL, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K (Nov 1999). "Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1". Oncogene. 18 (46): 6398–402. doi:10.1038/sj.onc.1203011. PMID 10597240.
- Wortman MJ, Krachmarov CP, Kim JH, Gordon RG, Chepenik LG, Brady JN, Gallia GL, Khalili K, Johnson EM (Feb 2000). "Interaction of HIV-1 Tat with Puralpha in nuclei of human glial cells: characterization of RNA-mediated protein-protein binding". Journal of Cellular Biochemistry. 77 (1): 65–74. doi:10.1002/(SICI)1097-4644(20000401)77:1<65::AID-JCB7>3.0.CO;2-U. PMID 10679817.