PURA

Purine-rich element binding protein A
Identifiers
Symbols PURA ; MRD31; PUR-ALPHA; PUR1; PURALPHA
External IDs OMIM: 600473 MGI: 103079 HomoloGene: 4279 GeneCards: PURA Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 5813 19290
Ensembl ENSG00000185129 ENSMUSG00000043991
UniProt Q00577 P42669
RefSeq (mRNA) NM_005859 NM_008989
RefSeq (protein) NP_005850 NP_033015
Location (UCSC) Chr 5:
140.11 – 140.13 Mb		 Chr 18:
36.28 – 36.3 Mb
PubMed search

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

  1. ↑ 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.
  2. 1 2 "Entrez Gene: PURA purine-rich element binding protein A".
  3. 1 2 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.
  4. ↑ "Pura Syndrome - PURA gene". PURA Medical Advisory Group.
  5. 1 2 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.
  6. ↑ 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.
  7. ↑ 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

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