PARL
| Presenilin associated, rhomboid-like | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | PARL ; PSARL; PSARL1; PSENIP2; RHBDS1 | ||||||||||||
| External IDs | OMIM: 607858 MGI: 1277152 HomoloGene: 10239 GeneCards: PARL Gene | ||||||||||||
| EC number | 3.4.21.105 | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 55486 | 381038 | |||||||||||
| Ensembl | ENSG00000175193 | ENSMUSG00000033918 | |||||||||||
| UniProt | Q9H300 | Q5XJY4 | |||||||||||
| RefSeq (mRNA) | NM_001037639 | NM_001005767 | |||||||||||
| RefSeq (protein) | NP_001032728 | NP_001005767 | |||||||||||
| Location (UCSC) | Chr 3: 183.55 – 183.6 Mb | Chr 16: 20.28 – 20.3 Mb | |||||||||||
| PubMed search | |||||||||||||
Presenilins-associated rhomboid-like protein, mitochondrial is a protein that in humans is encoded by the PARL gene.[1] It is a member of the rhomboid family of intramembrane serine proteases.[2]
This gene encodes a mitochondrial integral membrane protein. Following proteolytic processing of this protein, a small peptide (P-beta) is formed and translocated to the nucleus. This gene may be involved in signal transduction via regulated intramembrane proteolysis of membrane-tethered precursor proteins. Variation in this gene has been associated with increased risk for type 2 diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms.[1]
Interactions
PARL has been shown to interact with PINK1.[3]
Clinical Significance
It has been shown that the p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent caus of early-onset Parkinson’s disease.[4] Variation in presenilins-associated rhomboid-like protein (PSARL) sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.[5]
References
- ↑ 1.0 1.1 "Entrez Gene: PARL presenilin associated, rhomboid-like".
- ↑ G. A. McQuibban, S. Saurya, M. Freeman, Nature 423, 537 (2003)
- ↑ Shi, G; Lee, J. R.; Grimes, D. A.; Racacho, L; Ye, D; Yang, H; Ross, O. A.; Farrer, M; McQuibban, G. A.; Bulman, D. E. (2011). "Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease". Human Molecular Genetics 20 (10): 1966–74. doi:10.1093/hmg/ddr077. PMID 21355049.
- ↑ Heinitz, S; Klein, C; Djarmati, A (2011). "The p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent cause of early-onset Parkinson's disease". Movement Disorders 26 (13): 2441–2. doi:10.1002/mds.23889. PMID 21953724.
- ↑ Walder, K; Kerr-Bayles, L; Civitarese, A; Jowett, J; Curran, J; Elliott, K; Trevaskis, J; Bishara, N; Zimmet, P; Mandarino, L; Ravussin, E; Blangero, J; Kissebah, A; Collier, G. R. (2005). "The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes". Diabetologia 48 (3): 459–68. doi:10.1007/s00125-005-1675-9. PMID 15729572.
Further reading
- Jeyaraju DV, Xu L, Letellier MC et al. (2007). "Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology.". Proc. Natl. Acad. Sci. U.S.A. 103 (49): 18562–7. doi:10.1073/pnas.0604983103. PMC 1693702. PMID 17116872.
- Fawcett KA, Wareham NJ, Luan J et al. (2007). "PARL Leu262Val is not associated with fasting insulin levels in UK populations.". Diabetologia 49 (11): 2649–52. doi:10.1007/s00125-006-0443-9. PMC 2672784. PMID 17019603.
- Walder K, Kerr-Bayles L, Civitarese A et al. (2005). "The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes.". Diabetologia 48 (3): 459–68. doi:10.1007/s00125-005-1675-9. PMID 15729572.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Sík A, Passer BJ, Koonin EV, Pellegrini L (2004). "Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide.". J. Biol. Chem. 279 (15): 15323–9. doi:10.1074/jbc.M313756200. PMID 14732705.
- McQuibban GA, Saurya S, Freeman M (2003). "Mitochondrial membrane remodelling regulated by a conserved rhomboid protease.". Nature 423 (6939): 537–41. doi:10.1038/nature01633. PMID 12774122.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Pellegrini L, Passer BJ, Canelles M et al. (2001). "PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2.". J. Alzheimers Dis. 3 (2): 181–190. PMID 12214059.