PARL

This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

Full Name

Presenilin Associated Rhomboid Like

Function

Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity).
Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088).
Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872).

Biological Process

Membrane protein proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrial fusionIEA:Ensembl
Negative regulation of intrinsic apoptotic signaling pathwayIEA:Ensembl
Negative regulation of release of cytochrome c from mitochondriaIEA:Ensembl
ProteolysisManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of autophagy of mitochondrionIEA:Ensembl
Regulation of mitochondrion organizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of protein targeting to mitochondrionManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Regulation of proteolysisManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Signal peptide processingManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Mitochondrion inner membrane
P-beta
Nucleus
Translocated into the nucleus by an unknown mechanism (PubMed:17116872).

Topology

Mitochondrial matrix: 53-101
Helical: 102-121
Mitochondrial intermembrane: 122-167
Helical: 168-187
Mitochondrial matrix: 188-207
Helical: 208-230
Mitochondrial intermembrane: 231-244
Helical: 245-262
Mitochondrial matrix: 263-272
Helical: 273-289
Mitochondrial intermembrane: 290-295
Helical: 296-318
Mitochondrial matrix: 319-332
Helical: 333-354
Mitochondrial intermembrane: 355-379

PTM

P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated.