Human Gene PARL (uc003fmd.3) Description and Page Index
Description: Homo sapiens presenilin associated, rhomboid-like (PARL), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA. RefSeq Summary (NM_018622): 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]. Transcript (Including UTRs) Position: hg19 chr3:183,547,173-183,602,693 Size: 55,521 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr3:183,547,386-183,602,634 Size: 55,249 Coding Exon Count: 10
ID:PARL_HUMAN DESCRIPTION: RecName: Full=Presenilins-associated rhomboid-like protein, mitochondrial; EC=188.8.131.52; AltName: Full=Mitochondrial intramembrane cleaving protease PARL; Contains: RecName: Full=P-beta; Short=Pbeta; Flags: Precursor; 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 apoptoptic signals (By similarity). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain. CATALYTIC ACTIVITY: Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains. SUBUNIT: Interacts with PSEN1 and PSEN2. Binds OPA1. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: P-beta: Nucleus. Note=Translocated into the nucleus by an unknown mechanism. 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. SIMILARITY: Belongs to the peptidase S54 family.
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): PARL CDC HuGE Published Literature: PARL Positive Disease Associations: diabetes, type 2 Related Studies:
diabetes, type 2 M Hatunic , et al. Diabetes research and clinical practice 2009 83(3):316-9, The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population., Diabetes research and clinical practice 2009 83(3):316-9.
The Leu262Val polymorphism of PARL is not associated with markers of insulin resistance.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9H300
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.