PARL_RAT
ID PARL_RAT Reviewed; 377 AA.
AC Q3B8P0; Q5I0L2;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Presenilins-associated rhomboid-like protein, mitochondrial;
DE EC=3.4.21.105 {ECO:0000250|UniProtKB:Q9H300};
DE AltName: Full=Mitochondrial intramembrane-cleaving protease PARL;
DE Contains:
DE RecName: Full=P-beta;
DE Short=Pbeta;
DE Flags: Precursor;
GN Name=Parl {ECO:0000250|UniProtKB:Q9H300};
GN Synonyms=Psarl {ECO:0000312|RGD:1306191};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAI05908.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver {ECO:0000312|EMBL:AAH88226.1}, and
RC Thymus {ECO:0000312|EMBL:AAI05908.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Required for the control of apoptosis during postnatal
CC growth. Essential for proteolytic processing of an antiapoptotic form
CC of OPA1 which prevents the release of mitochondrial cytochrome c in
CC response to intrinsic apoptotic signals (By similarity). Required for
CC the maturation of PINK1 into its 52kDa mature form after its cleavage
CC by mitochondrial-processing peptidase (MPP). Promotes changes in
CC mitochondria morphology regulated by phosphorylation of P-beta domain
CC (By similarity). {ECO:0000250|UniProtKB:Q5XJY4,
CC ECO:0000250|UniProtKB:Q9H300}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad
CC composed of serine and histidine that are contributed by different
CC transmembrane domains.; EC=3.4.21.105;
CC Evidence={ECO:0000250|UniProtKB:Q9H300};
CC -!- SUBUNIT: Interacts with PSEN1 and PSEN2. Binds OPA1 (By similarity).
CC {ECO:0000250|UniProtKB:Q5XJY4, ECO:0000250|UniProtKB:Q9H300}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9H300}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9H300}.
CC -!- SUBCELLULAR LOCATION: [P-beta]: Nucleus {ECO:0000250|UniProtKB:Q9H300}.
CC Note=Translocated into the nucleus by an unknown mechanism.
CC {ECO:0000250|UniProtKB:Q9H300}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15489334};
CC IsoId=Q3B8P0-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q3B8P0-2; Sequence=VSP_052185;
CC -!- PTM: P-beta is proteolytically processed (beta-cleavage) in a PARL-
CC dependent manner. {ECO:0000250|UniProtKB:Q9H300}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000255}.
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DR EMBL; BC088226; AAH88226.1; -; mRNA.
DR EMBL; BC105907; AAI05908.1; -; mRNA.
DR RefSeq; NP_001030326.1; NM_001035249.1. [Q3B8P0-1]
DR AlphaFoldDB; Q3B8P0; -.
DR STRING; 10116.ENSRNOP00000029124; -.
DR iPTMnet; Q3B8P0; -.
DR PhosphoSitePlus; Q3B8P0; -.
DR jPOST; Q3B8P0; -.
DR PRIDE; Q3B8P0; -.
DR GeneID; 287979; -.
DR KEGG; rno:287979; -.
DR CTD; 55486; -.
DR RGD; 1306191; Parl.
DR eggNOG; KOG2980; Eukaryota.
DR InParanoid; Q3B8P0; -.
DR PhylomeDB; Q3B8P0; -.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:Q3B8P0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0033619; P:membrane protein proteolysis; ISO:RGD.
DR GO; GO:0008053; P:mitochondrial fusion; ISO:RGD.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030182; P:neuron differentiation; IEP:RGD.
DR GO; GO:0006508; P:proteolysis; ISS:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:RGD.
DR GO; GO:0010821; P:regulation of mitochondrion organization; ISO:RGD.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; ISO:RGD.
DR GO; GO:0030162; P:regulation of proteolysis; ISO:RGD.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006465; P:signal peptide processing; IBA:GO_Central.
DR Gene3D; 1.20.1540.10; -; 1.
DR InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR InterPro; IPR035952; Rhomboid-like_sf.
DR Pfam; PF01694; Rhomboid; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Hydrolase; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Serine protease; Transit peptide; Transmembrane;
KW Transmembrane helix.
FT TRANSIT 1..50
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q9H300"
FT CHAIN 51..377
FT /note="Presenilins-associated rhomboid-like protein,
FT mitochondrial"
FT /id="PRO_0000257987"
FT PEPTIDE 51..75
FT /note="P-beta"
FT /evidence="ECO:0000250|UniProtKB:Q9H300"
FT /id="PRO_0000257988"
FT TOPO_DOM 51..95
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..165
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..214
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..242
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..268
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..293
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..331
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..377
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT ACT_SITE 275
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 333
FT /evidence="ECO:0000250"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H300"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H300"
FT VAR_SEQ 93..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052185"
SQ SEQUENCE 377 AA; 42126 MW; 4E27E9216BC0548C CRC64;
MALYSWVQRG WRCGQTWAPL LGGGYRELSA TQARQLLGRR FNLLLQQKCG FRKAPRKVEP
RRSDTGSSGE AYKRSALIPP LEETVFYPSP YPVRTLLKPF FFTVGFTGCA FGSAAIWQYE
SLKSRVQSYF DGIKADWLDS IRPQKEGNLR KEINKWWNSL SDGQRTVTGI IAANALVFCL
WRVPSLHRTM IRYFTSNPAS KVLCSPMLLS TFSHFSLFHM AANMYVLWSF STSIVNILGQ
EQFVAVYLSA GVISNFVSYV CKVATGRYGP SLGASGAIMT VLAAVCTKIP EGRLAIIFLP
VFTFTAGNAL KAIIAMDTAG MILGWKFFDH AAHLGGALFG IWYITYGHEL IWKNREPLVK
IWHEIRTNGP KKGGGSK
