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   27-MAR-2024, entry version 120.
DE   RecName: Full=Presenilin-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 Thymus
RC   {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. Required for the maturation of
CC       PINK1 into its 52kDa mature form after its cleavage by mitochondrial-
CC       processing peptidase (MPP). Promotes cleavage of serine/threonine-
CC       protein phosphatase PGAM5 in damaged mitochondria in response to loss
CC       of mitochondrial membrane potential. Mediates differential cleavage of
CC       PINK1 and PGAM5 depending on the health status of mitochondria,
CC       disassociating from PINK1 and associating with PGAM5 in response to
CC       mitochondrial membrane potential loss. Required for processing of CLPB
CC       into a form with higher protein disaggregase activity by removing an
CC       autoinhibitory N-terminal peptide. Promotes processing of DIABLO/SMAC
CC       in the mitochondrion which is required for DIABLO apoptotic activity.
CC       Also required for cleavage of STARD7 and TTC19. Promotes changes in
CC       mitochondria morphology regulated by phosphorylation of P-beta domain.
CC       {ECO:0000250|UniProtKB:Q5XJY4, 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   SMR; Q3B8P0; -.
DR   STRING; 10116.ENSRNOP00000029124; -.
DR   iPTMnet; Q3B8P0; -.
DR   PhosphoSitePlus; Q3B8P0; -.
DR   jPOST; Q3B8P0; -.
DR   PaxDb; 10116-ENSRNOP00000029124; -.
DR   GeneID; 287979; -.
DR   KEGG; rno:287979; -.
DR   AGR; RGD:1306191; -.
DR   CTD; 55486; -.
DR   RGD; 1306191; Parl.
DR   eggNOG; KOG2980; Eukaryota.
DR   InParanoid; Q3B8P0; -.
DR   OrthoDB; 2910971at2759; -.
DR   PhylomeDB; Q3B8P0; -.
DR   Reactome; R-RNO-8949664; Processing of SMDT1.
DR   PRO; PR:Q3B8P0; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004175; F:endopeptidase activity; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
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:0016485; P:protein processing; ISS:UniProtKB.
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; Rhomboid-like; 1.
DR   InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR   InterPro; IPR035952; Rhomboid-like_sf.
DR   PANTHER; PTHR43731:SF31; PRESENILINS-ASSOCIATED RHOMBOID-LIKE PROTEIN, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR43731; RHOMBOID PROTEASE; 1.
DR   Pfam; PF01694; Rhomboid; 1.
DR   SUPFAM; SSF144091; Rhomboid-like; 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="Presenilin-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
//