ID   PARL_MOUSE              Reviewed;         377 AA.
AC   Q5XJY4; Q3U9T5; Q641T5;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   27-MAR-2024, entry version 154.
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; Synonyms=Psarl;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryonic stem cell;
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).
RN   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH OPA, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=16839884; DOI=10.1016/j.cell.2006.06.021;
RA   Cipolat S., Rudka T., Hartmann D., Costa V., Serneels L., Craessaerts K.,
RA   Metzger K., Frezza C., Annaert W., D'Adamio L., Derks C., Dejaegere T.,
RA   Pellegrini L., D'Hooge R., Scorrano L., De Strooper B.;
RT   "Mitochondrial rhomboid PARL regulates cytochrome c release during
RT   apoptosis via OPA1-dependent cristae remodeling.";
RL   Cell 126:163-175(2006).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Required for the control of apoptosis during postnatal growth
CC       (PubMed:16839884). Essential for proteolytic processing of an
CC       antiapoptotic form of OPA1 which prevents the release of mitochondrial
CC       cytochrome c in response to intrinsic apoptotic signals
CC       (PubMed:16839884). Required for the maturation of PINK1 into its 52kDa
CC       mature form after its cleavage by mitochondrial-processing peptidase
CC       (MPP) (By similarity). Promotes cleavage of serine/threonine-protein
CC       phosphatase PGAM5 in damaged mitochondria in response to loss of
CC       mitochondrial membrane potential (By similarity). Mediates differential
CC       cleavage of PINK1 and PGAM5 depending on the health status of
CC       mitochondria, disassociating from PINK1 and associating with PGAM5 in
CC       response to mitochondrial membrane potential loss (By similarity).
CC       Required for processing of CLPB into a form with higher protein
CC       disaggregase activity by removing an autoinhibitory N-terminal peptide
CC       (By similarity). Promotes processing of DIABLO/SMAC in the
CC       mitochondrion which is required for DIABLO apoptotic activity (By
CC       similarity). Also required for cleavage of STARD7 and TTC19 (By
CC       similarity). Promotes changes in mitochondria morphology regulated by
CC       phosphorylation of P-beta domain (By similarity).
CC       {ECO:0000250|UniProtKB:Q9H300, ECO:0000269|PubMed:16839884}.
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 (By similarity). Binds OPA1.
CC       {ECO:0000250, ECO:0000269|PubMed:16839884}.
CC   -!- INTERACTION:
CC       Q5XJY4; O35387: Hax1; NbExp=2; IntAct=EBI-5395457, EBI-642449;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:16839884}; 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 (By
CC       similarity). {ECO:0000250|UniProtKB:Q9H300}.
CC   -!- PTM: P-beta is proteolytically processed (beta-cleavage) in a PARL-
CC       dependent manner. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Mice develop normally until 4 weeks of age. They
CC       show subsequent progressive growth retardation, atrophy of muscle,
CC       spleen, and thymus as well as severe apoptosis of T and B lymphocytes
CC       leading to premature death between 8-12 weeks of age. Mouse embryonic
CC       fibroblasts lacking Parl show high susceptibility to intrinsic
CC       apoptotic signals. This defect can be complemented by Parl or a soluble
CC       form of Opa1. {ECO:0000269|PubMed:16839884}.
CC   -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
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DR   EMBL; AK151652; BAE30581.1; -; mRNA.
DR   EMBL; BC083153; AAH83153.1; -; mRNA.
DR   CCDS; CCDS28044.1; -.
DR   RefSeq; NP_001005767.1; NM_001005767.4.
DR   AlphaFoldDB; Q5XJY4; -.
DR   SMR; Q5XJY4; -.
DR   BioGRID; 237750; 1.
DR   DIP; DIP-59825N; -.
DR   IntAct; Q5XJY4; 2.
DR   STRING; 10090.ENSMUSP00000045361; -.
DR   ChEMBL; CHEMBL3259502; -.
DR   PhosphoSitePlus; Q5XJY4; -.
DR   EPD; Q5XJY4; -.
DR   jPOST; Q5XJY4; -.
DR   MaxQB; Q5XJY4; -.
DR   PaxDb; 10090-ENSMUSP00000045361; -.
DR   ProteomicsDB; 294014; -.
DR   Pumba; Q5XJY4; -.
DR   DNASU; 381038; -.
DR   Ensembl; ENSMUST00000048642.15; ENSMUSP00000045361.9; ENSMUSG00000033918.17.
DR   GeneID; 381038; -.
DR   KEGG; mmu:381038; -.
DR   UCSC; uc007ypm.1; mouse.
DR   AGR; MGI:1277152; -.
DR   CTD; 55486; -.
DR   MGI; MGI:1277152; Parl.
DR   VEuPathDB; HostDB:ENSMUSG00000033918; -.
DR   eggNOG; KOG2980; Eukaryota.
DR   GeneTree; ENSGT00390000013063; -.
DR   HOGENOM; CLU_034022_0_1_1; -.
DR   InParanoid; Q5XJY4; -.
DR   OMA; WHEMRTR; -.
DR   OrthoDB; 2910971at2759; -.
DR   PhylomeDB; Q5XJY4; -.
DR   TreeFam; TF313603; -.
DR   Reactome; R-MMU-8949664; Processing of SMDT1.
DR   BioGRID-ORCS; 381038; 4 hits in 77 CRISPR screens.
DR   ChiTaRS; Parl; mouse.
DR   PRO; PR:Q5XJY4; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; Q5XJY4; Protein.
DR   Bgee; ENSMUSG00000033918; Expressed in primary oocyte and 125 other cell types or tissues.
DR   ExpressionAtlas; Q5XJY4; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IMP:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004175; F:endopeptidase activity; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0033619; P:membrane protein proteolysis; ISO:MGI.
DR   GO; GO:0008053; P:mitochondrial fusion; IMP:UniProtKB.
DR   GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR   GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR   GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0010821; P:regulation of mitochondrion organization; ISO:MGI.
DR   GO; GO:1901524; P:regulation of mitophagy; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1903214; P:regulation of protein targeting to mitochondrion; ISO:MGI.
DR   GO; GO:0030162; P:regulation of proteolysis; ISO:MGI.
DR   GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:MGI.
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   1: Evidence at protein level;
KW   Hydrolase; Membrane; Mitochondrion; Mitochondrion inner membrane; Nucleus;
KW   Phosphoprotein; Protease; Reference proteome; Serine protease;
KW   Transit peptide; Transmembrane; Transmembrane helix.
FT   TRANSIT         1..50
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           51..377
FT                   /note="Presenilin-associated rhomboid-like protein,
FT                   mitochondrial"
FT                   /id="PRO_0000027388"
FT   PEPTIDE         51..75
FT                   /note="P-beta"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000027389"
FT   TOPO_DOM        51..99
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        100..119
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        120..165
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        166..185
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        186..205
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        206..228
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        229..242
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        243..260
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        261..270
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        271..287
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        288..293
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        294..316
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        317..330
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        331..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"
SQ   SEQUENCE   377 AA;  41964 MW;  41C81310031A2EC4 CRC64;
     MALQGWVQRG WRCGPAWAPP LGGGYRELSA TQAPRLLGRR FNLFVQQKCG FRKAPRKVEP
     RRSDTGSSGE AYKRSALIPP LEETVFYPSP YPIRTLVKPF FFTIGFTGCA FGSAAIWQYE
     SLKSRVQSYF DGIKADWLDS IRPQKEGNLR KEINKWWNSL SDGQRTVTGI IAANALVFCL
     WRVPSLQRTM IRYFTSNPAS KVLCSPMLLS TFSHFSLFHM AANMYVLWSF SSSIVNILGQ
     EQFVAVYLSA GVISNFVSYV CKVATGRYGP SLGASGAIMT VLAAVCTKIP EGRLAIIFLP
     VFTFTAGNAL KAIIAMDTAG MILGWKFFDH AAHLGGALFG IWYITYGHEL IWKNREPLVK
     IWHEIRTNGP KKGGGSK
//