PARL_MOUSE
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 03-AUG-2022, entry version 146.
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; 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 changes in mitochondria morphology
CC regulated by 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 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; Q5XJY4; -.
DR PRIDE; Q5XJY4; -.
DR ProteomicsDB; 294014; -.
DR DNASU; 381038; -.
DR Ensembl; ENSMUST00000048642; ENSMUSP00000045361; ENSMUSG00000033918.
DR GeneID; 381038; -.
DR KEGG; mmu:381038; -.
DR UCSC; uc007ypm.1; mouse.
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; WRCWARA; -.
DR OrthoDB; 1554324at2759; -.
DR PhylomeDB; Q5XJY4; -.
DR TreeFam; TF313603; -.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 381038; 4 hits in 72 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 122 other tissues.
DR ExpressionAtlas; Q5XJY4; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IMP:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
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:0006508; P:proteolysis; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010821; P:regulation of mitochondrion organization; ISO:MGI.
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; -; 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 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="Presenilins-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
