PARL_DROME
ID PARL_DROME Reviewed; 351 AA.
AC A1Z8R8; Q8MQY3;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Presenilins-associated rhomboid-like protein, mitochondrial {ECO:0000250|UniProtKB:Q5XJY4};
DE EC=3.4.21.105 {ECO:0000250|UniProtKB:P20350};
DE AltName: Full=Mitochondrial intramembrane-cleaving protease Parl {ECO:0000250|UniProtKB:Q5XJY4};
DE AltName: Full=Rhomboid-7 {ECO:0000303|PubMed:16713954};
DE Flags: Precursor;
GN Name=rho-7 {ECO:0000312|FlyBase:FBgn0033672};
GN Synonyms=Parl {ECO:0000250|UniProtKB:Q5XJY4},
GN R7 {ECO:0000303|PubMed:19048081};
GN ORFNames=CG8972 {ECO:0000312|FlyBase:FBgn0033672};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM52748.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM52748.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAM52748.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16713954; DOI=10.1016/j.cub.2006.03.062;
RA McQuibban G.A., Lee J.R., Zheng L., Juusola M., Freeman M.;
RT "Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila
RT lifespan and neuronal function.";
RL Curr. Biol. 16:982-989(2006).
RN [5] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH PINK1 AND HTRA2.
RX PubMed=19048081; DOI=10.1242/dmm.000109;
RA Whitworth A.J., Lee J.R., Ho V.M., Flick R., Chowdhury R., McQuibban G.A.;
RT "Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's
RT disease factors Pink1 and Parkin.";
RL Dis. Model. Mech. 1:168-174(2008).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=21945938; DOI=10.1016/j.bbrc.2011.09.047;
RA Rahman M., Kylsten P.;
RT "Rhomboid-7 over-expression results in Opa1-like processing and
RT malfunctioning mitochondria.";
RL Biochem. Biophys. Res. Commun. 414:315-320(2011).
CC -!- FUNCTION: Mitochondrial intramembrane protease which plays a critical
CC role in the regulation of mitochondrial function (PubMed:16713954,
CC PubMed:21945938). Essential for mitochondrial development and fusion
CC during spermatogenesis and the development of neurons and muscles
CC (PubMed:16713954, PubMed:21945938). Essential for proteolytic
CC processing of Pink1 and HtrA2 into their mature forms
CC (PubMed:19048081). May also be involved, but not required, for the
CC proteolytic processing of Opa1 (PubMed:19048081, PubMed:21945938).
CC {ECO:0000269|PubMed:16713954, ECO:0000269|PubMed:19048081,
CC ECO:0000269|PubMed:21945938}.
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:P20350};
CC -!- SUBUNIT: Interacts with Pink1 and HtrA2. {ECO:0000269|PubMed:19048081}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:16713954}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Lethal with most dying before pupation
CC (PubMed:16713954). Mitochondria in the testis and skeletal muscles
CC display morphological defects indicative of defective mitochondrial
CC fusion (PubMed:16713954). The few escapers that survive to adulthood,
CC display neurological defects, male sterility, and do not survive for
CC longer than three days (PubMed:16713954). Also displays photoreceptor
CC degeneration after prolonged light stimulation and abnormal
CC photoreceptor synaptic function which specifically affects both the
CC generation of light responses and the signal transfer across the first
CC visual synapse (PubMed:16713954). {ECO:0000269|PubMed:16713954}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM52748.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF58598.1; -; Genomic_DNA.
DR EMBL; AE013599; AHN56122.1; -; Genomic_DNA.
DR EMBL; AY122236; AAM52748.1; ALT_INIT; mRNA.
DR RefSeq; NP_001286324.1; NM_001299395.1.
DR RefSeq; NP_523704.1; NM_078980.4.
DR AlphaFoldDB; A1Z8R8; -.
DR STRING; 7227.FBpp0087151; -.
DR MEROPS; S54.A12; -.
DR PaxDb; A1Z8R8; -.
DR PRIDE; A1Z8R8; -.
DR DNASU; 36281; -.
DR EnsemblMetazoa; FBtr0088045; FBpp0087151; FBgn0033672.
DR EnsemblMetazoa; FBtr0339555; FBpp0308636; FBgn0033672.
DR GeneID; 36281; -.
DR KEGG; dme:Dmel_CG8972; -.
DR UCSC; CG8972-RA; d. melanogaster.
DR CTD; 36281; -.
DR FlyBase; FBgn0033672; rho-7.
DR VEuPathDB; VectorBase:FBgn0033672; -.
DR eggNOG; KOG2980; Eukaryota.
DR GeneTree; ENSGT00390000013063; -.
DR HOGENOM; CLU_034022_0_0_1; -.
DR InParanoid; A1Z8R8; -.
DR OMA; HYSAMHI; -.
DR OrthoDB; 1554324at2759; -.
DR PhylomeDB; A1Z8R8; -.
DR BioGRID-ORCS; 36281; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36281; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033672; Expressed in capitellum (Drosophila) and 27 other tissues.
DR ExpressionAtlas; A1Z8R8; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IMP:FlyBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008053; P:mitochondrial fusion; IMP:FlyBase.
DR GO; GO:0016485; P:protein processing; IMP:FlyBase.
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;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..50
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 51..351
FT /note="Presenilins-associated rhomboid-like protein,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000451457"
FT TOPO_DOM 51..73
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..146
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..182
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..223
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..247
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..276
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..311
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..351
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT REGION 39..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 256
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P20350"
FT ACT_SITE 314
FT /evidence="ECO:0000250|UniProtKB:P20350"
SQ SEQUENCE 351 AA; 38932 MW; CE9E774868BA30A8 CRC64;
MLMSRALCRS WLPQVARRCH ANVNVPILRI NSGHPAARSC RQIHSNRKQS SNLKPTTGEP
AAAEQNTPVP VNNVIKAVAF TGAFTVGCFA GATILEYENT RSLILEKARQ ARFGWWQSRS
LADRDYWTQI KQDIRRHWDS LTPGDKMFAP ILLCNLVAFA MWRVPALKST MITYFTSNPA
AKVVCWPMFL STFSHYSAMH LFANMYVMHS FANAAAVSLG KEQFLAVYLS AGVFSSLMSV
LYKAATSQAG MSLGASGAIM TLLAYVCTQY PDTQLSILFL PALTFSAGAG IKVLMGIDFA
GVVMGWKFFD HAAHLGGAMF GIFWATYGAQ IWAKRIGLLN YYHDLRRTKQ K
