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Protein

Presenilins-associated rhomboid-like protein, mitochondrial

Gene

Parl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptoptic signals (By similarity).By similarity1 Publication

Catalytic activityi

Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei275NucleophileBy similarity1
Active sitei333By similarity1

GO - Molecular functioni

  • endopeptidase activity Source: ParkinsonsUK-UCL
  • serine-type endopeptidase activity Source: GO_Central

GO - Biological processi

  • negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • protein processing Source: GO_Central
  • proteolysis Source: ParkinsonsUK-UCL
  • regulation of mitochondrion organization Source: MGI
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • regulation of protein targeting to mitochondrion Source: MGI
  • regulation of proteolysis Source: MGI
  • regulation of reactive oxygen species metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Names & Taxonomyi

Protein namesi
Recommended name:
Presenilins-associated rhomboid-like protein, mitochondrial (EC:3.4.21.105)
Alternative name(s):
Mitochondrial intramembrane-cleaving protease PARL
Cleaved into the following chain:
P-beta
Short name:
Pbeta
Gene namesi
Name:Parl
Synonyms:Psarl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1277152. Parl.

Subcellular locationi

P-beta :
  • Nucleus By similarity

  • Note: Translocated into the nucleus by an unknown mechanism (By similarity).By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini51 – 99Mitochondrial matrixSequence analysisAdd BLAST49
Transmembranei100 – 119HelicalSequence analysisAdd BLAST20
Topological domaini120 – 165Mitochondrial intermembraneSequence analysisAdd BLAST46
Transmembranei166 – 185HelicalSequence analysisAdd BLAST20
Topological domaini186 – 205Mitochondrial matrixSequence analysisAdd BLAST20
Transmembranei206 – 228HelicalSequence analysisAdd BLAST23
Topological domaini229 – 242Mitochondrial intermembraneSequence analysisAdd BLAST14
Transmembranei243 – 260HelicalSequence analysisAdd BLAST18
Topological domaini261 – 270Mitochondrial matrixSequence analysis10
Transmembranei271 – 287HelicalSequence analysisAdd BLAST17
Topological domaini288 – 293Mitochondrial intermembraneSequence analysis6
Transmembranei294 – 316HelicalSequence analysisAdd BLAST23
Topological domaini317 – 330Mitochondrial matrixSequence analysisAdd BLAST14
Transmembranei331 – 352HelicalSequence analysisAdd BLAST22
Topological domaini353 – 377Mitochondrial intermembraneSequence analysisAdd BLAST25

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrion Source: MGI
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop normally until 4 weeks of age. They show subsequent progressive growth retardation, atrophy of muscle, spleen, and thymus as well as severe apoptosis of T and B lymphocytes leading to premature death between 8-12 weeks of age. Mouse embryonic fibroblasts lacking Parl show high susceptibility to intrinsic apoptotic signals. This defect can be complemented by Parl or a soluble form of Opa1.1 Publication

Chemistry databases

ChEMBLiCHEMBL3259502.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 50MitochondrionBy similarityAdd BLAST50
ChainiPRO_000002738851 – 377Presenilins-associated rhomboid-like protein, mitochondrialAdd BLAST327
PeptideiPRO_000002738951 – 75P-betaBy similarityAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei63PhosphoserineBy similarity1
Modified residuei68PhosphoserineBy similarity1

Post-translational modificationi

P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5XJY4.
MaxQBiQ5XJY4.
PaxDbiQ5XJY4.
PRIDEiQ5XJY4.

PTM databases

PhosphoSitePlusiQ5XJY4.

Expressioni

Gene expression databases

BgeeiENSMUSG00000033918.
CleanExiMM_PARL.
ExpressionAtlasiQ5XJY4. baseline and differential.

Interactioni

Subunit structurei

Interacts with PSEN1 and PSEN2 (By similarity). Binds OPA1.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-59825N.
IntActiQ5XJY4. 1 interactor.
STRINGi10090.ENSMUSP00000045361.

Structurei

3D structure databases

ProteinModelPortaliQ5XJY4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase S54 family.Curated

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2980. Eukaryota.
COG0705. LUCA.
GeneTreeiENSGT00390000013063.
HOGENOMiHOG000230670.
HOVERGENiHBG082107.
InParanoidiQ5XJY4.
KOiK09650.
OMAiHEMRTNS.
OrthoDBiEOG091G0B3Z.
PhylomeDBiQ5XJY4.
TreeFamiTF313603.

Family and domain databases

Gene3Di1.20.1540.10. 1 hit.
InterProiIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
[Graphical view]
PANTHERiPTHR22936. PTHR22936. 1 hit.
PfamiPF01694. Rhomboid. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q5XJY4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALQGWVQRG WRCGPAWAPP LGGGYRELSA TQAPRLLGRR FNLFVQQKCG
60 70 80 90 100
FRKAPRKVEP RRSDTGSSGE AYKRSALIPP LEETVFYPSP YPIRTLVKPF
110 120 130 140 150
FFTIGFTGCA FGSAAIWQYE SLKSRVQSYF DGIKADWLDS IRPQKEGNLR
160 170 180 190 200
KEINKWWNSL SDGQRTVTGI IAANALVFCL WRVPSLQRTM IRYFTSNPAS
210 220 230 240 250
KVLCSPMLLS TFSHFSLFHM AANMYVLWSF SSSIVNILGQ EQFVAVYLSA
260 270 280 290 300
GVISNFVSYV CKVATGRYGP SLGASGAIMT VLAAVCTKIP EGRLAIIFLP
310 320 330 340 350
VFTFTAGNAL KAIIAMDTAG MILGWKFFDH AAHLGGALFG IWYITYGHEL
360 370
IWKNREPLVK IWHEIRTNGP KKGGGSK
Length:377
Mass (Da):41,964
Last modified:November 23, 2004 - v1
Checksum:i41C81310031A2EC4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK151652 mRNA. Translation: BAE30581.1.
BC083153 mRNA. Translation: AAH83153.1.
CCDSiCCDS28044.1.
RefSeqiNP_001005767.1. NM_001005767.4.
UniGeneiMm.371737.

Genome annotation databases

EnsembliENSMUST00000048642; ENSMUSP00000045361; ENSMUSG00000033918.
GeneIDi381038.
KEGGimmu:381038.
UCSCiuc007ypm.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK151652 mRNA. Translation: BAE30581.1.
BC083153 mRNA. Translation: AAH83153.1.
CCDSiCCDS28044.1.
RefSeqiNP_001005767.1. NM_001005767.4.
UniGeneiMm.371737.

3D structure databases

ProteinModelPortaliQ5XJY4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59825N.
IntActiQ5XJY4. 1 interactor.
STRINGi10090.ENSMUSP00000045361.

Chemistry databases

ChEMBLiCHEMBL3259502.

PTM databases

PhosphoSitePlusiQ5XJY4.

Proteomic databases

EPDiQ5XJY4.
MaxQBiQ5XJY4.
PaxDbiQ5XJY4.
PRIDEiQ5XJY4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048642; ENSMUSP00000045361; ENSMUSG00000033918.
GeneIDi381038.
KEGGimmu:381038.
UCSCiuc007ypm.1. mouse.

Organism-specific databases

CTDi55486.
MGIiMGI:1277152. Parl.

Phylogenomic databases

eggNOGiKOG2980. Eukaryota.
COG0705. LUCA.
GeneTreeiENSGT00390000013063.
HOGENOMiHOG000230670.
HOVERGENiHBG082107.
InParanoidiQ5XJY4.
KOiK09650.
OMAiHEMRTNS.
OrthoDBiEOG091G0B3Z.
PhylomeDBiQ5XJY4.
TreeFamiTF313603.

Miscellaneous databases

PROiQ5XJY4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000033918.
CleanExiMM_PARL.
ExpressionAtlasiQ5XJY4. baseline and differential.

Family and domain databases

Gene3Di1.20.1540.10. 1 hit.
InterProiIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
[Graphical view]
PANTHERiPTHR22936. PTHR22936. 1 hit.
PfamiPF01694. Rhomboid. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPARL_MOUSE
AccessioniPrimary (citable) accession number: Q5XJY4
Secondary accession number(s): Q3U9T5, Q641T5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: November 23, 2004
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.