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Protein

Presenilins-associated rhomboid-like protein, mitochondrial

Gene

PARL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain.By similarity2 Publications

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 sitei277NucleophileBy similarity1
Active sitei335By similarity1

GO - Molecular functioni

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

GO - Biological processi

  • membrane protein proteolysis Source: ParkinsonsUK-UCL
  • proteolysis Source: ParkinsonsUK-UCL
  • regulation of mitochondrion organization Source: ParkinsonsUK-UCL
  • regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • regulation of proteolysis Source: ParkinsonsUK-UCL
  • regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

ReactomeiR-HSA-8949664 Processing of SMDT1

Protein family/group databases

MEROPSiS54.009
TCDBi9.B.104.1.6 the rhomboid protease (rhomboid) family

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
ORF Names:PRO2207
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000175193.12
HGNCiHGNC:18253 PARL
MIMi607858 gene
neXtProtiNX_Q9H300

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini53 – 101Mitochondrial matrixSequence analysisAdd BLAST49
Transmembranei102 – 121HelicalSequence analysisAdd BLAST20
Topological domaini122 – 167Mitochondrial intermembraneSequence analysisAdd BLAST46
Transmembranei168 – 187HelicalSequence analysisAdd BLAST20
Topological domaini188 – 207Mitochondrial matrixSequence analysisAdd BLAST20
Transmembranei208 – 230HelicalSequence analysisAdd BLAST23
Topological domaini231 – 244Mitochondrial intermembraneSequence analysisAdd BLAST14
Transmembranei245 – 262HelicalSequence analysisAdd BLAST18
Topological domaini263 – 272Mitochondrial matrixSequence analysis10
Transmembranei273 – 289HelicalSequence analysisAdd BLAST17
Topological domaini290 – 295Mitochondrial intermembraneSequence analysis6
Transmembranei296 – 318HelicalSequence analysisAdd BLAST23
Topological domaini319 – 332Mitochondrial matrixSequence analysisAdd BLAST14
Transmembranei333 – 354HelicalSequence analysisAdd BLAST22
Topological domaini355 – 379Mitochondrial intermembraneSequence analysisAdd BLAST25

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65S → D: Strongly reduces the beta cleavage; when associated with D-69 and D-70. 1 Publication1
Mutagenesisi69T → D: Strongly reduces the beta cleavage; when associated with D-65 and D-70. 1 Publication1
Mutagenesisi70S → D: Strongly reduces the beta cleavage; when associated with D-65 and D-69. 1 Publication1
Mutagenesisi76R → E: Abolishes the beta cleavage. 1 Publication1
Mutagenesisi76R → G: Abolishes the beta cleavage. 1 Publication1
Mutagenesisi77S → E: Abolishes the beta cleavage. 1 Publication1
Mutagenesisi78A → E: Abolishes the beta cleavage. 1 Publication1
Mutagenesisi79L → E: Abolishes the beta cleavage. 1 Publication1

Organism-specific databases

DisGeNETi55486
OpenTargetsiENSG00000175193
PharmGKBiPA134939789

Polymorphism and mutation databases

BioMutaiPARL
DMDMi143811433

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 52Mitochondrion1 PublicationAdd BLAST52
ChainiPRO_000002738653 – 379Presenilins-associated rhomboid-like protein, mitochondrialAdd BLAST327
PeptideiPRO_000002738753 – 77P-beta1 PublicationAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei65Phosphoserine1 Publication1
Modified residuei69Phosphothreonine1 Publication1
Modified residuei70Phosphoserine1 Publication1

Post-translational modificationi

P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9H300
MaxQBiQ9H300
PaxDbiQ9H300
PeptideAtlasiQ9H300
PRIDEiQ9H300
ProteomicsDBi80637
80638 [Q9H300-2]

PTM databases

iPTMnetiQ9H300
PhosphoSitePlusiQ9H300

Miscellaneous databases

PMAP-CutDBiQ9H300

Expressioni

Gene expression databases

BgeeiENSG00000175193
CleanExiHS_PARL
ExpressionAtlasiQ9H300 baseline and differential
GenevisibleiQ9H300 HS

Organism-specific databases

HPAiHPA019545

Interactioni

Subunit structurei

Interacts with PSEN1 and PSEN2. Binds OPA1.1 Publication

Protein-protein interaction databases

BioGridi120678, 13 interactors
IntActiQ9H300, 1 interactor
STRINGi9606.ENSP00000325421

Structurei

3D structure databases

ProteinModelPortaliQ9H300
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
InParanoidiQ9H300
KOiK09650
OMAiHEMRTNS
OrthoDBiEOG091G0B3Z
PhylomeDBiQ9H300
TreeFamiTF313603

Family and domain databases

Gene3Di1.20.1540.10, 1 hit
InterProiView protein in InterPro
IPR022764 Peptidase_S54_rhomboid_dom
IPR035952 Rhomboid-like_sf
PfamiView protein in Pfam
PF01694 Rhomboid, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H300-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAWRGWAQRG WGCGQAWGAS VGGRSCEELT AVLTPPQLLG RRFNFFIQQK
60 70 80 90 100
CGFRKAPRKV EPRRSDPGTS GEAYKRSALI PPVEETVFYP SPYPIRSLIK
110 120 130 140 150
PLFFTVGFTG CAFGSAAIWQ YESLKSRVQS YFDGIKADWL DSIRPQKEGD
160 170 180 190 200
FRKEINKWWN NLSDGQRTVT GIIAANVLVF CLWRVPSLQR TMIRYFTSNP
210 220 230 240 250
ASKVLCSPML LSTFSHFSLF HMAANMYVLW SFSSSIVNIL GQEQFMAVYL
260 270 280 290 300
SAGVISNFVS YVGKVATGRY GPSLGASGAI MTVLAAVCTK IPEGRLAIIF
310 320 330 340 350
LPMFTFTAGN ALKAIIAMDT AGMILGWKFF DHAAHLGGAL FGIWYVTYGH
360 370
ELIWKNREPL VKIWHEIRTN GPKKGGGSK
Length:379
Mass (Da):42,190
Last modified:April 3, 2007 - v2
Checksum:i2B07EF04C7130B0B
GO
Isoform 2 (identifier: Q9H300-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     203-253: KVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAG → S

Show »
Length:329
Mass (Da):36,589
Checksum:i55E752160C632DBF
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029801137A → G. Corresponds to variant dbSNP:rs4912470Ensembl.1
Natural variantiVAR_021578262V → L2 PublicationsCorresponds to variant dbSNP:rs3732581Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013310203 – 253KVLCS…YLSAG → S in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF197937 mRNA Translation: AAG28519.1
BC003653 mRNA Translation: AAH03653.1
BC014058 mRNA Translation: AAH14058.1
AF116692 mRNA Translation: AAF71112.1
CCDSiCCDS3248.1 [Q9H300-1]
CCDS33897.1 [Q9H300-2]
RefSeqiNP_001032728.1, NM_001037639.2 [Q9H300-2]
NP_061092.3, NM_018622.6 [Q9H300-1]
UniGeneiHs.478469

Genome annotation databases

EnsembliENST00000311101; ENSP00000310676; ENSG00000175193 [Q9H300-2]
ENST00000317096; ENSP00000325421; ENSG00000175193 [Q9H300-1]
GeneIDi55486
KEGGihsa:55486
UCSCiuc003fmd.4 human [Q9H300-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPARL_HUMAN
AccessioniPrimary (citable) accession number: Q9H300
Secondary accession number(s): Q96CQ4, Q9BTJ6, Q9P1E3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 3, 2007
Last modified: June 20, 2018
This is version 145 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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