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Q9H300 (PARL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. P-beta
    Short name=Pbeta
Gene names
Name:PARL
Synonyms:PSARL
ORF Names:PRO2207
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length379 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5

Catalytic activity

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

Subunit structure

Interacts with PSEN1 and PSEN2. Binds OPA1. Ref.1

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein Ref.5.

P-beta: Nucleus. Note: Translocated into the nucleus by an unknown mechanism. Ref.5

Post-translational modification

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. Ref.5

Sequence similarities

Belongs to the peptidase S54 family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H300-1)

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.
Isoform 2 (identifier: Q9H300-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5252Mitochondrion Ref.4
Chain53 – 379327Presenilins-associated rhomboid-like protein, mitochondrial
PRO_0000027386
Peptide53 – 7725P-beta
PRO_0000027387

Regions

Topological domain53 – 10149Mitochondrial matrix Potential
Transmembrane102 – 12120Helical; Potential
Topological domain122 – 16746Mitochondrial intermembrane Potential
Transmembrane168 – 18720Helical; Potential
Topological domain188 – 20720Mitochondrial matrix Potential
Transmembrane208 – 23023Helical; Potential
Topological domain231 – 24414Mitochondrial intermembrane Potential
Transmembrane245 – 26218Helical; Potential
Topological domain263 – 27210Mitochondrial matrix Potential
Transmembrane273 – 28917Helical; Potential
Topological domain290 – 2956Mitochondrial intermembrane Potential
Transmembrane296 – 31823Helical; Potential
Topological domain319 – 33214Mitochondrial matrix Potential
Transmembrane333 – 35422Helical; Potential
Topological domain355 – 37925Mitochondrial intermembrane Potential

Sites

Active site2771Nucleophile By similarity
Active site3351 By similarity

Amino acid modifications

Modified residue651Phosphoserine Ref.5
Modified residue691Phosphothreonine Ref.5
Modified residue701Phosphoserine Ref.5

Natural variations

Alternative sequence203 – 25351KVLCS…YLSAG → S in isoform 2.
VSP_013310
Natural variant1371A → G.
Corresponds to variant rs4912470 [ dbSNP | Ensembl ].
VAR_029801
Natural variant2621V → L. Ref.1 Ref.3
Corresponds to variant rs3732581 [ dbSNP | Ensembl ].
VAR_021578

Experimental info

Mutagenesis651S → D: Strongly reduces the beta cleavage; when associated with D-69 and D-70. Ref.5
Mutagenesis691T → D: Strongly reduces the beta cleavage; when associated with D-65 and D-70. Ref.5
Mutagenesis701S → D: Strongly reduces the beta cleavage; when associated with D-65 and D-69. Ref.5
Mutagenesis761R → E: Abolishes the beta cleavage. Ref.4
Mutagenesis761R → G: Abolishes the beta cleavage. Ref.4
Mutagenesis771S → E: Abolishes the beta cleavage. Ref.4
Mutagenesis781A → E: Abolishes the beta cleavage. Ref.4
Mutagenesis791L → E: Abolishes the beta cleavage. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: 2B07EF04C7130B0B

FASTA37942,190
        10         20         30         40         50         60 
MAWRGWAQRG WGCGQAWGAS VGGRSCEELT AVLTPPQLLG RRFNFFIQQK CGFRKAPRKV 

        70         80         90        100        110        120 
EPRRSDPGTS GEAYKRSALI PPVEETVFYP SPYPIRSLIK PLFFTVGFTG CAFGSAAIWQ 

       130        140        150        160        170        180 
YESLKSRVQS YFDGIKADWL DSIRPQKEGD FRKEINKWWN NLSDGQRTVT GIIAANVLVF 

       190        200        210        220        230        240 
CLWRVPSLQR TMIRYFTSNP ASKVLCSPML LSTFSHFSLF HMAANMYVLW SFSSSIVNIL 

       250        260        270        280        290        300 
GQEQFMAVYL SAGVISNFVS YVGKVATGRY GPSLGASGAI MTVLAAVCTK IPEGRLAIIF 

       310        320        330        340        350        360 
LPMFTFTAGN ALKAIIAMDT AGMILGWKFF DHAAHLGGAL FGIWYVTYGH ELIWKNREPL 

       370 
VKIWHEIRTN GPKKGGGSK 

« Hide

Isoform 2 [UniParc].

Checksum: 55E752160C632DBF
Show »

FASTA32936,589

References

« Hide 'large scale' references
[1]"PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of presenilin-1 and -2."
Pellegrini L., Passer B.J., Canelles M., Lefterov I., Ganjei J.K., Fowlkes B.J., Koonin E.V., D'Adamio L.
J. Alzheimers Dis. 3:181-190(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-262, INTERACTION WITH PSEN1 AND PSEN2.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Lung.
[3]"Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver."
Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., Liu M., He F.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 192-379 (ISOFORM 1), VARIANT LEU-262.
Tissue: Fetal liver.
[4]"Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide."
Sik A., Passer B.J., Koonin E.V., Pellegrini L.
J. Biol. Chem. 279:15323-15329(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 53-61 AND 78-85, FUNCTION IN BETA CLEAVAGE, MUTAGENESIS OF ARG-76; SER-77; ALA-78 AND LEU-79.
[5]"Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology."
Jeyaraju D.V., Xu L., Letellier M.-C., Bandaru S., Zunino R., Berg E.A., McBride H.M., Pellegrini L.
Proc. Natl. Acad. Sci. U.S.A. 103:18562-18567(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-65; THR-69 AND SER-70 OF P-BETA, MUTAGENESIS OF SER-65; THR-69 AND SER-70, SUBCELLULAR LOCATION, TOPOLOGY, BETA-CLEAVAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF197937 mRNA. Translation: AAG28519.1.
BC003653 mRNA. Translation: AAH03653.1.
BC014058 mRNA. Translation: AAH14058.1.
AF116692 mRNA. Translation: AAF71112.1.
CCDSCCDS3248.1. [Q9H300-1]
CCDS33897.1. [Q9H300-2]
RefSeqNP_001032728.1. NM_001037639.1. [Q9H300-2]
NP_061092.3. NM_018622.5. [Q9H300-1]
UniGeneHs.478469.

3D structure databases

ProteinModelPortalQ9H300.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120678. 2 interactions.
STRING9606.ENSP00000325421.

Protein family/group databases

MEROPSS54.009.

PTM databases

PhosphoSiteQ9H300.

Polymorphism databases

DMDM143811433.

Proteomic databases

MaxQBQ9H300.
PaxDbQ9H300.
PRIDEQ9H300.

Protocols and materials databases

DNASU55486.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311101; ENSP00000310676; ENSG00000175193. [Q9H300-2]
ENST00000317096; ENSP00000325421; ENSG00000175193. [Q9H300-1]
GeneID55486.
KEGGhsa:55486.
UCSCuc003fmd.3. human. [Q9H300-1]
uc003fme.3. human. [Q9H300-2]

Organism-specific databases

CTD55486.
GeneCardsGC03M183547.
HGNCHGNC:18253. PARL.
HPAHPA019545.
MIM607858. gene.
neXtProtNX_Q9H300.
PharmGKBPA134939789.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0705.
HOGENOMHOG000230670.
HOVERGENHBG082107.
InParanoidQ9H300.
KOK09650.
OMAHEMRTNS.
OrthoDBEOG7NGQBT.
PhylomeDBQ9H300.
TreeFamTF313603.

Gene expression databases

ArrayExpressQ9H300.
BgeeQ9H300.
CleanExHS_PARL.
GenevestigatorQ9H300.

Family and domain databases

Gene3D1.20.1540.10. 1 hit.
InterProIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
[Graphical view]
PANTHERPTHR22936. PTHR22936. 1 hit.
PfamPF01694. Rhomboid. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPARL.
GenomeRNAi55486.
NextBio59867.
PMAP-CutDBQ9H300.
PROQ9H300.
SOURCESearch...

Entry information

Entry namePARL_HUMAN
AccessionPrimary (citable) accession number: Q9H300
Secondary accession number(s): Q96CQ4, Q9BTJ6, Q9P1E3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 3, 2007
Last modified: July 9, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM