Human Gene PARL (uc003fmd.3) Description and Page Index
  Description: Homo sapiens presenilin associated, rhomboid-like (PARL), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA.
RefSeq Summary (NM_018622): This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016].
Transcript (Including UTRs)
   Position: hg19 chr3:183,547,173-183,602,693 Size: 55,521 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr3:183,547,386-183,602,634 Size: 55,249 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr3:183,547,173-183,602,693)mRNA (may differ from genome)Protein (379 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Presenilins-associated rhomboid-like protein, mitochondrial; EC=; AltName: Full=Mitochondrial intramembrane cleaving protease PARL; Contains: RecName: Full=P-beta; Short=Pbeta; Flags: Precursor;
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.
CATALYTIC ACTIVITY: Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.
SUBUNIT: Interacts with PSEN1 and PSEN2. Binds OPA1.
SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein.
SUBCELLULAR LOCATION: P-beta: Nucleus. Note=Translocated into the nucleus by an unknown mechanism.
PTM: 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.
SIMILARITY: Belongs to the peptidase S54 family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PARL
CDC HuGE Published Literature: PARL
Positive Disease Associations: diabetes, type 2
Related Studies:
  1. diabetes, type 2
    M Hatunic , et al. Diabetes research and clinical practice 2009 83(3):316-9, The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population., Diabetes research and clinical practice 2009 83(3):316-9. [PubMed 19185381]
    The Leu262Val polymorphism of PARL is not associated with markers of insulin resistance.

-  MalaCards Disease Associations
  MalaCards Gene Search: PARL
Diseases sorted by gene-association score: primary angle-closure glaucoma (8), spastic paraplegia 7, autosomal recessive (7), leber optic atrophy (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 31.06 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 1173.96 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -13.9059-0.236 Picture PostScript Text
3' UTR -59.90213-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002610 - Peptidase_S54_rhomboid
IPR022764 - Peptidase_S54_rhomboid_dom

Pfam Domains:
PF01694 - Rhomboid family

ModBase Predicted Comparative 3D Structure on Q9H300
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene Details  Gene DetailsGene DetailsGene Details
Gene Sorter  Gene SorterGene SorterGene Sorter
  Protein SequenceProtein SequenceProtein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0006508 proteolysis
GO:0010821 regulation of mitochondrion organization
GO:0030162 regulation of proteolysis
GO:0033619 membrane protein proteolysis
GO:1903214 regulation of protein targeting to mitochondrion
GO:2000377 regulation of reactive oxygen species metabolic process

Cellular Component:
GO:0005634 nucleus
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  AK024765 - Homo sapiens cDNA: FLJ21112 fis, clone CAS05418, highly similar to AF116692 Homo sapiens PRO2207 mRNA.
BC014058 - Homo sapiens presenilin associated, rhomboid-like, mRNA (cDNA clone MGC:19916 IMAGE:3937238), complete cds.
BC003653 - Homo sapiens presenilin associated, rhomboid-like, mRNA (cDNA clone MGC:4756 IMAGE:3537438), complete cds.
AF116692 - Homo sapiens PRO2207 mRNA, complete cds.
JD072708 - Sequence 53732 from Patent EP1572962.
JD541509 - Sequence 522533 from Patent EP1572962.
JD443138 - Sequence 424162 from Patent EP1572962.
JD482491 - Sequence 463515 from Patent EP1572962.
JD037503 - Sequence 18527 from Patent EP1572962.
AF197937 - Homo sapiens presenilins associated rhomboid-like protein (PARL) mRNA, complete cds.
DQ893442 - Synthetic construct clone IMAGE:100006072; FLH199533.01X; RZPDo839H0682D presenilin associated, rhomboid-like (PARL) gene, encodes complete protein.
KJ899142 - Synthetic construct Homo sapiens clone ccsbBroadEn_08536 PARL gene, encodes complete protein.
DQ896749 - Synthetic construct Homo sapiens clone IMAGE:100011209; FLH199440.01L; RZPDo839H0681D presenilin associated, rhomboid-like (PARL) gene, encodes complete protein.
CU678558 - Synthetic construct Homo sapiens gateway clone IMAGE:100018962 5' read PARL mRNA.
LF346052 - JP 2014500723-A/153555: Polycomb-Associated Non-Coding RNAs.
JD446173 - Sequence 427197 from Patent EP1572962.
JD139072 - Sequence 120096 from Patent EP1572962.
MA581629 - JP 2018138019-A/153555: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9H300 (Reactome details) participates in the following event(s):

R-HSA-8949664 Processing of SMDT1
R-HSA-8949215 Mitochondrial calcium ion transport
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: NM_018622, NP_061092, PARL_HUMAN, PRO2207, PSARL, Q96CQ4, Q9BTJ6, Q9H300, Q9P1E3
UCSC ID: uc003fmd.3
RefSeq Accession: NM_018622
Protein: Q9H300 (aka PARL_HUMAN)
CCDS: CCDS3248.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_018622.5
exon count: 10CDS single in 3' UTR: no RNA size: 1423
ORF size: 1140CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2457.00frame shift in genome: no % Coverage: 99.23
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.