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PARL presenilin associated rhomboid like [ Homo sapiens (human) ]

Gene ID: 55486, updated on 3-Apr-2024

Summary

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Official Symbol
PARLprovided by HGNC
Official Full Name
presenilin associated rhomboid likeprovided by HGNC
Primary source
HGNC:HGNC:18253
See related
Ensembl:ENSG00000175193 MIM:607858; AllianceGenome:HGNC:18253
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PSARL; PSARL1; RHBDS1; PRO2207; PSENIP2
Summary
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]
Expression
Ubiquitous expression in fat (RPKM 16.5), colon (RPKM 14.6) and 25 other tissues See more
Orthologs
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Genomic context

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See PARL in Genome Data Viewer
Location:
3q27.1
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (183826489..183884880, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (186635981..186694605, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (183547059..183602668, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene YEATS domain containing 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:183527422-183528621 Neighboring gene YEATS2 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:183535409-183536020 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14948 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14949 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14950 Neighboring gene MAP6 domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14951 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:183602698-183602848 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20898 Neighboring gene microRNA 4448 Neighboring gene ribosomal protein SA pseudogene 31

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PARL Protease: A Glimpse at Intramembrane Proteolysis in the Inner Mitochondrial Membrane. Lysyk L, et al. J Mol Biol, 2020 Aug 21. PMID 32320686
  2. Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease. Wüst R, et al. Neurobiol Aging, 2016 Mar. PMID 26778534
  3. Identification of the variants in PARL, the nuclear modifier gene, responsible for the expression of LHON patients in Thailand. Istikharah R, et al. Exp Eye Res, 2013 Nov. PMID 23973714
  4. The p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent cause of early-onset Parkinson's disease. Heinitz S, et al. Mov Disord, 2011 Nov. PMID 21953724
  5. The PARL family of mitochondrial rhomboid proteases. Hill RB, et al. Semin Cell Dev Biol, 2010 Aug. PMID 20045481, Free PMC Article

See all (59) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.
    Title: Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.
  2. Accumulation of HAX-1 and PARL in brainstem- and cortical-type Lewy bodies in Parkinson's disease and dementia with Lewy bodies.
    Title: Accumulation of HAX-1 and PARL in brainstem- and cortical-type Lewy bodies in Parkinson's disease and dementia with Lewy bodies.
  3. Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.
    Title: Proapoptotic Mitochondrial Carrier Homolog Protein PSAP Mediates Death Receptor 6 Induced Apoptosis.
  4. PARL Protease: A Glimpse at Intramembrane Proteolysis in the Inner Mitochondrial Membrane.
    Title: PARL Protease: A Glimpse at Intramembrane Proteolysis in the Inner Mitochondrial Membrane.
  5. PARL preserves mitochondrial membrane homeostasis via STARD7 processing and is emerging as a critical regulator of protein localization between mitochondria and the cytosol
    Title: PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria.
  6. Study confirmed that common variants in PARL and PINK1 were associated with leprosy. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes.
    Title: Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China.
  7. PDK2/PARL senses defects in mitochondrial bioenergetics.
    Title: The Mitochondrial Rhomboid Protease PARL Is Regulated by PDK2 to Integrate Mitochondrial Quality Control and Metabolism.
  8. Adipogenic process can be dissected into 3 stages according to the participation of PARL-PINK1-Parkin system. Findings reveal the sequential adipogenic events directed by PARL-PINK1-Parkin system, add more evidence supporting the convergence of pathogenesis leading to neurodegenerative and metabolic disease
    Title: Role of PARL-PINK1-Parkin pathway in adipocyte differentiation.
  9. These findings enrich the allelic spectrum of ABCC5 in PACG. We identified no tagging SNP responsible for the association of the whole region.
    Title: Genetic Association of the PARL-ABCC5-HTR3D-HTR3C Locus With Primary Angle-Closure Glaucoma in Chinese.
  10. These results reveal a pro-apoptotic function of PARL and identify PARL-mediated Smac processing and cytochrome c release facilitated by OPA1-dependent cristae remodelling as two independent pro-apoptotic pathways in mitochondria.
    Title: PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis.
Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables endopeptidase activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
enables endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in membrane protein proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in membrane protein proteolysis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in membrane protein proteolysis TAS
Traceable Author Statement
more info
 PubMed 
involved_in mitochondrial fusion IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of intrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of release of cytochrome c from mitochondria IEA
Inferred from Electronic Annotation
more info
  
involved_in protein processing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteolysis IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in proteolysis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of mitochondrion organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of mitophagy ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in regulation of protein targeting to mitochondrion IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in regulation of protein targeting to mitochondrion NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of proteolysis IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in regulation of reactive oxygen species metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in signal peptide processing IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
presenilin-associated rhomboid-like protein, mitochondrial
Names
mitochondrial intramembrane-cleaving protease PARL
presenilins-associated rhomboid-like protein, mitochondrial
rhomboid 7 homolog 1
NP_001032728.1
NP_001311365.1
NP_001311366.1
NP_001311367.1
NP_061092.3
XP_005247639.1
XP_016862289.1
XP_016862290.1
XP_016862291.1
XP_024309396.1
XP_024309397.1
XP_024309399.1
XP_047304474.1
XP_054203151.1
XP_054203152.1
XP_054203153.1
XP_054203154.1
XP_054203155.1
XP_054203156.1
XP_054203157.1
XP_054203158.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_046164.2 RefSeqGene

    Range
    5000..60609
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001037639.3 → NP_001032728.1  presenilin-associated rhomboid-like protein, mitochondrial isoform 2

    See identical proteins and their annotated locations for NP_001032728.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1. The encoded isoform (2) may be localized to the mitochondria.
    Source sequence(s)
    AC131160, BC003653, BC014058, CA417847
    Consensus CDS
    CCDS33897.1
    UniProtKB/Swiss-Prot
    Q9H300
    Related
    ENSP00000310676.5, ENST00000311101.9
    Conserved Domains (1) summary
    cl21536
    Location:201 → 304
    Rhomboid; Rhomboid family

  2. NM_001324436.2 → NP_001311365.1  presenilin-associated rhomboid-like protein, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) encodes isoform 3, which may be localized to the mitochondria.
    Source sequence(s)
    AC068644, AC131160, CA417847
    Conserved Domains (1) summary
    cl21536
    Location:209 → 316
    Rhomboid; Rhomboid family

  3. NM_001324437.2 → NP_001311366.1  presenilin-associated rhomboid-like protein, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) encodes isoform 4, which may be localized to the mitochondria.
    Source sequence(s)
    AC068644, AC131160, CA417847
    Consensus CDS
    CCDS82878.1
    UniProtKB/TrEMBL
    C9JNP8
    Related
    ENSP00000402137.1, ENST00000435888.5
    Conserved Domains (1) summary
    cl21536
    Location:219 → 270
    Rhomboid; Rhomboid family

  4. NM_001324438.2 → NP_001311367.1  presenilin-associated rhomboid-like protein, mitochondrial isoform 5 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) encodes isoform 5, which is localized to the mitochondria.
    Source sequence(s)
    AC068644, AC131160, CA417847

  5. NM_018622.7 → NP_061092.3  presenilin-associated rhomboid-like protein, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_061092.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1), which is localized to the mitochondria.
    Source sequence(s)
    AC131160, BC014058, CA417847, CB122278
    Consensus CDS
    CCDS3248.1
    UniProtKB/Swiss-Prot
    Q96CQ4, Q9BTJ6, Q9H300, Q9P1E3
    UniProtKB/TrEMBL
    A0A1W2PP11
    Related
    ENSP00000325421.5, ENST00000317096.9
    Conserved Domains (1) summary
    pfam01694
    Location:209 → 350
    Rhomboid; Rhomboid family

RNA

  1. NR_136893.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC068644, AC131160, CA417847
    Related
    ENST00000421484.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    183826489..183884880 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017006802.2 → XP_016862291.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X4

    Conserved Domains (1) summary
    cl21536
    Location:219 → 267
    Rhomboid; Rhomboid family

  2. XM_017006801.2 → XP_016862290.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X3

  3. XM_017006800.3 → XP_016862289.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X2

  4. XM_005247582.6 → XP_005247639.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X1

    UniProtKB/TrEMBL
    A0A1W2PP11
    Conserved Domains (1) summary
    pfam01694
    Location:209 → 351
    Rhomboid; Rhomboid family

  5. XM_024453628.2 → XP_024309396.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

    Conserved Domains (1) summary
    pfam01694
    Location:18 → 160
    Rhomboid; Rhomboid family

  6. XM_047448518.1 → XP_047304474.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

  7. XM_024453629.2 → XP_024309397.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

    Conserved Domains (1) summary
    pfam01694
    Location:18 → 160
    Rhomboid; Rhomboid family

  8. XM_024453631.2 → XP_024309399.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

    Conserved Domains (1) summary
    pfam01694
    Location:18 → 160
    Rhomboid; Rhomboid family

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    186635981..186694605 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054347179.1 → XP_054203154.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X4

  2. XM_054347178.1 → XP_054203153.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X3

  3. XM_054347177.1 → XP_054203152.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X2

  4. XM_054347176.1 → XP_054203151.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X1

  5. XM_054347180.1 → XP_054203155.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

  6. XM_054347183.1 → XP_054203158.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

  7. XM_054347181.1 → XP_054203156.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

  8. XM_054347182.1 → XP_054203157.1  presenilin-associated rhomboid-like protein, mitochondrial isoform X5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001037640.1: Suppressed sequence

    Description
    NM_001037640.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H300.2 GenPept UniProtKB/Swiss-Prot:Q9H300

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