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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
    mouse all
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    Genomic context

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    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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