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

Summary

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

Location:: 3q27.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (183826489..183884880, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (186635981..186694605, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (183547059..183602668, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
PDK2/PARL senses defects in mitochondrial bioenergetics.
Title: The Mitochondrial Rhomboid Protease PARL Is Regulated by PDK2 to Integrate Mitochondrial Quality Control and Metabolism.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH79821 (e-PCR)
- UniSTS:84525

D3S2822E (e-PCR)
- UniSTS:150858

SHGC-33411 (e-PCR)
- UniSTS:81583

SHGC-77603 (e-PCR)
- UniSTS:3505

RH66907 (e-PCR)
- UniSTS:85710

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	HTP 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

EC 3.4.21.105

NP_001311365.1

EC 3.4.21.105

NP_001311366.1

EC 3.4.21.105

NP_001311367.1

EC 3.4.21.105

NP_061092.3

EC 3.4.21.105

XP_005247639.1

EC 3.4.21.105

XP_016862289.1

EC 3.4.21.105

XP_016862290.1

EC 3.4.21.105

XP_016862291.1

EC 3.4.21.105

XP_024309396.1

EC 3.4.21.105

XP_024309397.1

EC 3.4.21.105

XP_024309399.1

EC 3.4.21.105

XP_047304474.1

EC 3.4.21.105

XP_054203151.1

EC 3.4.21.105

XP_054203152.1

EC 3.4.21.105

XP_054203153.1

EC 3.4.21.105

XP_054203154.1

EC 3.4.21.105

XP_054203155.1

EC 3.4.21.105

XP_054203156.1

EC 3.4.21.105

XP_054203157.1

EC 3.4.21.105

XP_054203158.1

EC 3.4.21.105

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

NG_046164.2 RefSeqGene

Range

5000..60609

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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

NR_136893.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC068644, AC131160, CA417847

Related

ENST00000421484.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

183826489..183884880 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
XM_017006801.2 → XP_016862290.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X3
XM_017006800.3 → XP_016862289.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X2
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
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
XM_047448518.1 → XP_047304474.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X5
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
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

NC_060927.1 Alternate T2T-CHM13v2.0

Range

186635981..186694605 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054347179.1 → XP_054203154.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X4
XM_054347178.1 → XP_054203153.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X3
XM_054347177.1 → XP_054203152.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X2
XM_054347176.1 → XP_054203151.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X1

UniProtKB/TrEMBL

A0A1W2PP11
XM_054347180.1 → XP_054203155.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X5
XM_054347183.1 → XP_054203158.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X5
XM_054347181.1 → XP_054203156.1 presenilin-associated rhomboid-like protein, mitochondrial isoform X5
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

NM_001037640.1: Suppressed sequence

Description

NM_001037640.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.