PITRM1 pitrilysin metallopeptidase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PITRM1provided by HGNC
Official Full Name: pitrilysin metallopeptidase 1provided by HGNC
Primary source: HGNC:HGNC:17663
See related: Ensembl:ENSG00000107959 MIM:618211; AllianceGenome:HGNC:17663
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: MP1; PreP; SCAR30
Summary: The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]
Annotation information: Note: The official gene symbol PREP (prolyl endopeptidase) on GeneID: 5550 can be confused with the alias for presequence protease (PREP) on GeneID: 10531 whose official symbol is PITRM1 (pitrilysin metallopeptidase 1). [20 Jun 2018]
Expression: Ubiquitous expression in testis (RPKM 24.8), adrenal (RPKM 18.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10p15.2

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (3137727..3172841, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (3138971..3174045, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (3179919..3215033, complement)

Chromosome 10 - NC_000010.11 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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PITRM1 interaction studies with amyloidogenic nonapeptide mutants of familial Alzheimer's disease.
Title: PITRM1 interaction studies with amyloidogenic nonapeptide mutants of familial Alzheimer's disease.
Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.
Title: Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.
Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease.
Title: Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease.
Functional coupling of presequence processing and degradation in human mitochondria.
Title: Functional coupling of presequence processing and degradation in human mitochondria.
Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: effect of hypoxia and glucose deprivation.
Title: Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: effect of hypoxia and glucose deprivation.
Single nucleotide polymorphism in PITRM1 gene is associated with smoking in African americans.
Title: An Exome-Wide Association Study Identifies New Susceptibility Loci for Age of Smoking Initiation in African- and European-American Populations.
PITRM1 T931M mutation results in childhood-onset recessive cerebellar pathology. Severity of PITRM1-related disease may be affected by the degree of impairment in cleavage of mitochondrial long peptides. Disruption and deletion of X linked regulatory segments may also contribute to severity.
Title: Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar atrophy.
Mutational disruption of electrostatic interactions in proximity of Pitrm1 arginine 183 residue contributes to the loss of enzyme activity.The arginine-to-glutamine substitution mutant Pitrm1 R183Q has been implicated in inherited amyloidogenic neuropathy.
Title: Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy.
Redox control of hPreP in the mitochondrial matrix and the protective role of the conserved methionine 206 residue as an internal antioxidant.
Title: In vitro oxidative inactivation of human presequence protease (hPreP).
The authors identified two siblings carrying a homozygous PITRM1 missense mutation (c.548G>A, p.Arg183Gln) associated with an autosomal recessive, slowly progressive syndrome characterised by mental retardation, spinocerebellar ataxia, cognitive decline and psychosis.
Title: Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Spinocerebellar ataxia, autosomal recessive 30 MedGen: C5543620 OMIM: 619405 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. 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

T15877 (e-PCR)
- UniSTS:11537

G62086 (e-PCR)
- UniSTS:139092

GDB:193844 (e-PCR)
- UniSTS:155760

PFKP_8538 (e-PCR)
- UniSTS:467826

RH15729 (e-PCR)
- UniSTS:37765

SHGC-64843 (e-PCR)
- UniSTS:55534

D11S2875 (e-PCR)
- UniSTS:152053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme activator activity	TAS Traceable Author Statement more info	PubMed
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metalloendopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metallopeptidase activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein targeting to mitochondrion	TAS Traceable Author Statement more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in mitochondrial matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: presequence protease, mitochondrial

Names: PreP peptidasome; metalloprotease 1 (pitrilysin family); pitrilysin metalloproteinase 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

NG_052908.1 RefSeqGene

Range

5060..40114

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001242307.2 → NP_001229236.1 presequence protease, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF061243, AL451164, BC005025

Consensus CDS

CCDS55699.1

UniProtKB/TrEMBL

A0A7I2YQT2

Related

ENSP00000370377.2, ENST00000380989.6

Conserved Domains (4) summary

COG1026
Location:44 → 1010

Cym1; Zn-dependent peptidase, M16 (insulinase) family [Posttranslational modification, protein turnover, chaperones]

pfam00675
Location:71 → 177

Peptidase_M16; Insulinase (Peptidase family M16)

pfam05193
Location:245 → 432

Peptidase_M16_C; Peptidase M16 inactive domain

pfam08367
Location:506 → 750

M16C_assoc; Peptidase M16C associated
NM_001242309.1 → NP_001229238.1 presequence protease, mitochondrial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at an alternate AUG and results an isoform (3) with a distinct N-terminus, compared to isoform 1. The encoded protein likely does not localize to the mitochondrion.

Source sequence(s)

AK002061, AK303406, AL451164, BC095422, DA331909

Consensus CDS

CCDS55700.1

UniProtKB/TrEMBL

B4DH07

Related

ENSP00000401201.2, ENST00000451104.6

Conserved Domains (4) summary

COG1026
Location:20 → 911

Cym1; Zn-dependent peptidase, M16 (insulinase) family [Posttranslational modification, protein turnover, chaperones]

pfam00675
Location:39 → 145

Peptidase_M16; Insulinase (Peptidase family M16)

pfam05193
Location:213 → 400

Peptidase_M16_C; Peptidase M16 inactive domain

pfam08367
Location:474 → 651

M16C_assoc; Peptidase M16C associated
NM_001347725.2 → NP_001334654.1 presequence protease, mitochondrial isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes isoform 4.

Source sequence(s)

AL451164

Consensus CDS

CCDS91206.1

UniProtKB/TrEMBL

A0A7I2V397, A0A7I2YQT2

Related

ENSP00000503187.1, ENST00000678436.1
NM_001347726.2 → NP_001334655.1 presequence protease, mitochondrial isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) encodes isoform 5, which likely does not localize to the mitochondrion.

Source sequence(s)

AL451164
NM_001347727.2 → NP_001334656.1 presequence protease, mitochondrial isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (6) encodes isoform 6, which likely does not localize to the mitochondrion.

Source sequence(s)

AL451164

Consensus CDS

CCDS91205.1

UniProtKB/TrEMBL

A0A0A0MRX9, B4DRW8

Related

ENSP00000370382.2, ENST00000380994.6
NM_001347728.2 → NP_001334657.1 presequence protease, mitochondrial isoform 7

Status: REVIEWED

Description

Transcript Variant: This variant (7) encodes isoform 7, which likely does not localize to the mitochondrion.

Source sequence(s)

AL451164

UniProtKB/TrEMBL

B3KN37
NM_001347729.1 → NP_001334658.1 presequence protease, mitochondrial isoform 8

Status: REVIEWED

Description

Transcript Variant: This variant (8) encodes isoform 8, which likely does not localize to the mitochondrion.

Source sequence(s)

AL451164

UniProtKB/TrEMBL

A0A7I2YQT2
NM_001347730.1 → NP_001334659.1 presequence protease, mitochondrial isoform 9

Status: REVIEWED

Description

Transcript Variant: This variant (9) encodes isoform 9, which likely does not localize to the mitochondrion.

Source sequence(s)

AL451164

UniProtKB/TrEMBL

A0A7I2YQT2
NM_014889.4 → NP_055704.2 presequence protease, mitochondrial isoform 2 precursor

See identical proteins and their annotated locations for NP_055704.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AL451164, BC005025, BC113369

Consensus CDS

CCDS59208.1

UniProtKB/Swiss-Prot

B3KMJ6, B4E0J8, C9JSL2, E7ES23, O95204, Q2M2G6, Q4VBR1, Q5JRW7, Q5JRX3, Q7L5Z7, Q9BSI6, Q9BVJ5, Q9UPP8

UniProtKB/TrEMBL

A0A7I2YQT2

Related

ENSP00000224949.4, ENST00000224949.9

Conserved Domains (4) summary

COG1026
Location:44 → 1009

Cym1; Zn-dependent peptidase, M16 (insulinase) family [Posttranslational modification, protein turnover, chaperones]

pfam00675
Location:71 → 177

Peptidase_M16; Insulinase (Peptidase family M16)

pfam05193
Location:245 → 432

Peptidase_M16_C; Peptidase M16 inactive domain

pfam08367
Location:506 → 749

M16C_assoc; Peptidase M16C associated

RNA

NR_144638.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL451164

Related

ENST00000677001.1
NR_144639.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL451164
NR_144640.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL451164
NR_144641.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL451164

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_000010.11 Reference GRCh38.p14 Primary Assembly

Range

3137727..3172841 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047424446.1 → XP_047280402.1 presequence protease, mitochondrial isoform X2

Related

ENSP00000391526.2, ENST00000430362.2
XM_047424445.1 → XP_047280401.1 presequence protease, mitochondrial isoform X1

Related

ENSP00000503630.1, ENST00000677817.1

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

3138971..3174045 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364491.1 → XP_054220466.1 presequence protease, mitochondrial isoform X4
XM_054364490.1 → XP_054220465.1 presequence protease, mitochondrial isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_014968.1: Suppressed sequence

Description

NM_014968.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.