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PITRM1 pitrilysin metallopeptidase 1 [ Homo sapiens (human) ]

Gene ID: 10531, updated on 13-Apr-2024

Summary

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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

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Location:
10p15.2
Exon count:
28
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (3137727..3172841, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (3138971..3174045, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (3179919..3215033, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene wiskott-Aldrich syndrome protein family member 1-like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2069 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2070 Neighboring gene PFKP divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2071 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2905 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:3110992-3111172 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2072 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3115641-3116142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3118349-3118913 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3118914-3119477 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:3119931-3120866 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:3126799-3126967 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:3132863-3134062 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3134597-3135394 Neighboring gene phosphofructokinase, platelet Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:3137343-3138542 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:3146075-3147274 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:3171407-3171920 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3178175-3178676 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3178677-3179176 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3183533-3184034 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3184035-3184534 Neighboring gene small nucleolar RNA, C/D box 142 Neighboring gene PITRM1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2908 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2073 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2074 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:3215987-3216524 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3256260-3256760 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3256761-3257261 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:3279001-3279500 Neighboring gene long intergenic non-protein coding RNA 2668 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:3290932-3292131 Neighboring gene mucin-5AC-like Neighboring gene ReSE screen-validated silencer GRCh37_chr10:3305040-3305205 Neighboring gene uncharacterized LOC124902537 Neighboring gene uncharacterized LOC107987146

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. PITRM1 interaction studies with amyloidogenic nonapeptide mutants of familial Alzheimer's disease. Wilson Alphonse CR, et al. J Biomol Struct Dyn, 2023 Jul-Aug. PMID 35751131
  2. Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease. Du F, et al. Aging Cell, 2021 May. PMID 33951271, Free PMC Article
  3. Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids. PĂ©rez MJ, et al. Mol Psychiatry, 2021 Oct. PMID 32632204, Free PMC Article
  4. Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy. Smith-Carpenter JE, et al. Protein Sci, 2018 Apr. PMID 29383861, Free PMC Article
  5. In vitro oxidative inactivation of human presequence protease (hPreP). Teixeira PF, et al. Free Radic Biol Med, 2012 Dec 1. PMID 23041349, Free PMC Article

See all (72) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. Functional coupling of presequence processing and degradation in human mitochondria.
    Title: Functional coupling of presequence processing and degradation in human mitochondria.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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).
  10. 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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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
Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.
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

Clone Names

  • KIAA1104, MGC138192, MGC141929

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 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 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
NP_001229236.1
NP_001229238.1
NP_001334654.1
NP_001334655.1
NP_001334656.1
NP_001334657.1
NP_001334658.1
NP_001334659.1
NP_055704.2
XP_047280401.1
XP_047280402.1
XP_054220465.1
XP_054220466.1

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_052908.1 RefSeqGene

    Range
    5060..40114
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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

  7. 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

  8. 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

  9. 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

  1. NR_144638.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL451164
    Related
    ENST00000677001.1

  2. NR_144639.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL451164

  3. NR_144640.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL451164

  4. NR_144641.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL451164

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_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    3137727..3172841 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    Related
    ENSP00000391526.2, ENST00000430362.2

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

    Related
    ENSP00000503630.1, ENST00000677817.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    3138971..3174045 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054364491.1 → XP_054220466.1  presequence protease, mitochondrial isoform X4

  2. XM_054364490.1 → XP_054220465.1  presequence protease, mitochondrial isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q5JRX3.3 GenPept UniProtKB/Swiss-Prot:Q5JRX3

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