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    PITRM1 pitrilysin metallopeptidase 1 [ Homo sapiens (human) ]

    Gene ID: 10531, updated on 12-Dec-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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    See PITRM1 in Genome Data Viewer
    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_000010.11Genomic 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. [Ecological sterotypes of defensive behavior in fish under the action of chemical danger signals]. Marusov EV. Nauchnye Doki Vyss Shkoly Biol Nauki, 1976. PMID 1036083
    2. Decreased proteolytic activity of the mitochondrial amyloid-β degrading enzyme, PreP peptidasome, in Alzheimer's disease brain mitochondria. Alikhani N, et al. J Alzheimers Dis, 2011. PMID 21750375, 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. Pérez MJ, et al. Mol Psychiatry, 2021 Oct. PMID 32632204, Free PMC Article
    4. 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
    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 (78) 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)

    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 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 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

    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_2024_08

    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

      UniProtKB/TrEMBL
      H0Y4F7
      Related
      ENSP00000391526.2, ENST00000430362.2

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

      UniProtKB/TrEMBL
      H0Y4F7
      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

      UniProtKB/TrEMBL
      H0Y4F7

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

      UniProtKB/TrEMBL
      H0Y4F7

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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