LOCUS       NM_014889               3427 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens pitrilysin metallopeptidase 1 (PITRM1), transcript
            variant 2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_014889
VERSION     NM_014889.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3427)
  AUTHORS   Wilson Alphonse,C.R., Rajesh Kannan,R. and Nagarajan,N.
  TITLE     PITRM1 interaction studies with amyloidogenic nonapeptide mutants
            of familial Alzheimer's disease
  JOURNAL   J Biomol Struct Dyn 41 (12), 5660-5671 (2023)
   PUBMED   35751131
  REMARK    GeneRIF: PITRM1 interaction studies with amyloidogenic nonapeptide
            mutants of familial Alzheimer's disease.
REFERENCE   2  (bases 1 to 3427)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 3427)
  AUTHORS   Perez,M.J., Ivanyuk,D., Panagiotakopoulou,V., Di Napoli,G.,
            Kalb,S., Brunetti,D., Al-Shaana,R., Kaeser,S.A., Fraschka,S.A.,
            Jucker,M., Zeviani,M., Viscomi,C. and Deleidi,M.
  TITLE     Loss of function of the mitochondrial peptidase PITRM1 induces
            proteotoxic stress and Alzheimer's disease-like pathology in human
            cerebral organoids
  JOURNAL   Mol Psychiatry 26 (10), 5733-5750 (2021)
   PUBMED   32632204
  REMARK    GeneRIF: Loss of function of the mitochondrial peptidase PITRM1
            induces proteotoxic stress and Alzheimer's disease-like pathology
            in human cerebral organoids.
REFERENCE   4  (bases 1 to 3427)
  AUTHORS   Du,F., Yu,Q., Yan,S., Zhang,Z., Vangavaragu,J.R., Chen,D., Yan,S.F.
            and Yan,S.S.
  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
  JOURNAL   Aging Cell 20 (5), e13368 (2021)
   PUBMED   33951271
  REMARK    GeneRIF: Gain of PITRM1 peptidase in cortical neurons affords
            protection of mitochondrial and synaptic function in an advanced
            age mouse model of Alzheimer's disease.
REFERENCE   5  (bases 1 to 3427)
  AUTHORS   Minchenko,D.O., Khita,O.O., Tsymbal,D.O., Danilovskyi,S.V.,
            Rudnytska,O.V., Halkin,O.V., Kryvdiuk,I.V., Smeshkova,M.V.,
            Yakymchuk,M.M., Bezrodnyi,B.H. and Minchenko,O.H.
  TITLE     Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma
            cells: effect of hypoxia and glucose deprivation
  JOURNAL   Endocr Regul 54 (3), 183-195 (2020)
   PUBMED   32857715
  REMARK    GeneRIF: Expression of IDE and PITRM1 genes in ERN1 knockdown U87
            glioma cells: effect of hypoxia and glucose deprivation.
REFERENCE   6  (bases 1 to 3427)
  AUTHORS   Pinho,C.M., Bjork,B.F., Alikhani,N., Backman,H.G., Eneqvist,T.,
            Fratiglioni,L., Glaser,E. and Graff,C.
  TITLE     Genetic and biochemical studies of SNPs of the mitochondrial A
            beta-degrading protease, hPreP
  JOURNAL   Neurosci Lett 469 (2), 204-208 (2010)
   PUBMED   19962426
  REMARK    GeneRIF: our data suggest that genetic variation in the hPreP gene
            PITRM1 may potentially contribute to mitochondrial dysfunctions
            GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   7  (bases 1 to 3427)
  AUTHORS   Chow,K.M., Gakh,O., Payne,I.C., Juliano,M.A., Juliano,L., Isaya,G.
            and Hersh,L.B.
  TITLE     Mammalian pitrilysin: substrate specificity and mitochondrial
            targeting
  JOURNAL   Biochemistry 48 (13), 2868-2877 (2009)
   PUBMED   19196155
  REMARK    GeneRIF: The substrate specificity of the mitochondrial
            metallopeptidase proteinase 1 (MP1) was investigated and its
            mitochondrial targeting signal identified.
REFERENCE   8  (bases 1 to 3427)
  AUTHORS   Falkevall,A., Alikhani,N., Bhushan,S., Pavlov,P.F., Busch,K.,
            Johnson,K.A., Eneqvist,T., Tjernberg,L., Ankarcrona,M. and
            Glaser,E.
  TITLE     Degradation of the amyloid beta-protein by the novel mitochondrial
            peptidasome, PreP
  JOURNAL   J Biol Chem 281 (39), 29096-29104 (2006)
   PUBMED   16849325
REFERENCE   9  (bases 1 to 3427)
  AUTHORS   Mzhavia,N., Berman,Y.L., Qian,Y., Yan,L. and Devi,L.A.
  TITLE     Cloning, expression, and characterization of human metalloprotease
            1: a novel member of the pitrilysin family of metalloendoproteases
  JOURNAL   DNA Cell Biol 18 (5), 369-380 (1999)
   PUBMED   10360838
REFERENCE   10 (bases 1 to 3427)
  AUTHORS   Schaeffer,H.J., Catling,A.D., Eblen,S.T., Collier,L.S., Krauss,A.
            and Weber,M.J.
  TITLE     MP1: a MEK binding partner that enhances enzymatic activation of
            the MAP kinase cascade
  JOURNAL   Science 281 (5383), 1668-1671 (1998)
   PUBMED   9733512
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC113369.1, AL451164.13 and
            BC005025.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_014889.3.
            
            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].
            
            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.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC095422.1, AK225084.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000224949.9/
                                                  ENSP00000224949.4
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-291               BC113369.1         16-306
            292-292             AL451164.13        66622-66622         c
            293-690             BC113369.1         308-705
            691-691             AL451164.13        64092-64092         c
            692-991             BC113369.1         707-1006
            992-992             AL451164.13        60130-60130         c
            993-1199            BC113369.1         1008-1214
            1200-1200           AL451164.13        58357-58357         c
            1201-3119           BC113369.1         1216-3134
            3120-3120           AL451164.13        38292-38292         c
            3121-3427           BC005025.1         3115-3421
FEATURES             Location/Qualifiers
     source          1..3427
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p15.2"
     gene            1..3427
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /note="pitrilysin metallopeptidase 1"
                     /db_xref="GeneID:10531"
                     /db_xref="HGNC:HGNC:17663"
                     /db_xref="MIM:618211"
     exon            1..66
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     CDS             11..3124
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2; pitrilysin metalloproteinase 1; PreP
                     peptidasome; metalloprotease 1 (pitrilysin family);
                     presequence protease, mitochondrial"
                     /codon_start=1
                     /product="presequence protease, mitochondrial isoform 2
                     precursor"
                     /protein_id="NP_055704.2"
                     /db_xref="CCDS:CCDS59208.1"
                     /db_xref="GeneID:10531"
                     /db_xref="HGNC:HGNC:17663"
                     /db_xref="MIM:618211"
                     /translation="MWRCGGRQGLCVLRRLSGGHAHHRAWRWNSNRACERALQYKLGD
                     KIHGFTVNQVTSVPELFLTAVKLTHDDTGARYLHLAREDTNNLFSVQFRTTPMDSTGV
                     PHILEHTVLCGSQKYPCRDPFFKMLNRSLSTFMNAFTASDYTLYPFSTQNPKDFQNLL
                     SVYLDATFFPCLRELDFWQEGWRLEHENPSDPQTPLVFKGVVFNEMKGAFTDNERIFS
                     QHLQNRLLPDHTYSVVSGGDPLCIPELTWEQLKQFHATHYHPSNARFFTYGNFPLEQH
                     LKQIHEEALSKFQKIEPSTVVPAQTPWDKPREFQITCGPDSFATDPSKQTTISVSFLL
                     PDITDTFEAFTLSLLSSLLTSGPNSPFYKALIESGLGTDFSPDVGYNGYTREAYFSVG
                     LQGIAEKDIETVRSLIDRTIDEVVEKGFEDDRIEALLHKIEIQMKHQSTSFGLMLTSY
                     IASCWNHDGDPVELLKLGNQLAKFRQCLQENPKFLQEKVKQYFKNNQHKLTLSMRPDD
                     KYHEKQAQVEATKLKQKVEALSPGDRQQIYEKGLELRSQQSKPQDASCLPALKVSDIE
                     PTIPVTELDVVLTAGDIPVQYCAQPTNGMVYFRAFSSLNTLPEELRPYVPLFCSVLTK
                     LGCGLLDYREQAQQIELKTGGMSASPHVLPDDSHMDTYEQGVLFSSLCLDRNLPDMMQ
                     LWSEIFNNPCFEEEEHFKVLVKMTAQELANGIPDSGHLYASIRAGRTLTPAGDLQETF
                     SGMDQVRLMKRIAEMTDIKPILRKLPRIKKHLLNGDNMRCSVNATPQQMPQTEKAVED
                     FLRSIGRSKKERRPVRPHTVEKPVPSSSGGDAHVPHGSQVIRKLVMEPTFKPWQMKTH
                     FLMPFPVNYVGECIRTVPYTDPDHASLKILARLMTAKFLHTEIREKGGAYGGGAKLSH
                     NGIFTLYSYRDPNTIETLQSFGKAVDWAKSGKFTQQDIDEAKLSVFSTVDAPVAPSDK
                     GMDHFLYGLSDEMKQAHREQLFAVSHDKLLAVSDRYLGTGKSTHGLAILGPENPKIAK
                     DPSWIIQ"
     exon            67..169
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            170..276
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            277..428
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            429..543
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            544..640
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            641..801
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            802..928
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            929..1017
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1018..1146
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1147..1260
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1261..1357
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1358..1492
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1493..1631
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1632..1748
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1881
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            1882..2002
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2003..2079
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2080..2245
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2246..2346
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2347..2467
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2468..2542
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2543..2655
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2656..2781
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2782..2927
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            2928..3030
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     exon            3031..3427
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3405..3410
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /note="hexamer: AATAAA"
     polyA_site      3427
                     /gene="PITRM1"
                     /gene_synonym="MP1; PreP; SCAR30"
                     /note="major polyA site"
ORIGIN      
        1 gtcatgcgca atgtggcgct gcggcgggcg gcagggcctg tgtgtgctga ggcggctgag
       61 cggcggacat gcacaccaca gagcgtggcg atggaacagt aaccgggctt gtgagagggc
      121 tctgcagtat aaactaggag acaagatcca tggattcacc gtaaaccagg tgacatctgt
      181 tcccgagctg ttcctgactg cagtgaagct cacccatgat gacacaggag ccaggtattt
      241 acacctggcc agagaagaca cgaataatct gttcagcgtg cagttccgta ctactcccat
      301 ggacagtact ggtgttcctc acattcttga gcataccgtc ctttgtgggt ctcagaaata
      361 tccgtgcaga gaccctttct tcaaaatgtt gaaccggtcc ctctccacgt tcatgaacgc
      421 cttcacagct agtgattata ctctgtatcc attttccaca caaaatccca aggactttca
      481 gaatctcctc tcggtgtatt tggatgccac ctttttccca tgtttacgcg agctggattt
      541 ctggcaggaa ggatggcggc tggaacatga gaatccgagc gacccccaga cgcccttggt
      601 ctttaaagga gtcgtcttta atgagatgaa gggagcgttt acagacaatg agaggatatt
      661 ctcccagcac cttcagaaca gacttcttcc tgaccacacg tactcagtgg tctccggggg
      721 tgacccactg tgcatcccgg agcttacatg ggagcagctt aagcagtttc atgccactca
      781 ctatcaccca agcaatgcta ggttcttcac gtacggtaat tttccattag aacagcatct
      841 gaaacaaatt cacgaggaag cactgagcaa attccagaaa attgaaccaa gcaccgtggt
      901 gccagctcag acaccctggg acaagcctag ggaattccag ataacatgtg gcccggattc
      961 atttgctaca gatccctcta aacaaacaac catcagcgtt agcttcctct taccggacat
     1021 caccgacaca tttgaagcct tcacattaag tcttctgtct tcactcttga cttctgggcc
     1081 caattctccc ttttacaaag ccttgattga atctggcctt ggcacagact tttctcctga
     1141 tgttggatat aatggctaca cgagggaggc ctactttagt gtcggcctcc aagggattgc
     1201 ggagaaagac attgagaccg tcagaagcct catagacaga acgattgatg aagtagttga
     1261 gaaaggattt gaagatgatc gaattgaggc tttacttcat aaaattgaaa tacagatgaa
     1321 acatcagtct accagctttg ggctgatgct gacatcatac atagcttctt gctggaacca
     1381 tgatggggac cctgtggagc tcttgaagtt gggaaatcag ttagctaaat tcagacagtg
     1441 cctgcaggaa aatccaaaat ttttgcaaga aaaagtaaaa cagtatttta agaataacca
     1501 gcataagctg actttatcga tgaggccaga tgacaagtat cacgagaagc aggcacaggt
     1561 ggaagccacg aagctcaagc agaaggtcga ggctctgtcc cccggagaca ggcagcagat
     1621 ctacgagaaa ggtctagaat tacggagtca acaaagcaaa cctcaagatg cctcttgtct
     1681 gccagcgttg aaagtttccg atattgaacc caccatacct gtcacagagt tggacgtggt
     1741 cctgacagct ggagatatcc ctgttcagta ctgcgcccag cccaccaatg gcatggtgta
     1801 tttccgggcc ttctccagcc tgaacacact ccccgaggag ctgaggccct atgtgcccct
     1861 cttctgcagc gtcctcacca agctgggctg cggccttctt gactaccggg agcaggctca
     1921 gcagatagaa ttgaagaccg gagggatgag tgcttctccc cacgtgctcc ccgacgactc
     1981 acacatggac acctacgagc agggtgtgct tttctcctct ctctgcctgg atcgaaacct
     2041 gccagacatg atgcagctat ggagtgaaat atttaacaac ccgtgctttg aagaagagga
     2101 gcacttcaag gtgctggtga agatgaccgc ccaggagctc gccaatggaa ttcctgactc
     2161 tgggcacctg tacgcatcca tcagggcagg ccggaccctc acgcccgcag gggacctgca
     2221 ggagaccttc agcgggatgg atcaggtgcg gctgatgaag aggattgcag aaatgacaga
     2281 tatcaaaccc atcctgagga agctcccgcg tatcaagaaa cacttgttaa atggtgataa
     2341 tatgaggtgt tcagtgaatg cgactcctca gcagatgcct cagacagaaa aagcggtcga
     2401 agacttcctt agaagcatcg gtcggagtaa aaaggaacgg aggcctgtgc gcccacacac
     2461 ggtcgagaaa cctgtgccca gcagctctgg tggagatgcc cacgttcccc atggctccca
     2521 ggtcattagg aagctggtca tggaacccac cttcaagccc tggcagatga agactcactt
     2581 cctgatgccc ttcccggtga attacgtggg tgaatgcatc cgaactgtcc cctacacgga
     2641 cccagatcat gccagtctta aaatccttgc acgtttgatg actgccaaat tcttgcatac
     2701 agaaattcga gaaaaaggcg gtgcttatgg tggaggcgca aaactcagcc acaatgggat
     2761 tttcaccctt tactcttaca gggacccaaa tacaatagag acgctccagt cttttgggaa
     2821 ggctgtcgac tgggctaagt ctggaaaatt cacacagcaa gacatcgacg aagccaaact
     2881 ttctgtcttc tcaaccgtag atgctcctgt cgctccttca gacaaaggaa tggaccactt
     2941 cttgtacggc ctctcggatg agatgaagca ggcccacaga gagcagctct ttgctgtcag
     3001 ccacgacaag ctcctggccg tgagcgatag atacctcggc actgggaaga gcacacacgg
     3061 cctggccatc ctcggacccg agaacccgaa aattgccaag gacccatcct ggatcatcca
     3121 atgagcagcc gtggcgctcg actgcacagg agcccgagac aatacacctc cgagctgaat
     3181 atgaaaagtc agaaatgcta ctgctttttc caagaatatt atgtcattga gtgtcgccaa
     3241 agcccttgac tggcgagtca aaaactcaga tctatcttaa gagtgaccag gaagaggttc
     3301 attgaaataa tcatgcatga agcgccaaag atgcaccatg tagaattttc actttgtact
     3361 ggcaggctcg ttttacctca ttctagaata tttaagaatc taaaaataaa gggcaactct
     3421 gacttaa
//
