LOCUS       NM_005588               2893 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens meprin A subunit alpha (MEP1A), mRNA.
ACCESSION   NM_005588
VERSION     NM_005588.3
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 2893)
  AUTHORS   Arnold,P., Otte,A. and Becker-Pauly,C.
  TITLE     Meprin metalloproteases: Molecular regulation and function in
            inflammation and fibrosis
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1864 (11 Pt B), 2096-2104 (2017)
   PUBMED   28502593
  REMARK    GeneRIF: In this review we report on recent findings that summarize
            the complex molecular regulation of meprins, particular folding,
            activation and shedding. Dysregulation of meprin alpha and meprin
            beta is often associated with pathological conditions such as
            neurodegeneration, inflammatory bowel disease and fibrosis
            Review article
REFERENCE   2  (bases 1 to 2893)
  AUTHORS   Breig,O., Yates,M., Neaud,V., Couchy,G., Grigoletto,A.,
            Lucchesi,C., Prox,J., Zucman-Rossi,J., Becker-Pauly,C. and
            Rosenbaum,J.
  TITLE     Metalloproteinase meprin alpha regulates migration and invasion of
            human hepatocarcinoma cells and is a mediator of the oncoprotein
            Reptin
  JOURNAL   Oncotarget 8 (5), 7839-7851 (2017)
   PUBMED   27999200
  REMARK    GeneRIF: Mep1A is overexpressed in most hepatocellular carcinomas
            and induces tumor cell migration and invasion. Mep1A expression is
            regulated by Reptin, and Mep1A mediates Reptin-induced migration.
REFERENCE   3  (bases 1 to 2893)
  AUTHORS   Wang,X., Chen,J., Wang,J., Yu,F., Zhao,S., Zhang,Y., Tang,H. and
            Peng,Z.
  TITLE     Metalloproteases meprin-a (MEP1A) is a prognostic biomarker and
            promotes proliferation and invasion of colorectal cancer
  JOURNAL   BMC Cancer 16, 383 (2016)
   PUBMED   27378469
  REMARK    GeneRIF: Results showed that MEP1A expression was elevated in
            colorectal cancer (CRC) tissues at both the mRNA and protein
            levels, and provided evidence for its functionally crucial role in
            CRC carcinogenesis as tumor proliferation and invasion.
            Erratum:[BMC Cancer. 2018 Jan 11;18(1):70. doi:
            10.1186/s12885-017-3767-6.. PMID: 29325540]
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2893)
  AUTHORS   Keiffer,T.R. and Bond,J.S.
  TITLE     Meprin metalloproteases inactivate interleukin 6
  JOURNAL   J Biol Chem 289 (11), 7580-7588 (2014)
   PUBMED   24474695
  REMARK    GeneRIF: Meprin metalloproteases A and B inactivate interleukin 6
REFERENCE   5  (bases 1 to 2893)
  AUTHORS   Lam,U.D., Lerchbaum,E., Schweighofer,N., Trummer,O., Eberhard,K.,
            Genser,B., Pieber,T.R. and Obermayer-Pietsch,B.
  TITLE     Association of MEP1A gene variants with insulin metabolism in
            central European women with polycystic ovary syndrome
  JOURNAL   Gene 537 (2), 245-252 (2014)
   PUBMED   24388959
  REMARK    GeneRIF: Variants rs17468190 (G/T) in the MEP1A gene are associated
            with glucose and insulin metabolism in overweight/obese central
            European women with polycystic ovary syndrome.
REFERENCE   6  (bases 1 to 2893)
  AUTHORS   Bond,J.S., Rojas,K., Overhauser,J., Zoghbi,H.Y. and Jiang,W.
  TITLE     The structural genes, MEP1A and MEP1B, for the alpha and beta
            subunits of the metalloendopeptidase meprin map to human
            chromosomes 6p and 18q, respectively
  JOURNAL   Genomics 25 (1), 300-303 (1995)
   PUBMED   7774936
REFERENCE   7  (bases 1 to 2893)
  AUTHORS   Kaushal,G.P., Walker,P.D. and Shah,S.V.
  TITLE     An old enzyme with a new function: purification and
            characterization of a distinct matrix-degrading metalloproteinase
            in rat kidney cortex and its identification as meprin
  JOURNAL   J Cell Biol 126 (5), 1319-1327 (1994)
   PUBMED   8063866
REFERENCE   8  (bases 1 to 2893)
  AUTHORS   Dumermuth,E., Eldering,J.A., Grunberg,J., Jiang,W. and Sterchi,E.E.
  TITLE     Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha)
            from human small intestine and its expression in COS-1 cells
  JOURNAL   FEBS Lett 335 (3), 367-375 (1993)
   PUBMED   8262185
REFERENCE   9  (bases 1 to 2893)
  AUTHORS   Dumermuth,E., Sterchi,E.E., Jiang,W.P., Wolz,R.L., Bond,J.S.,
            Flannery,A.V. and Beynon,R.J.
  TITLE     The astacin family of metalloendopeptidases
  JOURNAL   J Biol Chem 266 (32), 21381-21385 (1991)
   PUBMED   1939172
REFERENCE   10 (bases 1 to 2893)
  AUTHORS   Kargel,H.J., Dettmer,R., Etzold,G., Kirschke,H., Bohley,P. and
            Langner,J.
  TITLE     Action of rat liver cathepsin L on glucagon
  JOURNAL   Acta Biol Med Ger 40 (9), 1139-1143 (1981)
   PUBMED   7340337
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA432559.1 and AF478685.1.
            
            On Nov 23, 2018 this sequence version replaced NM_005588.2.
            
            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 :: AF478685.1, AK315840.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000230588.9/ ENSP00000230588.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-539               DA432559.1         33-571
            540-2893            AF478685.1         540-2893
FEATURES             Location/Qualifiers
     source          1..2893
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p12.3"
     gene            1..2893
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /note="meprin A subunit alpha"
                     /db_xref="GeneID:4224"
                     /db_xref="HGNC:HGNC:7015"
                     /db_xref="MIM:600388"
     exon            1..79
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     CDS             11..2251
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /EC_number="3.4.24.18"
                     /note="bA268F1.1 (meprin A alpha (PABA peptide
                     hydrolase)); PPH alpha; endopeptidase-2;
                     N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit
                     alpha; meprin A, alpha (PABA peptide hydrolase)"
                     /codon_start=1
                     /product="meprin A subunit alpha precursor"
                     /protein_id="NP_005579.2"
                     /db_xref="CCDS:CCDS4918.1"
                     /db_xref="GeneID:4224"
                     /db_xref="HGNC:HGNC:7015"
                     /db_xref="MIM:600388"
                     /translation="MAWIRSTCILFFTLLFAHIAAVPIKYLPEENVHDADFGEQKDIS
                     EINLAAGLDLFQGDILLQKSRNGLRDPNTRWTFPIPYILADNLGLNAKGAILYAFEMF
                     RLKSCVDFKPYEGESSYIIFQQFDGCWSEVGDQHVGQNISIGQGCAYKAIIEHEILHA
                     LGFYHEQSRTDRDDYVNIWWDQILSGYQHNFDTYDDSLITDLNTPYDYESLMHYQPFS
                     FNKNASVPTITAKIPEFNSIIGQRLDFSAIDLERLNRMYNCTTTHTLLDHCTFEKANI
                     CGMIQGTRDDTDWAHQDSAQAGEVDHTLLGQCTGAGYFMQFSTSSGSAEEAALLESRI
                     LYPKRKQQCLQFFYKMTGSPSDRLVVWVRRDDSTGNVRKLVKVQTFQGDDDHNWKIAH
                     VVLKEEQKFRYLFQGTKGDPQNSTGGIYLDDITLTETPCPTGVWTVRNFSQVLENTSK
                     GDKLQSPRFYNSEGYGFGVTLYPNSRESSGYLRLAFHVCSGENDAILEWPVENRQVII
                     TILDQEPDVRNRMSSSMVFTTSKSHTSPAINDTVIWDRPSRVGTYHTDCNCFRSIDLG
                     WSGFISHQMLKRRSFLKNDDLIIFVDFEDITHLSQTEVPTKGKRLSPQGLILQGQEQQ
                     VSEEGSGKAMLEEALPVSLSQGQPSRQKRSVENTGPLEDHNWPQYFRDPCDPNPCQND
                     GICVNVKGMASCRCISGHAFFYTGERCQAVQVHGSVLGMVIGGTAGVIFLTFSIIAIL
                     SQRPRK"
     exon            80..104
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            105..155
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            156..196
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            197..272
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            273..390
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            391..566
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            567..788
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            789..938
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            939..1154
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1155..1619
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1620..1793
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            1794..2094
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     exon            2095..2893
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2640..2645
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /note="hexamer: AATGAA"
     polyA_site      2656
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /note="major polyA site"
     regulatory      2875..2880
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /note="hexamer: AATAAA"
     polyA_site      2893
                     /gene="MEP1A"
                     /gene_synonym="PPHA"
                     /note="major polyA site"
ORIGIN      
        1 acttgcagca atggcttgga ttagatccac ttgcattctc ttttttacct tgctttttgc
       61 ccacatagca gctgtaccga ttaagtatct tcctgaagaa aatgtacatg atgcagattt
      121 tggtgaacag aaggatattt cagaaatcaa tttagctgca ggcttggacc tctttcaagg
      181 ggacatcctc ttgcagaaat ccagaaatgg cctgagagac ccaaacacca ggtggacgtt
      241 ccccattcct tacatcttgg ctgataattt ggggctgaat gctaaaggag ccattctgta
      301 tgcctttgag atgttccgtc tcaagtcctg tgtggatttc aagccctatg aaggagagag
      361 ctcatatatc atatttcaac agtttgatgg gtgctggtct gaggttggtg accaacatgt
      421 gggacagaac atttccattg gccaaggatg tgcctataag gccatcatag aacacgagat
      481 cctgcatgct ttgggatttt accacgagca gtcaaggacg gaccgggatg attatgtgaa
      541 catctggtgg gaccaaattc tttcaggtta ccagcacaac tttgacacct atgatgatag
      601 cttaatcaca gacctcaata caccctatga ttatgagtct ttgatgcact accagccttt
      661 ctcatttaac aagaatgcaa gtgttcccac catcacagcc aagatccctg agtttaactc
      721 cattatcgga cagcgcctgg atttcagtgc cattgattta gagaggctga accgaatgta
      781 caattgcacc acaactcaca ctcttttgga ccactgtact tttgagaagg caaacatctg
      841 tggaatgatt cagggcacca gagatgacac tgactgggcc catcaggaca gtgctcaggc
      901 tggagaagtg gatcacacct tgttgggaca atgcacaggt gccggctact tcatgcagtt
      961 cagcaccagc tcggggtccg cggaagaggc agccctactg gagtctcgga ttctttaccc
     1021 aaagaggaag cagcagtgcc tgcaattttt ctataaaatg acgggaagtc cttcagacag
     1081 actcgttgtc tgggtcagga gggatgacag cacaggcaat gttcgcaagt tggtgaaggt
     1141 gcagactttt caaggagatg atgaccacaa ttggaaaatt gcccatgtgg tgctcaaaga
     1201 ggaacagaag tttcgctacc ttttccaggg cacaaaaggc gaccctcaga actcaactgg
     1261 gggaatttac ctagatgaca tcactctgac agaaaccccc tgccccacag gggtctggac
     1321 agtccggaat ttctcccaag tccttgagaa caccagcaaa ggggacaagc ttcagagccc
     1381 tcgattctac aattcggagg gatatggttt tggggtaact ttatacccaa atagcagaga
     1441 aagctctggt tacttgagac ttgcttttca tgtgtgcagt ggggagaacg atgctatcct
     1501 ggagtggccg gtagaaaaca gacaggtgat aattaccatc cttgaccagg agcctgatgt
     1561 ccggaacagg atgtcctcaa gcatggtgtt cactacctcg aagtcgcaca catctccagc
     1621 gataaatgac actgtcatct gggacaggcc gtccagggtg ggaacctatc atacggactg
     1681 taattgtttt agaagcatcg acttgggctg gagtggtttc atttcccacc aaatgctgaa
     1741 aaggaggagt ttcctgaaaa atgatgacct catcatattt gtggactttg aagatatcac
     1801 ccacctcagc cagactgaag ttcccactaa aggcaaaaga ctgagccccc aaggcctcat
     1861 tctccaaggc caggagcagc aggtctccga agaaggttcg ggaaaggcca tgttagagga
     1921 agccctacct gtcagcctga gccaggggca gcccagccga cagaagcggt cggtggagaa
     1981 cacaggcccc ctggaggacc ataactggcc acagtacttc agagacccat gtgacccaaa
     2041 cccttgccaa aatgacggca tctgtgtgaa cgtgaagggg atggcgagct gcaggtgcat
     2101 ctctggacat gctttcttct acacggggga gcgctgtcag gccgtgcagg tgcacggcag
     2161 tgtcctgggc atggtgatcg gaggcacggc tggcgtgatc ttcttgacct tctccatcat
     2221 cgccatcctt tcccaaaggc caaggaagtg acctgcctgc tggcattggc cagaccacag
     2281 cagcacctcc tccatgcagg ccttaacttt cccatggtca atgcagtttt tatcagcctt
     2341 gctttggata ggacctccaa ggactaaggc ctccagcccc atgtgtgacc cttgtcatct
     2401 ctctgcccca cataattctg ttactttgct atgtgctcct aatgtatcta gtgtgtcctg
     2461 tgacaacact catcacactt cattgtaaat cacttgtttt attgactgtc tttcctatag
     2521 actgtaagct ccatgagggc aggcacatgt tgttctcatt gaccgtgctg gccccagtgc
     2581 ctagatgcat ggctggcaca ttgttggcac tcaacaatgg ttgaatgaat aaaacaataa
     2641 atgaatgaat aactaagata tagaaactct catttatatt gcagattgaa tatatatgat
     2701 gaaattctta tgttgaatat gttagaatca aatactcatt tttcattaga tacagtagtg
     2761 tcatcactct tttaagatct tgttaaagat ttcaaataaa ggtacttctg ggcagccagg
     2821 ctgcacagca tttgctttcc tctgagattc taagagaagg cctttaataa atttaataaa
     2881 tattgagtta gca
//
