LOCUS       NM_005317                924 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens granzyme M (GZMM), transcript variant 1, mRNA.
ACCESSION   NM_005317
VERSION     NM_005317.4
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 924)
  AUTHORS   Saccon,E., Mikaeloff,F., Figueras Ivern,P., Vegvari,A.,
            Sonnerborg,A., Neogi,U. and van Domselaar,R.
  TITLE     Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme M-Mediated
            Cleavage
  JOURNAL   Front Immunol 12, 669347 (2021)
   PUBMED   33953729
  REMARK    GeneRIF: Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme
            M-Mediated Cleavage.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 924)
  AUTHORS   Bovenschen,N., de Koning,P.J., Quadir,R., Broekhuizen,R.,
            Damen,J.M., Froelich,C.J., Slijper,M. and Kummer,J.A.
  TITLE     NK cell protease granzyme M targets alpha-tubulin and disorganizes
            the microtubule network
  JOURNAL   J Immunol 180 (12), 8184-8191 (2008)
   PUBMED   18523284
  REMARK    GeneRIF: Granzyme M targets major components of the cytoskeleton
            that likely contribute to natural killer (NK) cell-induced cell
            death.
REFERENCE   3  (bases 1 to 924)
  AUTHORS   Lu,H., Hou,Q., Zhao,T., Zhang,H., Zhang,Q., Wu,L. and Fan,Z.
  TITLE     Granzyme M directly cleaves inhibitor of caspase-activated DNase
            (CAD) to unleash CAD leading to DNA fragmentation
  JOURNAL   J Immunol 177 (2), 1171-1178 (2006)
   PUBMED   16818775
  REMARK    GeneRIF: Granzyme (Gzm)M can directly degrade inhibitor of
            caspase-activated DNase (ICAD) to activate CAD, leading to DNA
            damage; GzmM cleaves DNA damage sensor enzyme poly(ADP-ribose)
            polymerase to prevent cellular DNA repair and force apoptosis.
REFERENCE   4  (bases 1 to 924)
  AUTHORS   Mahrus,S., Kisiel,W. and Craik,C.S.
  TITLE     Granzyme M is a regulatory protease that inactivates proteinase
            inhibitor 9, an endogenous inhibitor of granzyme B
  JOURNAL   J Biol Chem 279 (52), 54275-54282 (2004)
   PUBMED   15494398
  REMARK    GeneRIF: proteinase inhibitor 9 was effectively hydrolyzed and
            inactivated by human granzyme M, raising the possibility that this
            orphan granzyme bypasses proteinase inhibitor 9 inhibition of
            granzyme B
REFERENCE   5  (bases 1 to 924)
  AUTHORS   Kelly,J.M., Waterhouse,N.J., Cretney,E., Browne,K.A., Ellis,S.,
            Trapani,J.A. and Smyth,M.J.
  TITLE     Granzyme M mediates a novel form of perforin-dependent cell death
  JOURNAL   J Biol Chem 279 (21), 22236-22242 (2004)
   PUBMED   15028722
  REMARK    GeneRIF: granzyme M represents a third major and specialized
            perforin-dependent cell death pathway that plays a significant role
            in death mediated by NK cells
REFERENCE   6  (bases 1 to 924)
  AUTHORS   Krenacs,L., Smyth,M.J., Bagdi,E., Krenacs,T., Kopper,L.,
            Rudiger,T., Zettl,A., Muller-Hermelink,H.K., Jaffe,E.S. and
            Raffeld,M.
  TITLE     The serine protease granzyme M is preferentially expressed in
            NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas:
            evidence of origin from lymphocytes involved in innate immunity
  JOURNAL   Blood 101 (9), 3590-3593 (2003)
   PUBMED   12506019
  REMARK    GeneRIF: GM expression is a distinctive feature of the nasal
            NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and
            suggest that these tumors develop from lymphocytes involved in
            innate immunity.
REFERENCE   7  (bases 1 to 924)
  AUTHORS   Smyth,M.J., O'Connor,M.D. and Trapani,J.A.
  TITLE     Granzymes: a variety of serine protease specificities encoded by
            genetically distinct subfamilies
  JOURNAL   J Leukoc Biol 60 (5), 555-562 (1996)
   PUBMED   8929545
  REMARK    Review article
REFERENCE   8  (bases 1 to 924)
  AUTHORS   Pilat,D., Fink,T., Obermaier-Skrobanek,B., Zimmer,M., Wekerle,H.,
            Lichter,P. and Jenne,D.E.
  TITLE     The human Met-ase gene (GZMM): structure, sequence, and close
            physical linkage to the serine protease gene cluster on 19p13.3
  JOURNAL   Genomics 24 (3), 445-450 (1994)
   PUBMED   7713495
REFERENCE   9  (bases 1 to 924)
  AUTHORS   Baker,E., Sutherland,G.R. and Smyth,M.J.
  TITLE     The gene encoding a human natural killer cell granule serine
            protease, Met-ase 1, maps to chromosome 19p13.3
  JOURNAL   Immunogenetics 39 (4), 294-295 (1994)
   PUBMED   8119738
REFERENCE   10 (bases 1 to 924)
  AUTHORS   Smyth,M.J., Sayers,T.J., Wiltrout,T., Powers,J.C. and Trapani,J.A.
  TITLE     Met-ase: cloning and distinct chromosomal location of a serine
            protease preferentially expressed in human natural killer cells
  JOURNAL   J Immunol 151 (11), 6195-6205 (1993)
   PUBMED   8245461
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011556.9.
            
            On Nov 23, 2018 this sequence version replaced NM_005317.3.
            
            Summary: Human natural killer (NK) cells and activated lymphocytes
            express and store a distinct subset of neutral serine proteases
            together with proteoglycans and other immune effector molecules in
            large cytoplasmic granules. These serine proteases are collectively
            termed granzymes and include 4 distinct gene products: granzyme A,
            granzyme B, granzyme H, and the protein encoded by this gene,
            granzyme M. Two transcript variants encoding different isoforms
            have been found for this gene. [provided by RefSeq, Apr 2012].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: BC025701.1, L23134.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000264553.6/ ENSP00000264553.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-74                AC011556.9         12535-12608
            75-231              AC011556.9         15762-15918
            232-367             AC011556.9         17024-17159
            368-631             AC011556.9         17404-17667
            632-924             AC011556.9         18112-18404
FEATURES             Location/Qualifiers
     source          1..924
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.3"
     gene            1..924
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /note="granzyme M"
                     /db_xref="GeneID:3004"
                     /db_xref="HGNC:HGNC:4712"
                     /db_xref="MIM:600311"
     exon            1..74
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /inference="alignment:Splign:2.1.0"
     CDS             20..793
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; lymphocyte met-ase 1; HU-Met-1; Met-1 serine
                     protease; natural killer cell granular protease"
                     /codon_start=1
                     /product="granzyme M isoform 1 preproprotein"
                     /protein_id="NP_005308.2"
                     /db_xref="CCDS:CCDS12031.1"
                     /db_xref="GeneID:3004"
                     /db_xref="HGNC:HGNC:4712"
                     /db_xref="MIM:600311"
                     /translation="MEACVSSLLVLALGALSVGSSFGTQIIGGREVIPHSRPYMASLQ
                     RNGSHLCGGVLVHPKWVLTAAHCLAQRMAQLRLVLGLHTLDSPGLTFHIKAAIQHPRY
                     KPVPALENDLALLQLDGKVKPSRTIRPLALPSKRQVVAAGTRCSMAGWGLTHQGGRLS
                     RVLRELDLQVLDTRMCNNSRFWNGSLSPSMVCLAADSKDQAPCKGDSGGPLVCGKGRV
                     LARVLSFSSRVCTDIFKPPVATAVAPYVSWIRKVTGRSA"
     exon            75..231
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /inference="alignment:Splign:2.1.0"
     exon            232..367
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /inference="alignment:Splign:2.1.0"
     exon            368..631
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /inference="alignment:Splign:2.1.0"
     exon            632..924
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      897..902
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /note="hexamer: AATAAA"
     polyA_site      924
                     /gene="GZMM"
                     /gene_synonym="LMET1; MET1"
                     /note="major polyA site"
ORIGIN      
        1 actgggtctc cacagcggca tggaggcctg cgtgtcttca ctgctggtgc tggccctggg
       61 ggccctgtca gtaggcagct cctttgggac ccagatcatc gggggccggg aggtgatccc
      121 ccactcgcgc ccgtacatgg cctcactgca gagaaatggc tcccacctgt gcgggggtgt
      181 cctggtgcac ccaaagtggg tgctgacggc tgcccactgc ctggcccagc ggatggccca
      241 gctgaggctg gtgctggggc tccacaccct ggacagcccc ggtctcacct tccacatcaa
      301 ggcagccatc cagcaccctc gctacaagcc cgtccctgcc ctggagaacg acctcgcgct
      361 gcttcagctg gacgggaaag tgaagcccag ccggaccatc cggccgttgg ccctgcccag
      421 taagcgccag gtggtggcag cagggactcg gtgcagcatg gccggctggg ggctgaccca
      481 ccagggcggg cgcctgtccc gggtgctgcg ggagctggac ctccaagtgc tggacacccg
      541 catgtgtaac aacagccgct tctggaacgg cagcctctcc cccagcatgg tctgcctggc
      601 ggccgactcc aaggaccagg ctccctgcaa gggtgactcg ggcgggcccc tggtgtgtgg
      661 caaaggccgg gtgttggcca gagtcctgtc cttcagctcc agggtctgca ctgacatctt
      721 caagcctccc gtggccaccg ctgtggcgcc ttacgtgtcc tggatcagga aggtcaccgg
      781 ccgatcggcc tgatgccctg gggtgatggg gaccccctcg ctgtctccac aggacccttc
      841 ccctccaggg gtgcagtggg gtgggtgagg acgggtggga gggacaggga gggaccaata
      901 aatcataatg aagaaacgct caga
//
