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 ... See more...

Aliases for GZMM Gene

Aliases for GZMM Gene

  • Granzyme M 2 3 4 5
  • MET1 2 3 4
  • Natural Killer Cell Granular Protease 3 4
  • Met-1 Serine Protease 3 4
  • Lymphocyte Met-Ase 1 2 3
  • Met-Ase 3 4
  • LMET1 2 3
  • Granzyme M (Lymphocyte Met-Ase 1) 2
  • EC 3.4.21.- 4
  • EC 3.4.21 50
  • HU-Met-1 3
  • Hu-Met-1 4
  • GZMM 5

External Ids for GZMM Gene

Previous GeneCards Identifiers for GZMM Gene

  • GC19P000554
  • GC19P000579
  • GC19P000484
  • GC19P000495
  • GC19P000314

Summaries for GZMM Gene

Entrez Gene Summary for GZMM Gene

  • 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]

GeneCards Summary for GZMM Gene

GZMM (Granzyme M) is a Protein Coding gene. Diseases associated with GZMM include Larsen-Like Syndrome B3gat3 Type and Cataract 38. Among its related pathways are Granzyme Pathway and Creation of C4 and C2 activators. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and endopeptidase activity. An important paralog of this gene is PRSS57.

UniProtKB/Swiss-Prot Summary for GZMM Gene

  • Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR, alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of target cells.

Gene Wiki entry for GZMM Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GZMM Gene

Genomics for GZMM Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GZMM Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J000543 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 257.5 +0.3 250 2.2 ZNF600 IKZF1 SSRP1 TBP KLF7 ZNF148 MCM3 SP2 RBM22 FOSL2 GZMM DAZAP1 PTBP1 ENSG00000267317 TMEM259 CDC34 MIER2 CNN2 FSTL3 BSG-AS1
GH19J000657 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 22.3 +116.8 116766 7 BCLAF1 SP1 MYC ZNF600 ZNF592 POLR2A ZIC2 YY1 MXD4 NONO RNF126 GZMM ENSG00000267666 ARHGAP45 ABCA7 TMEM259 R3HDM4 lnc-POLRMT-4 lnc-POLRMT-7 FGF22
GH19J000510 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 20.6 -32.2 -32222 3.1 BCLAF1 ZNF654 ZNF207 MYC ZNF600 SSRP1 ZNF580 ZNF592 ATF2 ZNF10 GZMM TPGS1 MADCAM1 RNF126 ENSG00000266933 HSALNG0122877 CDC34
GH19J000995 Enhancer 1.1 FANTOM5 ENCODE 19.9 +452.4 452359 0.9 ZNF600 JUND ZNF580 ATF2 ZNF223 ZNF10 POLR2A NFIC ZIC2 ZBTB10 HSALNG0122957 WDR18 GZMM MIER2 ARHGAP45 CIRBP RNF126 TMEM259 ABCA7 GRIN3B
GH19J000906 Promoter/Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 12.6 +364.5 364524 4.7 SP1 ZNF207 MYC NCOR1 ZNF592 NFIC ZIC2 NONO CTCF REST ARHGAP45 R3HDM4 MIDN ABCA7 CFD ELANE PRTN3 GZMM DAZAP1 SBNO2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GZMM on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GZMM

Top Transcription factor binding sites by QIAGEN in the GZMM gene promoter:
  • ATF-2
  • c-Jun
  • MyoD

Genomic Locations for GZMM Gene

Latest Assembly
chr19:544,034-549,924
(GRCh38/hg38)
Size:
5,891 bases
Orientation:
Plus strand

Previous Assembly
chr19:544,053-549,922
(GRCh37/hg19 by Entrez Gene)
Size:
5,870 bases
Orientation:
Plus strand

chr19:544,034-549,919
(GRCh37/hg19 by Ensembl)
Size:
5,886 bases
Orientation:
Plus strand

Genomic View for GZMM Gene

Genes around GZMM on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GZMM Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GZMM Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GZMM Gene

Proteins for GZMM Gene

  • Protein details for GZMM Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51124-GRAM_HUMAN
    Recommended name:
    Granzyme M
    Protein Accession:
    P51124

    Protein attributes for GZMM Gene

    Size:
    257 amino acids
    Molecular mass:
    27545 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for GZMM Gene

neXtProt entry for GZMM Gene

Selected DME Specific Peptides for GZMM Gene

P51124:
  • VLTAAHC
  • GDSGGPL
  • CGGVLVH
  • DLALLQL
  • SGGPLVC
  • CKGDSGG
  • PHSRPYMA
  • WVLTAAH

Post-translational modifications for GZMM Gene

  • Glycosylation at Asn177
  • Modification sites at PhosphoSitePlus

Other Protein References for GZMM Gene

Antibodies for research

  • Boster Bio Antibodies for GZMM

Domains & Families for GZMM Gene

Gene Families for GZMM Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for GZMM Gene

InterPro:
Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature

Suggested Antigen Peptide Sequences for GZMM Gene

GenScript: Design optimal peptide antigens:
  • Natural killer cell granular protease (GRAM_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P51124

UniProtKB/Swiss-Prot:

GRAM_HUMAN :
  • Belongs to the peptidase S1 family. Granzyme subfamily.
Family:
  • Belongs to the peptidase S1 family. Granzyme subfamily.
genes like me logo Genes that share domains with GZMM: view

Function for GZMM Gene

Molecular function for GZMM Gene

UniProtKB/Swiss-Prot Function:
Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR, alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of target cells.
GENATLAS Biochemistry:
natural killer cells granule serine protease,cleaving after methionine (Met-ase)

Enzyme Numbers (IUBMB) for GZMM Gene

Phenotypes From GWAS Catalog for GZMM Gene

Gene Ontology (GO) - Molecular Function for GZMM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IEA --
GO:0004252 serine-type endopeptidase activity IMP 21857942
GO:0005515 protein binding IPI 21857942
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity TAS 7713495
genes like me logo Genes that share ontologies with GZMM: view
genes like me logo Genes that share phenotypes with GZMM: view

Animal Models for research

  • Taconic Biosciences Mouse Models for GZMM

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMM

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GZMM Gene

Localization for GZMM Gene

Subcellular locations from UniProtKB/Swiss-Prot for GZMM Gene

Secreted. Cytoplasmic granule. Note=Granules of large granular lymphocytes.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GZMM gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for GZMM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0016020 membrane HDA 19946888
genes like me logo Genes that share ontologies with GZMM: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GZMM Gene

Pathways & Interactions for GZMM Gene

genes like me logo Genes that share pathways with GZMM: view

Pathways by source for GZMM Gene

1 Qiagen pathway for GZMM Gene
  • Granzyme Pathway

Gene Ontology (GO) - Biological Process for GZMM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001913 T cell mediated cytotoxicity IEA --
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0006915 apoptotic process IEA --
GO:0008219 cell death IMP 21857942
genes like me logo Genes that share ontologies with GZMM: view

No data available for SIGNOR curated interactions for GZMM Gene

Drugs & Compounds for GZMM Gene

(1) Drugs for GZMM Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with GZMM: view

Transcripts for GZMM Gene

mRNA/cDNA for GZMM Gene

2 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMM

Alternative Splicing Database (ASD) splice patterns (SP) for GZMM Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b
SP1:
SP2:

Relevant External Links for GZMM Gene

GeneLoc Exon Structure for
GZMM

Expression for GZMM Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GZMM Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GZMM Gene

This gene is overexpressed in Whole Blood (x34.6) and Spleen (x4.7).

Protein differential expression in normal tissues from HIPED for GZMM Gene

This gene is overexpressed in NK cells (30.2), CD8 Tcells (11.9), Peripheral blood mononuclear cells (11.5), Monocytes (6.9), and Blymphocyte (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GZMM Gene



Protein tissue co-expression partners for GZMM Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GZMM

SOURCE GeneReport for Unigene cluster for GZMM Gene:

Hs.465511

mRNA Expression by UniProt/SwissProt for GZMM Gene:

P51124-GRAM_HUMAN
Tissue specificity: Highly and constitutively expressed in activated natural killer (NK) cells.

Evidence on tissue expression from TISSUES for GZMM Gene

  • Spleen(4.4)
  • Pancreas(4.2)
  • Blood(2.6)
  • Lymph node(2.1)
genes like me logo Genes that share expression patterns with GZMM: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for GZMM Gene

Orthologs for GZMM Gene

This gene was present in the common ancestor of chordates.

Orthologs for GZMM Gene

Organism Taxonomy Gene Similarity Type Details
Cow
(Bos Taurus)
Mammalia GZMM 29 30
  • 77.4 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Gzmm 29 16 30
  • 74.07 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gzmm 29
  • 73.94 (n)
Oppossum
(Monodelphis domestica)
Mammalia GZMM 30
  • 48 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GZMM 29 30
  • 62.81 (n)
OneToOne
Species where no ortholog for GZMM was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for GZMM Gene

ENSEMBL:
Gene Tree for GZMM (if available)
TreeFam:
Gene Tree for GZMM (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GZMM: view image
Alliance of Genome Resources:
Additional Orthologs for GZMM

Paralogs for GZMM Gene

Variants for GZMM Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GZMM Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs146201764 Benign: not provided 548,955(+) C/T
NM_005317.4(GZMM):c.382C>T (p.Arg128Trp)
MISSENSE
rs59235301 Benign: not provided 549,077(+) C/T
NM_005317.4(GZMM):c.504C>T (p.Leu168=)
SYNONYMOUS
rs77680573 Benign: not provided 548,630(+) C/A
NM_005317.4(GZMM):c.301C>A (p.Arg101Ser)
MISSENSE
rs1599882 -- p.Arg221Gly

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GZMM Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for GZMM Gene

Variant ID Type Subtype PubMed ID
esv2656977 CNV deletion 23128226
esv2661476 CNV deletion 23128226
nsv1077681 CNV insertion 25765185
nsv1141783 CNV insertion 24896259
nsv1142246 CNV tandem duplication 24896259
nsv428360 CNV gain 18775914
nsv470101 CNV loss 18288195
nsv509712 CNV insertion 20534489
nsv577978 CNV gain 21841781
nsv578129 CNV loss 21841781
nsv953938 CNV deletion 24416366

Variation tolerance for GZMM Gene

Residual Variation Intolerance Score: 90.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.77; 47.11% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GZMM Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GZMM
Leiden Open Variation Database (LOVD)
GZMM

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GZMM Gene

Disorders for GZMM Gene

MalaCards: The human disease database

(7) MalaCards diseases for GZMM Gene - From: COP

- elite association - COSMIC cancer census association via MalaCards
Search GZMM in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GZMM

genes like me logo Genes that share disorders with GZMM: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GZMM Gene

Publications for GZMM Gene

  1. Cleavage of survivin by Granzyme M triggers degradation of the survivin-X-linked inhibitor of apoptosis protein (XIAP) complex to free caspase activity leading to cytolysis of target tumor cells. (PMID: 20406824) Hu D … Fan Z (The Journal of biological chemistry 2010) 3 4 22
  2. Structural basis for proteolytic specificity of the human apoptosis-inducing granzyme M. (PMID: 19542453) Wu L … Fan Z (Journal of immunology (Baltimore, Md. : 1950) 2009) 3 4 22
  3. The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3. (PMID: 7713495) Pilat D … Jenne DE (Genomics 1994) 3 4 22
  4. Met-ase: cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells. (PMID: 8245461) Smyth MJ … Trapani JA (Journal of immunology (Baltimore, Md. : 1950) 1993) 3 4 22
  5. Nucleophosmin is cleaved and inactivated by the cytotoxic granule protease granzyme M during natural killer cell-mediated killing. (PMID: 19103589) Cullen SP … Martin SJ (The Journal of biological chemistry 2009) 3 22

Products for GZMM Gene

Sources for GZMM Gene