GZMM granzyme M [Homo sapiens (human)] - Gene

Summary

Official Symbol: GZMMprovided by HGNC
Official Full Name: granzyme Mprovided by HGNC
Primary source: HGNC:HGNC:4712
See related: Ensembl:ENSG00000197540 MIM:600311; AllianceGenome:HGNC:4712
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: MET1; LMET1
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]
Expression: Biased expression in spleen (RPKM 8.2), lymph node (RPKM 6.5) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (544053..549922)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (497822..503990)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (544053..549922)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme M-Mediated Cleavage.
Title: Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme M-Mediated Cleavage.
Granzyme B and granzyme M cleave IE1 after Asp398 and Leu414, respectively, likely resulting in IE1 aberrant cellular localization.
Title: Killer cell proteases can target viral immediate-early proteins to control human cytomegalovirus infection in a noncytotoxic manner.
GzMM has a critical role during early stages of inflammation in ulcerative colitis; in its absence colonic inflammation is enhanced.
Title: Granzyme M has a critical role in providing innate immune protection in ulcerative colitis.
We also report that TNFalpha induces the attachment of Met1-linked Ub chains directly to TNF receptor 1, which do not seem to be attached covalently to Lys63-linked or other types of ubiquitin chain.
Title: Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling.
Granzym M may be important in regulating HCMV latency and reactivation in SCT patients.
Title: Elevated granzyme M-expressing lymphocytes during cytomegalovirus latency and reactivation after allogeneic stem cell transplantation.
GrM is expressed in HCMV-specific CD8thorn T cells and cleaves host cell protein hnRNP K in the presence of RNA.
Title: Granzyme M targets host cell hnRNP K that is essential for human cytomegalovirus replication.
FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade.
Title: FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade.
Results indicate that cellular overexpression of SERPINB4 inhibits recombinant GrM-induced as well as NK cell-mediated cell death.
Title: Intracellular serine protease inhibitor SERPINB4 inhibits granzyme M-induced cell death.
GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF.
Title: Cleavage of von Willebrand factor by granzyme M destroys its factor VIII binding capacity.
Results describe the structural characterization of granzyme M by molecular modeling as well as by detailed comparison with other granzymes.
Title: Granzyme M: characterization with sites of post-translational modification and specific sites of interaction with substrates and inhibitors.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type peptidase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in killing of cells of another organism	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed

General protein information

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Preferred Names: granzyme M

Names: HU-Met-1; Met-1 serine protease; lymphocyte met-ase 1; met-ase; natural killer cell granular protease

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.

mRNA and Protein(s)

NM_001258351.2 → NP_001245280.2 granzyme M isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of a coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AC011556

Consensus CDS

CCDS74240.1

UniProtKB/TrEMBL

U3KQV5

Related

ENSP00000476255.2, ENST00000592501.5

Conserved Domains (1) summary

cd00190
Location:1 → 213

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
NM_005317.4 → NP_005308.2 granzyme M isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC011556

Consensus CDS

CCDS12031.1

UniProtKB/Swiss-Prot

P51124

Related

ENSP00000264553.1, ENST00000264553.6

Conserved Domains (1) summary

cd00190
Location:26 → 252

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...