GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GZMHprovided by HGNC
Official Full Name: granzyme H (cathepsin G-like 2, protein h-CCPX)provided by HGNC
Primary source: HGNC:4710
See related: Ensembl:ENSG00000100450; HPRD:00290; MIM:116831; Vega:OTTHUMG00000140185
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: CCP-X; CGL-2; CSP-C; CTLA1; CTSGL2
Summary: The protein encoded by this gene is a member of the granzyme family. Members of this family are highly conserved serine proteases that eliminate transformed cells and virus-infected cells. This protein, which has chymotrypsin-like activity, has a preference for bulky aromatic amino acids at the P1 position and for acidic residues at the P3' and P4' positions. This protein is reported to be constitutively expressed in NK cells and may play a role in the cytotoxic arm of the innate immune response by inducing target cell death and by directly cleaving substrates in pathogen-infected cells. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

Genomic context

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Location :: 14q11.2

Sequence :: Chromosome: 14; NC_000014.8 (25075686..25078926, complement)

See GZMH in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Upon reactive center loop cleavage at Phe-343,SERPINB1 covalently complexes with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell-mediated cytotoxicity. Crystal structures show possible conformational changes in GzmH for the suicide inhibition.
Title: Identification of SERPINB1 as a physiological inhibitor of human granzyme H.
An unusual RKR motif (Arg39-Lys40-Arg41), conserved only in GzmH, helps define the S3' and S4' binding regions, indicating the preference for acidic residues at the P3' and P4' sites.
Title: Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif.
GzmH suppresses viral replication through association with the hepatitis B virus x protein.
Title: Granzyme H of cytotoxic lymphocytes is required for clearance of the hepatitis B virus through cleavage of the hepatitis B virus X protein.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
Cleavage of La protein by granzyme H generates a COOH-terminal truncated form of La protein that loses nuclear localization and decreases hepatitis C virus-internal ribosome entry site-mediated translational activity.
Title: Cleavage of La protein by granzyme H induces cytoplasmic translocation and interferes with La-mediated HCV-IRES translational activity.
GzmH may play an essential role in caspase-dependent pathogen clearance in the innate immunity that may complement the proapoptotic function of GzmB in human NK cells.
Title: Granzyme H induces apoptosis of target tumor cells characterized by DNA fragmentation and Bid-dependent mitochondrial damage.
Granzyme H could have evolved a proteolytic specificity that both interferes directly with adenovirus replication and prevents the virus from blocking the potent pro-apoptotic activity of granzyme B.
Title: H is for helper: granzyme H helps granzyme B kill adenovirus-infected cells.
Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition.
Title: Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition.
Expression levels of GzmH in naive natural killer cells and its killing ability support the role of the protease in triggering an alternative cell-death pathway in innate immunity.
Title: Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program.

Submit: New GeneRIF Correction See all (12)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Pathways from BioSystems

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Metabolism of Angiotensinogen to Angiotensins, organism-specific biosystem (from REACTOME)
Metabolism of Angiotensinogen to Angiotensins, organism-specific biosystemAngiotensinogen, a prohormone, is synthesized and secreted mainly by the liver but also from other tissues (reviewed in Fyhrquist and Saijonmaa 2008, Cat and Touyz 2011). Renin, an aspartyl protease ...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...
Regulation of Insulin-like Growth Factor (IGF) Transport and Uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs), organism-specific biosystem (from REACTOME)
Regulation of Insulin-like Growth Factor (IGF) Transport and Uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs), organism-specific biosystemThe family of Insulin like Growth Factor Binding Proteins (IGFBPs) share 50% amino acid identity with conserved N terminal and C terminal regions responsible for binding Insulin like Growth Factors I...

General gene information

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Markers

RH71382 (e-PCR)
- UniSTS:52236

STS-R53038 (e-PCR)
- UniSTS:9096

Homology

Homologs of the GZMH gene: The GZMH gene is conserved in chimpanzee, dog, cow, and mouse.
Map Viewer (Mouse)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
serine-type endopeptidase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	NAS Non-traceable Author Statement more info	PubMed
cytolysis	IEA Inferred from Electronic Annotation more info
proteolysis	NAS Non-traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	NAS Non-traceable Author Statement more info

General protein information

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Preferred Names: granzyme H

Names: granzyme H; cytotoxin serine protease-C; cytotoxic T-lymphocyte proteinase; cytotoxic T-lymphocyte-associated serine esterase 1

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_001270780.1 → NP_001257709.1 granzyme H isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region compared to variant 1. It encodes isoform 2 which is shorter than isoform 1.

Source sequence(s)

AL136018, AW204493, BQ054303, CD000418

Conserved Domains (2) summary

cd00190
Location:21 – 135
Blast Score: 353

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 ...

cl00149
Location:135 – 175
Blast Score: 171

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_001270781.1 → NP_001257710.1 granzyme H isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the coding region compared to variant 1. It encodes isoform 3 which is shorter than isoform 1.

Source sequence(s)

AL136018, AW204493, AY232657, BQ054303

Consensus CDS

CCDS59243.1

UniProtKB/TrEMBL

Q6XGZ1

Related

ENSP00000371988, OTTHUMP00000245745, ENST00000382548, OTTHUMT00000412825

Conserved Domains (2) summary

cd00190
Location:21 – 113
Blast Score: 293

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 ...

cl00149
Location:113 – 153
Blast Score: 170

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_033423.4 → NP_219491.1 granzyme H isoform 1 precursor

Status: REVIEWED

Description

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

Source sequence(s)

AL136018, AW204493, BC027974, BQ054303

Consensus CDS

CCDS9632.1

UniProtKB/Swiss-Prot

P20718

Related

ENSP00000216338, OTTHUMP00000178753, ENST00000216338, OTTHUMT00000276538

Conserved Domains (1) summary

cd00190
Location:21 – 242
Blast Score: 616

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 ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p10 Primary Assembly

Range

25075686..25078926, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

5190499..5193739, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018925.1 Alternate CHM1_1.0

Range

6073015..6076255, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01061345.1 (189084..192324)	None
genomic	AL136018.4 (49840..53011)	None
genomic	AMYH01005614.1 (116704..119944)	None
genomic	CH471078.2	EAW66004.1
		EAW66005.1
genomic	J02907.1	AAA76859.1
genomic	M57888.1	AAA03514.1
genomic	M59718.1	None
genomic	M72150.1	AAA74885.1
mRNA	AW204493.1	None
mRNA	AY232657.1	AAP70247.1
mRNA	AY232658.1	AAP70248.1
mRNA	BC027974.1	AAH27974.1
mRNA	BQ054303.1	None
mRNA	CD000418.1	None
mRNA	M36118.1	AAA03248.1
other-genetic	DQ892068.2	ABM82994.1
other-genetic	DQ895261.2	ABM86187.1