GZMH granzyme H [Homo sapiens (human)] - Gene

Summary

Official Symbol: GZMHprovided by HGNC
Official Full Name: granzyme Hprovided by HGNC
Primary source: HGNC:HGNC:4710
See related: Ensembl:ENSG00000100450 MIM:116831; AllianceGenome:HGNC:4710
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: This gene encodes a member of the peptidase S1 family of serine proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a chymotrypsin-like protease. This protein is reported to be constitutively expressed in the NK (natural killer) cells of the immune system 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. This gene is present in a gene cluster with another member of the granzyme subfamily on chromosome 14. [provided by RefSeq, Nov 2015]
Expression: Broad expression in spleen (RPKM 9.5), bone marrow (RPKM 8.3) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q12

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (24606480..24609685, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (18805362..18808567, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (25075686..25078891, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Natural Killer Cells Disrupt Nerve Fibers by Granzyme H in Atheriosclerotic Cerebral Small Vessel Disease.
Title: Natural Killer Cells Disrupt Nerve Fibers by Granzyme H in Atheriosclerotic Cerebral Small Vessel Disease.
Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.
Title: Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.
Granzyme H did directly process DFF45, potentially leading to DNA damage.
Title: Granzyme H induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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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Markers

RH71382 (e-PCR)
- UniSTS:52236

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in killing of cells of another organism	IEA Inferred from Electronic Annotation more info
involved_in protein maturation	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytolytic granule	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	HDA more info	PubMed

General protein information

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Preferred Names: granzyme H

Names: cathepsin G-like 2, protein h-CCPX; cytotoxic T-lymphocyte proteinase; cytotoxic T-lymphocyte-associated serine esterase 1; cytotoxin serine protease-C

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_001270780.2 → 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. This isoform (2) may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AW204493, BQ054303, CD000418

Conserved Domains (2) summary

smart00020
Location:20 → 175

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:21 → 178

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_001270781.2 → NP_001257710.1 granzyme H isoform 3 precursor

See identical proteins and their annotated locations for NP_001257710.1

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. This isoform (3) may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AW204493, AY232657

Consensus CDS

CCDS59243.1

UniProtKB/Swiss-Prot

P20718

Related

ENSP00000371988.4, ENST00000382548.4

Conserved Domains (2) summary

smart00020
Location:20 → 153

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:21 → 156

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_033423.5 → NP_219491.1 granzyme H isoform 1 preproprotein

See identical proteins and their annotated locations for NP_219491.1

Status: REVIEWED

Description

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

Source sequence(s)

AW204493, BC027974, BQ054303

Consensus CDS

CCDS9632.1

UniProtKB/Swiss-Prot

G3V2C5, P20718, Q6XGZ0, Q6XGZ1

Related

ENSP00000216338.4, ENST00000216338.9

Conserved Domains (1) summary

cd00190
Location:21 → 242

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 ...