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Protein

Granzyme H

Gene

GZMH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication.2 Publications

Enzyme regulationi

Inhibited by SERPINB1.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei64Charge relay systemBy similarity1
Active sitei108Charge relay systemBy similarity1
Active sitei202Charge relay systemBy similarity1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cytolysis Source: UniProtKB-KW
  • immune response Source: GO_Central
  • protein processing Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Cytolysis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100450-MONOMER.
ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Protein family/group databases

MEROPSiS01.147.

Names & Taxonomyi

Protein namesi
Recommended name:
Granzyme H (EC:3.4.21.-)
Alternative name(s):
CCP-X
Cathepsin G-like 2
Short name:
CTSGL2
Cytotoxic T-lymphocyte proteinase
Cytotoxic serine protease C
Short name:
CSP-C
Gene namesi
Name:GZMH
Synonyms:CGL2, CTSGL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:4710. GZMH.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • intracellular membrane-bounded organelle Source: GO_Central
  • membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi2999.
OpenTargetsiENSG00000100450.
PharmGKBiPA29088.

Polymorphism and mutation databases

DMDMi121590.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Add BLAST18
PropeptideiPRO_000002741319 – 20Activation peptide2
ChainiPRO_000002741421 – 246Granzyme HAdd BLAST226

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 65
Glycosylationi71N-linked (GlcNAc...)Sequence analysis1
Glycosylationi104N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi142 ↔ 208
Disulfide bondi172 ↔ 187
Glycosylationi179N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP20718.
PeptideAtlasiP20718.
PRIDEiP20718.

PTM databases

PhosphoSitePlusiP20718.

Expressioni

Tissue specificityi

Constituvely expressed in NK cells.1 Publication

Gene expression databases

BgeeiENSG00000100450.
CleanExiHS_GZMH.
ExpressionAtlasiP20718. baseline and differential.
GenevisibleiP20718. HS.

Organism-specific databases

HPAiHPA029200.

Interactioni

Protein-protein interaction databases

BioGridi109254. 1 interactor.
IntActiP20718. 1 interactor.
MINTiMINT-4790347.
STRINGi9606.ENSP00000216338.

Structurei

Secondary structure

1246
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 44Combined sources10
Beta strandi46 – 55Combined sources10
Beta strandi58 – 61Combined sources4
Helixi63 – 65Combined sources3
Beta strandi68 – 75Combined sources8
Beta strandi87 – 96Combined sources10
Helixi98 – 100Combined sources3
Turni102 – 105Combined sources4
Beta strandi110 – 116Combined sources7
Beta strandi121 – 123Combined sources3
Beta strandi141 – 147Combined sources7
Beta strandi149 – 153Combined sources5
Beta strandi160 – 167Combined sources8
Helixi169 – 175Combined sources7
Turni176 – 178Combined sources3
Turni182 – 184Combined sources3
Beta strandi185 – 189Combined sources5
Turni199 – 203Combined sources5
Beta strandi205 – 208Combined sources4
Beta strandi211 – 218Combined sources8
Beta strandi221 – 223Combined sources3
Beta strandi227 – 231Combined sources5
Turni232 – 235Combined sources4
Helixi236 – 244Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LXVmodel-A21-246[»]
3TJUX-ray2.70A21-246[»]
3TJVX-ray2.40A21-246[»]
3TK9X-ray2.20A21-246[»]
4GAWX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L21-246[»]
ProteinModelPortaliP20718.
SMRiP20718.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 244Peptidase S1PROSITE-ProRule annotationAdd BLAST224

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 48Mediates the preference for acidic residues at the P3' and P4' sites3

Sequence similaritiesi

Belongs to the peptidase S1 family. Granzyme subfamily.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP20718.
KOiK09616.
OMAiLVCKDVA.
OrthoDBiEOG091G0G5F.
PhylomeDBiP20718.
TreeFamiTF333630.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20718-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQPFLLLLAF LLTPGAGTEE IIGGHEAKPH SRPYMAFVQF LQEKSRKRCG
60 70 80 90 100
GILVRKDFVL TAAHCQGSSI NVTLGAHNIK EQERTQQFIP VKRPIPHPAY
110 120 130 140 150
NPKNFSNDIM LLQLERKAKW TTAVRPLRLP SSKAQVKPGQ LCSVAGWGYV
160 170 180 190 200
SMSTLATTLQ EVLLTVQKDC QCERLFHGNY SRATEICVGD PKKTQTGFKG
210 220 230 240
DSGGPLVCKD VAQGILSYGN KKGTPPGVYI KVSHFLPWIK RTMKRL
Length:246
Mass (Da):27,315
Last modified:February 1, 1991 - v1
Checksum:iCA6A87F3DA5F1E71
GO
Isoform 2 (identifier: P20718-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-199: Missing.

Show »
Length:160
Mass (Da):17,790
Checksum:i5EC04B6A4EAE8E19
GO
Isoform 3 (identifier: P20718-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     69-199: Missing.

Show »
Length:115
Mass (Da):12,609
Checksum:i06D2C85F733515FC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti68S → R in AAP70248 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01455684R → Q.Corresponds to variant rs20545dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04757369 – 199Missing in isoform 3. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_047073114 – 199Missing in isoform 2. 1 PublicationAdd BLAST86

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02907 Genomic DNA. Translation: AAA76859.1.
M57888 Genomic DNA. Translation: AAA03514.1.
M36118 mRNA. Translation: AAA03248.1.
M72150 Genomic DNA. Translation: AAA74885.1.
AY232657 mRNA. Translation: AAP70247.1.
AY232658 mRNA. Translation: AAP70248.1.
AL136018 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66004.1.
BC027974 mRNA. Translation: AAH27974.1.
CCDSiCCDS59243.1. [P20718-2]
CCDS9632.1. [P20718-1]
PIRiA32692.
RefSeqiNP_001257710.1. NM_001270781.1. [P20718-2]
NP_219491.1. NM_033423.4. [P20718-1]
UniGeneiHs.348264.

Genome annotation databases

EnsembliENST00000216338; ENSP00000216338; ENSG00000100450. [P20718-1]
ENST00000382548; ENSP00000371988; ENSG00000100450. [P20718-2]
GeneIDi2999.
KEGGihsa:2999.
UCSCiuc001wpr.3. human. [P20718-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02907 Genomic DNA. Translation: AAA76859.1.
M57888 Genomic DNA. Translation: AAA03514.1.
M36118 mRNA. Translation: AAA03248.1.
M72150 Genomic DNA. Translation: AAA74885.1.
AY232657 mRNA. Translation: AAP70247.1.
AY232658 mRNA. Translation: AAP70248.1.
AL136018 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66004.1.
BC027974 mRNA. Translation: AAH27974.1.
CCDSiCCDS59243.1. [P20718-2]
CCDS9632.1. [P20718-1]
PIRiA32692.
RefSeqiNP_001257710.1. NM_001270781.1. [P20718-2]
NP_219491.1. NM_033423.4. [P20718-1]
UniGeneiHs.348264.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LXVmodel-A21-246[»]
3TJUX-ray2.70A21-246[»]
3TJVX-ray2.40A21-246[»]
3TK9X-ray2.20A21-246[»]
4GAWX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L21-246[»]
ProteinModelPortaliP20718.
SMRiP20718.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109254. 1 interactor.
IntActiP20718. 1 interactor.
MINTiMINT-4790347.
STRINGi9606.ENSP00000216338.

Protein family/group databases

MEROPSiS01.147.

PTM databases

PhosphoSitePlusiP20718.

Polymorphism and mutation databases

DMDMi121590.

Proteomic databases

PaxDbiP20718.
PeptideAtlasiP20718.
PRIDEiP20718.

Protocols and materials databases

DNASUi2999.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216338; ENSP00000216338; ENSG00000100450. [P20718-1]
ENST00000382548; ENSP00000371988; ENSG00000100450. [P20718-2]
GeneIDi2999.
KEGGihsa:2999.
UCSCiuc001wpr.3. human. [P20718-1]

Organism-specific databases

CTDi2999.
DisGeNETi2999.
GeneCardsiGZMH.
HGNCiHGNC:4710. GZMH.
HPAiHPA029200.
MIMi116831. gene.
neXtProtiNX_P20718.
OpenTargetsiENSG00000100450.
PharmGKBiPA29088.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP20718.
KOiK09616.
OMAiLVCKDVA.
OrthoDBiEOG091G0G5F.
PhylomeDBiP20718.
TreeFamiTF333630.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100450-MONOMER.
ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Miscellaneous databases

GeneWikiiGZMH.
GenomeRNAii2999.
PROiP20718.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100450.
CleanExiHS_GZMH.
ExpressionAtlasiP20718. baseline and differential.
GenevisibleiP20718. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRAH_HUMAN
AccessioniPrimary (citable) accession number: P20718
Secondary accession number(s): G3V2C5, Q6XGZ0, Q6XGZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: November 2, 2016
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.