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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei64 – 641Charge relay systemBy similarity
Active sitei108 – 1081Charge relay systemBy similarity
Active sitei202 – 2021Charge relay systemBy similarity

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. cytolysis Source: UniProtKB-KW
  3. immune response Source: GO_Central
  4. protein processing Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Cytolysis

Enzyme and pathway databases

ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.
REACT_15428. 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
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:4710. GZMH.

Subcellular locationi

  1. Cytoplasmic granule

  2. Note: Cytoplasmic granules of cytolytic T-lymphocytes.

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. intracellular membrane-bounded organelle Source: GO_Central
  3. membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29088.

Polymorphism and mutation databases

DMDMi121590.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Propeptidei19 – 202Activation peptidePRO_0000027413
Chaini21 – 246226Granzyme HPRO_0000027414Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi49 ↔ 65
Glycosylationi71 – 711N-linked (GlcNAc...)Sequence Analysis
Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi142 ↔ 208
Disulfide bondi172 ↔ 187
Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP20718.
PRIDEiP20718.

PTM databases

PhosphoSiteiP20718.

Expressioni

Tissue specificityi

Constituvely expressed in NK cells.1 Publication

Gene expression databases

BgeeiP20718.
CleanExiHS_GZMH.
GenevestigatoriP20718.

Organism-specific databases

HPAiHPA029200.

Interactioni

Protein-protein interaction databases

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

Structurei

Secondary structure

1
246
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi35 – 4410Combined sources
Beta strandi46 – 5510Combined sources
Beta strandi58 – 614Combined sources
Helixi63 – 653Combined sources
Beta strandi68 – 758Combined sources
Beta strandi87 – 9610Combined sources
Helixi98 – 1003Combined sources
Turni102 – 1054Combined sources
Beta strandi110 – 1167Combined sources
Beta strandi121 – 1233Combined sources
Beta strandi141 – 1477Combined sources
Beta strandi149 – 1535Combined sources
Beta strandi160 – 1678Combined sources
Helixi169 – 1757Combined sources
Turni176 – 1783Combined sources
Turni182 – 1843Combined sources
Beta strandi185 – 1895Combined sources
Turni199 – 2035Combined sources
Beta strandi205 – 2084Combined sources
Beta strandi211 – 2188Combined sources
Beta strandi221 – 2233Combined sources
Beta strandi227 – 2315Combined sources
Turni232 – 2354Combined sources
Helixi236 – 2449Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 21-246.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 244224Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni46 – 483Mediates the preference for acidic residues at the P3' and P4' sites

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

eggNOGiCOG5640.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP20718.
KOiK09616.
OMAiLVCKDVA.
OrthoDBiEOG7RRF7Z.
PhylomeDBiP20718.
TreeFamiTF333630.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681S → R in AAP70248 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti84 – 841R → Q.
Corresponds to variant rs20545 [ dbSNP | Ensembl ].
VAR_014556

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei69 – 199131Missing in isoform 3. 1 PublicationVSP_047573Add
BLAST
Alternative sequencei114 – 19986Missing in isoform 2. 1 PublicationVSP_047073Add
BLAST

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.2. human. [P20718-1]
uc010aly.2. human.

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
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. Positions 21-246.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protein family/group databases

MEROPSiS01.147.

PTM databases

PhosphoSiteiP20718.

Polymorphism and mutation databases

DMDMi121590.

Proteomic databases

PaxDbiP20718.
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.2. human. [P20718-1]
uc010aly.2. human.

Organism-specific databases

CTDi2999.
GeneCardsiGC14M025075.
HGNCiHGNC:4710. GZMH.
HPAiHPA029200.
MIMi116831. gene.
neXtProtiNX_P20718.
PharmGKBiPA29088.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118895.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP20718.
KOiK09616.
OMAiLVCKDVA.
OrthoDBiEOG7RRF7Z.
PhylomeDBiP20718.
TreeFamiTF333630.

Enzyme and pathway databases

ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.
REACT_15428. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Miscellaneous databases

GeneWikiiGZMH.
GenomeRNAii2999.
NextBioi11892.
PROiP20718.
SOURCEiSearch...

Gene expression databases

BgeeiP20718.
CleanExiHS_GZMH.
GenevestigatoriP20718.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a gene that encodes a new member of the human cytotoxic cell protease family."
    Meier M., Kwong P.C., Fregeau C.J., Atkinson E.A., Burrington M., Ehrman N., Sorensen O., Lin C.C., Wilkins J., Bleackley R.C.
    Biochemistry 29:4042-4049(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Structure and evolutionary origin of the human granzyme H gene."
    Haddad P., Jenne D.E., Tschopp J., Clement M.-V., Mathieu-Mahul D., Sasportes M.
    Int. Immunol. 3:57-66(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Characterization of a novel, human cytotoxic lymphocyte-specific serine protease cDNA clone (CSP-C)."
    Klein J.L., Selvakumar A., Trapani J.A., Dupont B.
    Tissue Antigens 35:220-228(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "Identification and characterization of granzyme H splice variants 2 and 3 from large granular lymphocyte leukemia."
    Kothapalli R., Kusmartseva I., Loughran T.P. Jr.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
    Tissue: Leukemic T-cell.
  5. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Pancreas.
  8. "Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif."
    Wang L., Zhang K., Wu L., Liu S., Zhang H., Zhou Q., Tong L., Sun F., Fan Z.
    J. Immunol. 188:765-773(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-246 OF MUTANT ASN-102 ALONE AND IN COMPLEX WITH SUBSTRATE PEPTIDE AND INHIBITOR, FUNCTION, SUBSTRATE SPECIFICITY, DISULFIDE BONDS.
  9. "Identification of SERPINB1 as a physiological inhibitor of human granzyme H."
    Wang L., Li Q., Wu L., Liu S., Zhang Y., Yang X., Zhu P., Zhang H., Zhang K., Lou J., Liu P., Tong L., Sun F., Fan Z.
    J. Immunol. 190:1319-1330(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 21-246 IN COMPLEX WITH SERPINB1, FUNCTION, DISULFIDE BONDS, TISSUE SPECIFICITY, ENZYME REGULATION.

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: March 4, 2015
This is version 144 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

External Data

Dasty 3

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 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.