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P20718

- GRAH_HUMAN

UniProt

P20718 - GRAH_HUMAN

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Protein

Granzyme H

Gene
GZMH, CGL2, CTSGL2
Organism
Homo sapiens (Human)
Status
Reviewed - 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 system By similarity
Active sitei108 – 1081Charge relay system By similarity
Active sitei202 – 2021Charge relay system By 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. proteolysis Source: RefGenome
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: Chromosome 14

Organism-specific databases

HGNCiHGNC:4710. GZMH.

Subcellular locationi

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

GO - Cellular componenti

  1. secretory granule Source: RefGenome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29088.

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 ↔ 652 Publications
Glycosylationi71 – 711N-linked (GlcNAc...) Reviewed prediction
Glycosylationi104 – 1041N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi142 ↔ 2082 Publications
Disulfide bondi172 ↔ 1872 Publications
Glycosylationi179 – 1791N-linked (GlcNAc...) Reviewed prediction

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

ArrayExpressiP20718.
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 – 4410
Beta strandi46 – 5510
Beta strandi58 – 614
Helixi63 – 653
Beta strandi68 – 758
Beta strandi87 – 9610
Helixi98 – 1003
Turni102 – 1054
Beta strandi110 – 1167
Beta strandi121 – 1233
Beta strandi141 – 1477
Beta strandi149 – 1535
Beta strandi160 – 1678
Helixi169 – 1757
Turni176 – 1783
Turni182 – 1843
Beta strandi185 – 1895
Turni199 – 2035
Beta strandi205 – 2084
Beta strandi211 – 2188
Beta strandi221 – 2233
Beta strandi227 – 2315
Turni232 – 2354
Helixi236 – 2449

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 244224Peptidase S1Add
BLAST

Region

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

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG5640.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP20718.
KOiK09616.
OMAiRKRCGGI.
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. Align

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

MQPFLLLLAF LLTPGAGTEE IIGGHEAKPH SRPYMAFVQF LQEKSRKRCG    50
GILVRKDFVL TAAHCQGSSI NVTLGAHNIK EQERTQQFIP VKRPIPHPAY 100
NPKNFSNDIM LLQLERKAKW TTAVRPLRLP SSKAQVKPGQ LCSVAGWGYV 150
SMSTLATTLQ EVLLTVQKDC QCERLFHGNY SRATEICVGD PKKTQTGFKG 200
DSGGPLVCKD VAQGILSYGN KKGTPPGVYI KVSHFLPWIK RTMKRL 246
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

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. VSP_047573Add
BLAST
Alternative sequencei114 – 19986Missing in isoform 2. VSP_047073Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681S → R in AAP70248. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
ENST00000557220; ENSP00000450576; ENSG00000100450.
GeneIDi2999.
KEGGihsa:2999.
UCSCiuc001wpr.2. human. [P20718-1]
uc010aly.2. human.

Polymorphism databases

DMDMi121590.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS59243.1. [P20718-2 ]
CCDS9632.1. [P20718-1 ]
PIRi A32692.
RefSeqi NP_001257710.1. NM_001270781.1. [P20718-2 ]
NP_219491.1. NM_033423.4. [P20718-1 ]
UniGenei Hs.348264.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LXV model - A 21-246 [» ]
3TJU X-ray 2.70 A 21-246 [» ]
3TJV X-ray 2.40 A 21-246 [» ]
3TK9 X-ray 2.20 A 21-246 [» ]
4GAW X-ray 3.00 A/B/C/D/E/F/G/H/I/J/K/L 21-246 [» ]
ProteinModelPortali P20718.
SMRi P20718. Positions 21-246.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109254. 1 interaction.
IntActi P20718. 1 interaction.
MINTi MINT-4790347.
STRINGi 9606.ENSP00000216338.

Protein family/group databases

MEROPSi S01.147.

PTM databases

PhosphoSitei P20718.

Polymorphism databases

DMDMi 121590.

Proteomic databases

PaxDbi P20718.
PRIDEi P20718.

Protocols and materials databases

DNASUi 2999.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000216338 ; ENSP00000216338 ; ENSG00000100450 . [P20718-1 ]
ENST00000382548 ; ENSP00000371988 ; ENSG00000100450 . [P20718-2 ]
ENST00000557220 ; ENSP00000450576 ; ENSG00000100450 .
GeneIDi 2999.
KEGGi hsa:2999.
UCSCi uc001wpr.2. human. [P20718-1 ]
uc010aly.2. human.

Organism-specific databases

CTDi 2999.
GeneCardsi GC14M025075.
HGNCi HGNC:4710. GZMH.
HPAi HPA029200.
MIMi 116831. gene.
neXtProti NX_P20718.
PharmGKBi PA29088.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5640.
HOGENOMi HOG000251820.
HOVERGENi HBG013304.
InParanoidi P20718.
KOi K09616.
OMAi RKRCGGI.
OrthoDBi EOG7RRF7Z.
PhylomeDBi P20718.
TreeFami TF333630.

Enzyme and pathway databases

Reactomei REACT_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

GeneWikii GZMH.
GenomeRNAii 2999.
NextBioi 11892.
PROi P20718.
SOURCEi Search...

Gene expression databases

ArrayExpressi P20718.
Bgeei P20718.
CleanExi HS_GZMH.
Genevestigatori P20718.

Family and domain databases

InterProi IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF00089. Trypsin. 1 hit.
[Graphical view ]
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 138 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

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