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P20718 (GRAH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GZMH
Synonyms:CGL2, CTSGL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length246 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Enzyme regulation

Inhibited by SERPINB1. Ref.9

Subcellular location

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

Tissue specificity

Constituvely expressed in NK cells. Ref.9

Sequence similarities

Belongs to the peptidase S1 family. Granzyme subfamily.

Contains 1 peptidase S1 domain.

Ontologies

Keywords
   Biological processCytolysis
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Non-traceable author statement Ref.1Ref.3. Source: UniProtKB

cytolysis

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentsecretory granule

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionserine-type endopeptidase activity

Non-traceable author statement Ref.1Ref.3. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P20718-1)

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.
Isoform 2 (identifier: P20718-2)

The sequence of this isoform differs from the canonical sequence as follows:
     114-199: Missing.
Isoform 3 (identifier: P20718-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818
Propeptide19 – 202Activation peptide
PRO_0000027413
Chain21 – 246226Granzyme H
PRO_0000027414

Regions

Domain21 – 244224Peptidase S1
Region46 – 483Mediates the preference for acidic residues at the P3' and P4' sites

Sites

Active site641Charge relay system By similarity
Active site1081Charge relay system By similarity
Active site2021Charge relay system By similarity

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1791N-linked (GlcNAc...) Potential
Disulfide bond49 ↔ 65 Ref.8 Ref.9
Disulfide bond142 ↔ 208 Ref.8 Ref.9
Disulfide bond172 ↔ 187 Ref.8 Ref.9

Natural variations

Alternative sequence69 – 199131Missing in isoform 3.
VSP_047573
Alternative sequence114 – 19986Missing in isoform 2.
VSP_047073
Natural variant841R → Q.
Corresponds to variant rs20545 [ dbSNP | Ensembl ].
VAR_014556

Experimental info

Sequence conflict681S → R in AAP70248. Ref.4

Secondary structure

............................................. 246
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: CA6A87F3DA5F1E71

FASTA24627,315
        10         20         30         40         50         60 
MQPFLLLLAF LLTPGAGTEE IIGGHEAKPH SRPYMAFVQF LQEKSRKRCG GILVRKDFVL 

        70         80         90        100        110        120 
TAAHCQGSSI NVTLGAHNIK EQERTQQFIP VKRPIPHPAY NPKNFSNDIM LLQLERKAKW 

       130        140        150        160        170        180 
TTAVRPLRLP SSKAQVKPGQ LCSVAGWGYV SMSTLATTLQ EVLLTVQKDC QCERLFHGNY 

       190        200        210        220        230        240 
SRATEICVGD PKKTQTGFKG DSGGPLVCKD VAQGILSYGN KKGTPPGVYI KVSHFLPWIK 


RTMKRL 

« Hide

Isoform 2 [UniParc].

Checksum: 5EC04B6A4EAE8E19
Show »

FASTA16017,790
Isoform 3 [UniParc].

Checksum: 06D2C85F733515FC
Show »

FASTA11512,609

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA32692.
RefSeqNP_001257710.1. NM_001270781.1.
NP_219491.1. NM_033423.4.
UniGeneHs.348264.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP20718.
SMRP20718. Positions 21-246.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109254. 1 interaction.
IntActP20718. 1 interaction.
MINTMINT-4790347.
STRING9606.ENSP00000216338.

Protein family/group databases

MEROPSS01.147.

PTM databases

PhosphoSiteP20718.

Polymorphism databases

DMDM121590.

Proteomic databases

PaxDbP20718.
PRIDEP20718.

Protocols and materials databases

DNASU2999.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216338; ENSP00000216338; ENSG00000100450. [P20718-1]
ENST00000382548; ENSP00000371988; ENSG00000100450. [P20718-2]
ENST00000557220; ENSP00000450576; ENSG00000100450.
GeneID2999.
KEGGhsa:2999.
UCSCuc001wpr.2. human. [P20718-1]

Organism-specific databases

CTD2999.
GeneCardsGC14M025075.
HGNCHGNC:4710. GZMH.
HPAHPA029200.
MIM116831. gene.
neXtProtNX_P20718.
PharmGKBPA29088.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP20718.
KOK09616.
OMALVCKDVA.
OrthoDBEOG7RRF7Z.
PhylomeDBP20718.
TreeFamTF333630.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP20718.
BgeeP20718.
CleanExHS_GZMH.
GenevestigatorP20718.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGZMH.
GenomeRNAi2999.
NextBio11892.
PROP20718.
SOURCESearch...

Entry information

Entry nameGRAH_HUMAN
AccessionPrimary (citable) accession number: P20718
Secondary accession number(s): G3V2C5, Q6XGZ0, Q6XGZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM