P12544 · GRAA_HUMAN
- ProteinGranzyme A
- GeneGZMA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids262 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubMed:12819770, PubMed:32299851, PubMed:3257574, PubMed:3262682, PubMed:3263427).
It cleaves after Lys or Arg (PubMed:12819770, PubMed:32299851).
Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming moiety of GSDMB, thereby triggering pyroptosis and target cell death (PubMed:32299851, PubMed:34022140, PubMed:36157507, PubMed:36899106).
Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity (PubMed:12524539).
Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA (PubMed:11555662, PubMed:12628186, PubMed:16818237).
It cleaves after Lys or Arg (PubMed:12819770, PubMed:32299851).
Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming moiety of GSDMB, thereby triggering pyroptosis and target cell death (PubMed:32299851, PubMed:34022140, PubMed:36157507, PubMed:36899106).
Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity (PubMed:12524539).
Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA (PubMed:11555662, PubMed:12628186, PubMed:16818237).
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 69 | Charge relay system | ||||
Sequence: H | ||||||
Active site | 114 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 212 | Charge relay system | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | extracellular space | |
Cellular Component | immunological synapse | |
Cellular Component | nucleus | |
Molecular Function | protein homodimerization activity | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | apoptotic process | |
Biological Process | cytotoxic T cell pyroptotic cell death | |
Biological Process | granzyme-mediated programmed cell death signaling pathway | |
Biological Process | immune response | |
Biological Process | killing of cells of another organism | |
Biological Process | negative regulation of DNA binding | |
Biological Process | negative regulation of endodeoxyribonuclease activity | |
Biological Process | negative regulation of oxidoreductase activity | |
Biological Process | positive regulation of apoptotic process | |
Biological Process | protein maturation | |
Biological Process | proteolysis involved in protein catabolic process | |
Biological Process | pyroptotic inflammatory response | |
Biological Process | response to bacterium |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGranzyme A
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP12544
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform alpha
Note: Delivered into the target cell by perforin.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_024291 | 121 | in dbSNP:rs3104233 | |||
Sequence: M → T | ||||||
Mutagenesis | 212 | Abolished protease activity. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 331 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, propeptide, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MRNSYRFLASSLSVVVSLLLIPEDVC | ||||||
Propeptide | PRO_0000027393 | 27-28 | Activation peptide | |||
Sequence: EK | ||||||
Chain | PRO_0000027394 | 29-262 | Granzyme A | |||
Sequence: IIGGNEVTPHSRPYMVLLSLDRKTICAGALIAKDWVLTAAHCNLNKRSQVILGAHSITREEPTKQIMLVKKEFPYPCYDPATREGDLKLLQLMEKAKINKYVTILHLPKKGDDVKPGTMCQVAGWGRTHNSASWSDTLREVNITIIDRKVCNDRNHYNFNPVIGMNMVCAGSLRGGRDSCNGDSGSPLLCEGVFRGVTSFGLENKCGDPRGPGVYILLSKKHLNWIIMTIKGAV | ||||||
Disulfide bond | 54↔70 | |||||
Sequence: CAGALIAKDWVLTAAHC | ||||||
Disulfide bond | 148↔218 | |||||
Sequence: CQVAGWGRTHNSASWSDTLREVNITIIDRKVCNDRNHYNFNPVIGMNMVCAGSLRGGRDSCNGDSGSPLLC | ||||||
Glycosylation | 170 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 179↔197 | |||||
Sequence: CNDRNHYNFNPVIGMNMVC | ||||||
Disulfide bond | 208↔234 | |||||
Sequence: CNGDSGSPLLCEGVFRGVTSFGLENKC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Dexamethasone (DEX) induces expression of isoform beta and represses expression of isoform alpha. The alteration in expression is mediated by binding of glucocorticoid receptor to independent promoters adjacent to the alternative first exons of isoform alpha and isoform beta.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 29-259 | Peptidase S1 | ||||
Sequence: IIGGNEVTPHSRPYMVLLSLDRKTICAGALIAKDWVLTAAHCNLNKRSQVILGAHSITREEPTKQIMLVKKEFPYPCYDPATREGDLKLLQLMEKAKINKYVTILHLPKKGDDVKPGTMCQVAGWGRTHNSASWSDTLREVNITIIDRKVCNDRNHYNFNPVIGMNMVCAGSLRGGRDSCNGDSGSPLLCEGVFRGVTSFGLENKCGDPRGPGVYILLSKKHLNWIIMTIK |
Sequence similarities
Belongs to the peptidase S1 family. Granzyme subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative promoter usage.
P12544-1
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.
- Namealpha
- Length262
- Mass (Da)28,999
- Last updated2011-01-11 v2
- ChecksumFD773628BA6F301B
P12544-2
- Namebeta
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038571 | 1-17 | in isoform beta | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_038572 | 18-23 | in isoform beta | |||
Sequence: LLLIPE → MTKGLR | ||||||
Sequence conflict | 33-34 | in Ref. 5; no nucleotide entry | ||||
Sequence: NE → DT | ||||||
Sequence conflict | 36 | in Ref. 5; no nucleotide entry | ||||
Sequence: T → V | ||||||
Sequence conflict | 47 | in Ref. 5; no nucleotide entry | ||||
Sequence: S → K | ||||||
Sequence conflict | 49-52 | in Ref. 5; no nucleotide entry | ||||
Sequence: DRKT → KPDS | ||||||
Sequence conflict | 62 | in Ref. 5; no nucleotide entry | ||||
Sequence: D → N | ||||||
Sequence conflict | 71-72 | in Ref. 5; no nucleotide entry | ||||
Sequence: NL → IP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M18737 EMBL· GenBank· DDBJ | AAA52647.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456968 EMBL· GenBank· DDBJ | CAG33249.1 EMBL· GenBank· DDBJ | mRNA | ||
AC091977 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC015739 EMBL· GenBank· DDBJ | AAH15739.1 EMBL· GenBank· DDBJ | mRNA | ||
AB284134 EMBL· GenBank· DDBJ | BAF56159.1 EMBL· GenBank· DDBJ | mRNA | ||
U40006 EMBL· GenBank· DDBJ | AAD00009.1 EMBL· GenBank· DDBJ | Genomic DNA |