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Protein

Granzyme A

Gene

GZMA

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

Functioni

Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. 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.4 Publications

Caution

Exons 1a and 1b of the sequence reported in PubMed:17180578 are of human origin, however exon 2 shows strong similarity to the rat sequence.Curated

Catalytic activityi

Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei69Charge relay system1
Active sitei114Charge relay system1
Active sitei212Charge relay system1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis, Cytolysis

Enzyme and pathway databases

BRENDAi3.4.21.78 2681
SIGNORiP12544

Protein family/group databases

MEROPSiS01.135

Names & Taxonomyi

Protein namesi
Recommended name:
Granzyme A (EC:3.4.21.78)
Alternative name(s):
CTL tryptase
Cytotoxic T-lymphocyte proteinase 1
Fragmentin-1
Granzyme-1
Hanukkah factor
Short name:
H factor
Short name:
HF
Gene namesi
Name:GZMA
Synonyms:CTLA3, HFSP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145649.7
HGNCiHGNC:4708 GZMA
MIMi140050 gene
neXtProtiNX_P12544

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3001
OpenTargetsiENSG00000145649
PharmGKBiPA29086

Chemistry databases

ChEMBLiCHEMBL4307

Polymorphism and mutation databases

BioMutaiGZMA
DMDMi317373360

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26In isoform alphaAdd BLAST26
PropeptideiPRO_000002739327 – 28Activation peptide (in isoform alpha)3 Publications2
ChainiPRO_000002739429 – 262Granzyme AAdd BLAST234

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 70
Disulfide bondi148 ↔ 218
Glycosylationi170N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi179 ↔ 197
Disulfide bondi208 ↔ 234

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP12544
PaxDbiP12544
PeptideAtlasiP12544
PRIDEiP12544
ProteomicsDBi52858
52859 [P12544-2]

PTM databases

iPTMnetiP12544
PhosphoSitePlusiP12544

Expressioni

Inductioni

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.1 Publication

Gene expression databases

BgeeiENSG00000145649 Expressed in 150 organ(s), highest expression level in leukocyte
CleanExiHS_GZMA
GenevisibleiP12544 HS

Organism-specific databases

HPAiHPA054134

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with APEX1.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109256, 17 interactors
IntActiP12544, 4 interactors
STRINGi9606.ENSP00000274306

Structurei

Secondary structure

1262
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP12544
SMRiP12544
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12544

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 259Peptidase S1PROSITE-ProRule annotationAdd BLAST231

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118895
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiP12544
KOiK01352
OMAiKEFPYPC
OrthoDBiEOG091G0AH5
PhylomeDBiP12544
TreeFamiTF333630

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket
Isoform alpha (identifier: P12544-1) [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
MRNSYRFLAS SLSVVVSLLL IPEDVCEKII GGNEVTPHSR PYMVLLSLDR
60 70 80 90 100
KTICAGALIA KDWVLTAAHC NLNKRSQVIL GAHSITREEP TKQIMLVKKE
110 120 130 140 150
FPYPCYDPAT REGDLKLLQL MEKAKINKYV TILHLPKKGD DVKPGTMCQV
160 170 180 190 200
AGWGRTHNSA SWSDTLREVN ITIIDRKVCN DRNHYNFNPV IGMNMVCAGS
210 220 230 240 250
LRGGRDSCNG DSGSPLLCEG VFRGVTSFGL ENKCGDPRGP GVYILLSKKH
260
LNWIIMTIKG AV
Length:262
Mass (Da):28,999
Last modified:January 11, 2011 - v2
Checksum:iFD773628BA6F301B
GO
Isoform beta (identifier: P12544-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: Missing.
     18-23: LLLIPE → MTKGLR

Show »
Length:245
Mass (Da):27,109
Checksum:i7489DB5C158483F6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33 – 34NE → DT no nucleotide entry (PubMed:17180578).Curated2
Sequence conflicti36T → V no nucleotide entry (PubMed:17180578).Curated1
Sequence conflicti47S → K no nucleotide entry (PubMed:17180578).Curated1
Sequence conflicti49 – 52DRKT → KPDS no nucleotide entry (PubMed:17180578).Curated4
Sequence conflicti62D → N no nucleotide entry (PubMed:17180578).Curated1
Sequence conflicti71 – 72NL → IP no nucleotide entry (PubMed:17180578).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024291121M → T3 PublicationsCorresponds to variant dbSNP:rs3104233Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0385711 – 17Missing in isoform beta. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_03857218 – 23LLLIPE → MTKGLR in isoform beta. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18737 mRNA Translation: AAA52647.1
CR456968 mRNA Translation: CAG33249.1
AC091977 Genomic DNA No translation available.
BC015739 mRNA Translation: AAH15739.1
AB284134 mRNA Translation: BAF56159.1
U40006 Genomic DNA Translation: AAD00009.1
CCDSiCCDS3965.1 [P12544-1]
PIRiA31372
RefSeqiNP_006135.1, NM_006144.3
UniGeneiHs.90708

Genome annotation databases

EnsembliENST00000274306; ENSP00000274306; ENSG00000145649 [P12544-1]
GeneIDi3001
KEGGihsa:3001
UCSCiuc003jpm.4 human [P12544-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18737 mRNA Translation: AAA52647.1
CR456968 mRNA Translation: CAG33249.1
AC091977 Genomic DNA No translation available.
BC015739 mRNA Translation: AAH15739.1
AB284134 mRNA Translation: BAF56159.1
U40006 Genomic DNA Translation: AAD00009.1
CCDSiCCDS3965.1 [P12544-1]
PIRiA31372
RefSeqiNP_006135.1, NM_006144.3
UniGeneiHs.90708

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HF1model-A29-262[»]
1OP8X-ray2.50A/B/C/D/E/F29-262[»]
1ORFX-ray2.40A29-262[»]
ProteinModelPortaliP12544
SMRiP12544
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109256, 17 interactors
IntActiP12544, 4 interactors
STRINGi9606.ENSP00000274306

Chemistry databases

ChEMBLiCHEMBL4307

Protein family/group databases

MEROPSiS01.135

PTM databases

iPTMnetiP12544
PhosphoSitePlusiP12544

Polymorphism and mutation databases

BioMutaiGZMA
DMDMi317373360

Proteomic databases

MaxQBiP12544
PaxDbiP12544
PeptideAtlasiP12544
PRIDEiP12544
ProteomicsDBi52858
52859 [P12544-2]

Protocols and materials databases

DNASUi3001
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274306; ENSP00000274306; ENSG00000145649 [P12544-1]
GeneIDi3001
KEGGihsa:3001
UCSCiuc003jpm.4 human [P12544-1]

Organism-specific databases

CTDi3001
DisGeNETi3001
EuPathDBiHostDB:ENSG00000145649.7
GeneCardsiGZMA
HGNCiHGNC:4708 GZMA
HPAiHPA054134
MIMi140050 gene
neXtProtiNX_P12544
OpenTargetsiENSG00000145649
PharmGKBiPA29086
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118895
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiP12544
KOiK01352
OMAiKEFPYPC
OrthoDBiEOG091G0AH5
PhylomeDBiP12544
TreeFamiTF333630

Enzyme and pathway databases

BRENDAi3.4.21.78 2681
SIGNORiP12544

Miscellaneous databases

EvolutionaryTraceiP12544
GeneWikiiGZMA
GenomeRNAii3001
PROiPR:P12544
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145649 Expressed in 150 organ(s), highest expression level in leukocyte
CleanExiHS_GZMA
GenevisibleiP12544 HS

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRAA_HUMAN
AccessioniPrimary (citable) accession number: P12544
Secondary accession number(s): A4PHN1, Q6IB36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 11, 2011
Last modified: September 12, 2018
This is version 189 of the entry and version 2 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. UniProtKB entry view manual
    User manual for the UniProtKB entry view
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  8. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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