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Protein

Granzyme A

Gene

Gzma

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Caution

The predicted cleavage site for the activation peptide of HF2 is uncertain. It could have either 2 (ER) or 7 (KRGGCER) AA.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 systemBy similarity1
Active sitei113Charge relay systemBy similarity1
Active sitei211Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis, Cytolysis

Enzyme and pathway databases

BRENDAi3.4.21.78 3474

Protein family/group databases

MEROPSiS01.135

Names & Taxonomyi

Protein namesi
Recommended name:
Granzyme A (EC:3.4.21.78)
Alternative name(s):
Autocrine thymic lymphoma granzyme-like serine protease
CTLA-3
Fragmentin-1
T cell-specific serine protease 1
Short name:
TSP-1
Gene namesi
Name:Gzma
Synonyms:Ctla-3, Ctla3, Mtsp-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:109266 Gzma

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Add BLAST26
PropeptideiPRO_000002739527 – 28Activation peptide2 Publications2
ChainiPRO_000002739629 – 260Granzyme AAdd BLAST232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 70PROSITE-ProRule annotation
Disulfide bondi147 ↔ 217PROSITE-ProRule annotation
Glycosylationi157N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi169N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi178 ↔ 196PROSITE-ProRule annotation
Disulfide bondi207 ↔ 232PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP11032
PeptideAtlasiP11032
PRIDEiP11032

PTM databases

PhosphoSitePlusiP11032

Expressioni

Tissue specificityi

Found in cytotoxic lymphocytes and in normal lymphoid tissues such as thymus and spleen.

Gene expression databases

BgeeiENSMUSG00000023132 Expressed in 105 organ(s), highest expression level in blood
CleanExiMM_GZMA
ExpressionAtlasiP11032 baseline and differential
GenevisibleiP11032 MM

Interactioni

Subunit structurei

Interacts with APEX1 (By similarity). Homodimer; disulfide-linked.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiP11032, 1 interactor
MINTiP11032
STRINGi10090.ENSMUSP00000023897

Structurei

3D structure databases

ProteinModelPortaliP11032
SMRiP11032
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 257Peptidase S1PROSITE-ProRule annotationAdd BLAST229

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
InParanoidiP11032
KOiK01352
OMAiKQIMFVK
OrthoDBiEOG091G0AH5
PhylomeDBiP11032
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 splicing. AlignAdd to basket
Isoform HF1 (identifier: P11032-1) [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
MRNASGPRGP SLATLLFLLL IPEGGCERII GGDTVVPHSR PYMALLKLSS
60 70 80 90 100
NTICAGALIE KNWVLTAAHC NVGKRSKFIL GAHSINKEPE QQILTVKKAF
110 120 130 140 150
PYPCYDEYTR EGDLQLVRLK KKATVNRNVA ILHLPKKGDD VKPGTRCRVA
160 170 180 190 200
GWGRFGNKSA PSETLREVNI TVIDRKICND EKHYNFHPVI GLNMICAGDL
210 220 230 240 250
RGGKDSCNGD SGSPLLCDGI LRGITSFGGE KCGDRRWPGV YTFLSDKHLN
260
WIKKIMKGSV
Note: More abundant in lymphoid tissues than isoform HF2.
Length:260
Mass (Da):28,599
Last modified:July 1, 1993 - v2
Checksum:i7705352F08DEED8D
GO
Isoform HF2 (identifier: P11032-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MRNASGPRGPSLATLLFLLLIPE → MSKEMNEILLSWEINLSSKR

Show »
Length:257
Mass (Da):28,541
Checksum:i7D67F97E532F7440
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0053731 – 23MRNAS…LLIPE → MSKEMNEILLSWEINLSSKR in isoform HF2. CuratedAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14799 mRNA Translation: CAA32905.1
X62542
, X62543, X60310, X60311 Genomic DNA Translation: CAA44426.1
L01429
, L01426, L01427, L01441 Genomic DNA Translation: AAA99898.1
L01429
, L01426, L01427, L01441 Genomic DNA Translation: AAA99897.1
BC061146 mRNA Translation: AAH61146.1
M26183 mRNA Translation: AAA37735.1
M13226 mRNA Translation: AAA40134.1
CCDSiCCDS26782.1 [P11032-1]
PIRiA24807
A45061
B45061
RefSeqiNP_034500.1, NM_010370.2 [P11032-1]
UniGeneiMm.15510

Genome annotation databases

EnsembliENSMUST00000023897; ENSMUSP00000023897; ENSMUSG00000023132 [P11032-1]
ENSMUST00000224282; ENSMUSP00000153593; ENSMUSG00000023132 [P11032-2]
GeneIDi14938
KEGGimmu:14938
UCSCiuc007rxc.1 mouse [P11032-1]
uc011zeu.1 mouse [P11032-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14799 mRNA Translation: CAA32905.1
X62542
, X62543, X60310, X60311 Genomic DNA Translation: CAA44426.1
L01429
, L01426, L01427, L01441 Genomic DNA Translation: AAA99898.1
L01429
, L01426, L01427, L01441 Genomic DNA Translation: AAA99897.1
BC061146 mRNA Translation: AAH61146.1
M26183 mRNA Translation: AAA37735.1
M13226 mRNA Translation: AAA40134.1
CCDSiCCDS26782.1 [P11032-1]
PIRiA24807
A45061
B45061
RefSeqiNP_034500.1, NM_010370.2 [P11032-1]
UniGeneiMm.15510

3D structure databases

ProteinModelPortaliP11032
SMRiP11032
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP11032, 1 interactor
MINTiP11032
STRINGi10090.ENSMUSP00000023897

Protein family/group databases

MEROPSiS01.135

PTM databases

PhosphoSitePlusiP11032

Proteomic databases

PaxDbiP11032
PeptideAtlasiP11032
PRIDEiP11032

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023897; ENSMUSP00000023897; ENSMUSG00000023132 [P11032-1]
ENSMUST00000224282; ENSMUSP00000153593; ENSMUSG00000023132 [P11032-2]
GeneIDi14938
KEGGimmu:14938
UCSCiuc007rxc.1 mouse [P11032-1]
uc011zeu.1 mouse [P11032-2]

Organism-specific databases

CTDi3001
MGIiMGI:109266 Gzma

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118895
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiP11032
KOiK01352
OMAiKQIMFVK
OrthoDBiEOG091G0AH5
PhylomeDBiP11032
TreeFamiTF333630

Enzyme and pathway databases

BRENDAi3.4.21.78 3474

Miscellaneous databases

PROiPR:P11032
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023132 Expressed in 105 organ(s), highest expression level in blood
CleanExiMM_GZMA
ExpressionAtlasiP11032 baseline and differential
GenevisibleiP11032 MM

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_MOUSE
AccessioniPrimary (citable) accession number: P11032
Secondary accession number(s): P15118
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1993
Last modified: November 7, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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