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Protein

Granzyme A

Gene

Gzma

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Apoptosis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:109266. Gzma.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi169N-linked (GlcNAc...)Sequence 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.
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.
MINTiMINT-4096608.
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
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[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 (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]
GeneIDi14938.
KEGGimmu:14938.
UCSCiuc007rxc.1. mouse. [P11032-1]
uc011zeu.1. mouse. [P11032-2]

Keywords - Coding sequence diversityi

Alternative splicing

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.
MINTiMINT-4096608.
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]
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.
OMAiMKKATIN.
OrthoDBiEOG091G0AH5.
PhylomeDBiP11032.
TreeFamiTF333630.

Enzyme and pathway databases

BRENDAi3.4.21.78. 3474.

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023132.
CleanExiMM_GZMA.
ExpressionAtlasiP11032. baseline and differential.
GenevisibleiP11032. MM.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[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]
ProtoNetiSearch...

Entry informationi

Entry nameiGRAA_MOUSE
AccessioniPrimary (citable) accession number: P11032
Secondary accession number(s): P15118
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1993
Last modified: November 2, 2016
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The predicted cleavage site for the activation peptide of HF2 is uncertain. It could have either 2 (ER) or 7 (KRGGCER) AA.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.