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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei69 – 691Charge relay systemBy similarity
Active sitei113 – 1131Charge relay systemBy similarity
Active sitei211 – 2111Charge relay systemBy similarity

GO - Molecular functioni

  1. protein homodimerization activity Source: UniProtKB
  2. serine-type endopeptidase activity Source: UniProtKB
  3. serine-type peptidase activity Source: MGI

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cytolysis Source: UniProtKB-KW
  3. negative regulation of DNA binding Source: UniProtKB
  4. negative regulation of endodeoxyribonuclease activity Source: UniProtKB
  5. negative regulation of oxidoreductase activity Source: UniProtKB
  6. positive regulation of apoptotic process Source: UniProtKB
  7. proteolysis involved in cellular protein catabolic process Source: UniProtKB
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
ProteomesiUP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:109266. Gzma.

Subcellular locationi

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

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Add
BLAST
Propeptidei27 – 282Activation peptide2 PublicationsPRO_0000027395
Chaini29 – 260232Granzyme APRO_0000027396Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi54 ↔ 70PROSITE-ProRule annotation
Disulfide bondi147 ↔ 217PROSITE-ProRule annotation
Glycosylationi157 – 1571N-linked (GlcNAc...)Sequence Analysis
Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi178 ↔ 196PROSITE-ProRule annotation
Disulfide bondi207 ↔ 232PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP11032.
PaxDbiP11032.
PRIDEiP11032.

PTM databases

PhosphoSiteiP11032.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP11032.
CleanExiMM_GZMA.
ExpressionAtlasiP11032. baseline and differential.
GenevestigatoriP11032.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

IntActiP11032. 1 interaction.
MINTiMINT-4096608.

Structurei

3D structure databases

ProteinModelPortaliP11032.
SMRiP11032. Positions 29-258.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 257229Peptidase S1PROSITE-ProRule annotationAdd
BLAST

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

eggNOGiCOG5640.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP11032.
KOiK01352.
OMAiPGTHEND.
OrthoDBiEOG7W9RVH.
PhylomeDBiP11032.
TreeFamiTF333630.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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:June 30, 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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2323MRNAS…LLIPE → MSKEMNEILLSWEINLSSKR in isoform HF2. CuratedVSP_005373Add
BLAST

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. Positions 29-258.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP11032. 1 interaction.
MINTiMINT-4096608.

Protein family/group databases

MEROPSiS01.135.

PTM databases

PhosphoSiteiP11032.

Proteomic databases

MaxQBiP11032.
PaxDbiP11032.
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

eggNOGiCOG5640.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP11032.
KOiK01352.
OMAiPGTHEND.
OrthoDBiEOG7W9RVH.
PhylomeDBiP11032.
TreeFamiTF333630.

Enzyme and pathway databases

BRENDAi3.4.21.78. 3474.

Miscellaneous databases

NextBioi287259.
PROiP11032.
SOURCEiSearch...

Gene expression databases

BgeeiP11032.
CleanExiMM_GZMA.
ExpressionAtlasiP11032. baseline and differential.
GenevestigatoriP11032.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[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...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA clones from autocrine thymic lymphoma cells encode two mitogenic proteins, a serine protease and a truncated T-cell receptor beta-chain."
    Bogenberger J., Haas M.
    Oncogene Res. 3:301-312(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6.
  2. "Organization of the gene encoding the mouse T-cell-specific serine proteinase 'granzyme A'."
    Ebnet K., Kramer M.D., Simon M.M.
    Genomics 13:502-508(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C57BL/6.
  3. "Genomic organization of the mouse granzyme A gene. Two mRNAs encode the same mature granzyme A with different leader peptides."
    Hershberger R.J., Gershenfeld H.K., Weissman I.L., Su L.
    J. Biol. Chem. 267:25488-25493(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS HF1 AND HF2).
  4. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HF1).
  5. "Granzymes, a family of serine proteases released from granules of cytolytic T lymphocytes upon T cell receptor stimulation."
    Jenne D.E., Tschopp J.
    Immunol. Rev. 103:53-71(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-37.
  6. "Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte."
    Gershenfeld H.K., Weissman I.L.
    Science 232:854-858(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-260.
  7. "A family of serine esterases in lytic granules of cytolytic T lymphocytes."
    Masson D., Tschopp J.
    Cell 49:679-685(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 29-48.
  8. "Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes."
    Masson D., Zamai M., Tschopp J.
    FEBS Lett. 208:84-88(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 29-53.
  9. "Induction of T cell serine proteinase 1 (TSP-1)-specific mRNA in mouse T lymphocytes."
    Simon H.G., Fruth U., Eckerskorn C., Lottspeich F., Kramer M.D., Nerz G., Simon M.M.
    Eur. J. Immunol. 18:855-861(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 29-46.

Entry informationi

Entry nameiGRAA_MOUSE
AccessioniPrimary (citable) accession number: P11032
Secondary accession number(s): P15118
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 30, 1989
Last sequence update: June 30, 1993
Last modified: January 6, 2015
This is version 150 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

External Data

Dasty 3

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 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.