Reviewed, UniProtKB/Swiss-Prot P11032 (GRAA_MOUSE)

Names and origin

Protein names

Recommended name:
    Granzyme A
    EC=3.4.21.78
Alternative name(s):
    T cell-specific serine protease 1
      Short name=TSP-1
    CTLA-3
    Fragmentin-1
    Autocrine thymic lymphoma granzyme-like serine protease

Gene names

Name:	Gzma
Synonyms:	Ctla-3, Ctla3, Mtsp-1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	260 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. May be involved in apoptosis.
Catalytic activity	Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.
Subunit structure	Homodimer; disulfide-linked.
Subcellular location	Secreted. Cytoplasmic granule. Note: Cytoplasmic granules of cytolytic T-lymphocytes.
Tissue specificity	Found in cytotoxic lymphocytes and in normal lymphoid tissues such as thymus and spleen.
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.
Caution	The predicted cleavage site for the activation peptide of HF2 is uncertain. It could have either 2 (ER) or 7 (KRGGCER) AA.

Ontologies

Keywords
Biological process	Apoptosis Cytolysis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cleavage of lamin Inferred from sequence or structural similarity. Source: UniProtKB cytolysis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB serine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform HF1 (identifier: P11032-1)

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.

Note: More abundant in lymphoid tissues than isoform HF2.

Isoform HF2 (identifier: P11032-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26
	Propeptide	27 – 28	2	Activation peptide Ref.6 Ref.7		PRO_0000027395
	Chain	29 – 260	232	Granzyme A		PRO_0000027396
Regions
	Domain	29 – 257	229	Peptidase S1
Sites
	Active site	69	1	Charge relay system By similarity
	Active site	113	1	Charge relay system By similarity
	Active site	211	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	157	1	N-linked (GlcNAc...) Potential
	Glycosylation	169	1	N-linked (GlcNAc...) Potential
	Disulfide bond	54 ↔ 70		By similarity
	Disulfide bond	147 ↔ 217		By similarity
	Disulfide bond	178 ↔ 196		By similarity
	Disulfide bond	207 ↔ 232		By similarity
Natural variations
	Alternative sequence	1 – 23	23	MRNAS…LLIPE → MSKEMNEILLSWEINLSSKR in isoform HF2.		VSP_005373

Sequences

	Sequence		Length	Mass (Da)
	Isoform HF1 [UniParc]. Last modified July 1, 1993. Version 2. Checksum: 7705352F08DEED8D	FASTA	260	28,599
	10 20 30 40 50 60 MRNASGPRGP SLATLLFLLL IPEGGCERII GGDTVVPHSR PYMALLKLSS NTICAGALIE 70 80 90 100 110 120 KNWVLTAAHC NVGKRSKFIL GAHSINKEPE QQILTVKKAF PYPCYDEYTR EGDLQLVRLK 130 140 150 160 170 180 KKATVNRNVA ILHLPKKGDD VKPGTRCRVA GWGRFGNKSA PSETLREVNI TVIDRKICND 190 200 210 220 230 240 EKHYNFHPVI GLNMICAGDL RGGKDSCNGD SGSPLLCDGI LRGITSFGGE KCGDRRWPGV 250 260 YTFLSDKHLN WIKKIMKGSV
	Isoform HF2. Checksum: 7D67F97E532F7440	FASTA	257	28,541
	10 20 30 40 50 60 MSKEMNEILL SWEINLSSKR GGCERIIGGD TVVPHSRPYM ALLKLSSNTI CAGALIEKNW 70 80 90 100 110 120 VLTAAHCNVG KRSKFILGAH SINKEPEQQI LTVKKAFPYP CYDEYTREGD LQLVRLKKKA 130 140 150 160 170 180 TVNRNVAILH LPKKGDDVKP GTRCRVAGWG RFGNKSAPSE TLREVNITVI DRKICNDEKH 190 200 210 220 230 240 YNFHPVIGLN MICAGDLRGG KDSCNGDSGS PLLCDGILRG ITSFGGEKCG DRRWPGVYTF 250 LSDKHLNWIK KIMKGSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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(1992) [PubMed: 1639378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: C57BL/6.
[2]	"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(1988) [PubMed: 2976140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. 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(1992) [PubMed: 1460043] [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(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HF1). Tissue: Heart and Lung.
[5]	"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(1986) [PubMed: 2422755] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-260.
[6]	"A family of serine esterases in lytic granules of cytolytic T lymphocytes." Masson D., Tschopp J. Cell 49:679-685(1987) [PubMed: 3555842] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-48.
[7]	"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(1986) [PubMed: 3533635] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-53.
[8]	"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(1988) [PubMed: 3260181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 29-46.
[9]	"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(1988) [PubMed: 3292396] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-37.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X14799 mRNA. Translation: CAA32905.1. X62542 , X62543, X60310, X60311 Genomic DNA. Translation: CAA44426.1. M13226 mRNA. Translation: AAA40134.1. 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.
IPI	IPI00111385. IPI00229002.
PIR	A24807. A45061. B45061.
RefSeq	NP_034500.1.
UniGene	Mm.15510
3D structure databases
HSSP	HSSP built from PDB template 1OP8 based on UniProtKB P12544.
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000023132. Mus musculus. [Contig view]
GeneID	14938.
KEGG	mmu:14938.
Organism-specific databases
MGI	MGI:109266. Gzma.
Phylogenomic databases
HOGENOM	P11032.
HOVERGEN	P11032.
OMA	P11032. PGTHEND.
Enzyme and pathway databases
BRENDA	3.4.21.78. 244.
Gene expression databases
ArrayExpress	P11032.
Bgee	P11032.
CleanEx	MM_GZMA.
GermOnline	ENSMUSG00000023132. Mus musculus.
Family and domain databases
InterPro	IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Pfam	PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00020. Tryp_SPc. 1 hit. [Graphical view]
PROSITE	PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	287259.
SOURCE	Search...

Entry information

Entry name

GRAA_MOUSE

Accession

Primary (citable) accession number: P11032
Secondary accession number(s): P15118

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1993
Last modified:	June 16, 2009
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)