Granzyme A precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P12544 (GRAA_HUMAN)

Last modified June 16, 2009. Version 113. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Granzyme A
    EC=3.4.21.78
Alternative name(s):
    Granzyme-1
    Cytotoxic T-lymphocyte proteinase 1
    Hanukkah factor
      Short name=H factor
      Short name=HF
    CTL tryptase
    Fragmentin-1

Gene names

Name:	GZMA
Synonyms:	CTLA3, HFSP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	262 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

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Ontologies

Keywords
Biological process	Apoptosis Cytolysis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cleavage of lamin Inferred from direct assay. Source: UniProtKB cytolysis Inferred from electronic annotation. Source: UniProtKB-KW immune response Traceable author statement. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell immunological synapse Traceable author statement. Source: UniProtKB nucleus Traceable author statement. Source: UniProtKB
Molecular function	protein homodimerization activity Ref.11 Inferred from direct assay. Source: UniProtKB serine-type endopeptidase activity Ref.11 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-519800,EBI-519800
NDUFS3	O75489	1	EBI-519800,EBI-1224896

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

Propeptide

27 – 28

Activation peptide Ref.5 Ref.6 Ref.7

PRO_0000027393

Chain

29 – 262

234

Granzyme A

PRO_0000027394

Regions

Domain

29 – 259

231

Peptidase S1

Sites

Active site

Charge relay system

Active site

114

Charge relay system

Active site

212

Charge relay system

Amino acid modifications

Glycosylation

170

N-linked (GlcNAc...)

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Natural variant

121

T → M: dbSNP rs3104233.

VAR_024291

Secondary structure

262

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P12544-1 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: DA87363A0D92BAF4
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FASTA

262

28,969

        10         20         30         40         50         60 
MRNSYRFLAS SLSVVVSLLL IPEDVCEKII GGNEVTPHSR PYMVLLSLDR KTICAGALIA 

        70         80         90        100        110        120 
KDWVLTAAHC NLNKRSQVIL GAHSITREEP TKQIMLVKKE FPYPCYDPAT REGDLKLLQL 

       130        140        150        160        170        180 
TEKAKINKYV TILHLPKKGD DVKPGTMCQV AGWGRTHNSA SWSDTLREVN ITIIDRKVCN 

       190        200        210        220        230        240 
DRNHYNFNPV IGMNMVCAGS LRGGRDSCNG DSGSPLLCEG VFRGVTSFGL ENKCGDPRGP 

       250        260 
GVYILLSKKH LNWIIMTIKG AV

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease." Gershenfeld H.K., Hershberger R.J., Shows T.B., Weissman I.L. Proc. Natl. Acad. Sci. U.S.A. 85:1184-1188(1988) [PubMed: 3257574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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]. Tissue: Blood.
[4]	"The upstream region of the human granzyme A locus contains both positive and negative transcriptional regulatory elements." Goralski T.J., Krensky A.M. Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
[5]	"Human cytotoxic lymphocyte tryptase. Its purification from granules and the characterization of inhibitor and substrate specificity." Poe M., Bennett C.D., Biddison W.E., Blake J.T., Norton G.P., Rodkey J.A., Sigal N.H., Turner R.V., Wu J.K., Zweerink H.J. J. Biol. Chem. 263:13215-13222(1988) [PubMed: 3047119] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-53.
[6]	"Characterization of three serine esterases isolated from human IL-2 activated killer cells." Hameed A., Lowrey D.M., Lichtenheld M., Podack E.R. J. Immunol. 141:3142-3147(1988) [PubMed: 3262682] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-40, CHARACTERIZATION.
[7]	"Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes." Kraehenbuhl O., Rey C., Jenne D.E., Lanzavecchia A., Groscurth P., Carrel S., Tschopp J. J. Immunol. 141:3471-3477(1988) [PubMed: 3263427] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-39, CHARACTERIZATION.
[8]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-170, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes." Murphy M.E.P., Moult J., Bleackley R.C., Gershenfeld H., Weissman I.L., James M.N.G. Proteins 4:190-204(1988) [PubMed: 3237717] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 29-262.
[10]	"The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity." Bell J.K., Goetz D.H., Mahrus S., Harris J.L., Fletterick R.J., Craik C.S. Nat. Struct. Biol. 10:527-534(2003) [PubMed: 12819769] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-262 IN COMPLEX WITH A TRIPEPTIDE CMK INHIBITOR.
[11]	"Crystal structure of the apoptosis-inducing human granzyme A dimer." Hink-Schauer C., Estebanez-Perpina E., Kurschus F.C., Bode W., Jenne D.E. Nat. Struct. Biol. 10:535-540(2003) [PubMed: 12819770] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 29-262 IN COMPLEX WITH SUBSTRATE.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

M18737 mRNA. Translation: AAA52647.1.
CR456968 mRNA. Translation: CAG33249.1.
BC015739 mRNA. Translation: AAH15739.1.
U40006 Genomic DNA. Translation: AAD00009.1.

IPI

IPI00024657.

PIR

A31372.

RefSeq

NP_006135.1.

UniGene

Hs.90708

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HF1	model	-	A	29-262	[»]
1OP8	X-ray	2.50	A/B/C/D/E/F	29-262	[»]
1ORF	X-ray	2.40	A	29-262	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P12544. 4 interactions.

Protein family/group databases

MEROPS

S01.135.

Proteomic databases

PRIDE

P12544.

Genome annotation databases

Ensembl

ENSG00000145649. Homo sapiens. [Contig view]

GeneID

3001.

KEGG

hsa:3001.

Organism-specific databases

GeneCards

GC05P054434.

H-InvDB

HIX0004862.

HGNC

HGNC:4708. GZMA.

MIM

140050. gene.

PharmGKB

PA29086.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P12544.

HOVERGEN

P12544.

Enzyme and pathway databases

BRENDA

3.4.21.78. 247.

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.

Gene expression databases

ArrayExpress

P12544.

Bgee

P12544.

CleanEx

HS_GZMA.

GermOnline

ENSG00000145649. Homo sapiens.

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

11900.

SOURCE

Search...

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Entry information

Entry name

GRAA_HUMAN

Accession

Primary (citable) accession number: P12544
Secondary accession number(s): Q6IB36

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	June 16, 2009
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents