Granzyme B precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Granzyme B
    EC=3.4.21.79
Alternative name(s):
    Granzyme-2
    T-cell serine protease 1-3E
    Cytotoxic T-lymphocyte proteinase 2
      Short name=Lymphocyte protease
    SECT
    Cathepsin G-like 1
      Short name=CTSGL1
    CTLA-1
    Fragmentin-2
    Human lymphocyte protein
      Short name=HLP
    C11

Gene names

Name:	GZMB
Synonyms:	CGL1, CSPB, CTLA1, GRB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Hide | Top

Protein attributes

Sequence length	247 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis.
Catalytic activity	Preferential cleavage: -Asp-\|-Xaa- >> -Asn-\|-Xaa- > -Met-\|-Xaa-, -Ser-\|-Xaa-.
Subcellular location	Cytoplasmic granule. Note= Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells.
Induction	By staphylococcal enterotoxin A (SEA) in peripheral blood leukocytes.
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Hide | Top

Ontologies

Keywords
Biological process	Apoptosis Cytolysis
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Uncategorized	granzyme B activity Inferred from Experiment. Source: Reactome
Biological process	cleavage of lamin Inferred from direct assay. Source: UniProtKB cytolysis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome immunological synapse Traceable author statement. Source: UniProtKB nucleus Traceable author statement. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Propeptide

19 – 20

2

Activation peptide

PRO_0000027399

Chain

21 – 247

227

Granzyme B

PRO_0000027400

Regions

Domain

21 – 245

225

Peptidase S1

Sites

Active site

64

1

Charge relay system

Active site

108

1

Charge relay system

Active site

203

1

Charge relay system

Amino acid modifications

Glycosylation

71

1

N-linked (GlcNAc...)

Glycosylation

104

1

N-linked (GlcNAc...) Potential

Disulfide bond

49 ↔ 65

Disulfide bond

142 ↔ 209

Disulfide bond

173 ↔ 188

Natural variations

Natural variant

55

1

Q → R: dbSNP rs8192917.

VAR_018371

Natural variant

94

1

P → A: dbSNP rs11539752.

VAR_047409

Natural variant

247

1

Y → H: dbSNP rs2236338.

VAR_018381

Experimental info

Sequence conflict

72

1

V → G in AAA52118. Ref.3

Sequence conflict

212

1

V → C in AAB59528. Ref.4

Secondary structure

1

.

247

Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

P10144-1 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 684FF605D6F2F4FB
Show »

FASTA

247

27,688

        10         20         30         40         50         60 
MQPILLLLAF LLLPRADAGE IIGGHEAKPH SRPYMAYLMI WDQKSLKRCG GFLIQDDFVL 

        70         80         90        100        110        120 
TAAHCWGSSI NVTLGAHNIK EQEPTQQFIP VKRPIPHPAY NPKNFSNDIM LLQLERKAKR 

       130        140        150        160        170        180 
TRAVQPLRLP SNKAQVKPGQ TCSVAGWGQT APLGKHSHTL QEVKMTVQED RKCESDLRHY 

       190        200        210        220        230        240 
YDSTIELCVG DPEIKKTSFK GDSGGPLVCN KVAQGIVSYG RNNGMPPRAC TKVSSFVHWI 


KKTMKRY

« Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes." Schmid J., Weissmann C. J. Immunol. 139:250-256(1987) [PubMed: 2953813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and differential mechanisms of regulation of expression of a serine esterase gene in activated human T lymphocytes." Caputo A., Fahey D., Lloyd C., Vozab R., McCairns E., Rowe P.B. J. Biol. Chem. 263:6363-6369(1988) [PubMed: 3258865] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-55 AND ALA-94.
[3]	"Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes." Trapani J.A., Klein J.L., White P.C., Dupont B. Proc. Natl. Acad. Sci. U.S.A. 85:6924-6928(1988) [PubMed: 3261871] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genomic organization and chromosomal assignment for a serine protease gene (CSPB) expressed by human cytotoxic lymphocytes." Klein J.L., Shows T.B., Dupont B., Trapani J.A. Genomics 5:110-117(1989) [PubMed: 2788607] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Nucleotide sequence and genomic organization of a human T lymphocyte serine protease gene." Caputo A., Sauer D.E., Rowe P.B. J. Immunol. 145:737-744(1990) [PubMed: 2365998] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Structural organization of the hCTLA-1 gene encoding human granzyme B." Haddad P., Clement M.-V., Bernard O., Larsen C.-J., Degos L., Sasportes M., Mathieu-Mahul D. Gene 87:265-271(1990) [PubMed: 2332171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-94.
[7]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-55.
[8]	"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], VARIANT HIS-247. Tissue: Pancreas.
[9]	"Isolation of a cDNA clone encoding a novel form of granzyme B from human NK cells and mapping to chromosome 14." Dahl C.A., Bach F.H., Chan W., Huebner K., Russo G., Croce C.M., Herfurth T., Cairns J.S. Hum. Genet. 84:465-470(1990) [PubMed: 2323780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-23.
[10]	"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 21-40, CHARACTERIZATION.
[11]	"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 21-40, CHARACTERIZATION.
[12]	"Human cytotoxic lymphocyte granzyme B. Its purification from granules and the characterization of substrate and inhibitor specificity." Poe M., Blake J.T., Boulton D.A., Gammon M., Sigal N.H., Wu J.K., Zweerink H.J. J. Biol. Chem. 266:98-103(1991) [PubMed: 1985927] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-38.
[13]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-33.
[14]	"Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue." Estebanez-Perpina E., Fuentes-Prior P., Belorgey D., Braun M., Kiefersauer R., Maskos K., Huber R., Rubin H., Bode W. Biol. Chem. 381:1203-1214(2000) [PubMed: 11209755] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
[15]	"The three-dimensional structure of human granzyme B compared to caspase-3, key mediators of cell death with cleavage specificity for aspartic acid in P1." Rotonda J., Garcia-Calvo M., Bull H.G., Geissler W.M., McKeever B.M., Willoughby C.A., Thornberry N.A., Becker J.W. Chem. Biol. 8:357-368(2001) [PubMed: 11325591] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247.
[16]	"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population." Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y. J. Hum. Genet. 48:249-270(2003) [PubMed: 12721789] [Abstract] Cited for: VARIANTS ARG-55 AND HIS-247.
+	Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases

M17016 mRNA. Translation: AAA36627.1.
J03189 mRNA. Translation: AAA36603.1.
J04071 mRNA. Translation: AAA52118.1.
J03072 Genomic DNA. Translation: AAB59528.1.
M38193 Genomic DNA. Translation: AAA67124.1.
M28879 Genomic DNA. Translation: AAA75490.1.
AL136018 Genomic DNA. No translation available.
BC030195 mRNA. Translation: AAH30195.1.

PIR

A61021.

RefSeq

NP_004122.1.

UniGene

Hs.1051

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FQ3	X-ray	3.10	A/B	21-247	[»]
1IAU	X-ray	2.00	A	21-247	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.010.

Genome annotation databases

Ensembl

ENSG00000100453. Homo sapiens. [Contig view]

GeneID

3002.

KEGG

hsa:3002.

Organism-specific databases

H-InvDB

HIX0011578.

HGNC

HGNC:4709. GZMB.

HPA

CAB000376.
HPA003418.

MIM

123910. gene.

PharmGKB

PA29087.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P10144.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P10144.

CleanEx

HS_GZMB.

GermOnline

ENSG00000100453. Homo sapiens.

Family and domain databases

InterPro

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

11904.

SOURCE

Search...

Hide | Top

Entry information

Entry name

GRAB_HUMAN

Accession

Primary (citable) accession number: P10144
Secondary accession number(s): Q8N1D2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	November 25, 2008
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top