P10144 (GRAB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granzyme B
EC=3.4.21.79

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

Gene names

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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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

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-. Ref.12
Enzyme regulation	Inactivated by the serine protease inhibitor diisopropylfluorophosphate. Ref.12
Subcellular location	Cytoplasmic granule. Note: Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells. Ref.12
Induction	By staphylococcal enterotoxin A (SEA) in peripheral blood leukocytes. Ref.12
Sequence similarities	Belongs to the peptidase S1 family. Granzyme subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Apoptosis Cytolysis
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cleavage of lamin involved in execution phase of apoptosis Inferred from direct assay PubMed 11331782. Source: UniProtKB cytolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome immunological synapse Traceable author statement PubMed 12524539. Source: UniProtKB nucleus Traceable author statement PubMed 11909973. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Traceable author statement PubMed 12524539. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRF1	P14222	3	EBI-2505785,EBI-724466
SRGN	P10124	2	EBI-2505785,EBI-744915

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.14

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

Site

228

1

Mediates preference for Asp-containing substrates By similarity

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

R → Q. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.17
Corresponds to variant rs8192917 [ dbSNP | Ensembl ].

VAR_018371

Natural variant

94

1

P → A. Ref.2 Ref.6
Corresponds to variant rs11539752 [ dbSNP | Ensembl ].

VAR_047409

Natural variant

247

1

Y → H. Ref.8 Ref.17
Corresponds to variant rs2236338 [ dbSNP | Ensembl ].

VAR_018381

Experimental info

Sequence conflict

32 – 33

2

RP → PR AA sequence Ref.12

Sequence conflict

72

1

V → G in AAA52118. Ref.3

Sequence conflict

212

1

V → C in AAB59528. Ref.4

Secondary structure

1

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247

Helix Strand Turn

Details...

Beta strand

35 – 41

7

Beta strand

46 – 55

10

Beta strand

58 – 61

4

Helix

63 – 65

3

Beta strand

68 – 75

8

Turn

79 – 82

4

Beta strand

87 – 96

10

Turn

102 – 104

3

Beta strand

110 – 116

7

Beta strand

141 – 148

8

Beta strand

150 – 154

5

Beta strand

161 – 167

7

Helix

170 – 176

7

Turn

177 – 180

4

Turn

183 – 185

3

Beta strand

186 – 190

5

Beta strand

205 – 209

5

Beta strand

212 – 220

9

Beta strand

228 – 232

5

Helix

233 – 236

4

Helix

237 – 245

9

Sequences

	Sequence		Length	Mass (Da)
	P10144 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: C652271918EF24F9	FASTA	247	27,716
	10 20 30 40 50 60 MQPILLLLAF LLLPRADAGE IIGGHEAKPH SRPYMAYLMI WDQKSLKRCG GFLIRDDFVL 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

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-55.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-55.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-55.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-55.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-55 AND 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. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLN-55 AND 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-40, CHARACTERIZATION.
[12]	"Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes." Froelich C.J., Zhang X., Turbov J., Hudig D., Winkler U., Hanna W.L. J. Immunol. 151:7161-7171(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-39, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION. Tissue: Lymphocyte.
[13]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-38.
[14]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-33.
[15]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
[16]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-55 AND HIS-247.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00744785.

PIR

A61021.

RefSeq

NP_004122.2. NM_004131.4.

UniGene

Hs.1051.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P10144.

SMR

P10144. Positions 21-246.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10144. 3 interactions.

MINT

MINT-4528791.

STRING

9606.ENSP00000216341.

Protein family/group databases

MEROPS

S01.010.

PTM databases

PhosphoSite

P10144.

Polymorphism databases

DMDM

121583.

Proteomic databases

PaxDb

P10144.

PRIDE

P10144.

Protocols and materials databases

DNASU

3002.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216341; ENSP00000216341; ENSG00000100453.

GeneID

3002.

KEGG

hsa:3002.

UCSC

uc001wps.2. human.

Organism-specific databases

CTD

3002.

GeneCards

GC14M025100.

H-InvDB

HIX0011578.

HGNC

HGNC:4709. GZMB.

HPA

CAB000376.
HPA003418.

MIM

123910. gene.

neXtProt

NX_P10144.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P10144.

KO

K01353.

OrthoDB

EOG4KWJTW.

PhylomeDB

P10144.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_2pathway. IL12-mediated signaling events.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P10144.

Bgee

P10144.

CleanEx

HS_GZMB.

Genevestigator

P10144.

GermOnline

ENSG00000100453. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P10144.

ChEMBL

CHEMBL2316.

ChiTaRS

GZMB. human.

EvolutionaryTrace

P10144.

GenomeRNAi

3002.

NextBio

11904.

PMAP-CutDB

P10144.

SOURCE

Search...

Entry information

Entry name

GRAB_HUMAN

Accession

Primary (citable) accession number: P10144
Secondary accession number(s): Q8N1D2, Q9UCC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 11, 2011
Last modified:	April 3, 2013
This is version 152 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.