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P10144 (GRAB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length247 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processApoptosis
Cytolysis
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement PubMed 12524539. Source: UniProtKB

cytolysis

Inferred from electronic annotation. Source: UniProtKB-KW

granzyme-mediated apoptotic signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

immunological synapse

Traceable author statement PubMed 12524539. Source: UniProtKB

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nucleus

Traceable author statement PubMed 11909973. Source: UniProtKB

secretory granule

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionserine-type endopeptidase activity

Inferred from direct assay PubMed 11331782. Source: UniProtKB

serine-type peptidase activity

Traceable author statement PubMed 2402757. Source: ProtInc

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.14
Propeptide19 – 202Activation peptide
PRO_0000027399
Chain21 – 247227Granzyme B
PRO_0000027400

Regions

Domain21 – 245225Peptidase S1

Sites

Active site641Charge relay system
Active site1081Charge relay system
Active site2031Charge relay system
Site2281Mediates preference for Asp-containing substrates By similarity

Amino acid modifications

Glycosylation711N-linked (GlcNAc...)
Glycosylation1041N-linked (GlcNAc...) Potential
Disulfide bond49 ↔ 65
Disulfide bond142 ↔ 209
Disulfide bond173 ↔ 188

Natural variations

Natural variant551R → Q. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.17
Corresponds to variant rs8192917 [ dbSNP | Ensembl ].
VAR_018371
Natural variant941P → A. Ref.2 Ref.6
Corresponds to variant rs11539752 [ dbSNP | Ensembl ].
VAR_047409
Natural variant2471Y → H. Ref.8 Ref.17
Corresponds to variant rs2236338 [ dbSNP | Ensembl ].
VAR_018381

Experimental info

Sequence conflict32 – 332RP → PR AA sequence Ref.12
Sequence conflict721V → G in AAA52118. Ref.3
Sequence conflict2121V → C in AAB59528. Ref.4

Secondary structure

....................................... 247
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10144 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: C652271918EF24F9

FASTA24727,716
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
PIRA61021.
RefSeqNP_004122.2. NM_004131.4.
UniGeneHs.1051.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FQ3X-ray3.10A/B21-247[»]
1IAUX-ray2.00A21-247[»]
ProteinModelPortalP10144.
SMRP10144. Positions 21-246.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109257. 30 interactions.
IntActP10144. 6 interactions.
MINTMINT-4528791.
STRING9606.ENSP00000216341.

Chemistry

BindingDBP10144.
ChEMBLCHEMBL2316.

Protein family/group databases

MEROPSS01.010.

PTM databases

PhosphoSiteP10144.

Polymorphism databases

DMDM317373361.

Proteomic databases

PaxDbP10144.
PRIDEP10144.

Protocols and materials databases

DNASU3002.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216341; ENSP00000216341; ENSG00000100453.
GeneID3002.
KEGGhsa:3002.
UCSCuc001wps.2. human.

Organism-specific databases

CTD3002.
GeneCardsGC14M025100.
H-InvDBHIX0011578.
HGNCHGNC:4709. GZMB.
HPACAB000376.
HPA003418.
MIM123910. gene.
neXtProtNX_P10144.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP10144.
KOK01353.
PhylomeDBP10144.
TreeFamTF333630.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_578. Apoptosis.

Gene expression databases

ArrayExpressP10144.
BgeeP10144.
CleanExHS_GZMB.
GenevestigatorP10144.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGZMB. human.
EvolutionaryTraceP10144.
GeneWikiGZMB.
GenomeRNAi3002.
NextBio11904.
PMAP-CutDBP10144.
PROP10144.
SOURCESearch...

Entry information

Entry nameGRAB_HUMAN
AccessionPrimary (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 16, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM