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Reviewed, UniProtKB/Swiss-Prot P10144 (GRAB_HUMAN)

Last modified November 25, 2008. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
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-.

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.

Ontologies

Keywords

   Biological processApoptosis
Cytolysis
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMGlycoprotein
Zymogen
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Uncategorizedgranzyme B activity

Inferred from Experiment. Source: Reactome

   Biological processcleavage of lamin

Inferred from direct assay. Source: UniProtKB

cytolysis

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentcytosol

Inferred from Experiment. Source: Reactome

immunological synapse

Traceable author statement. Source: UniProtKB

nucleus

Traceable author statement. Source: UniProtKB

   Molecular functionprotein binding

Inferred from physical interaction. Source: UniProtKB

serine-type endopeptidase activity

Traceable author statement. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818
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

Amino acid modifications

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

Natural variations

Natural variant551Q → R: dbSNP rs8192917.
VAR_018371
Natural variant941P → A: dbSNP rs11539752.
VAR_047409
Natural variant2471Y → H: dbSNP rs2236338.
VAR_018381

Experimental info

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
P10144-1 [UniParc].

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

FASTA24727,688
        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

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: 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. 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: 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.

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.
PIRA61021.
RefSeqNP_004122.1.
UniGeneHs.1051

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1FQ3X-ray3.10A/B21-247[»]
1IAUX-ray2.00A21-247[»]
ModBaseSearch...

Protein family/group databases

MEROPSS01.010.

Genome annotation databases

EnsemblENSG00000100453. Homo sapiens. [Contig view]
GeneID3002.
KEGGhsa:3002.

Organism-specific databases

H-InvDBHIX0011578.
HGNCHGNC:4709. GZMB.
HPACAB000376.
HPA003418.
MIM123910. gene.
PharmGKBPA29087.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP10144.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP10144.
CleanExHS_GZMB.
GermOnlineENSG00000100453. Homo sapiens.

Family and domain databases

InterProIPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio11904.
SOURCESearch...

Entry information

Entry nameGRAB_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 14

Human chromosome 14: 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

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

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