ID   GRAB_HUMAN              Reviewed;         247 AA.
AC   P10144; Q8N1D2; Q9UCC1;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   27-MAR-2024, entry version 228.
DE   RecName: Full=Granzyme B {ECO:0000303|PubMed:2332171};
DE            EC=3.4.21.79 {ECO:0000269|PubMed:1985927, ECO:0000269|PubMed:32188940, ECO:0000269|PubMed:8258716, ECO:0000269|PubMed:9852092};
DE   AltName: Full=C11;
DE   AltName: Full=CTLA-1 {ECO:0000303|PubMed:2332171};
DE   AltName: Full=Cathepsin G-like 1;
DE            Short=CTSGL1;
DE   AltName: Full=Cytotoxic T-lymphocyte proteinase 2;
DE            Short=Lymphocyte protease;
DE   AltName: Full=Fragmentin-2;
DE   AltName: Full=Granzyme-2;
DE   AltName: Full=Human lymphocyte protein;
DE            Short=HLP;
DE   AltName: Full=SECT;
DE   AltName: Full=T-cell serine protease 1-3E;
DE   Flags: Precursor;
GN   Name=GZMB {ECO:0000303|PubMed:32188940, ECO:0000312|HGNC:HGNC:4709};
GN   Synonyms=CGL1, CSPB, CTLA1 {ECO:0000303|PubMed:2332171}, GRB
GN   {ECO:0000303|PubMed:9852092};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-55.
RX   PubMed=2953813;
RA   Schmid J., Weissmann C.;
RT   "Induction of mRNA for a serine protease and a beta-thromboglobulin-like
RT   protein in mitogen-stimulated human leukocytes.";
RL   J. Immunol. 139:250-256(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-94.
RX   PubMed=3258865; DOI=10.1016/s0021-9258(18)68794-0;
RA   Caputo A., Fahey D., Lloyd C., Vozab R., McCairns E., Rowe P.B.;
RT   "Structure and differential mechanisms of regulation of expression of a
RT   serine esterase gene in activated human T lymphocytes.";
RL   J. Biol. Chem. 263:6363-6369(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-55.
RX   PubMed=3261871; DOI=10.1073/pnas.85.18.6924;
RA   Trapani J.A., Klein J.L., White P.C., Dupont B.;
RT   "Molecular cloning of an inducible serine esterase gene from human
RT   cytotoxic lymphocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:6924-6928(1988).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-55.
RX   PubMed=2788607; DOI=10.1016/0888-7543(89)90093-1;
RA   Klein J.L., Shows T.B., Dupont B., Trapani J.A.;
RT   "Genomic organization and chromosomal assignment for a serine protease gene
RT   (CSPB) expressed by human cytotoxic lymphocytes.";
RL   Genomics 5:110-117(1989).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-55.
RX   PubMed=2365998;
RA   Caputo A., Sauer D.E., Rowe P.B.;
RT   "Nucleotide sequence and genomic organization of a human T lymphocyte
RT   serine protease gene.";
RL   J. Immunol. 145:737-744(1990).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-55 AND ALA-94.
RX   PubMed=2332171; DOI=10.1016/0378-1119(90)90311-e;
RA   Haddad P., Clement M.-V., Bernard O., Larsen C.-J., Degos L., Sasportes M.,
RA   Mathieu-Mahul D.;
RT   "Structural organization of the hCTLA-1 gene encoding human granzyme B.";
RL   Gene 87:265-271(1990).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-55 AND HIS-247.
RC   TISSUE=Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-23.
RX   PubMed=2323780; DOI=10.1007/bf00195821;
RA   Dahl C.A., Bach F.H., Chan W., Huebner K., Russo G., Croce C.M.,
RA   Herfurth T., Cairns J.S.;
RT   "Isolation of a cDNA clone encoding a novel form of granzyme B from human
RT   NK cells and mapping to chromosome 14.";
RL   Hum. Genet. 84:465-470(1990).
RN   [10]
RP   PROTEIN SEQUENCE OF 21-40, AND FUNCTION.
RX   PubMed=3262682;
RA   Hameed A., Lowrey D.M., Lichtenheld M., Podack E.R.;
RT   "Characterization of three serine esterases isolated from human IL-2
RT   activated killer cells.";
RL   J. Immunol. 141:3142-3147(1988).
RN   [11]
RP   PROTEIN SEQUENCE OF 21-40, AND FUNCTION.
RX   PubMed=3263427;
RA   Kraehenbuhl O., Rey C., Jenne D.E., Lanzavecchia A., Groscurth P.,
RA   Carrel S., Tschopp J.;
RT   "Characterization of granzymes A and B isolated from granules of cloned
RT   human cytotoxic T lymphocytes.";
RL   J. Immunol. 141:3471-3477(1988).
RN   [12]
RP   PROTEIN SEQUENCE OF 21-39, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND
RP   ACTIVITY REGULATION.
RC   TISSUE=Lymphocyte;
RX   PubMed=8258716;
RA   Froelich C.J., Zhang X., Turbov J., Hudig D., Winkler U., Hanna W.L.;
RT   "Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by
RT   chondrocytes.";
RL   J. Immunol. 151:7161-7171(1993).
RN   [13]
RP   PROTEIN SEQUENCE OF 21-38, FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=1985927; DOI=10.1016/s0021-9258(18)52407-8;
RA   Poe M., Blake J.T., Boulton D.A., Gammon M., Sigal N.H., Wu J.K.,
RA   Zweerink H.J.;
RT   "Human cytotoxic lymphocyte granzyme B. Its purification from granules and
RT   the characterization of substrate and inhibitor specificity.";
RL   J. Biol. Chem. 266:98-103(1991).
RN   [14]
RP   PROTEIN SEQUENCE OF 19-33.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [15]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=9852092; DOI=10.1074/jbc.273.51.34278;
RA   Yang X., Stennicke H.R., Wang B., Green D.R., Jaenicke R.U., Srinivasan A.,
RA   Seth P., Salvesen G.S., Froelich C.J.;
RT   "Granzyme B mimics apical caspases. Description of a unified pathway for
RT   trans-activation of executioner caspase-3 and -7.";
RL   J. Biol. Chem. 273:34278-34283(1998).
RN   [16]
RP   SUBCELLULAR LOCATION.
RX   PubMed=20038786; DOI=10.1182/blood-2009-10-246116;
RA   Thiery J., Keefe D., Saffarian S., Martinvalet D., Walch M., Boucrot E.,
RA   Kirchhausen T., Lieberman J.;
RT   "Perforin activates clathrin- and dynamin-dependent endocytosis, which is
RT   required for plasma membrane repair and delivery of granzyme B for
RT   granzyme-mediated apoptosis.";
RL   Blood 115:1582-1593(2010).
RN   [17]
RP   SUBCELLULAR LOCATION.
RX   PubMed=24088571; DOI=10.1091/mbc.e13-05-0259;
RA   Tuli A., Thiery J., James A.M., Michelet X., Sharma M., Garg S.,
RA   Sanborn K.B., Orange J.S., Lieberman J., Brenner M.B.;
RT   "Arf-like GTPase Arl8b regulates lytic granule polarization and natural
RT   killer cell-mediated cytotoxicity.";
RL   Mol. Biol. Cell 24:3721-3735(2013).
RN   [18]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=32188940; DOI=10.1038/s41586-020-2071-9;
RA   Zhang Z., Zhang Y., Xia S., Kong Q., Li S., Liu X., Junqueira C.,
RA   Meza-Sosa K.F., Mok T.M.Y., Ansara J., Sengupta S., Yao Y., Wu H.,
RA   Lieberman J.;
RT   "Gasdermin E suppresses tumour growth by activating anti-tumour immunity.";
RL   Nature 579:415-420(2020).
RN   [19]
RP   FUNCTION.
RX   PubMed=31953257; DOI=10.1126/sciimmunol.aax7969;
RA   Liu Y., Fang Y., Chen X., Wang Z., Liang X., Zhang T., Liu M., Zhou N.,
RA   Lv J., Tang K., Xie J., Gao Y., Cheng F., Zhou Y., Zhang Z., Hu Y.,
RA   Zhang X., Gao Q., Zhang Y., Huang B.;
RT   "Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers
RT   cytokine release syndrome.";
RL   Sci. Immunol. 5:0-0(2020).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
RX   PubMed=11209755; DOI=10.1515/bc.2000.148;
RA   Estebanez-Perpina E., Fuentes-Prior P., Belorgey D., Braun M.,
RA   Kiefersauer R., Maskos K., Huber R., Rubin H., Bode W.;
RT   "Crystal structure of the caspase activator human granzyme B, a proteinase
RT   highly specific for an Asp-P1 residue.";
RL   Biol. Chem. 381:1203-1214(2000).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247, AND GLYCOSYLATION AT
RP   ASN-71 AND ASN-104.
RX   PubMed=11325591; DOI=10.1016/s1074-5521(01)00018-7;
RA   Rotonda J., Garcia-Calvo M., Bull H.G., Geissler W.M., McKeever B.M.,
RA   Willoughby C.A., Thornberry N.A., Becker J.W.;
RT   "The three-dimensional structure of human granzyme B compared to caspase-3,
RT   key mediators of cell death with cleavage specificity for aspartic acid in
RT   P1.";
RL   Chem. Biol. 8:357-368(2001).
RN   [22]
RP   VARIANTS GLN-55 AND HIS-247.
RX   PubMed=12721789; DOI=10.1007/s10038-003-0021-7;
RA   Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C.,
RA   Nakamura Y.;
RT   "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine
RT   esterase genes, and two other genes in the Japanese population.";
RL   J. Hum. Genet. 48:249-270(2003).
CC   -!- FUNCTION: Abundant protease in the cytosolic granules of cytotoxic T-
CC       cells and NK-cells which activates caspase-independent pyroptosis when
CC       delivered into the target cell through the immunological synapse
CC       (PubMed:3262682, PubMed:3263427, PubMed:1985927). It cleaves after Asp
CC       (PubMed:8258716, PubMed:1985927). Once delivered into the target cell,
CC       acts by catalyzing cleavage of gasdermin-E (GSDME), releasing the pore-
CC       forming moiety of GSDME, thereby triggering pyroptosis and target cell
CC       death (PubMed:32188940, PubMed:31953257). Seems to be linked to an
CC       activation cascade of caspases (aspartate-specific cysteine proteases)
CC       responsible for apoptosis execution. Cleaves caspase-3, -9 and -10
CC       (CASP3, CASP9 and CASP10, respectively) to give rise to active enzymes
CC       mediating apoptosis (PubMed:9852092). Cleaves and activates CASP7 in
CC       response to bacterial infection, promoting plasma membrane repair (By
CC       similarity). {ECO:0000250|UniProtKB:P04187, ECO:0000269|PubMed:1985927,
CC       ECO:0000269|PubMed:31953257, ECO:0000269|PubMed:32188940,
CC       ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:3263427,
CC       ECO:0000269|PubMed:8258716, ECO:0000269|PubMed:9852092}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-
CC         Xaa-, -Ser-|-Xaa-.; EC=3.4.21.79;
CC         Evidence={ECO:0000269|PubMed:1985927, ECO:0000269|PubMed:32188940,
CC         ECO:0000269|PubMed:8258716, ECO:0000269|PubMed:9852092};
CC   -!- ACTIVITY REGULATION: Inactivated by the serine protease inhibitor
CC       diisopropylfluorophosphate. {ECO:0000269|PubMed:8258716}.
CC   -!- INTERACTION:
CC       P10144; P14222: PRF1; NbExp=3; IntAct=EBI-2505785, EBI-724466;
CC       P10144; P10124: SRGN; NbExp=2; IntAct=EBI-2505785, EBI-744915;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20038786,
CC       ECO:0000269|PubMed:8258716}. Cytolytic granule
CC       {ECO:0000269|PubMed:1985927, ECO:0000269|PubMed:24088571,
CC       ECO:0000269|PubMed:8258716}. Note=Delivered into the target cell by
CC       perforin (PubMed:20038786). {ECO:0000269|PubMed:20038786,
CC       ECO:0000269|PubMed:8258716}.
CC   -!- INDUCTION: By staphylococcal enterotoxin A (SEA) in peripheral blood
CC       leukocytes.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR   EMBL; M17016; AAA36627.1; -; mRNA.
DR   EMBL; J03189; AAA36603.1; -; mRNA.
DR   EMBL; J04071; AAA52118.1; -; mRNA.
DR   EMBL; J03072; AAB59528.1; -; Genomic_DNA.
DR   EMBL; M38193; AAA67124.1; -; Genomic_DNA.
DR   EMBL; M28879; AAA75490.1; -; Genomic_DNA.
DR   EMBL; AL136018; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC030195; AAH30195.1; -; mRNA.
DR   CCDS; CCDS9633.1; -.
DR   PIR; A61021; A61021.
DR   RefSeq; NP_004122.2; NM_004131.5.
DR   PDB; 1FQ3; X-ray; 3.10 A; A/B=21-247.
DR   PDB; 1IAU; X-ray; 2.00 A; A=21-247.
DR   PDBsum; 1FQ3; -.
DR   PDBsum; 1IAU; -.
DR   AlphaFoldDB; P10144; -.
DR   SMR; P10144; -.
DR   BioGRID; 109257; 30.
DR   IntAct; P10144; 6.
DR   MINT; P10144; -.
DR   STRING; 9606.ENSP00000216341; -.
DR   BindingDB; P10144; -.
DR   ChEMBL; CHEMBL2316; -.
DR   GuidetoPHARMACOLOGY; 2369; -.
DR   MEROPS; S01.010; -.
DR   GlyCosmos; P10144; 3 sites, 2 glycans.
DR   GlyGen; P10144; 3 sites, 2 O-linked glycans (1 site).
DR   iPTMnet; P10144; -.
DR   PhosphoSitePlus; P10144; -.
DR   BioMuta; GZMB; -.
DR   DMDM; 317373361; -.
DR   jPOST; P10144; -.
DR   MassIVE; P10144; -.
DR   PaxDb; 9606-ENSP00000216341; -.
DR   PeptideAtlas; P10144; -.
DR   ProteomicsDB; 52569; -.
DR   ABCD; P10144; 3 sequenced antibodies.
DR   Antibodypedia; 187; 1316 antibodies from 51 providers.
DR   DNASU; 3002; -.
DR   Ensembl; ENST00000216341.9; ENSP00000216341.4; ENSG00000100453.14.
DR   GeneID; 3002; -.
DR   KEGG; hsa:3002; -.
DR   MANE-Select; ENST00000216341.9; ENSP00000216341.4; NM_004131.6; NP_004122.2.
DR   UCSC; uc001wps.4; human.
DR   AGR; HGNC:4709; -.
DR   CTD; 3002; -.
DR   DisGeNET; 3002; -.
DR   GeneCards; GZMB; -.
DR   HGNC; HGNC:4709; GZMB.
DR   HPA; ENSG00000100453; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 123910; gene.
DR   neXtProt; NX_P10144; -.
DR   OpenTargets; ENSG00000100453; -.
DR   VEuPathDB; HostDB:ENSG00000100453; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT01030000234551; -.
DR   HOGENOM; CLU_006842_1_0_1; -.
DR   InParanoid; P10144; -.
DR   OMA; PAYNPEK; -.
DR   OrthoDB; 2540265at2759; -.
DR   PhylomeDB; P10144; -.
DR   TreeFam; TF333630; -.
DR   BRENDA; 3.4.21.79; 2681.
DR   PathwayCommons; P10144; -.
DR   Reactome; R-HSA-2197563; NOTCH2 intracellular domain regulates transcription.
DR   Reactome; R-HSA-5620971; Pyroptosis.
DR   Reactome; R-HSA-75108; Activation, myristolyation of BID and translocation to mitochondria.
DR   SignaLink; P10144; -.
DR   SIGNOR; P10144; -.
DR   BioGRID-ORCS; 3002; 13 hits in 1156 CRISPR screens.
DR   ChiTaRS; GZMB; human.
DR   EvolutionaryTrace; P10144; -.
DR   GeneWiki; GZMB; -.
DR   GenomeRNAi; 3002; -.
DR   Pharos; P10144; Tchem.
DR   PRO; PR:P10144; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; P10144; Protein.
DR   Bgee; ENSG00000100453; Expressed in granulocyte and 127 other cell types or tissues.
DR   ExpressionAtlas; P10144; baseline and differential.
DR   GO; GO:0044194; C:cytolytic granule; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0001772; C:immunological synapse; TAS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR   GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; IDA:UniProtKB.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR   GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; IDA:CACAO.
DR   GO; GO:0051604; P:protein maturation; IDA:UniProt.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB.
DR   GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24271:SF81; GRANZYME B; 1.
DR   PANTHER; PTHR24271; KALLIKREIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
DR   Genevisible; P10144; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Apoptosis; Cytolysis; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Protease;
KW   Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   PROPEP          19..20
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:1985927,
FT                   ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:3263427,
FT                   ECO:0000269|PubMed:8258716"
FT                   /id="PRO_0000027399"
FT   CHAIN           21..247
FT                   /note="Granzyme B"
FT                   /id="PRO_0000027400"
FT   DOMAIN          21..245
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        64
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   ACT_SITE        108
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   ACT_SITE        203
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   SITE            228
FT                   /note="Mediates preference for Asp-containing substrates"
FT                   /evidence="ECO:0000250|UniProtKB:P18291"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11325591"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11325591"
FT   DISULFID        49..65
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   DISULFID        142..209
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   DISULFID        173..188
FT                   /evidence="ECO:0000269|PubMed:11209755,
FT                   ECO:0000269|PubMed:11325591"
FT   VARIANT         55
FT                   /note="R -> Q (in dbSNP:rs8192917)"
FT                   /evidence="ECO:0000269|PubMed:12721789,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2332171,
FT                   ECO:0000269|PubMed:2365998, ECO:0000269|PubMed:2788607,
FT                   ECO:0000269|PubMed:2953813, ECO:0000269|PubMed:3261871"
FT                   /id="VAR_018371"
FT   VARIANT         94
FT                   /note="P -> A (in dbSNP:rs11539752)"
FT                   /evidence="ECO:0000269|PubMed:2332171,
FT                   ECO:0000269|PubMed:3258865"
FT                   /id="VAR_047409"
FT   VARIANT         247
FT                   /note="Y -> H (in dbSNP:rs2236338)"
FT                   /evidence="ECO:0000269|PubMed:12721789,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_018381"
FT   CONFLICT        32..33
FT                   /note="RP -> PR (in Ref. 12; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        72
FT                   /note="V -> G (in Ref. 3; AAA52118)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        212
FT                   /note="V -> C (in Ref. 4; AAB59528)"
FT                   /evidence="ECO:0000305"
FT   STRAND          35..41
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          46..55
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          58..61
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   HELIX           63..65
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          68..75
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   TURN            79..82
FT                   /evidence="ECO:0007829|PDB:1FQ3"
FT   STRAND          87..96
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   TURN            102..104
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          110..116
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          141..148
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          150..154
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          161..167
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   HELIX           170..176
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   TURN            177..180
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   TURN            183..185
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          186..190
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          205..209
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          212..220
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   STRAND          228..232
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   HELIX           233..236
FT                   /evidence="ECO:0007829|PDB:1IAU"
FT   HELIX           237..245
FT                   /evidence="ECO:0007829|PDB:1IAU"
SQ   SEQUENCE   247 AA;  27716 MW;  C652271918EF24F9 CRC64;
     MQPILLLLAF LLLPRADAGE IIGGHEAKPH SRPYMAYLMI WDQKSLKRCG GFLIRDDFVL
     TAAHCWGSSI NVTLGAHNIK EQEPTQQFIP VKRPIPHPAY NPKNFSNDIM LLQLERKAKR
     TRAVQPLRLP SNKAQVKPGQ TCSVAGWGQT APLGKHSHTL QEVKMTVQED RKCESDLRHY
     YDSTIELCVG DPEIKKTSFK GDSGGPLVCN KVAQGIVSYG RNNGMPPRAC TKVSSFVHWI
     KKTMKRY
//