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P10144

- GRAB_HUMAN

UniProt

P10144 - GRAB_HUMAN

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Protein

Granzyme B

Gene
GZMB, CGL1, CSPB, CTLA1, GRB
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-.1 Publication

Enzyme regulationi

Inactivated by the serine protease inhibitor diisopropylfluorophosphate.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei64 – 641Charge relay system
Active sitei108 – 1081Charge relay system
Active sitei203 – 2031Charge relay system
Sitei228 – 2281Mediates preference for Asp-containing substrates By similarity

GO - Molecular functioni

  1. protein binding Source: UniProtKB
  2. serine-type endopeptidase activity Source: UniProtKB
  3. serine-type peptidase activity Source: ProtInc

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. cytolysis Source: UniProtKB-KW
  3. granzyme-mediated apoptotic signaling pathway Source: RefGenome
  4. intrinsic apoptotic signaling pathway Source: Reactome
  5. Notch signaling pathway Source: Reactome
  6. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  7. proteolysis Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Apoptosis, Cytolysis

Enzyme and pathway databases

ReactomeiREACT_163910. NOTCH2 intracellular domain regulates transcription.
REACT_701. Activation, myristolyation of BID and translocation to mitochondria.

Protein family/group databases

MEROPSiS01.010.

Names & Taxonomyi

Protein namesi
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 namesi
Name:GZMB
Synonyms:CGL1, CSPB, CTLA1, GRB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:4709. GZMB.

Subcellular locationi

Cytoplasmic granule
Note: Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. immunological synapse Source: UniProtKB
  4. intracellular membrane-bounded organelle Source: HPA
  5. nucleus Source: UniProtKB
  6. secretory granule Source: RefGenome
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18181 PublicationAdd
BLAST
Propeptidei19 – 202Activation peptidePRO_0000027399
Chaini21 – 247227Granzyme BPRO_0000027400Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi49 ↔ 65
Glycosylationi71 – 711N-linked (GlcNAc...)
Glycosylationi104 – 1041N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi142 ↔ 209
Disulfide bondi173 ↔ 188

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP10144.
PRIDEiP10144.

PTM databases

PhosphoSiteiP10144.

Miscellaneous databases

PMAP-CutDBP10144.

Expressioni

Inductioni

By staphylococcal enterotoxin A (SEA) in peripheral blood leukocytes.1 Publication

Gene expression databases

ArrayExpressiP10144.
BgeeiP10144.
CleanExiHS_GZMB.
GenevestigatoriP10144.

Organism-specific databases

HPAiCAB000376.
HPA003418.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
PRF1P142223EBI-2505785,EBI-724466
SRGNP101242EBI-2505785,EBI-744915

Protein-protein interaction databases

BioGridi109257. 30 interactions.
IntActiP10144. 6 interactions.
MINTiMINT-4528791.
STRINGi9606.ENSP00000216341.

Structurei

Secondary structure

1
247
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi35 – 417
Beta strandi46 – 5510
Beta strandi58 – 614
Helixi63 – 653
Beta strandi68 – 758
Turni79 – 824
Beta strandi87 – 9610
Turni102 – 1043
Beta strandi110 – 1167
Beta strandi141 – 1488
Beta strandi150 – 1545
Beta strandi161 – 1677
Helixi170 – 1767
Turni177 – 1804
Turni183 – 1853
Beta strandi186 – 1905
Beta strandi205 – 2095
Beta strandi212 – 2209
Beta strandi228 – 2325
Helixi233 – 2364
Helixi237 – 2459

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FQ3X-ray3.10A/B21-247[»]
1IAUX-ray2.00A21-247[»]
ProteinModelPortaliP10144.
SMRiP10144. Positions 21-246.

Miscellaneous databases

EvolutionaryTraceiP10144.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 245225Peptidase S1Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG5640.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiP10144.
KOiK01353.
PhylomeDBiP10144.
TreeFamiTF333630.

Family and domain databases

InterProiIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P10144-1 [UniParc]FASTAAdd to Basket

« Hide

MQPILLLLAF LLLPRADAGE IIGGHEAKPH SRPYMAYLMI WDQKSLKRCG    50
GFLIRDDFVL TAAHCWGSSI NVTLGAHNIK EQEPTQQFIP VKRPIPHPAY 100
NPKNFSNDIM LLQLERKAKR TRAVQPLRLP SNKAQVKPGQ TCSVAGWGQT 150
APLGKHSHTL QEVKMTVQED RKCESDLRHY YDSTIELCVG DPEIKKTSFK 200
GDSGGPLVCN KVAQGIVSYG RNNGMPPRAC TKVSSFVHWI KKTMKRY 247
Length:247
Mass (Da):27,716
Last modified:January 11, 2011 - v2
Checksum:iC652271918EF24F9
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551R → Q.7 Publications
Corresponds to variant rs8192917 [ dbSNP | Ensembl ].
VAR_018371
Natural varianti94 – 941P → A.2 Publications
Corresponds to variant rs11539752 [ dbSNP | Ensembl ].
VAR_047409
Natural varianti247 – 2471Y → H.2 Publications
Corresponds to variant rs2236338 [ dbSNP | Ensembl ].
VAR_018381

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti32 – 332RP → PR AA sequence 1 Publication
Sequence conflicti72 – 721V → G in AAA52118. 1 Publication
Sequence conflicti212 – 2121V → C in AAB59528. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS9633.1.
PIRiA61021.
RefSeqiNP_004122.2. NM_004131.4.
UniGeneiHs.1051.

Genome annotation databases

EnsembliENST00000216341; ENSP00000216341; ENSG00000100453.
GeneIDi3002.
KEGGihsa:3002.
UCSCiuc001wps.2. human.

Polymorphism databases

DMDMi317373361.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS9633.1.
PIRi A61021.
RefSeqi NP_004122.2. NM_004131.4.
UniGenei Hs.1051.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FQ3 X-ray 3.10 A/B 21-247 [» ]
1IAU X-ray 2.00 A 21-247 [» ]
ProteinModelPortali P10144.
SMRi P10144. Positions 21-246.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109257. 30 interactions.
IntActi P10144. 6 interactions.
MINTi MINT-4528791.
STRINGi 9606.ENSP00000216341.

Chemistry

BindingDBi P10144.
ChEMBLi CHEMBL2316.

Protein family/group databases

MEROPSi S01.010.

PTM databases

PhosphoSitei P10144.

Polymorphism databases

DMDMi 317373361.

Proteomic databases

PaxDbi P10144.
PRIDEi P10144.

Protocols and materials databases

DNASUi 3002.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000216341 ; ENSP00000216341 ; ENSG00000100453 .
GeneIDi 3002.
KEGGi hsa:3002.
UCSCi uc001wps.2. human.

Organism-specific databases

CTDi 3002.
GeneCardsi GC14M025100.
H-InvDB HIX0011578.
HGNCi HGNC:4709. GZMB.
HPAi CAB000376.
HPA003418.
MIMi 123910. gene.
neXtProti NX_P10144.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5640.
HOGENOMi HOG000251820.
HOVERGENi HBG013304.
InParanoidi P10144.
KOi K01353.
PhylomeDBi P10144.
TreeFami TF333630.

Enzyme and pathway databases

Reactomei REACT_163910. NOTCH2 intracellular domain regulates transcription.
REACT_701. Activation, myristolyation of BID and translocation to mitochondria.

Miscellaneous databases

ChiTaRSi GZMB. human.
EvolutionaryTracei P10144.
GeneWikii GZMB.
GenomeRNAii 3002.
NextBioi 11904.
PMAP-CutDB P10144.
PROi P10144.
SOURCEi Search...

Gene expression databases

ArrayExpressi P10144.
Bgeei P10144.
CleanExi HS_GZMB.
Genevestigatori P10144.

Family and domain databases

InterProi IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF00089. Trypsin. 1 hit.
[Graphical view ]
PRINTSi PR00722. CHYMOTRYPSIN.
SMARTi SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
PROSITEi PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiGRAB_HUMAN
AccessioniPrimary (citable) accession number: P10144
Secondary accession number(s): Q8N1D2, Q9UCC1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 11, 2011
Last modified: September 3, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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