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Protein

Granzyme B

Gene

GZMB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity regulationi

Inactivated by the serine protease inhibitor diisopropylfluorophosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei64Charge relay system1
Active sitei108Charge relay system1
Active sitei203Charge relay system1
Sitei228Mediates preference for Asp-containing substratesBy similarity1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis, Cytolysis

Enzyme and pathway databases

ReactomeiR-HSA-2197563 NOTCH2 intracellular domain regulates transcription
R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria
SIGNORiP10144

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
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100453.12
HGNCiHGNC:4709 GZMB
MIMi123910 gene
neXtProtiNX_P10144

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi3002
OpenTargetsiENSG00000100453

Chemistry databases

ChEMBLiCHEMBL2316
GuidetoPHARMACOLOGYi2369

Polymorphism and mutation databases

BioMutaiGZMB
DMDMi317373361

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
PropeptideiPRO_000002739919 – 20Activation peptide4 Publications2
ChainiPRO_000002740021 – 247Granzyme BAdd BLAST227

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 65
Glycosylationi71N-linked (GlcNAc...) asparagine1
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi142 ↔ 209
Disulfide bondi173 ↔ 188

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP10144
PeptideAtlasiP10144
PRIDEiP10144
ProteomicsDBi52569

PTM databases

iPTMnetiP10144
PhosphoSitePlusiP10144

Miscellaneous databases

PMAP-CutDBiP10144

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000100453 Expressed in 134 organ(s), highest expression level in leukocyte
CleanExiHS_GZMB
ExpressionAtlasiP10144 baseline and differential
GenevisibleiP10144 HS

Organism-specific databases

HPAiCAB000376
HPA003418

Interactioni

Binary interactionsi

Protein-protein interaction databases

BioGridi109257, 30 interactors
IntActiP10144, 6 interactors
MINTiP10144
STRINGi9606.ENSP00000216341

Chemistry databases

BindingDBiP10144

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10144
SMRiP10144
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10144

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 245Peptidase S1PROSITE-ProRule annotationAdd BLAST225

Sequence similaritiesi

Belongs to the peptidase S1 family. Granzyme subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118895
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiP10144
KOiK01353
OMAiCVGDPEI
OrthoDBiEOG091G0G5F
PhylomeDBiP10144
TreeFamiTF333630

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR037553 Granzyme_B
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR24271:SF41 PTHR24271:SF41, 1 hit
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

P10144-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MQPILLLLAF LLLPRADAGE IIGGHEAKPH SRPYMAYLMI WDQKSLKRCG
60 70 80 90 100
GFLIRDDFVL TAAHCWGSSI NVTLGAHNIK EQEPTQQFIP VKRPIPHPAY
110 120 130 140 150
NPKNFSNDIM LLQLERKAKR TRAVQPLRLP SNKAQVKPGQ TCSVAGWGQT
160 170 180 190 200
APLGKHSHTL QEVKMTVQED RKCESDLRHY YDSTIELCVG DPEIKKTSFK
210 220 230 240
GDSGGPLVCN KVAQGIVSYG RNNGMPPRAC TKVSSFVHWI KKTMKRY
Length:247
Mass (Da):27,716
Last modified:January 11, 2011 - v2
Checksum:iC652271918EF24F9
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KPK2J3KPK2_HUMAN
Granzyme B
GZMB
202Annotation score:
Q6XGZ2Q6XGZ2_HUMAN
Granzyme B splice variant 2
GZMB
152Annotation score:
J3KQ52J3KQ52_HUMAN
Granzyme B (Granzyme 2, cytotoxic T...
GZMB hCG_40183
235Annotation score:
E9PRD7E9PRD7_HUMAN
Granzyme B
GZMB
90Annotation score:
E9PID1E9PID1_HUMAN
Granzyme B
GZMB
35Annotation score:
E9PLX4E9PLX4_HUMAN
Granzyme B
GZMB
44Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32 – 33RP → PR AA sequence (PubMed:8258716).Curated2
Sequence conflicti72V → G in AAA52118 (PubMed:3261871).Curated1
Sequence conflicti212V → C in AAB59528 (PubMed:2788607).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01837155R → Q7 PublicationsCorresponds to variant dbSNP:rs8192917Ensembl.1
Natural variantiVAR_04740994P → A2 PublicationsCorresponds to variant dbSNP:rs11539752Ensembl.1
Natural variantiVAR_018381247Y → H2 PublicationsCorresponds to variant dbSNP:rs2236338Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_004131.5
UniGeneiHs.1051

Genome annotation databases

EnsembliENST00000216341; ENSP00000216341; ENSG00000100453
GeneIDi3002
KEGGihsa:3002
UCSCiuc001wps.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_004131.5
UniGeneiHs.1051

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FQ3X-ray3.10A/B21-247[»]
1IAUX-ray2.00A21-247[»]
ProteinModelPortaliP10144
SMRiP10144
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109257, 30 interactors
IntActiP10144, 6 interactors
MINTiP10144
STRINGi9606.ENSP00000216341

Chemistry databases

BindingDBiP10144
ChEMBLiCHEMBL2316
GuidetoPHARMACOLOGYi2369

Protein family/group databases

MEROPSiS01.010

PTM databases

iPTMnetiP10144
PhosphoSitePlusiP10144

Polymorphism and mutation databases

BioMutaiGZMB
DMDMi317373361

Proteomic databases

PaxDbiP10144
PeptideAtlasiP10144
PRIDEiP10144
ProteomicsDBi52569

Protocols and materials databases

DNASUi3002
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216341; ENSP00000216341; ENSG00000100453
GeneIDi3002
KEGGihsa:3002
UCSCiuc001wps.4 human

Organism-specific databases

CTDi3002
DisGeNETi3002
EuPathDBiHostDB:ENSG00000100453.12
GeneCardsiGZMB
H-InvDBiHIX0011578
HGNCiHGNC:4709 GZMB
HPAiCAB000376
HPA003418
MIMi123910 gene
neXtProtiNX_P10144
OpenTargetsiENSG00000100453
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118895
HOGENOMiHOG000251820
HOVERGENiHBG013304
InParanoidiP10144
KOiK01353
OMAiCVGDPEI
OrthoDBiEOG091G0G5F
PhylomeDBiP10144
TreeFamiTF333630

Enzyme and pathway databases

ReactomeiR-HSA-2197563 NOTCH2 intracellular domain regulates transcription
R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria
SIGNORiP10144

Miscellaneous databases

ChiTaRSiGZMB human
EvolutionaryTraceiP10144
GeneWikiiGZMB
GenomeRNAii3002
PMAP-CutDBiP10144
PROiPR:P10144
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100453 Expressed in 134 organ(s), highest expression level in leukocyte
CleanExiHS_GZMB
ExpressionAtlasiP10144 baseline and differential
GenevisibleiP10144 HS

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR037553 Granzyme_B
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR24271:SF41 PTHR24271:SF41, 1 hit
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRAB_HUMAN
AccessioniPrimary (citable) accession number: P10144
Secondary accession number(s): Q8N1D2, Q9UCC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 11, 2011
Last modified: September 12, 2018
This is version 196 of the entry and version 2 of the sequence. See 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. UniProtKB entry view manual
    User manual for the UniProtKB entry view
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  7. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  8. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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