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Protein

Granzyme B

Gene

GZMB

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

  • apoptotic process Source: UniProtKB
  • cytolysis Source: UniProtKB-KW
  • natural killer cell mediated cytotoxicity Source: UniProtKB
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  • protein processing Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Apoptosis, Cytolysis

Enzyme and pathway databases

BioCyciZFISH:HS02090-MONOMER.
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

HGNCiHGNC:4709. GZMB.

Subcellular locationi

  • Cytoplasmic granule 1 Publication

  • Note: Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • immunological synapse Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • mitochondrion Source: GOC
  • nucleus Source: UniProtKB
Complete GO annotation...

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...)1
Glycosylationi104N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi142 ↔ 209
Disulfide bondi173 ↔ 188

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP10144.
PeptideAtlasiP10144.
PRIDEiP10144.

PTM databases

iPTMnetiP10144.
PhosphoSitePlusiP10144.

Miscellaneous databases

PMAP-CutDBP10144.

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000100453.
CleanExiHS_GZMB.
ExpressionAtlasiP10144. baseline and differential.
GenevisibleiP10144. HS.

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 interactors.
IntActiP10144. 6 interactors.
MINTiMINT-4528791.
STRINGi9606.ENSP00000216341.

Chemistry databases

BindingDBiP10144.

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 41Combined sources7
Beta strandi46 – 55Combined sources10
Beta strandi58 – 61Combined sources4
Helixi63 – 65Combined sources3
Beta strandi68 – 75Combined sources8
Turni79 – 82Combined sources4
Beta strandi87 – 96Combined sources10
Turni102 – 104Combined sources3
Beta strandi110 – 116Combined sources7
Beta strandi141 – 148Combined sources8
Beta strandi150 – 154Combined sources5
Beta strandi161 – 167Combined sources7
Helixi170 – 176Combined sources7
Turni177 – 180Combined sources4
Turni183 – 185Combined sources3
Beta strandi186 – 190Combined sources5
Beta strandi205 – 209Combined sources5
Beta strandi212 – 220Combined sources9
Beta strandi228 – 232Combined sources5
Helixi233 – 236Combined sources4
Helixi237 – 245Combined sources9

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...

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
Contains 1 peptidase S1 domain.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.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[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

        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

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 → Q.7 PublicationsCorresponds to variant rs8192917dbSNPEnsembl.1
Natural variantiVAR_04740994P → A.2 PublicationsCorresponds to variant rs11539752dbSNPEnsembl.1
Natural variantiVAR_018381247Y → H.2 PublicationsCorresponds to variant rs2236338dbSNPEnsembl.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

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.
MINTiMINT-4528791.
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.

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.
GeneCardsiGZMB.
H-InvDBHIX0011578.
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

BioCyciZFISH:HS02090-MONOMER.
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-CutDBP10144.
PROiP10144.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100453.
CleanExiHS_GZMB.
ExpressionAtlasiP10144. baseline and differential.
GenevisibleiP10144. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[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]
ProtoNetiSearch...

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: November 30, 2016
This is version 187 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.