Human Gene GZMB (uc001wps.2) Description and Page Index
  Description: Homo sapiens granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) (GZMB), mRNA.
RefSeq Summary (NM_004131): This gene encodes a member of the granzyme subfamily of proteins, part of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) and proteolytically processed to generate the active protease, which induces target cell apoptosis. This protein also processes cytokines and degrades extracellular matrix proteins, and these roles are implicated in chronic inflammation and wound healing. Expression of this gene may be elevated in human patients with cardiac fibrosis. [provided by RefSeq, Sep 2016].
Transcript (Including UTRs)
   Position: hg19 chr14:25,100,161-25,103,432 Size: 3,272 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg19 chr14:25,100,277-25,103,366 Size: 3,090 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr14:25,100,161-25,103,432)mRNA (may differ from genome)Protein (247 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Granzyme B; EC=; AltName: Full=C11; AltName: Full=CTLA-1; AltName: Full=Cathepsin G-like 1; Short=CTSGL1; AltName: Full=Cytotoxic T-lymphocyte proteinase 2; Short=Lymphocyte protease; AltName: Full=Fragmentin-2; AltName: Full=Granzyme-2; AltName: Full=Human lymphocyte protein; Short=HLP; AltName: Full=SECT; AltName: Full=T-cell serine protease 1-3E; Flags: Precursor;
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-.
ENZYME REGULATION: Inactivated by the serine protease inhibitor diisopropylfluorophosphate.
INTERACTION: P14222:PRF1; NbExp=3; IntAct=EBI-2505785, EBI-724466; P10124:SRGN; NbExp=2; IntAct=EBI-2505785, EBI-744915;
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.
SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
SIMILARITY: Contains 1 peptidase S1 domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GZMB
CDC HuGE Published Literature: GZMB
Positive Disease Associations: Alzheimer Disease , Fibrinogen , Urinalysis , Vitiligo
Related Studies:
  1. Alzheimer Disease
    S J Furney et al. Molecular psychiatry 2011, Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease., Molecular psychiatry. [PubMed 21116278]
  2. Fibrinogen
    , , . [PubMed 0]
  3. Urinalysis
    Emelia J Benjamin et al. BMC medical genetics 2007, Genome-wide association with select biomarker traits in the Framingham Heart Study., BMC medical genetics. [PubMed 17903293]
    The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: GZMB
Diseases sorted by gene-association score: lymphocytic gastritis (23), natural killer cell leukemia (23), subcutaneous panniculitis-like t-cell lymphoma (18), peripheral t-cell lymphoma (16), hypersensitivity syndrome, carbamazepine-induced (15), composite lymphoma (14), breast medullary carcinoma (14), anaplastic large cell lymphoma (14), keratoacanthoma (13), papillon-lefevre syndrome (13), lymphomatoid granulomatosis (13), lymphomatoid papulosis (11), panniculitis (11), alopecia areata (10), reticulosarcoma (9), lichen planus (9), t-cell large granular lymphocyte leukemia (9), orbit lymphoma (9), acute necrotizing encephalitis (9), lichen sclerosus (8), viral esophagitis (7), hepatosplenic t-cell lymphoma (7), erythema multiforme (7), hemophagocytic lymphohistiocytosis (7), giardiasis (7), acute graft versus host disease (6), primary cutaneous anaplastic large cell lymphoma (6), bronchiolitis obliterans (6), discoid lupus erythematosus (6), cutaneous lupus erythematosus (6), choriocarcinoma of the testis (6), infiltrating lipoma (5), necrotizing sialometaplasia (5), sialolithiasis (5), rasmussen encephalitis (4), cutaneous t cell lymphoma (4), lung lymphoma (4), celiac disease (4), hodgkin lymphoma (3), b-cell expansion with nfkb and t-cell anergy (3), mycosis fungoides (3), lymphoma, non-hodgkin (2), cardiomyopathy, familial hypertrophic (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 39.62 RPKM in Whole Blood
Total median expression: 73.11 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -13.0066-0.197 Picture PostScript Text
3' UTR -27.00116-0.233 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009003 - Pept_cys/ser_Trypsin-like
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A

Pfam Domains:
PF00089 - Trypsin
PF13365 - Trypsin-like peptidase domain

SCOP Domains:
50494 - Trypsin-like serine proteases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P10144
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0006508 proteolysis
GO:0006915 apoptotic process
GO:0008626 granzyme-mediated apoptotic signaling pathway
GO:0019835 cytolysis
GO:0042267 natural killer cell mediated cytotoxicity
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Cellular Component:
GO:0001772 immunological synapse
GO:0005634 nucleus
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0016020 membrane
GO:0030141 secretory granule

-  Descriptions from all associated GenBank mRNAs
  AY232654 - Homo sapiens granzyme B variant mRNA, complete cds; alternatively spliced.
BC030195 - Homo sapiens granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1), mRNA (cDNA clone MGC:34374 IMAGE:5223876), complete cds.
J04071 - Human serine esterase (HSE26.1) mRNA, complete cds.
J03189 - Human proteolytic serine esterase-like protein (SECT) gene, complete cds.
LP880238 - Sequence 42 from Patent WO2017181111.
LP882067 - Sequence 9 from Patent WO2017181079.
LQ882904 - Sequence 53 from Patent WO2018160841.
M17016 - Human serine protease-like protein mRNA, complete cds.
AY372494 - Homo sapiens endogenous granzyme B precursor, mRNA, complete cds.
AY232655 - Homo sapiens granzyme B splice variant 1 mRNA, complete cds; alternatively spliced.
AY232656 - Homo sapiens granzyme B splice variant 2 mRNA, complete cds; alternatively spliced.
KJ901036 - Synthetic construct Homo sapiens clone ccsbBroadEn_10430 GZMB gene, encodes complete protein.
EU176524 - Synthetic construct Homo sapiens clone IMAGE:100011638; FLH263994.01L; RZPDo839C08245D granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) (GZMB) gene, encodes complete protein.
AB590431 - Synthetic construct DNA, clone: pFN21AE1494, Homo sapiens GZMB gene for granzyme B, without stop codon, in Flexi system.
LF334596 - JP 2014500723-A/142099: Polycomb-Associated Non-Coding RNAs.
LF334597 - JP 2014500723-A/142100: Polycomb-Associated Non-Coding RNAs.
LQ927226 - Sequence 3 from Patent WO2018191660.
MA570173 - JP 2018138019-A/142099: Polycomb-Associated Non-Coding RNAs.
MA570174 - JP 2018138019-A/142100: Polycomb-Associated Non-Coding RNAs.
MP202740 - Sequence 51 from Patent WO2019090263.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04940 - Type I diabetes mellitus
hsa05320 - Autoimmune thyroid disease
hsa05330 - Allograft rejection
hsa05332 - Graft-versus-host disease

BioCarta from NCI Cancer Genome Anatomy Project
h_caspasePathway - Caspase Cascade in Apoptosis
h_d4gdiPathway - D4-GDI Signaling Pathway
h_DNAfragmentPathway - Apoptotic DNA fragmentation and tissue homeostasis
h_setPathway - Granzyme A mediated Apoptosis Pathway
h_ctlPathway - CTL mediated immune response against target cells

Reactome (by CSHL, EBI, and GO)

Protein P10144 (Reactome details) participates in the following event(s):

R-HSA-139893 Granzyme-B activates BID by cleavage
R-HSA-2197563 NOTCH2 intracellular domain regulates transcription
R-HSA-1980145 Signaling by NOTCH2
R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria
R-HSA-157118 Signaling by NOTCH
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-162582 Signal Transduction
R-HSA-109581 Apoptosis
R-HSA-5357801 Programmed Cell Death

-  Other Names for This Gene
  Alternate Gene Symbols: CGL1, CSPB, CTLA1, GRAB_HUMAN, GRB, NM_004131, NP_004122, P10144, Q8N1D2, Q9UCC1
UCSC ID: uc001wps.2
RefSeq Accession: NM_004131
Protein: P10144 (aka GRAB_HUMAN)
CCDS: CCDS9633.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_004131.4
exon count: 5CDS single in 3' UTR: no RNA size: 941
ORF size: 744CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1688.00frame shift in genome: no % Coverage: 98.41
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.