Human Gene GZMA (uc003jpm.3) Description and Page Index
  Description: Homo sapiens granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) (GZMA), mRNA.
RefSeq Summary (NM_006144): Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here is a T cell- and natural killer cell-specific serine protease that may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BC015739.1, SRR5189667.281315.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000274306.7/ ENSP00000274306.6 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr5:54,398,474-54,406,080 Size: 7,607 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr5:54,398,511-54,406,010 Size: 7,500 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 (chr5:54,398,474-54,406,080)mRNA (may differ from genome)Protein (262 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Granzyme A; EC=; AltName: Full=CTL tryptase; AltName: Full=Cytotoxic T-lymphocyte proteinase 1; AltName: Full=Fragmentin-1; AltName: Full=Granzyme-1; AltName: Full=Hanukkah factor; Short=H factor; Short=HF; Flags: Precursor;
FUNCTION: This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.
CATALYTIC ACTIVITY: Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-|- Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.
SUBUNIT: Homodimer; disulfide-linked. Interacts with APEX1.
SUBCELLULAR LOCATION: Isoform alpha: Secreted. Cytoplasmic granule.
INDUCTION: Dexamethasone (DEX) induces expression of isoform beta and represses expression of isoform alpha. The alteration in expression is mediated by binding of glucocorticoid receptor to independent promoters adjacent to the alternative first exons of isoform alpha and isoform beta.
SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
SIMILARITY: Contains 1 peptidase S1 domain.
CAUTION: Exons 1a and 1b of the sequence reported in PubMed:17180578 are of human origin, however exon 2 shows strong similarity to the rat sequence.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GZMA
CDC HuGE Published Literature: GZMA

-  MalaCards Disease Associations
  MalaCards Gene Search: GZMA
Diseases sorted by gene-association score: smallpox (3), chilblain lupus (2)

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

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 33.74 RPKM in Spleen
Total median expression: 107.65 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -7.3037-0.197 Picture PostScript Text
3' UTR -1.9070-0.027 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

SCOP Domains:
50494 - Trypsin-like serine proteases

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

- Model

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P12544
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 orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  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
GO:0042803 protein homodimerization activity

Biological Process:
GO:0006508 proteolysis
GO:0006915 apoptotic process
GO:0006955 immune response
GO:0019835 cytolysis
GO:0032078 negative regulation of endodeoxyribonuclease activity
GO:0043065 positive regulation of apoptotic process
GO:0043392 negative regulation of DNA binding
GO:0051354 negative regulation of oxidoreductase activity
GO:0051603 proteolysis involved in cellular protein catabolic process

Cellular Component:
GO:0001772 immunological synapse
GO:0005576 extracellular region
GO:0005634 nucleus

-  Descriptions from all associated GenBank mRNAs
  BC015739 - Homo sapiens granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3), mRNA (cDNA clone MGC:23007 IMAGE:4849202), complete cds.
DQ896326 - Synthetic construct Homo sapiens clone IMAGE:100010786; FLH193298.01L; RZPDo839E1068D granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) (GZMA) gene, encodes complete protein.
DQ893071 - Synthetic construct clone IMAGE:100005701; FLH193302.01X; RZPDo839E1078D granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) (GZMA) gene, encodes complete protein.
AB528402 - Synthetic construct DNA, clone: pF1KB6337, Homo sapiens GZMA gene for granzyme A, without stop codon, in Flexi system.
CR456968 - Homo sapiens full open reading frame cDNA clone RZPDo834B105D for gene GZMA, granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3); complete cds, incl. stopcodon.
E01396 - cDNA encoding serine protease of human killer cell.
LP880236 - Sequence 40 from Patent WO2017181111.
LP882065 - Sequence 7 from Patent WO2017181079.
LQ882902 - Sequence 51 from Patent WO2018160841.
M18737 - Human Hanukah factor serine protease (HuHF) mRNA, complete cds.
KJ896952 - Synthetic construct Homo sapiens clone ccsbBroadEn_06346 GZMA gene, encodes complete protein.
AB284134 - Homo sapiens GZMA mRNA for granzyme A, partial cds.
JD250599 - Sequence 231623 from Patent EP1572962.
MP202738 - Sequence 49 from Patent WO2019090263.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

BioCarta from NCI Cancer Genome Anatomy Project
h_setPathway - Granzyme A mediated Apoptosis Pathway

-  Other Names for This Gene
  Alternate Gene Symbols: A4PHN1, CTLA3, GRAA_HUMAN, HFSP, NM_006144, NP_006135, P12544, Q6IB36
UCSC ID: uc003jpm.3
RefSeq Accession: NM_006144
Protein: P12544 (aka GRAA_HUMAN)
CCDS: CCDS3965.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_006144.3
exon count: 5CDS single in 3' UTR: no RNA size: 913
ORF size: 789CDS single in intron: no Alignment % ID: 99.78
txCdsPredict score: 1768.50frame shift in genome: no % Coverage: 98.14
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.