GZMK

Summary

GZMK (granzyme K, HGNC:4711) is a protein-coding gene on chromosome 5q11.2, encoding Granzyme K (P49863). Serine protease that initiates the GZMK pathway of the complement system, a cascade of proteins directly activated by CD8(+) T-cells that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

This gene product is a member of a group of related serine proteases from the cytoplasmic granules of cytotoxic lymphocytes. 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 lacks consensus sequences for N-glycosylation present in other granzymes.

Source: NCBI Gene 3003 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_002104

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4711
Approved symbol	GZMK
Name	granzyme K
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	TRYP2, PRSS
Ensembl gene	ENSG00000113088
Ensembl biotype	protein_coding
OMIM	600784
Entrez	3003

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000231009, ENST00000512089

RefSeq mRNA: 1 — MANE Select: NM_002104 NM_002104

CCDS: CCDS3964

Canonical transcript exons

ENST00000231009 — 5 exons

Exon	Start	End
ENSE00000743501	55024660	55024807
ENSE00000743506	55030434	55030584
ENSE00000743511	55031364	55031633
ENSE00000815160	55024256	55024386
ENSE00000815161	55033765	55034570

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 94.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.2094 / max 1640.0916, expressed in 160 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56458	9.1696	159
56459	0.0398	6

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	94.47	gold quality
granulocyte	CL:0000094	94.42	gold quality
spleen	UBERON:0002106	89.36	gold quality
blood	UBERON:0000178	88.10	gold quality
vermiform appendix	UBERON:0001154	87.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.27	gold quality
gall bladder	UBERON:0002110	84.04	gold quality
trabecular bone tissue	UBERON:0002483	83.44	gold quality
epithelium of nasopharynx	UBERON:0001951	83.43	gold quality
nasopharynx	UBERON:0001728	83.41	gold quality
thymus	UBERON:0002370	82.96	gold quality
caecum	UBERON:0001153	82.95	gold quality
bone marrow	UBERON:0002371	81.82	gold quality
superficial temporal artery	UBERON:0001614	81.44	gold quality
olfactory bulb	UBERON:0002264	81.10	gold quality
type B pancreatic cell	CL:0000169	80.97	gold quality
decidua	UBERON:0002450	79.68	gold quality
mucosa of urinary bladder	UBERON:0001259	79.16	silver quality
ileal mucosa	UBERON:0000331	77.51	gold quality
cervix epithelium	UBERON:0004801	77.20	silver quality
tongue squamous epithelium	UBERON:0006919	75.91	gold quality
bone marrow cell	CL:0002092	75.38	gold quality
rectum	UBERON:0001052	75.02	gold quality
tonsil	UBERON:0002372	74.38	gold quality
mucosa of transverse colon	UBERON:0004991	74.14	gold quality
smooth muscle tissue	UBERON:0001135	72.88	gold quality
cervix squamous epithelium	UBERON:0006922	72.63	gold quality
epithelial cell of pancreas	CL:0000083	72.46	gold quality
parietal pleura	UBERON:0002400	72.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.57	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-CURD-85	yes	2824.94
E-GEOD-139324	yes	2742.74
E-CURD-120	yes	2716.07
E-MTAB-8410	yes	2542.50
E-HCAD-36	yes	2461.07
E-CURD-79	yes	2090.64
E-GEOD-106540	yes	1729.82
E-CURD-95	yes	1724.88
E-MTAB-8207	yes	1703.81
E-MTAB-8530	yes	1688.09
E-CURD-46	yes	1676.70
E-CURD-122	yes	1453.82
E-HCAD-4	yes	1211.68
E-CURD-84	yes	1114.64
E-MTAB-8911	yes	1103.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting GZMK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-4451	98.82	68.17	1455

Literature-anchored findings (GeneRIF, showing 20)

• The 2.2-A crystal structure reveals a rigid zymogen with unusual features (PMID:12384499)
• The present findings thus introduce the possibility that human beta-tryptase, after mast cell degranulation and exposure to neutral pH in the tissue, may dissociate into active monomers with properties that are distinct from the tetrameric counterpart. (PMID:12387726)
• We found human GzmK triggers rapid cell death independently of caspase activation. The features of death are characterized by rapid externalization of phosphatidylserine, nuclear morphological changes and single-stranded DNA nicks. (PMID:17008916)
• GzmK-induced caspase-independent death occurs through Bid-dependent mitochondrial damage that is different from GzmA (PMID:17308307)
• Rsults indicate that plasma levels of Granzyme K could serve as a useful diagnostic marker to stage sepsis, permitting better classification, specific treatments of patients, and may play a functional role in the development of sepsis. (PMID:17438453)
• GrK not only constitutes a redundant functional backup mechanism that assists GrA-induced cell death but that it also displays a unique function by cleaving its own specific substrates. (PMID:19059912)
• p53 is as a cytotoxic bomb that can be triggered by granzyme K, leading to potentiating killing efficacy. (PMID:19201868)
• Gr3 proenzymes is activated by cathepsin C which concomitantly decreased the molecular weight to that of active Gr3. (PMID:20377743)
• Granzyme K plays an important physiological role in immunoregulation of adaptive immunity underlying the cytotoxicity of CD56(bright) natural killer (NK) cells toward activated T cells. (PMID:21666061)
• Extracellular GrK is an unexpected direct modulator of lipopolysaccharide-TLR4 signaling during the antimicrobial innate immune response. (PMID:24711407)
• Data indicate N-terminomics on the human and mouse granzymes A and K by combined fractional diagonal chromatography (COFRADIC). (PMID:25383893)
• Carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells. (PMID:25921628)
• Extracellular granzyme K mediates endothelial activation through the cleavage of PAR-1. (PMID:26936634)
• GzmK induced IL-6 expression in keratinocytes and skin fibroblasts that was dependent on PAR-1 activation. Re-epithelialization showed the greatest degree of improvement of all healing parameters, suggesting that keratinocytes are sensitive to GzmK-mediated proteolysis. In support, keratinocytes, but not skin fibroblasts, exposed to GzmK showed impaired wound healing in vitro (PMID:30395844)
• We here provide ex vivo evidence that CCR5highGZMK+CD4+ effector memory T cells are involved in immune surveillance during homeostasis, but could also play a role in pathology (PMID:31563951)
• Granzyme K contributes to endothelial microvascular damage and leakage during skin inflammation. (PMID:36652225)
• Human Granzyme K Is a Feature of Innate T Cells in Blood, Tissues, and Tumors, Responding to Cytokines Rather than TCR Stimulation. (PMID:37449888)
• Granzyme K- and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease. (PMID:38092138)
• High expression of angiotensin-converting enzyme 2 receptor (ACE-2), transmembrane protease serine (TMPRSS), and P-selectin in platelets lead to thrombosis formation in COVID-19 patients. (PMID:38497867)
• Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis. (PMID:38903528)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gzmk	ENSMUSG00000042385
rattus_norvegicus	Gzmk	ENSRNOG00000010661
drosophila_melanogaster	CG14780	FBGN0025383
drosophila_melanogaster	CG14227	FBGN0031058
drosophila_melanogaster	CG11664	FBGN0040341
drosophila_melanogaster	CG30287	FBGN0050287
drosophila_melanogaster	CG30288	FBGN0050288
drosophila_melanogaster	CG30289	FBGN0050289
drosophila_melanogaster	CG30414	FBGN0050414
drosophila_melanogaster	CG31205	FBGN0051205
drosophila_melanogaster	CG33225	FBGN0053225
drosophila_melanogaster	CG33226	FBGN0069056
drosophila_melanogaster	CG30283	FBGN0260477

Paralogs (5): HGF (ENSG00000019991), PIK3IP1 (ENSG00000100100), GZMA (ENSG00000145649), HABP2 (ENSG00000148702), MST1 (ENSG00000173531)

Protein

Protein identifiers

Granzyme K — P49863 (reviewed: P49863)

Alternative names: Fragmentin-3, Granzyme-3, NK-tryptase-2

All UniProt accessions (1): P49863

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that initiates the GZMK pathway of the complement system, a cascade of proteins directly activated by CD8(+) T-cells that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. GZMK is specifically secreted by CD8(+) T-cells and mediates both recognition and initiation steps of GZMK complement pathway. First acts as a pattern recognition receptor, which specifically recognizes and binds heparan sulfate glycosaminoglycans on the pathogen surface to drive opsonization. It then initiates the complement pathway cascade by catalyzing cleavage and activation of C2 and C4, the next components of the complement pathway. GZMK-mediated complement activation is an important contributor to tissue inflammation. Also able to cleave and activate F2R/PAR1 and PAR2/F2RL1, possibly promoting interleukin release. May also regulate apoptosis by catalyzing cleavage and activation of BID, thereby promoting cytochrome C release from mitochrondria.

Subcellular location. Secreted. Cell surface. Cytoplasmic granule.

Tissue specificity. Specifically expressed by CD8(+) T-cells.

Activity regulation. Specifically inhibited by D-Phe-Pro-Arg-chloromethylketone (PPACK) synthetic drug.

Similarity. Belongs to the peptidase S1 family. Granzyme subfamily.

RefSeq proteins (1): NP_002095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.B4 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (33 total): strand 15, disulfide bond 4, helix 3, active site 3, sequence conflict 2, signal peptide 1, propeptide 1, mutagenesis site 1, chain 1, turn 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1MZA	X-RAY DIFFRACTION	2.23
1MZD	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49863-F1	85.32	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 67 (charge relay system); 116 (charge relay system); 214 (charge relay system)

Disulfide bonds (4): 210–234, 52–68, 149–220, 181–199

Mutagenesis-validated functional residues (1):

Position	Phenotype
214	abolished serine protease activity, preventing activation of the gzmk complement pathway.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 232 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MODULE_172, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_INFLAMMATORY_RESPONSE, MODULE_45, MODULE_128, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, WIELAND_UP_BY_HBV_INFECTION, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA, GOLDRATH_ANTIGEN_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (11): opsonization (GO:0008228), zymogen activation (GO:0031638), positive regulation of inflammatory response (GO:0050729), protein maturation (GO:0051604), positive regulation of release of cytochrome c from mitochondria (GO:0090200), granzyme-mediated programmed cell death signaling pathway (GO:0140507), complement activation, GZMK pathway (GO:0160257), activation of membrane attack complex (GO:0001905), proteolysis (GO:0006508), complement activation (GO:0006956), killing of cells of another organism (GO:0031640)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), glycosaminoglycan binding (GO:0005539), serine-type peptidase activity (GO:0008236), pattern recognition receptor activity (GO:0038187), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), symbiont cell surface (GO:0106139), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune effector process	2
protein metabolic process	2
complement activation	2
phagocytosis, recognition	1
protein processing	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
gene expression	1
release of cytochrome c from mitochondria	1
positive regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
signal transduction	1
programmed cell death	1
innate immune response	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
cell killing	1
disruption of cell in another organism	1
endopeptidase activity	1
serine-type peptidase activity	1
carbohydrate derivative binding	1
peptidase activity	1
serine hydrolase activity	1
signaling receptor activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
other organism part	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GZMK	MSMB	P08118	980
GZMK	PRF1	P14222	793
GZMK	CD3D	P04234	739
GZMK	CCR7	P32248	722
GZMK	NKG7	Q16617	712
GZMK	KLRB1	Q12918	694
GZMK	CCL5	P13501	675
GZMK	GNLY	P09325	672
GZMK	CD69	Q07108	665
GZMK	CCL4	P13236	639
GZMK	CD8A	P01732	621
GZMK	CCR5	P51681	605
GZMK	TIGIT	Q495A1	598
GZMK	XCL1	P47992	594
GZMK	EOMES	O95936	583

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GZMK	TMBIM6	psi-mi:“MI:0915”(physical association)	0.560
GZMK	LIG4	psi-mi:“MI:0915”(physical association)	0.370
GZMK	PNKP	psi-mi:“MI:0915”(physical association)	0.370
GZMK	ITGB7	psi-mi:“MI:0914”(association)	0.350
TMBIM6	GZMK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): TMBIM6 (Two-hybrid), IGSF21 (Affinity Capture-MS), ITGB7 (Affinity Capture-MS), GZMM (Negative Genetic), VCP (Affinity Capture-MS), SET (Affinity Capture-MS), VCP (Affinity Capture-Western), GZMK (Affinity Capture-Western), VCP (Biochemical Activity), SET (Biochemical Activity), NPLOC4 (Biochemical Activity), UFD1L (Biochemical Activity), SET (Biochemical Activity), ACTG1 (Biochemical Activity), TUBB3 (Biochemical Activity)

ESM2 similar proteins: O35164, O35205, P00752, P00755, P00756, P00770, P04071, P04187, P07628, P07647, P08882, P08883, P08884, P09582, P09650, P11032, P11033, P11034, P12544, P13366, P15119, P15946, P15948, P15949, P18291, P21812, P21844, P36368, P36369, P36373, P36374, P36375, P36376, P43430, P49863, P49864, P50339, P50340, P50341, P85202

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00752, P00760, P00761, P00762, P00763, P00764, P00770, P00772, P00773, P04187, P06870, P06871, P07146, P07288, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12323, P12544, P12788, P13366, P15119, P16049, P17977, P18291

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

42 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

446 predictions. Top by Δscore:

Variant	Effect	Δscore
5:55024325:GAC:G	donor_gain	0.9900
5:55024327:C:CG	donor_gain	0.9800
5:55024327:C:G	donor_gain	0.9800
5:55024383:GTGT:G	donor_gain	0.9800
5:55027440:T:G	donor_gain	0.9800
5:55024804:ATCGG:A	donor_loss	0.9700
5:55024805:TCGGT:T	donor_loss	0.9700
5:55024806:CGG:C	donor_loss	0.9700
5:55024807:GGTGA:G	donor_loss	0.9700
5:55024808:G:GG	donor_gain	0.9700
5:55024808:GTGA:G	donor_loss	0.9700
5:55024809:T:TC	donor_loss	0.9700
5:55024810:GAG:G	donor_loss	0.9700
5:55033763:AG:A	acceptor_gain	0.9700
5:55033764:GG:G	acceptor_gain	0.9700
5:55024385:GT:G	donor_gain	0.9600
5:55024387:G:GG	donor_gain	0.9600
5:55024811:AGT:A	donor_loss	0.9600
5:55027484:G:GT	donor_gain	0.9600
5:55024812:G:C	donor_loss	0.9500
5:55027470:G:GT	donor_gain	0.9500
5:55031354:A:AG	acceptor_gain	0.9500
5:55031362:A:AG	acceptor_gain	0.9500
5:55031363:G:GG	acceptor_gain	0.9500
5:55024654:TTGTA:T	acceptor_loss	0.9400
5:55024655:TGTA:T	acceptor_loss	0.9400
5:55024656:GTA:G	acceptor_loss	0.9400
5:55024657:TA:T	acceptor_loss	0.9400
5:55024658:A:C	acceptor_loss	0.9400
5:55024659:G:GA	acceptor_loss	0.9400

AlphaMissense

1714 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:55031462:G:C	W154C	0.996
5:55031462:G:T	W154C	0.996
5:55031541:T:A	C181S	0.995
5:55031542:G:C	C181S	0.995
5:55031595:T:A	C199S	0.991
5:55031596:G:C	C199S	0.991
5:55033890:G:C	W253C	0.988
5:55033890:G:T	W253C	0.988
5:55031460:T:A	W154R	0.986
5:55031460:T:C	W154R	0.986
5:55031542:G:A	C181Y	0.985
5:55024797:T:A	C68S	0.984
5:55024798:G:C	C68S	0.984
5:55024722:T:C	S43P	0.983
5:55031445:T:A	C149S	0.983
5:55031446:G:C	C149S	0.983
5:55024713:T:C	F40L	0.982
5:55024715:T:A	F40L	0.982
5:55024715:T:G	F40L	0.982
5:55031506:G:C	R169P	0.982
5:55024749:T:A	C52S	0.981
5:55024750:G:C	C52S	0.981
5:55033769:A:T	D213V	0.981
5:55033774:G:T	G215W	0.980
5:55033775:G:T	G215V	0.980
5:55031595:T:C	C199R	0.978
5:55024783:T:C	L63P	0.977
5:55033768:G:C	D213H	0.977
5:55033769:A:C	D213A	0.977
5:55033770:C:A	D213E	0.977

dbSNP variants (sampled 300 via entrez): RS1000210696 (5:55022365 A>G), RS1000452940 (5:55026289 A>G), RS1000602596 (5:55029659 T>C), RS1000817616 (5:55024053 G>A), RS1001166469 (5:55023859 T>C), RS1001605931 (5:55031060 A>G,T), RS1001659807 (5:55031286 G>A), RS1001773093 (5:55025246 C>G), RS1002379904 (5:55027663 G>T), RS1002665974 (5:55032832 T>C), RS1002735744 (5:55027939 C>T), RS1002895960 (5:55024606 C>T), RS1003181056 (5:55026593 G>A), RS1003282652 (5:55022518 T>A,G), RS1003379756 (5:55029119 C>A)

Disease associations

OMIM: gene MIM:600784 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2475	Blood protein levels	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4930 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
testosterone undecanoate	increases expression	1
sodium arsenite	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Rosuvastatin Calcium	decreases reaction, increases expression	1
Choline	affects expression	1
Dichlorvos	decreases expression	1
Endosulfan	decreases expression, decreases reaction	1
Lipopolysaccharides	increases expression, decreases expression, decreases reaction	1
Nickel	increases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Zinc	decreases expression	1
Ziram	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 8 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4344610	Binding	Substrate activity at Granzyme K (unknown origin) expressed in Pichia pastoris incubated for 30 mins by fluorescence based assay	Detection of Active Granzyme A in NK92 Cells with Fluorescent Activity-Based Probe. — J Med Chem
CHEMBL768125	Functional	Amount of proteinase K required to release folin positive amino acids at a substrate concentration of 304 uM	The stability of pseudopeptides bearing sulfoximines as chiral backbone modifying element towards proteinase K. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.