KLK3

Summary

KLK3 (kallikrein related peptidase 3, HGNC:6364) is a protein-coding gene on chromosome 19q13.33, encoding Prostate-specific antigen (P07288). Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms.

Source: NCBI Gene 354 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6364
Approved symbol	KLK3
Name	kallikrein related peptidase 3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PSA
Ensembl gene	ENSG00000142515
Ensembl biotype	protein_coding
OMIM	176820
Entrez	354

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000326003, ENST00000360617, ENST00000422986, ENST00000593997, ENST00000595151, ENST00000595392, ENST00000595952, ENST00000596185, ENST00000596333, ENST00000597286, ENST00000597483, ENST00000598145, ENST00000601349, ENST00000601503, ENST00000601812

RefSeq mRNA: 3 — MANE Select: NM_001648 NM_001030047, NM_001030048, NM_001648

CCDS: CCDS12807, CCDS33083, CCDS46155

Canonical transcript exons

ENST00000326003 — 5 exons

Exon	Start	End
ENSE00001123926	50854915	50855001
ENSE00003490004	50856240	50856399
ENSE00003527635	50858029	50858315
ENSE00003615372	50858459	50858595
ENSE00003740615	50859972	50860764

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 97.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0044 / max 3.5969, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177180	1.7364	22
177179	0.0046	2
177181	0.0044	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prostate gland	UBERON:0002367	97.83	gold quality
frontal pole	UBERON:0002795	91.09	gold quality
paraflocculus	UBERON:0005351	90.55	gold quality
middle frontal gyrus	UBERON:0002702	89.42	silver quality
sperm	CL:0000019	88.28	gold quality
urethra	UBERON:0000057	87.47	gold quality
male germ cell	CL:0000015	86.36	gold quality
cerebellar vermis	UBERON:0004720	80.92	gold quality
mucosa of transverse colon	UBERON:0004991	79.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	78.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.04	gold quality
epithelial cell of pancreas	CL:0000083	75.65	gold quality
parotid gland	UBERON:0001831	74.56	gold quality
thymus	UBERON:0002370	74.54	silver quality
vermiform appendix	UBERON:0001154	74.53	gold quality
caecum	UBERON:0001153	73.37	gold quality
transverse colon	UBERON:0001157	73.27	gold quality
buccal mucosa cell	CL:0002336	73.22	gold quality
synovial joint	UBERON:0002217	72.70	gold quality
vastus lateralis	UBERON:0001379	72.20	gold quality
mammary duct	UBERON:0001765	71.24	silver quality
endometrium epithelium	UBERON:0004811	71.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.17	gold quality
type B pancreatic cell	CL:0000169	70.10	gold quality
gingival epithelium	UBERON:0001949	70.04	gold quality
right coronary artery	UBERON:0001625	69.52	gold quality
trachea	UBERON:0003126	69.48	silver quality
vena cava	UBERON:0004087	69.32	gold quality
germinal epithelium of ovary	UBERON:0001304	68.91	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	20993.19
E-ANND-3	yes	2.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AATF, AP1, AR, BTG2, CEBPA, CREB1, CTNNB1, EGR1, ELF3, ELF5, EP300, ESR1, ESRRA, FOXA1, FOXN1, FOXP1, FUS, HDAC1, HIF1A, HOXB13, ID1, JUN, KAT5, MYC, NCOA1, NCOA4, NCOR1, NCOR2, NFKB1, NFKB, NFKBIA, NKX3-1, NONO, NR2C1, NWD1, PA2G4, PAX6, PGR, POLR2B, PURA

Literature-anchored findings (GeneRIF, showing 40)

• The identification of unusual mRNA splice variants of the KLK2 and KLK3 genes that result from inclusion of intronic sequences adjacent to the first exon. (PMID:11834722)
• Evidence of determinant spreading in the antibody responses to prostate cell surface antigens in patients immunized with prostate-specific antigen. (PMID:11839651)
• NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer. (PMID:11909978)
• vitamin e succinate inhibitis expression of prostate-specific antigen in prostate cancer cells (PMID:12032296)
• Polymorphisms within the gene are biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement(SRD5A2) (PMID:12111704)
• Characterization of androgen receptor and nuclear receptor co-regulator expression in human breast cancer cell lines exhibiting differential regulation of kallikreins 2 and 3. (PMID:12124798)
• kallikrein expression in nipple aspirate fluid- ethnic variation (PMID:12209605)
• polymorphism of PSA gene promotor may be important biomarkers for prostate cancer risk, especially earlier onset of prostate cancer (PMID:12210484)
• analysis of mRNA levels in hyperplastic prostate stimulated with steroid hormones and growth factors (PMID:12362977)
• Prostate-specific antigen is increased in female patients with Cushing’s disease. (PMID:12398228)
• PSA was determined to ensure that mice were carrying the human prostate tumors. (PMID:12496487)
• Androgen-dependent association of the androgen receptor with coactivators (CBP/p300, ACTR/AIB1/SRC-3, SRC-1, TIF2/SRC-2) at the PSA gene regulatory region and the direct recruitment of RNA polymerase II to the enhancer of the PSA gene. (PMID:12589022)
• distinction in glycosylation between PSA from normal and tumor origins (PMID:12626390)
• role of GATATA-binding protein in androgen-mediated expression of prostate-specific antigen (PMID:12782640)
• Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values. (PMID:12865450)
• The PSA(152-160) and PSA(248-257) peptides could be appropriate target molecules in use for specific immunotherapy of HLA-A24+ prostate cancer patients. (PMID:12949939)
• With regard to the ratios of free prostate-specific antigen-to-total prostate-specific antigen for each age group we found no correlation between them (PMID:12970732)
• IL-4 enhances PSA expression through activation of the AR and Akt signaling pathways in LNCaP prostate cancer cells (PMID:12970746)
• The low incidence of AA polymorphism appears to be a trait of Asians that may reduce their risk of prostate cancer. (PMID:14584757)
• Review. PSA and, perhaps, other members of the hK family contribute critical control mechanisms to tumor invasion or progression. (PMID:14607215)
• H3-K4 methylation at the human prostate specific antigen (PSA) locus following gene activation and repression via androgen receptor (PMID:14627807)
• Downregulation of kallikrein 3 is associated with breast cancer (PMID:14696124)
• The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo. (PMID:14761877)
• Osteoblasts secrete factors, such as IL-6, that cause androgen-independent induction of PSA gene expression and proliferation of prostate cancer cells. (PMID:15014041)
• the prostate-specific antigen (PSA)/Zn2+ axis may play a role in human prostate cancer cell invasion (PMID:15050736)
• Serum prostate specific antigen level is higher in patients with polycystic ovary syndrome (PCOS) but decrease with antiandrogen treatment and might be a marker for hirsutism (PMID:15233555)
• The presence of short AR alleles and the G allele of the PSA gene may contribute to the development of prostate cancer in a 47,XXY patient (PMID:15350307)
• PSA-mediated activation of latent TGFbeta2 may be an important mechanism for autocrine TGFbeta regulation in the prostate and may potentially contribute to the formation of osteoblastic lesions in bone metastatic prostate cancer. (PMID:15389580)
• Serenoa repens inhibits steroid-5-alpha-reductase but does not suppress PSA secretion in prostate cancer. (PMID:15543614)
• The binding of Zn2+ to SgI and SgII and their involvment in regulating the activity of PSA are reported. (PMID:15563730)
• the PSA/androgen response element GG genotype confers an increased risk of prostate cancer especially among younger men (PMID:15599941)
• The values of interaction force between the same anti-PSMA antibodies and all studied cells were almost identical (45-64pN), indicating antigenic similarity of the membrane form of PSMA expressed in LNCaP, PC-3, and Du 145 cells. (PMID:15680901)
• PSA kinetics in patients with clinically localized prostate cancer undergoing radical prostatectomy (PMID:15936010)
• JFC1 differentially regulates the secretion of PSAP and PSA, and Rab27a and PI3K play a central role in the exocytosis of prostate-specific markers. (PMID:16004602)
• After 12 years of follow-up, we were not able to observe a significant reduction in prostate cancer mortality since the introduction of the PSA test in the age groups of 50-59, 60-69, and 80-89 years. (PMID:16091872)
• Measurements of free PSA and kallikrein 2 improve on our ability to counsel patients prior to treatment as to their risk of biochemical recurrence (PMID:16152616)
• PSA has a functional role in the progression of prostate cancer through their promotion of tumour cell migration. (PMID:16172196)
• PSA nadir seems to be a good predictor of androgen-independent progression in patients with metastatic prostate cancer after androgen deprivation therapy (PMID:16398402)
• epidermal growth factor receptor signaling pathway negatively regulates PSA expression which may be induced by the alteration of androgen expression via the PI3K-Akt pathway in LNCaP C-81 cells (PMID:16472761)
• Men with prostate cancer and those without prostate cancer but with PSA >2 ng/mL had significantly higher alpha 1-antitrypsin concentrations than those without these conditions. (PMID:16581345)

Cross-species orthologs

28 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klk1b16	ENSMUSG00000038968
mus_musculus	Klk1b11	ENSMUSG00000044485
mus_musculus	Klk1b26	ENSMUSG00000053719
mus_musculus	Klk1b9	ENSMUSG00000059042
mus_musculus	Klk1b22	ENSMUSG00000060177
mus_musculus	Klk1b8	ENSMUSG00000063089
mus_musculus	Klk1b1	ENSMUSG00000063133
mus_musculus	Klk1b27	ENSMUSG00000063177
mus_musculus	Klk1b24	ENSMUSG00000063713
mus_musculus	Klk1	ENSMUSG00000063903
mus_musculus	Klk1b5	ENSMUSG00000066512
mus_musculus	Klk1b4	ENSMUSG00000066513
mus_musculus	Klk1b3	ENSMUSG00000066515
mus_musculus	Klk1b21	ENSMUSG00000066516
rattus_norvegicus		ENSRNOG00000066972
rattus_norvegicus		ENSRNOG00000067174
rattus_norvegicus		ENSRNOG00000069479
drosophila_melanogaster	CG9673	FBGN0030775
drosophila_melanogaster	CG4477	FBGN0035971
drosophila_melanogaster	CG17404	FBGN0038001
drosophila_melanogaster	CG12256	FBGN0038002
drosophila_melanogaster	CG3916	FBGN0038003
drosophila_melanogaster	CG17477	FBGN0038479
drosophila_melanogaster	CG4053	FBGN0038482
drosophila_melanogaster	CG31269	FBGN0051269
drosophila_melanogaster	CG32808	FBGN0052808
drosophila_melanogaster	Phae2	FBGN0263235
drosophila_melanogaster	Send2	FBGN0264253

Paralogs (12): PRSS54 (ENSG00000103023), KLK14 (ENSG00000129437), KLK8 (ENSG00000129455), TMPRSS4 (ENSG00000137648), KLK1 (ENSG00000167748), KLK4 (ENSG00000167749), KLK2 (ENSG00000167751), KLK5 (ENSG00000167754), KLK11 (ENSG00000167757), KLK7 (ENSG00000169035), KLK12 (ENSG00000186474), PRSS58 (ENSG00000258223)

Protein

Protein identifiers

Prostate-specific antigen — P07288 (reviewed: P07288)

Alternative names: Gamma-seminoprotein, Kallikrein-3, P-30 antigen, Semenogelase

All UniProt accessions (9): P07288, A0A0B4J1X3, M0QX57, M0QZF9, M0R1F0, M0R1Z7, M0R294, Q546G3, Q7LBD2

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.

Subunit / interactions. Forms a heterodimer with SERPINA5.

Subcellular location. Secreted.

Activity regulation. Inhibited by SERPINA5. Activity is strongly inhibited by Zn2+, 100 times more abundant in semen than in serum. This inhibition is relieved by exposure to semenogelins, which are avid zinc binders.

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

Isoforms (5)

UniProt ID	Names	Canonical?
P07288-1	1	yes
P07288-2	2
P07288-3	3
P07288-4	4
P07288-5	5

RefSeq proteins (3): NP_001025218, NP_001025219, NP_001639* (*=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 3.4.21.77 — semenogelase (BRENDA: 5 organisms, 98 substrates, 244 inhibitors, 13 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-MORPHOLINECARBONYL-HSSKLQ-AMC	1.4–4.2	5
4-MORPHOLINECARBONYL-HSSKLQ-7-AMIDO-4-METHYLCOUM	1.58	1
4-MORPHOLINECARBONYL-SRKSQQY-7-AMIDO-4-METHYLCOU	0.14	1
ARG-PRO-TYR 4-NITROANILIDE	1.7	1
HSSKLQ-7-AMIDO-4-METHYLCOUMARIN	0.47	1
LYS-VAL-TYR 4-NITROANILIDE	1.3	1
MCA-QFYSSNK(EPSILON-DINITROPHENYL)	0.077	1
MEO-SUC-ARG-PRO-TYR-4-NITROANILIDE	5.72	1
N-SUCCINYL-L-ALA-L-ALA-L-PRO-L-PHE 4-NITROANILID	15.3	1

UniProt features (48 total): strand 15, sequence conflict 6, helix 6, disulfide bond 5, splice variant 5, sequence variant 3, active site 3, signal peptide 1, propeptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9F1I	X-RAY DIFFRACTION	1.38
9ZJQ	X-RAY DIFFRACTION	2.2
2ZCH	X-RAY DIFFRACTION	2.83
2ZCK	X-RAY DIFFRACTION	3.1
3QUM	X-RAY DIFFRACTION	3.2
2ZCL	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07288-F1	91.78	0.83

Antibody-complex structures (SAbDab): 5 — 2ZCH, 2ZCK, 2ZCL, 3QUM, 9F1I

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): 65 (charge relay system); 120 (charge relay system); 213 (charge relay system)

Disulfide bonds (5): 152–219, 184–198, 209–234, 31–173, 50–66

Glycosylation sites (1): 69

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-392499	Metabolism of proteins
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 116 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, LI_PROSTATE_CANCER_EPIGENETIC, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, TGACCTY_ERR1_Q2, CHANDRAN_METASTASIS_DN, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SOX9_B1, KEGG_PATHWAYS_IN_CANCER

GO Biological Process (5): positive regulation of antibacterial peptide production (GO:0002803), regulation of systemic arterial blood pressure (GO:0003073), proteolysis (GO:0006508), negative regulation of angiogenesis (GO:0016525), zymogen activation (GO:0031638)

GO Molecular Function (7): endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), secretory granule (GO:0030141), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Metabolism of proteins	1
RHO GTPases activate PKNs	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RHO GTPase Effectors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
positive regulation of antimicrobial peptide production	1
antibacterial peptide production	1
regulation of antibacterial peptide production	1
positive regulation of defense response to bacterium	1
regulation of blood pressure	1
protein metabolic process	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein processing	1
endopeptidase activity	1
serine-type peptidase activity	1
serine hydrolase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
endomembrane system	1
secretory vesicle	1
cellular_component	1
extracellular vesicle	1

Protein interactions and networks

STRING

2776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLK3	SERPINA3	P01011	994
KLK3	FOLH1	Q04609	939
KLK3	ACP3	P15309	937
KLK3	AR	P10275	935
KLK3	A2M	P01023	914
KLK3	SLC45A3	Q96JT2	893
KLK3	SERPINA1	P01009	888
KLK3	MSMB	P08118	884
KLK3	SERPINA5	P05154	881
KLK3	CEACAM5	P06731	821
KLK3	TGM4	P49221	804
KLK3	AMACR	Q9UHK6	803
KLK3	PSCA	O43653	777
KLK3	NKX3-1	Q99801	772
KLK3	AFP	P02771	767

IntAct

24 interactions, top by confidence:

A	B	Type	Score
AR	KLK3	psi-mi:“MI:0914”(association)	0.600
AR	KLK3	psi-mi:“MI:0915”(physical association)	0.600
AR	KLK3	psi-mi:“MI:2364”(proximity)	0.600
C1orf174	AHCYL1	psi-mi:“MI:0914”(association)	0.530
KLK3	UBA52	psi-mi:“MI:0915”(physical association)	0.400
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
MIF4GD	CTIF	psi-mi:“MI:0914”(association)	0.350
HAT1	CSTA	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
KLK3	HSPA5	psi-mi:“MI:0914”(association)	0.350
KLK3	PRTN3	psi-mi:“MI:0914”(association)	0.350
ZNF550	A2ML1	psi-mi:“MI:0914”(association)	0.350
DHH	MANBA	psi-mi:“MI:0914”(association)	0.350
NXPH2	VGF	psi-mi:“MI:0914”(association)	0.350
TMEM69	ACOX3	psi-mi:“MI:0914”(association)	0.350
KLK3	LRP5	psi-mi:“MI:0914”(association)	0.350
DCK	KLK3	psi-mi:“MI:0914”(association)	0.350
EGLN3	KLK3	psi-mi:“MI:0914”(association)	0.350
KLK3	FN1	psi-mi:“MI:2364”(proximity)	0.270
KLK3	A2M	psi-mi:“MI:2364”(proximity)	0.270
KLK3	SERPINA3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (58): UBA52 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), KLK3 (Affinity Capture-MS), AR (Co-localization), A2M (Co-localization), FN1 (Co-localization), UBA52 (Affinity Capture-MS), KLK3 (Affinity Capture-MS), KLK3 (Co-localization), KLK3 (Affinity Capture-MS), KLK3 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), KLK3 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), KLK3 (Affinity Capture-MS)

ESM2 similar proteins: A7WPL7, O35164, O35205, O46683, O88780, P00770, P04187, P07288, P08883, P08884, P09582, P09650, P10144, P11032, P11034, P13366, P15119, P17977, P20151, P20718, P21812, P21842, P21844, P23946, P28293, P33619, P36368, P36369, P43430, P49862, P50339, P50340, P50341, P52195, P56435, P79204, P80219, P80931, P85202, P97592

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

17 interactions.

A	Effect	B	Mechanism
NCOA4	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
FOXP1	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
RREB1	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
NFKB1	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
SRCAP	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
AR	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
BTG2	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
PA2G4	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
SIN3A	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”
AATF	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
KLK3	“down-regulates activity”	PTHLH	cleavage
KLK3	“up-regulates activity”	PTHLH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Platelet degranulation	5	20.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	11
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

892 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50858311:GGAGT:G	donor_gain	1.0000
19:50858312:GAGTG:G	donor_gain	1.0000
19:50858313:A:T	donor_gain	1.0000
19:50858314:GT:G	donor_gain	1.0000
19:50858027:A:AG	acceptor_gain	0.9900
19:50858028:G:GG	acceptor_gain	0.9900
19:50858028:GCA:G	acceptor_gain	0.9900
19:50858289:GC:G	donor_gain	0.9900
19:50858311:G:GT	donor_gain	0.9900
19:50858312:GAGT:G	donor_gain	0.9900
19:50858367:G:GT	donor_gain	0.9900
19:50858368:G:T	donor_gain	0.9900
19:50858457:A:AG	acceptor_gain	0.9900
19:50858458:G:GA	acceptor_gain	0.9900
19:50858458:GTCTT:G	acceptor_gain	0.9900
19:50856397:G:GT	donor_gain	0.9800
19:50858028:GCAAA:G	acceptor_gain	0.9800
19:50858330:GATG:G	donor_gain	0.9800
19:50858343:G:GT	donor_gain	0.9800
19:50859828:G:GT	donor_gain	0.9800
19:50858028:GC:G	acceptor_gain	0.9700
19:50858255:G:GT	donor_gain	0.9700
19:50858309:GAGGA:G	donor_gain	0.9700
19:50858359:GGTC:G	donor_gain	0.9700
19:50858458:GT:G	acceptor_gain	0.9700
19:50854998:ATTGG:A	donor_loss	0.9600
19:50855000:TGG:T	donor_loss	0.9600
19:50855001:GG:G	donor_loss	0.9600
19:50855002:G:A	donor_loss	0.9600
19:50855003:T:TG	donor_loss	0.9600

AlphaMissense

1697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50858293:G:C	W157C	0.999
19:50858293:G:T	W157C	0.999
19:50860097:G:C	W252C	0.999
19:50860097:G:T	W252C	0.999
19:50858181:A:C	D120A	0.997
19:50858181:A:T	D120V	0.997
19:50858515:T:A	C184S	0.997
19:50858516:G:C	C184S	0.997
19:50859976:A:T	D212V	0.997
19:50860095:T:A	W252R	0.997
19:50860095:T:C	W252R	0.997
19:50856368:T:A	W59R	0.996
19:50856368:T:C	W59R	0.996
19:50856370:G:C	W59C	0.996
19:50856370:G:T	W59C	0.996
19:50856390:G:A	C66Y	0.996
19:50858277:G:A	C152Y	0.996
19:50858278:C:G	C152W	0.996
19:50858291:T:A	W157R	0.996
19:50858291:T:C	W157R	0.996
19:50858557:T:A	C198S	0.996
19:50858558:G:C	C198S	0.996
19:50856391:C:G	C66W	0.995
19:50858181:A:G	D120G	0.995
19:50858276:T:A	C152S	0.995
19:50858276:T:C	C152R	0.995
19:50858277:G:C	C152S	0.995
19:50859976:A:C	D212A	0.995
19:50859981:G:T	G214W	0.995
19:50859982:G:T	G214V	0.995

dbSNP variants (sampled 300 via entrez): RS1000017069 (19:50854071 G>T), RS1000202085 (19:50858994 C>G,T), RS1000494085 (19:50859151 G>A,T), RS1000880200 (19:50857574 G>A), RS1001023093 (19:50855159 C>A,T), RS1001429649 (19:50854634 C>T), RS1001997993 (19:50859419 G>A,C), RS1002396638 (19:50859679 G>A), RS1002430513 (19:50855745 C>A), RS1002949095 (19:50860898 C>T), RS1003317348 (19:50855967 C>T), RS1003787108 (19:50860988 T>C), RS1003847635 (19:50856867 A>G), RS1003943298 (19:50856138 C>T), RS1004230842 (19:50857529 T>A)

Disease associations

OMIM: gene MIM:176820 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (1): Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2099 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,652 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1082407	ENZALUTAMIDE	4	9,652

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 20 [PMID: 23692593]	Inhibition	7.14	pKi

ChEMBL bioactivities

58 potent at pChembl≥5 of 70 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Ki	0.2	nM	CHEMBL574631
8.60	Ki	2.5	nM	CHEMBL574538
8.44	Ki	3.6	nM	CHEMBL574766
8.41	Ki	3.9	nM	CHEMBL583783
8.36	Ki	4.4	nM	CHEMBL574788
8.25	Ki	5.6	nM	CHEMBL574669
8.19	Ki	6.5	nM	CHEMBL574924
8.12	Ki	7.5	nM	CHEMBL583784
8.06	Ki	8.8	nM	CHEMBL574324
7.92	Ki	11.9	nM	CHEMBL574925
7.89	Ki	12.8	nM	CHEMBL575847
7.88	Ki	13.1	nM	CHEMBL574792
7.88	Ki	13.1	nM	CHEMBL574931
7.86	Ki	13.7	nM	CHEMBL574845
7.74	Ki	18.2	nM	CHEMBL583785
7.73	Ki	18.6	nM	CHEMBL574926
7.70	Ki	19.9	nM	CHEMBL573527
7.70	Ki	19.9	nM	CHEMBL574698
7.66	Ki	22.01	nM	CHEMBL2381666
7.66	Ki	21.8	nM	CHEMBL574851
7.62	Ki	24.23	nM	CHEMBL2381668
7.60	Ki	25.3	nM	CHEMBL577821
7.59	Ki	25.9	nM	CHEMBL573414
7.56	Ki	27.5	nM	CHEMBL573646
7.53	Ki	29.4	nM	CHEMBL574861
7.43	Ki	37.4	nM	CHEMBL574927
7.38	Ki	41.9	nM	CHEMBL574868
7.37	Ki	43.05	nM	CHEMBL2381665
7.36	Ki	43.8	nM	CHEMBL583786
7.32	Ki	48.4	nM	CHEMBL573645
7.28	Ki	52.11	nM	CHEMBL2381663
7.21	Ki	61.48	nM	CHEMBL2381661
7.19	Ki	65	nM	CHEMBL582947
7.19	Ki	64.41	nM	CHEMBL2381660
7.14	Ki	72	nM	CHEMBL2381669
7.14	Ki	72.29	nM	CHEMBL2381669
7.13	Ki	73.33	nM	CHEMBL2381670
7.12	Ki	75	nM	CHEMBL2381669
6.99	Ki	102.5	nM	CHEMBL2381658
6.89	IC50	130	nM	ENZALUTAMIDE
6.85	Ki	142	nM	CHEMBL2381669
6.78	Ki	164.5	nM	CHEMBL2381667
6.67	Ki	216	nM	CHEMBL5618119
6.65	IC50	226	nM	CHEMBL2011751
6.65	IC50	226	nM	CHEMBL286934
6.64	Ki	228.8	nM	CHEMBL2381659
6.52	Ki	300	nM	CHEMBL2171878
6.52	Ki	302.1	nM	CHEMBL2381664
6.51	Ki	310.3	nM	CHEMBL2381662
6.37	IC50	430	nM	CHEMBL4760141

PubChem BioAssay actives

57 with measured affinity, of 150 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(1R)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-[methyl(phenylmethoxycarbonyl)amino]propanoyl]amino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0002	uM
[(1R)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]-methylamino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0025	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0036	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0039	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0044	uM
[(1R)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-[methyl(phenylmethoxycarbonyl)amino]propanoyl]amino]propanoyl]-methylamino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0056	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0065	uM
benzyl N-[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S)-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0075	uM
benzyl N-[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S)-4-hydroxy-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0088	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0119	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfinyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0128	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0131	uM
benzyl N-[(2S)-1-[[(2S)-1-[cyclohexyl-[(2S)-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0131	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0137	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0182	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-3-(1H-imidazol-2-yl)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0186	uM
[(1R)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]-methylamino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0199	uM
benzyl N-[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0199	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0218	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-(6-aminohexanoylamino)-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-2-phenylethyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0220	uM
[(1S)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0242	uM
[(1R)-1-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(morpholine-4-carbonylamino)propanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0253	uM
benzyl N-[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S)-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methylsulfinyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0259	uM
[(1R)-1-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0275	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-hydroxy-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0294	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S,4S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0374	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0419	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-3-methylbutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0430	uM
benzyl N-[(2S)-3-hydroxy-1-[[(2S)-3-hydroxy-1-[[(2S,3R)-3-hydroxy-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0438	uM
[(1R)-1-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0484	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0521	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-2-phenylethyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0615	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-2-[6-[(4-iodobenzoyl)amino]hexanoylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0644	uM
[(1R)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid	436851: Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	ki	0.0650	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748194: Inhibition of PSA (unknown origin) in 50 mM TRIS.HCL and 100 mM NaCl buffer at pH 7.8	ki	0.0720	uM
(2S)-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-N-[(2S)-1-[[(1S)-4-bromo-1-[(1R,2S,6R,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxohexan-2-yl]pentanediamide	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.0733	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(3S)-3-(6-aminohexanoylamino)-4-naphthalen-2-ylbutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.1025	uM
Enzalutamide	1690667: Inhibition of prostate specific antigen in human LNCaP cells	ic50	0.1300	uM
[(1S)-1-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]hexanoyl]amino]hexanoyl]amino]-2-phenylethyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.1645	uM
[5-amino-3-(6-methoxy-3-pyridinyl)pyrazol-1-yl]-(3H-benzimidazol-5-yl)methanone	2130963: Inhibition of recombinant human semen PSA using Mu-HSSKLQAMC as substrate preincubated for 15 mins followed by substrate addition by fluorescence based assay	ki	0.2160	uM
2-O-benzyl 1-O-(3-phenylmethoxycarbonylphenyl) (2S,3S)-3-[(4-hydroxyphenyl)methyl]-4-oxoazetidine-1,2-dicarboxylate	652667: Inhibition of human kallikrein 3	ic50	0.2260	uM
benzyl (2S,3S)-3-[(4-hydroxyphenyl)methyl]-4-oxo-1-[2-(3-phenylmethoxycarbonylphenyl)acetyl]azetidine-2-carboxylate	748183: Inhibition of PSA (unknown origin)	ic50	0.2260	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(3S)-3-(6-aminohexanoylamino)-4-naphthalen-2-ylbutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-2-phenylethyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.2288	uM
2-(2-methyl-3-nitrophenyl)-3,1-benzoxazin-4-one	702050: Inhibition of KLK3	ki	0.3000	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-(6-aminohexanoylamino)-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.3021	uM
[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-(6-aminohexanoylamino)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-2-phenylethyl]boronic acid	748202: Inhibition of human seminal fluid PSA using Mu-SRKSQQY-AMC as substrate measured for 30 mins by fluorescence assay	ki	0.3103	uM
12-(4-bromophenyl)-11-azatetracyclo[8.7.0.02,7.013,17]heptadeca-1(10),2,4,6,8,15-hexaene	1690667: Inhibition of prostate specific antigen in human LNCaP cells	ic50	0.4300	uM
(3,4-dimethoxyphenyl)-(5-methyl-3-pyridin-3-yl-1,2,4-triazol-1-yl)methanone	702050: Inhibition of KLK3	ki	0.5000	uM
12-(2-chlorophenyl)-11-azatetracyclo[8.7.0.02,7.013,17]heptadeca-1(10),2,4,6,8,15-hexaene	1690667: Inhibition of prostate specific antigen in human LNCaP cells	ic50	1.4000	uM
(4S)-4-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S,3R)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	507748: Binding affinity to prostate specific antigen	kd	2.9000	uM

CTD chemical–gene interactions

173 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dihydrotestosterone	affects binding, affects cotreatment, decreases expression, decreases reaction, increases expression (+4 more)	45
bicalutamide	affects cotreatment, increases secretion, decreases secretion, affects binding, increases reaction (+4 more)	27
Metribolone	increases secretion, affects cotreatment, decreases reaction, increases activity, affects reaction (+5 more)	22
Resveratrol	decreases expression, decreases reaction, increases expression, decreases secretion, affects cotreatment	10
Estradiol	decreases reaction, increases expression, affects reaction, affects cotreatment, decreases expression (+1 more)	10
enzalutamide	affects cotreatment, decreases expression, affects expression, increases reaction, increases expression (+1 more)	9
Testosterone	affects cotreatment, affects binding, decreases reaction, increases expression	8
methylselenic acid	decreases expression, decreases reaction, affects expression, affects binding, increases reaction (+3 more)	6
Curcumin	decreases reaction, increases expression, affects binding, increases reaction, decreases expression (+1 more)	5
hydroxyflutamide	affects expression, affects secretion, decreases reaction, increases expression, increases secretion (+1 more)	4
mibolerone	decreases reaction, increases expression, increases secretion	4
1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane	increases secretion, affects cotreatment, affects expression, increases expression, decreases reaction (+1 more)	4
Flutamide	increases expression, decreases expression, decreases secretion, decreases reaction	4
Quercetin	decreases expression, decreases reaction, increases expression, increases reaction	4
Genistein	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression, decreases expression, decreases reaction	3
vinclozolin	decreases reaction, increases expression, increases secretion	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression, decreases secretion	3
Dutasteride	affects cotreatment, decreases expression	3
Fulvestrant	decreases expression, decreases reaction, increases expression	3
Niclosamide	affects binding, decreases reaction, increases reaction, decreases expression, affects cotreatment (+1 more)	3
Cyproterone Acetate	increases reaction, affects cotreatment, decreases expression, decreases reaction, increases activity (+2 more)	3
Sodium Selenite	decreases reaction, increases expression, decreases secretion, decreases expression	3
bisphenol A	decreases secretion, increases expression	2
sulindac sulfone	affects reaction, decreases expression	2
2,3-dibromopropyl-2,4,6-tribromophenyl ether	decreases reaction, increases expression, decreases expression	2
Docetaxel	decreases expression, decreases secretion	2
Decitabine	increases expression, affects cotreatment	2
Troglitazone	decreases expression	2
Androgens	affects cotreatment, affects reaction, increases expression, decreases expression	2

ChEMBL screening assays

51 unique, capped per target: 26 binding, 25 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1048364	Binding	Inhibition of prostate-specific antigen assessed as substrate hydrolysis by fluorescence assay	Optimization of peptide-based inhibitors of prostate-specific antigen (PSA) as targeted imaging agents for prostate cancer. — Bioorg Med Chem
CHEMBL3097438	ADMET	Drug metabolism assessed as PSA (unknown origin)-mediated digestion assessed as compound remaining after 50 hrs by HPLC analysis	Peptide conjugates of 4-aminocyclophosphamide as prodrugs of phosphoramide mustard for selective activation by prostate-specific antigen (PSA). — Bioorg Med Chem

Clinical trials (associated diseases)

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