PLAU

Summary

PLAU (plasminogen activator, urokinase, HGNC:9052) is a protein-coding gene on chromosome 10q22.2, encoding Urokinase-type plasminogen activator (P00749). Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer’s disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5328 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Quebec platelet disorder (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 8 total
• Phenotypes (HPO): 14
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9052
Approved symbol	PLAU
Name	plasminogen activator, urokinase
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	URK, UPA
Ensembl gene	ENSG00000122861
Ensembl biotype	protein_coding
OMIM	191840
Entrez	5328

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372764, ENST00000446342, ENST00000481390, ENST00000494287, ENST00000496926, ENST00000894723, ENST00000935791, ENST00000935792, ENST00000935793, ENST00000944838

RefSeq mRNA: 3 — MANE Select: NM_002658 NM_001145031, NM_001319191, NM_002658

CCDS: CCDS44442, CCDS7339

Canonical transcript exons

ENST00000372764 — 11 exons

Exon	Start	End
ENSE00001169164	73915251	73915399
ENSE00001169173	73914776	73914916
ENSE00001169178	73913980	73914128
ENSE00001169184	73913539	73913758
ENSE00001820360	73911132	73911218
ENSE00001892698	73916389	73917494
ENSE00003571253	73911525	73911612
ENSE00003580953	73912215	73912322
ENSE00003592011	73913290	73913381
ENSE00003612414	73912924	73913098
ENSE00003688080	73912041	73912068

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7616 / max 1251.9546, expressed in 1439 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105560	38.5905	1408
105555	0.6717	67
105553	0.2437	95
105554	0.1758	72
105556	0.0799	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	97.82	gold quality
stromal cell of endometrium	CL:0002255	94.63	gold quality
islet of Langerhans	UBERON:0000006	93.21	gold quality
cartilage tissue	UBERON:0002418	92.97	gold quality
metanephros cortex	UBERON:0010533	92.86	gold quality
omental fat pad	UBERON:0010414	91.15	gold quality
peritoneum	UBERON:0002358	91.13	gold quality
gall bladder	UBERON:0002110	91.03	gold quality
vena cava	UBERON:0004087	90.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.15	gold quality
right coronary artery	UBERON:0001625	90.02	gold quality
spleen	UBERON:0002106	89.17	gold quality
placenta	UBERON:0001987	87.76	gold quality
tendon of biceps brachii	UBERON:0008188	86.99	gold quality
layer of synovial tissue	UBERON:0007616	86.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.58	gold quality
pleura	UBERON:0000977	86.39	gold quality
parietal pleura	UBERON:0002400	86.25	gold quality
adult mammalian kidney	UBERON:0000082	86.24	gold quality
visceral pleura	UBERON:0002401	86.20	gold quality
smooth muscle tissue	UBERON:0001135	86.18	gold quality
vermiform appendix	UBERON:0001154	86.04	gold quality
heart right ventricle	UBERON:0002080	85.96	gold quality
nephron tubule	UBERON:0001231	85.93	gold quality
rectum	UBERON:0001052	85.86	gold quality
periodontal ligament	UBERON:0008266	85.32	gold quality
apex of heart	UBERON:0002098	85.29	gold quality
kidney	UBERON:0002113	85.26	gold quality
colonic epithelium	UBERON:0000397	84.99	gold quality
popliteal artery	UBERON:0002250	84.94	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	1618.44
E-GEOD-86618	yes	1065.39
E-HCAD-11	yes	1061.89
E-HCAD-13	yes	12.17
E-CURD-10	no	609.78
E-GEOD-110499	no	344.35
E-GEOD-36552	no	25.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF2, ATF4, COP1, CREB1, E2F1, EGR1, ETS1, ETS2, ETV1, ETV4, FOS, FOXC1, FOXM1, FOXO3, FOXP3, GATA6, GTF3A, HIF1A, HNF1B, HOXD3, ILF3, IRF6, JUN, JUNB, JUND, KAT7, KLF6, MBD2, MYC, MYOD1, NFKB1, NFKB, NFKBIB, NR3C1, POU2F1, RARA, RBPJ, REL

miRNA regulators (miRDB)

44 targeting PLAU, 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-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-3190-5P	98.87	64.89	1345

Literature-anchored findings (GeneRIF, showing 40)

• Pleiotrophic inhibition of pericellular urokinase-type plasminogen activator system by endogenous tumor suppressive maspin. (PMID:11751384)
• Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration (PMID:11805108)
• Exposure of cryptic domains in the alpha 1-chain of laminin-1 by elastase stimulates macrophages urokinase and matrix metalloproteinase-9 expression. (PMID:11827968)
• TPA & urokinase progressed to maximum levels in late pregnancy, but decreased in labor, favoring a coagulation state despite elevated D-dimer levels suggesting enhanced fibrinolysis. (PMID:11858184)
• significant decresase in PBM uPA activity in HIV infected and immunosuppresed patients independent from the presence of P. carinii lung infections (PMID:11906036)
• Substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. (PMID:11928806)
• bFGF up-regulated UPA in both normal and dystrophic myoblasts and weakly upregulated UPA receptor in normal satellite cells. (PMID:11928807)
• Random peptide bacteriophage display used as a probe to identify urokinase receptor binding sites other than the binding site of UPA residues 1-48. (PMID:11928809)
• In a study of the differential role of UPA and TPA as inducers of fibronectin mRNA, UPA led to an increase of FN mRNA expression in early G1, did not lead to FN assembly in the ECM, induced monomric FN (PMID:11928812)
• Coculture of monocytes and vascular smooth muscle results in 5-fold increase in UPA expression in monocytes, resulting in VSMC migration. (PMID:11928816)
• Osteopontin modulates prostate carcinoma invasive capacity through RGD-dependent upregulation of UPA. (PMID:11928818)
• Protease activity, growth factor-like and kringle domains of uPA differentially contribute to activation of p42/p44erk1,2 and p38 MAP-kinases. (PMID:11930938)
• Endogenous UPA is not only overexpressed in smooth muscle cells upon stimulation with PDGF/bFGF, but also mediates the mitogenic activity of the growth factors in a catalytic-domain-dependent manner. (PMID:11956327)
• possible role of fibroblast growth factors in expression of genes of the plasminogen activator system in breast fibroblasts (PMID:12008951)
• Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy. Review. (PMID:12023847)
• Diagnostic significance of measurement of the receptor for urokinase-type plasminogen activator on granulocytes and in plasma from patients with paroxysmal nocturnal hemoglobinuria. (PMID:12041678)
• interaction with urokinase receptor mediates inhibitory signal for HIV-1 replication (PMID:12084931)
• expression of uPA and uPAR is associated with the clinical behaviour of bladder neoplasms (PMID:12115506)
• Increased expression of urokinase during atherosclerotic lesion development causes arterial constriction and lumen loss, and accelerates lesion growth. (PMID:12149463)
• Characterization of the binding of human urokinase-type plasminogen activator to the asialoglycoprotein receptor of rat liver (PMID:12152683)
• Urokinase plasminogen activator receptor could be associated with BBB disruption and with promotion of CNS invasion by chemotactically active cells, macromolecules, and microbes. (PMID:12161038)
• upregulation of PAI-1, uPA, and tPA after long-term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity (PMID:12167592)
• the circluating level and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced NSCLC (PMID:12174885)
• the role of urokinase in the regulation of monocyte/macrophage functions, such as that occurring in inflammatory reactions (PMID:12183060)
• There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively) (PMID:12218297)
• uPA mrna stability is maintained through shuttling of uPA mRNABp between the nucleus and cytoplasm (PMID:12236587)
• u-PA present on the platelet surface interacts with u-PAR on the endothelial cell and induces u-PA synthesis in the vascular enodthelial cell. (PMID:12353084)
• promotion of mRNA stability in invasive brease cancer cells by Rac1-MKK3-p38-MAPKAPK2 pathway (PMID:12377770)
• recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind to both uPAR and alpha(M)beta(2); interaction of uPA with each receptor influences cell adhesion and migration (PMID:12393547)
• C/C genotype in exon 6 of uPA gene can be further considered as being related to colorectal cancer progression. (PMID:12430175)
• Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor kappa B-mediated secretion of this enzyme by inhibiting the phosphatidylinositol 3’-kinase activity in breast cancer cells. (PMID:12477728)
• recombinant kringle domain has anti-angiogenic activity (PMID:12529357)
• small, hormone-receptor-positive breast cancers (with a theoretical good prognosis) may carry an elevated risk of nodal involvement if accumulation of uPA-PAI-1 complexes is shown inside their tumour cells by means of immunohistochemistry. (PMID:12556966)
• Human/chicken chimeric uPA molecules & point mutants revealed the structural requirements for uPA autoactivation vs zymogen stability. The amino terminal fragment of chicken uPA engineered onto the human uPA molecule induces human uPA autoactivation. (PMID:12574820)
• PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response. (PMID:12576295)
• Induction of PAI-1 by exposure of lung epithelial cells to uPA is a newly recognized pathway by which PAI-1 could regulate local fibrinolysis in lung inflammation or neoplasia (PMID:12642587)
• High expression of Urokinase-type plasminogen activator is associated with melanoma (PMID:12684636)
• uPA regulates uPAR expression in NSCLC at a posttranscriptional level by increasing uPAR-stability through a cellular factor that binds the coding region of uPAR-mRNA (PMID:12704669)
• The expression of uPA was significantly correlated with depth of gastric tumor invasion, differentiation, lymphatic and vascular invasion. (PMID:12708473)
• tPA and plasma kallikrein-mediated uPA activation and tPA release contribute to endogenous fibrinolytic or thrombolytic mechanisms. (PMID:12719778)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plaub	ENSDARG00000039145
mus_musculus	Plau	ENSMUSG00000021822
rattus_norvegicus	Plau	ENSRNOG00000010516

Paralogs (3): PRSS3 (ENSG00000010438), PRSS1 (ENSG00000204983), PRSS2 (ENSG00000275896)

Protein

Protein identifiers

Urokinase-type plasminogen activator — P00749 (reviewed: P00749)

All UniProt accessions (3): E7ET40, P00749, S4R3G7

UniProt curated annotations — full annotation on UniProt →

Function. Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Subunit / interactions. Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR. Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP. The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA.

Subcellular location. Secreted.

Tissue specificity. Expressed in the prostate gland and prostate cancers.

Post-translational modifications. Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding. Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4.

Disease relevance. Quebec platelet disorder (QPD) [MIM:601709] An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5. Inhibited by SERPINE1.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P00749-1	1	yes
P00749-2	2

RefSeq proteins (3): NP_001138503, NP_001306120, NP_002649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00051, PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.73 — u-Plasminogen activator (BRENDA: 9 organisms, 133 substrates, 321 inhibitors, 56 Km, 26 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S2444	0.051–0.089	17
L-PYROGLU-GLY-L-ARG-4-NITROANILIDE	0.053–0.452	13
L-DIGLUTAMYL-GLYCYL-L-ARGININE-4-NITROANILIDE	0.297–0.608	4
PLASMINOGEN	0.0002–0.017	4
GSGRSA	0.052–0.6	2
HYGRSA	0.03–3.8	2
PFGRSA	0.014–2.2	2
PYROGLU-GLY-ARG-4-NITROANILIDE	0.1–0.13	2
QRGRSA	0.13–2.18	2
YGAKAY	0.13–2.3	2
L-PYROGLU-GLY-L-ARG-P-NA	0.08	1
N-BENZYLOXYCARBONYL-GLY-GLY-ARG-7-AMIDO-4-TRIFLU	0.053	1

UniProt features (91 total): strand 36, disulfide bond 12, helix 10, chain 4, sequence variant 4, sequence conflict 4, turn 4, active site 3, domain 3, modified residue 2, glycosylation site 2, mutagenesis site 2, region of interest 2, signal peptide 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

156 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5YC6	X-RAY DIFFRACTION	1.18
4ZKO	X-RAY DIFFRACTION	1.29
4ZKN	X-RAY DIFFRACTION	1.36
4ZKR	X-RAY DIFFRACTION	1.36
6XVD	X-RAY DIFFRACTION	1.4
2O8T	X-RAY DIFFRACTION	1.45
3MHW	X-RAY DIFFRACTION	1.45
5Z1C	X-RAY DIFFRACTION	1.45
5WXF	X-RAY DIFFRACTION	1.46
4MNW	X-RAY DIFFRACTION	1.49
1GJ7	X-RAY DIFFRACTION	1.5
4XSK	X-RAY DIFFRACTION	1.5
4GLY	X-RAY DIFFRACTION	1.52
4JK5	X-RAY DIFFRACTION	1.55
1GJA	X-RAY DIFFRACTION	1.56
3OX7	X-RAY DIFFRACTION	1.58
1OWE	X-RAY DIFFRACTION	1.6
4FU9	X-RAY DIFFRACTION	1.6
4FUH	X-RAY DIFFRACTION	1.6
4X1P	X-RAY DIFFRACTION	1.6
1OWH	X-RAY DIFFRACTION	1.61
5ZA9	X-RAY DIFFRACTION	1.62
1O5C	X-RAY DIFFRACTION	1.63
6AG9	X-RAY DIFFRACTION	1.63
1GJ8	X-RAY DIFFRACTION	1.64
5WXO	X-RAY DIFFRACTION	1.64
7ZRR	X-RAY DIFFRACTION	1.64
1C5Y	X-RAY DIFFRACTION	1.65
5ZAF	X-RAY DIFFRACTION	1.65
5ZAJ	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00749-F1	82.39	0.55

Antibody-complex structures (SAbDab): 6 — 2FD6, 3BT2, 4DW2, 4K24, 5HGG, 9PYF

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 (4): 224 (charge relay system); 275 (charge relay system); 376 (charge relay system); 177–178 (cleavage; during zymogen activation)

Post-translational modifications (2): 158, 323

Disulfide bonds (12): 31–39, 33–51, 53–62, 70–151, 91–133, 122–146, 168–299, 209–225, 217–288, 313–382, 345–361, 372–400

Glycosylation sites (2): 38, 322

Mutagenesis-validated functional residues (2):

Position	Phenotype
158	abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with e-323.
323	abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with e-158.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-75205	Dissolution of Fibrin Clot

MSigDB gene sets: 452 (showing top): MODULE_172, TSUNODA_CISPLATIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, LI_PROSTATE_CANCER_EPIGENETIC, GEORGES_CELL_CYCLE_MIR192_TARGETS, DITTMER_PTHLH_TARGETS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP

GO Biological Process (24): response to hypoxia (GO:0001666), proteolysis (GO:0006508), chemotaxis (GO:0006935), signal transduction (GO:0007165), blood coagulation (GO:0007596), regulation of plasminogen activation (GO:0010755), negative regulation of plasminogen activation (GO:0010757), smooth muscle cell migration (GO:0014909), regulation of smooth muscle cell migration (GO:0014910), regulation of cell adhesion (GO:0030155), positive regulation of cell migration (GO:0030335), plasminogen activation (GO:0031639), regulation of cell adhesion mediated by integrin (GO:0033628), urokinase plasminogen activator signaling pathway (GO:0038195), regulation of cell population proliferation (GO:0042127), fibrinolysis (GO:0042730), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), regulation of fibrinolysis (GO:0051917), negative regulation of fibrinolysis (GO:0051918), regulation of wound healing (GO:0061041), regulation of smooth muscle cell-matrix adhesion (GO:2000097), regulation of integrin-mediated signaling pathway (GO:2001044), epidermal growth factor receptor signaling pathway (GO:0007173), hemostasis (GO:0007599)

GO Molecular Function (6): serine-type endopeptidase activity (GO:0004252), receptor ligand activity (GO:0048018), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), serine protease inhibitor complex (GO:0097180), protein complex involved in cell-matrix adhesion (GO:0098637), serine-type endopeptidase complex (GO:1905370)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	3
wound healing	2
plasminogen activation	2
regulation of cell migration	2
fibrinolysis	2
cellular anatomical structure	2
secretory granule membrane	2
response to stress	1
response to decreased oxygen levels	1
protein metabolic process	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
hemostasis	1
coagulation	1
regulation of protein processing	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
muscle cell migration	1
smooth muscle cell migration	1
cell adhesion	1
cell migration	1
positive regulation of cell motility	1
zymogen activation	1
regulation of cell adhesion	1
cell adhesion mediated by integrin	1
cell surface receptor signaling pathway	1
cell population proliferation	1
negative regulation of blood coagulation	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
regulation of blood coagulation	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
negative regulation of biological process	1
regulation of fibrinolysis	1

Protein interactions and networks

STRING

3542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAU	SERPINE1	P05121	999
PLAU	PLAUR	Q03405	999
PLAU	VTN	P01141	988
PLAU	SERPINB2	P05120	959
PLAU	PLG	P00747	894
PLAU	IGF2R	P11717	863
PLAU	EGF	P01133	860
PLAU	MMP9	P14780	855
PLAU	MRC2	Q9UBG0	828
PLAU	FN1	P02751	825
PLAU	MMP1	P03956	822
PLAU	SERPINE2	P07093	771
PLAU	ANXA2	P07355	755
PLAU	MMP3	P08254	745
PLAU	CTSB	P07858	741

IntAct

57 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
pdhB	PLG	psi-mi:“MI:0194”(cleavage reaction)	0.830
SERPINE1	PLAU	psi-mi:“MI:0915”(physical association)	0.700
SERPINE1	PLAU	psi-mi:“MI:0407”(direct interaction)	0.700
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
SLURP1	PLAU	psi-mi:“MI:0407”(direct interaction)	0.590
PLAU	PLAUR	psi-mi:“MI:0407”(direct interaction)	0.560
PLAUR	PLAU	psi-mi:“MI:0407”(direct interaction)	0.560
PLAU	ADAM28	psi-mi:“MI:0915”(physical association)	0.560
PLAU	APP	psi-mi:“MI:0915”(physical association)	0.560
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
PLAU	SERPINE1	psi-mi:“MI:0407”(direct interaction)	0.440
PLAU	ANG	psi-mi:“MI:0915”(physical association)	0.400
PLAU	ALAS1	psi-mi:“MI:0915”(physical association)	0.370
BTK	PLAU	psi-mi:“MI:0915”(physical association)	0.370
PLAU	MYC	psi-mi:“MI:0915”(physical association)	0.370
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
PRKD1		psi-mi:“MI:0914”(association)	0.350
	TOR1B	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
PLAU	SERPINE2	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): PLAU (Affinity Capture-Western), PLAU (Affinity Capture-Western), SERPINE2 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), PPP4R4 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), KAT8 (Biochemical Activity), SERPINE1 (Reconstituted Complex), SERPINE2 (Reconstituted Complex), PLAU (Affinity Capture-MS), PLAU (Two-hybrid), PLAU (Affinity Capture-MS), PLAU (Reconstituted Complex), SERPINA5 (Reconstituted Complex)

ESM2 similar proteins: A6H6T1, A6MFK7, A6MFK8, O15393, O19045, O70169, P00741, P00742, P00749, P04185, P15638, P16227, P18292, P19221, P31394, P33587, P49150, P57727, P70375, P98119, P98121, Q05589, Q14520, Q1L658, Q1L659, Q3UQ41, Q4QXT9, Q56VR3, Q58L93, Q58L94, Q58L95, Q58L96, Q5E9Z2, Q5R537, Q5RF29, Q5U405, Q6AXZ6, Q6AY28, Q6DIV5, Q6L711

Diamond homologs: A0A126GUP6, A0A1S4H5M5, A0A1S4H5S2, A0A6I8TBG6, A0A6J1W8N1, A6MFK8, A6NIE9, B7YZU2, C0HKA2, C0HKA3, C0HKA4, F5HKX0, O97366, P00745, P00749, P00750, P00760, P00761, P00762, P00763, P00764, P00766, P03952, P04070, P06868, P06872, P07146, P08426, P11214, P14272, P15944, P19637, P20231, P21845, P27435, P31394, P33587, P35030, P35033, P40313

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PLAU	up-regulates	PLAUR	binding
SNAI1	“up-regulates quantity by expression”	PLAU	“transcriptional regulation”
PLAU	up-regulates	Epithelial-mesenchymal_transition
SRF	“up-regulates quantity by expression”	PLAU	“transcriptional regulation”
EIF3E	“up-regulates quantity”	PLAU	“translation regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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	10.0×	6e-03
Innate Immune System	8	4.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1676 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73911524:GA:G	acceptor_gain	1.0000
10:73911524:GAGCC:G	acceptor_gain	1.0000
10:73911611:AA:A	donor_gain	1.0000
10:73911611:AAG:A	donor_loss	1.0000
10:73911612:AGT:A	donor_loss	1.0000
10:73911613:G:GG	donor_gain	1.0000
10:73911614:T:A	donor_loss	1.0000
10:73911617:G:GG	donor_gain	1.0000
10:73912069:G:GG	donor_gain	1.0000
10:73912203:T:TA	acceptor_gain	1.0000
10:73912211:CCA:C	acceptor_loss	1.0000
10:73912213:A:AG	acceptor_gain	1.0000
10:73912213:AGC:A	acceptor_gain	1.0000
10:73912214:G:GT	acceptor_gain	1.0000
10:73912214:GC:G	acceptor_gain	1.0000
10:73912214:GCG:G	acceptor_gain	1.0000
10:73912214:GCGA:G	acceptor_gain	1.0000
10:73912214:GCGAA:G	acceptor_gain	1.0000
10:73912319:A:AG	donor_gain	1.0000
10:73912319:ATAG:A	donor_loss	1.0000
10:73912323:G:GA	donor_loss	1.0000
10:73912324:T:A	donor_loss	1.0000
10:73912919:TGTA:T	acceptor_loss	1.0000
10:73912920:GTA:G	acceptor_loss	1.0000
10:73912921:TA:T	acceptor_loss	1.0000
10:73912922:A:AG	acceptor_gain	1.0000
10:73912923:G:GG	acceptor_gain	1.0000
10:73912923:GATA:G	acceptor_gain	1.0000
10:73912923:GATAA:G	acceptor_gain	1.0000
10:73913097:AG:A	donor_loss	1.0000

AlphaMissense

2829 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73913012:G:C	W94C	0.999
10:73913012:G:T	W94C	0.999
10:73913739:A:C	S221R	0.999
10:73913741:C:A	S221R	0.999
10:73913741:C:G	S221R	0.999
10:73915361:T:A	C361S	0.998
10:73915362:G:C	C361S	0.998
10:73913704:G:A	C209Y	0.997
10:73913753:C:G	C225W	0.997
10:73914782:T:C	L279P	0.997
10:73916457:G:C	W396C	0.997
10:73916457:G:T	W396C	0.997
10:73912313:T:A	C62S	0.996
10:73912314:G:C	C62S	0.996
10:73913703:T:A	C209S	0.996
10:73913704:G:C	C209S	0.996
10:73913751:T:A	C225S	0.996
10:73913752:G:A	C225Y	0.996
10:73913752:G:C	C225S	0.996
10:73914009:T:A	V237D	0.996
10:73914123:A:C	D275A	0.996
10:73914123:A:T	D275V	0.996
10:73916452:A:C	S395R	0.996
10:73916454:C:A	S395R	0.996
10:73916454:C:G	S395R	0.996
10:73916523:G:C	W418C	0.996
10:73916523:G:T	W418C	0.996
10:73913703:T:C	C209R	0.995
10:73913705:T:G	C209W	0.995
10:73913712:A:C	S212R	0.995

dbSNP variants (sampled 300 via entrez): RS1000154092 (10:73908771 T>C), RS1000391832 (10:73910696 T>A), RS1000462630 (10:73907310 C>G,T), RS1000493840 (10:73907553 C>T), RS1000699832 (10:73910972 C>T), RS1000755680 (10:73917869 CAAG>C), RS1001108568 (10:73913649 C>A,T), RS1001800621 (10:73911221 G>A,T), RS1002001825 (10:73912855 A>AT), RS1002137585 (10:73912538 C>T), RS1002948069 (10:73916707 G>A), RS1003050730 (10:73910780 A>C), RS1003124324 (10:73911134 A>G), RS1003243497 (10:73915116 G>A), RS1003327673 (10:73916360 G>A,T)

Disease associations

OMIM: gene MIM:191840 | disease phenotypes: MIM:601709

GenCC curated gene-disease

Disease	Classification	Inheritance
Quebec platelet disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Quebec platelet disorder	Moderate	AD

Mondo (1): Quebec platelet disorder (MONDO:0011136)

Orphanet (1): Quebec platelet disorder (Orphanet:220436)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0000726	Dementia
HP:0000978	Bruising susceptibility
HP:0001300	Parkinsonism
HP:0001873	Thrombocytopenia
HP:0002185	Neurofibrillary tangles
HP:0002423	Long-tract sign
HP:0002511	Alzheimer disease
HP:0003581	Adult onset
HP:0005261	Joint hemorrhage
HP:0008148	Impaired epinephrine-induced platelet aggregation
HP:0410054	Decreased circulating GABA concentration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004132_74	Crohn’s disease	2.000000e-09
GCST005537_189	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-08
GCST007656_13	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536260	Quebec platelet disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111379 (SELECTIVITY GROUP), CHEMBL3286 (SINGLE PROTEIN), CHEMBL3883324 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 155,794 (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
CHEMBL1398126	AMILORIDE HYDROCHLORIDE	4	2,101
CHEMBL25105	HEXAMIDINE	4	5,666
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL945	AMILORIDE	4	63,705
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL50	QUERCETIN	3	74,559
CHEMBL87563	GABEXATE	3	2,031
CHEMBL9509	SILIBININ	3	130
CHEMBL30044	DIBROMPROPAMIDINE	2	1,799
CHEMBL4206119	UPAMOSTAT	2	248

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 4 [PMID: 18163548]	Inhibition	7.7	pIC50
UK-356202	Inhibition	7.4	pIC50
BB2-50F	Inhibition	6.74	pKi
WX-UK1	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

282 measured of 335 human assays (442 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R)-N-[(3-aminobenzene)sulfonyl]-2-[(4-carbamimidoyl-3-hydroxyphenyl)amino]-2-(3,5-diethoxy-2-fluorophenyl)acetamide	KI	0.35 nM
uPa_17	KI	0.892 nM
CDE-082	KD	5.3 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
Tannic Acid, A	IC50	7 nM
uPa_43	KI	9 nM
Isocoumarin, 9b	KI	10 nM
CDE-066	IC50	10 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
1-({4-chloro-1-[(diaminomethylidene)amino]isoquinoline-7-}(methyl)sulfonamido)cyclopentane-1-carboxylic acid	KI	11 nM
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-4-nitro-6-phenylbenzen-1-olate	KI	13 nM
uPa_26	KI	16 nM
2-(3-HYDROXY-PYRIDIN-2-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE	KI	17 nM
1-isoquinolinylguanidine 3	KI	17 nM
uPa_36	KI	18 nM
Isocoumarin, 7a	KI	20 nM
uPa_39	KI	21 nM
(2R)-2-({4-chloro-1-[(diaminomethylidene)amino]isoquinoline-7-}sulfonamido)propanoic acid	KI	28 nM
N-(3,4-dihydroxyphenyl)sulfonyl-N-heptyl-3,4-dihydroxybenzenesulfonamide	IC50	33 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
Isocoumarin, 5c	KI	33 nM
uPa_28	KI	33.3 nM
Isocoumarin, 8b	KI	34 nM
[2-(3,4-dihydroxybenzoyl)oxy-3-[[3-(trifluoromethyl)phenyl]sulfonylamino]propyl] 3,4-dihydroxybenzoate	IC50	35 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
Isocoumarin, 7b	KI	38 nM
6-Carbamimidoyl-naphthalene-2-carboxylic acid (4-aminomethyl-phenyl)-amide	KI	40 nM
uPa_10	KI	40 nM
uPa_41	KI	42 nM
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-6-bromo-4-methylbenzen-1-olate	KI	43 nM
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-6-bromo-4-(carboxymethyl)benzen-1-olate	KI	43 nM
3-({4-chloro-1-[(diaminomethylidene)amino]isoquinoline-7-}sulfonamido)-2,2-dimethylpropanoic acid	KI	43 nM
N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzenesulfonamide	IC50	51 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-4-(dimethylcarbamoyl)-6-phenylbenzen-1-olate	KI	52 nM
(2R)-1-({4-chloro-1-[(diaminomethylidene)amino]isoquinoline-7-}sulfonyl)pyrrolidine-2-carboxamide	KI	54 nM
Isocoumarin, 5d	KI	55 nM
uPa_18	KI	58.8 nM
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-6-chloro-4-methylbenzen-1-olate	KI	64 nM
uPa_31	KI	66 nM
2-(4-chloro-7-{[1-(hydroxymethyl)cyclopentyl]sulfamoyl}isoquinolin-1-yl)guanidine	KI	67 nM
{amino[2-(3,5-dichloro-2-hydroxyphenyl)-1H-indol-5-yl]methylidene}azanium	KI	70 nM
Isocoumarin, 9a	KI	84 nM
uPa_42	KI	94 nM
N-(3,4-dihydroxyphenyl)sulfonyl-N-(4-hexylphenyl)-3,4-dihydroxybenzenesulfonamide	IC50	120 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-4-methoxy-6-phenylbenzen-1-olate	KI	140 nM
CRA-8696	KI	160 nM
2-(4-chloro-7-{[(2R)-2-(hydroxymethyl)pyrrolidine-1-]sulfonyl}isoquinolin-1-yl)guanidine	KI	160 nM
N-(benzenesulfonyl)-N-[2-(3,4-dihydroxyphenyl)ethyl]-3,4-dihydroxybenzenesulfonamide	IC50	173 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-4-methyl-6-phenylbenzen-1-olate	KI	180 nM
N-(3,4-dihydroxyphenyl)sulfonyl-3,4-dihydroxy-N-nonylbenzenesulfonamide	IC50	180 nM	US-9718760: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof
uPa_40	KI	223 nM
2-{5-[amino(iminiumyl)methyl]-1H-indol-2-yl}-4-chloro-6-phenylbenzen-1-olate	KI	250 nM
CDE-031	IC50	280 nM	US-9120744: Plasminogen activator inhibitor-1 inhibitors and methods of use thereof to modulate lipid metabolism
uPa_29	KI	290 nM

ChEMBL bioactivities

948 potent at pChembl≥5 of 1220 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.34	Ki	0.46	nM	CHEMBL73737
9.21	IC50	0.62	nM	CHEMBL104166
9.21	Ki	0.62	nM	CHEMBL104166
9.20	Ki	0.631	nM	CHEMBL104166
9.10	IC50	0.8	nM	CHEMBL1767118
8.85	Ki	1.4	nM	CHEMBL226714
8.82	IC50	1.5	nM	CHEMBL385900
8.80	Ki	1.6	nM	CHEMBL228113
8.80	Ki	1.585	nM	CHEMBL562412
8.70	Ki	2	nM	CHEMBL104505
8.68	Ki	2.1	nM	CHEMBL320233
8.59	IC50	2.6	nM	CHEMBL385158
8.59	Ki	2.6	nM	CHEMBL227607
8.54	IC50	2.9	nM	CHEMBL1767120
8.51	IC50	3.1	nM	CHEMBL393591
8.51	IC50	3.1	nM	CHEMBL367004
8.47	IC50	3.4	nM	CHEMBL393979
8.46	IC50	3.5	nM	CHEMBL214814
8.46	IC50	3.5	nM	CHEMBL239118
8.40	IC50	4	nM	CHEMBL214814
8.38	IC50	4.2	nM	CHEMBL391968
8.37	IC50	4.3	nM	CHEMBL80844
8.36	IC50	4.4	nM	CHEMBL384263
8.30	Ki	5	nM	CHEMBL182959
8.30	IC50	5	nM	CHEMBL405546
8.30	IC50	5	nM	CHEMBL263977
8.30	Ki	5.012	nM	CHEMBL182959
8.29	IC50	5.1	nM	CHEMBL176515
8.24	IC50	5.8	nM	CHEMBL386275
8.24	IC50	5.8	nM	CHEMBL385897
8.24	Ki	5.8	nM	CHEMBL374378
8.22	IC50	6	nM	CHEMBL189823
8.21	IC50	6.2	nM	CHEMBL215961
8.20	Ki	6.3	nM	CHEMBL108447
8.20	Ki	6.31	nM	CHEMBL108447
8.18	IC50	6.6	nM	CHEMBL386249
8.18	IC50	6.6	nM	CHEMBL238493
8.17	IC50	6.7	nM	CHEMBL214539
8.16	IC50	6.9	nM	CHEMBL213216
8.15	IC50	7	nM	CHEMBL239535
8.15	IC50	7	nM	CHEMBL404226
8.14	IC50	7.2	nM	CHEMBL239747
8.13	Ki	7.4	nM	CHEMBL227666
8.13	Ki	7.4	nM	CHEMBL228170
8.11	Ki	7.7	nM	CHEMBL158405
8.11	IC50	7.7	nM	CHEMBL238491
8.10	IC50	7.9	nM	CHEMBL3770794
8.10	IC50	8	nM	CHEMBL411215
8.10	Ki	8	nM	CHEMBL227976
8.10	IC50	8	nM	CHEMBL239536

PubChem BioAssay actives

1172 with measured affinity, of 2333 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
benzyl N-[(2S)-1-[(2S)-2-[[5-hydrazinyl-5-sulfanylidene-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate;hydrobromide	215814: Binding affinity against Urokinase plasminogen activator	ki	<0.0001	uM
2-[3-(3-aminophenyl)-5-chloro-2-hydroxyphenyl]-3H-benzimidazole-5-carboximidamide	215836: Binding affinity towards urokinase-type plasminogen activator (microPa)	ki	0.0005	uM
N-[4-(aminomethyl)phenyl]-6-carbamimidoyl-4-(pyrimidin-2-ylamino)naphthalene-2-carboxamide	1385966: Inhibition of uPA (unknown origin)	ic50	0.0006	uM
(2S)-2-[[4-[3-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]phenyl]benzoyl]amino]-3-phenylpropanoic acid	593716: Inhibition of [125I]-labelled urokinase-type plasminogen activator binding to uPAR in human DU-145 cells by radioligand competition binding assay	ic50	0.0008	uM
2-[4-chloro-7-[[1-(4-methylpiperazine-1-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0014	uM
(2R)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxy-2-(thiophen-2-ylsulfonylamino)propanamide	270827: Inhibition of human uPA	ic50	0.0015	uM
6-carbamimidoyl-N-(1-propan-2-yl-3,4-dihydroisoquinolin-7-yl)-4-(pyrimidin-2-ylamino)naphthalene-2-carboxamide	419413: Inhibition of urokinase	ki	0.0016	uM
2-[4-chloro-7-[[1-(morpholine-4-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0016	uM
6-carbamimidoyl-N-phenyl-4-(pyrimidin-2-ylamino)naphthalene-2-carboxamide	213441: Binding affinity towards Urokinase-type plasminogen activator (urokinase)	ki	0.0020	uM
6-carbamimidoyl-N-(3-cyclopentyloxyphenyl)-4-(5-ethylsulfonylfuran-3-yl)naphthalene-2-carboxamide	213441: Binding affinity towards Urokinase-type plasminogen activator (urokinase)	ki	0.0021	uM
3-(5-carbamimidoyl-6-chloro-1H-indol-2-yl)-4-hydroxy-N,N-dimethyl-5-phenylbenzamide	1797196: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/s0022-2836(03)00399-1: “Elaborate manifold of short hydrogen bond arrays mediating binding of active site-directed serine protease inhibitors.”	ki	0.0022	uM
(2R)-2-(benzenesulfonamido)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270827: Inhibition of human uPA	ic50	0.0026	uM
6-chloro-2-(2-hydroxy-5-methoxy-3-phenylphenyl)-1H-indole-5-carboximidamide	1797196: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/s0022-2836(03)00399-1: “Elaborate manifold of short hydrogen bond arrays mediating binding of active site-directed serine protease inhibitors.”	ki	0.0026	uM
1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylic acid	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0026	uM
(4S)-4-amino-5-[[2-[[(3S)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	593718: Inhibition of high molecular weight fluorescent labelled urokinase-type plasminogen activator binding to uPAR in PMA-stimulated human U937 cells preincubated for 30 mins by flow cytometry	ic50	0.0029	uM
methyl N-[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]carbamate	304479: Inhibition of human uPA	ic50	0.0031	uM
(2R)-N-[(2S)-1-[[(3S)-1-carbamimidoyl-2-hydroxypiperidin-3-yl]amino]-1-oxopropan-2-yl]-3-hydroxy-2-(2-phenylethylsulfonylamino)propanamide;2,2,2-trifluoroacetic acid	215658: The compound was tested in vitro for its inhibitory activity against human urokinase enzyme, activity expressed as IC50	ic50	0.0031	uM
3-(5-carbamimidoyl-1H-indol-2-yl)-4-hydroxy-N,N-dimethyl-5-phenylbenzamide	1797196: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/s0022-2836(03)00399-1: “Elaborate manifold of short hydrogen bond arrays mediating binding of active site-directed serine protease inhibitors.”	ki	0.0032	uM
methyl N-[1-bis(4-acetamidophenoxy)phosphoryl-2-[4-(diaminomethylideneamino)phenyl]ethyl]carbamate	304479: Inhibition of human uPA	ic50	0.0034	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270827: Inhibition of human uPA	ic50	0.0035	uM
N-[4-[(4-acetamidophenoxy)-[2-[4-(diaminomethylideneamino)phenyl]-1-(methanesulfonamido)ethyl]phosphoryl]oxyphenyl]acetamide	304479: Inhibition of human uPA	ic50	0.0035	uM
benzyl N-[1-bis(4-acetamidophenoxy)phosphoryl-2-[4-(diaminomethylideneamino)phenyl]ethyl]carbamate	304479: Inhibition of human uPA	ic50	0.0042	uM
benzyl N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	270827: Inhibition of human uPA	ic50	0.0043	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]-3-methylbenzamide	270827: Inhibition of human uPA	ic50	0.0044	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]benzamide	270827: Inhibition of human uPA	ic50	0.0050	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]-2-methylbenzamide	270827: Inhibition of human uPA	ic50	0.0050	uM
6-(2-phenylcyclopropyl)-8-(pyrimidin-2-ylamino)naphthalene-2-carboximidamide	238828: Binding affinity value against urokinase plasminogen activator	ki	0.0050	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[[(3S)-1-carbamimidoyl-2-hydroxypiperidin-3-yl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	215658: The compound was tested in vitro for its inhibitory activity against human urokinase enzyme, activity expressed as IC50	ic50	0.0051	uM
(2R)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxy-2-(naphthalen-1-ylsulfonylamino)propanamide	270827: Inhibition of human uPA	ic50	0.0058	uM
(2R)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxy-2-[(4-methoxyphenyl)sulfonylamino]propanamide	270827: Inhibition of human uPA	ic50	0.0058	uM
1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylic acid	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0058	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]-2,6-dimethylbenzamide	270827: Inhibition of human uPA	ic50	0.0060	uM
(2R)-2-[(4-cyanophenyl)sulfonylamino]-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270827: Inhibition of human uPA	ic50	0.0062	uM
6-carbamimidoyl-N-(4-ethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-2-carboxamide	215835: Binding affinity to human urokinase-type plasminogen activator (microPa).	ki	0.0063	uM
(2R)-2-[(4-bromophenyl)sulfonylamino]-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270827: Inhibition of human uPA	ic50	0.0066	uM
[2,3-dihydroxy-5-[[3,4,5,6-tetrakis[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]oxan-2-yl]methoxycarbonyl]phenyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0066	uM
2-[4-[2-diphenoxyphosphoryl-2-(methanesulfonamido)ethyl]phenyl]guanidine	304479: Inhibition of human uPA	ic50	0.0066	uM
benzyl N-[(2R)-1-[[(2S)-1-[[1-bis(4-acetamidophenoxy)phosphoryl-2-[4-(diaminomethylideneamino)phenyl]ethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamate	270827: Inhibition of human uPA	ic50	0.0067	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]thiophene-2-carboxamide	270827: Inhibition of human uPA	ic50	0.0069	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]-4-methylbenzamide	270827: Inhibition of human uPA	ic50	0.0070	uM
benzyl N-[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]carbamate	304479: Inhibition of human uPA	ic50	0.0070	uM
N-[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]acetamide	304479: Inhibition of human uPA	ic50	0.0072	uM
4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]oxane-4-carboxylic acid	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0074	uM
1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclobutane-1-carboxylic acid	1797470: Determination of Inhibitor Potency and Selectivity from Article 10.1021/jm061066t: “Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines.”	ki	0.0074	uM
2-[4-[2-(benzylsulfonylamino)-2-diphenoxyphosphorylethyl]phenyl]guanidine	304479: Inhibition of human uPA	ic50	0.0077	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxopropan-2-yl]-3-hydroxypropanamide	228656: In vitro inhibition of plasminogen activator urokinase.	ki	0.0077	uM
ethyl N-[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]carbamate	304479: Inhibition of human uPA	ic50	0.0080	uM
2-(2-hydroxy-3-phenoxyphenyl)-1H-indole-5-carboximidamide	215987: Inhibition of urokinase-type plasminogen activator	ki	0.0080	uM
N-[(2R)-1-[[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]adamantane-2-carboxamide	270827: Inhibition of human uPA	ic50	0.0080	uM
2-(2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.0080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	8
sodium arsenite	decreases reaction, increases expression, decreases expression, affects cotreatment, increases abundance	7
Resveratrol	affects cotreatment, increases expression, decreases reaction, increases reaction, decreases expression (+2 more)	7
Estradiol	affects expression, affects binding, decreases expression, affects cotreatment, increases expression	7
Arsenic Trioxide	affects cotreatment, decreases reaction, decreases secretion, increases secretion, decreases expression (+2 more)	6
Benzo(a)pyrene	increases expression, increases methylation	6
Plant Extracts	affects expression, decreases reaction, increases expression, decreases expression, affects reaction (+3 more)	6
Decitabine	affects expression, affects methylation, decreases reaction, increases expression	5
Dexamethasone	increases expression, decreases activity, decreases expression, affects cotreatment	4
Doxorubicin	decreases response to substance, affects response to substance, decreases reaction, increases expression, increases secretion	4
Quercetin	decreases reaction, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression, increases methylation	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	4
bisphenol A	decreases expression, increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression, affects cotreatment	3
Amiloride	increases degradation, decreases activity, decreases reaction	3
Curcumin	decreases expression, decreases secretion, increases expression, increases reaction	3
Lipopolysaccharides	affects expression, increases expression, affects response to substance, affects reaction	3
Progesterone	affects cotreatment, decreases expression	3
Silicon Dioxide	increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Tretinoin	decreases expression, increases expression	3
Asbestos, Crocidolite	decreases expression, increases expression	3
graphene oxide	increases expression	2
sodium bichromate	decreases expression	2
U 0126	decreases reaction, increases expression	2
pyrazolanthrone	increases reaction, decreases reaction, increases activity, increases expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2

ChEMBL screening assays

312 unique, capped per target: 300 binding, 7 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL828458	Binding	Ki ratio of human alpha thrombin to two chain urokinase type plasminogen activator	In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design. — J Med Chem
CHEMBL3215182	Functional	PubChem BioAssay. qHTS for Inhibitors of Cell Surface uPA Generation: Confirmatory Assay for Cherry-picked Compounds. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4388479	ADMET	Inhibition of recombinant C-terminal 10His-tagged human urokinase (Met1 to Leu431 residues) expressed in mouse NS0 cells using Z-GGR-AMC as substrate after 40 mins by fluorescence intensity assay	Structure guided drug design to develop kallikrein 5 inhibitors to treat Netherton syndrome. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B9ZJ	Abcam THP-1 PLAU KO	Cancer cell line	Male
CVCL_C7B8	Abcam PC-3 PLAU KO	Cancer cell line	Male
CVCL_D7XT	Ubigene A-549 PLAU KO	Cancer cell line	Male
CVCL_D8T7	Ubigene HCT 116 PLAU KO	Cancer cell line	Male
CVCL_E0L4	Ubigene HeLa PLAU KO	Cancer cell line	Female
CVCL_E4HK	CHO SSF3/pMOZ uPA clone 1	Transformed cell line	Female
CVCL_E4HL	CHO SSF3/pMOZ uPA clone 8	Transformed cell line	Female
CVCL_TE16	HAP1 PLAU (-) 1	Cancer cell line	Male
CVCL_TE17	HAP1 PLAU (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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