PLAUR

Summary

PLAUR (plasminogen activator, urokinase receptor, HGNC:9053) is a protein-coding gene on chromosome 19q13, encoding Urokinase plasminogen activator surface receptor (Q03405). Acts as a receptor for urokinase plasminogen activator.

This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined.

Source: NCBI Gene 5329 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 73 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9053
Approved symbol	PLAUR
Name	plasminogen activator, urokinase receptor
Location	19q13
Locus type	gene with protein product
Status	Approved
Aliases	URKR, UPAR, CD87
Ensembl gene	ENSG00000011422
Ensembl biotype	protein_coding
OMIM	173391
Entrez	5329

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000221264, ENST00000339082, ENST00000340093, ENST00000593396, ENST00000593447, ENST00000593714, ENST00000593939, ENST00000594364, ENST00000595038, ENST00000597107, ENST00000598875, ENST00000599546, ENST00000599892, ENST00000601723, ENST00000601876, ENST00000602141, ENST00000856984, ENST00000927182, ENST00000947451, ENST00000947452, ENST00000947453, ENST00000947454, ENST00000947455, ENST00000947456

RefSeq mRNA: 4 — MANE Select: NM_002659 NM_001005376, NM_001005377, NM_001301037, NM_002659

CCDS: CCDS12628, CCDS33041, CCDS33042, CCDS74386

Canonical transcript exons

ENST00000340093 — 7 exons

Exon	Start	End
ENSE00000494759	43665316	43665459
ENSE00001048170	43670066	43670169
ENSE00003004913	43648579	43649143
ENSE00003494909	43667581	43667691
ENSE00003516101	43655439	43655573
ENSE00003786206	43656479	43656640
ENSE00003787154	43652225	43652371

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.9601 / max 9113.2308, expressed in 1735 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181327	98.7154	1616
181328	12.1909	1447
181326	3.9374	780
181329	1.0156	669
181324	0.5857	271
181316	0.4339	173
181317	0.3465	146
181314	0.2726	108
181323	0.1863	77
181325	0.1609	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	97.78	gold quality
monocyte	CL:0000576	97.63	gold quality
stromal cell of endometrium	CL:0002255	97.53	gold quality
mononuclear cell	CL:0000842	97.39	gold quality
leukocyte	CL:0000738	97.18	gold quality
vena cava	UBERON:0004087	96.53	gold quality
gall bladder	UBERON:0002110	96.24	gold quality
blood	UBERON:0000178	95.74	gold quality
bone marrow cell	CL:0002092	94.93	gold quality
cartilage tissue	UBERON:0002418	94.80	gold quality
granulocyte	CL:0000094	94.68	gold quality
bone marrow	UBERON:0002371	94.40	gold quality
right lung	UBERON:0002167	94.15	gold quality
upper lobe of left lung	UBERON:0008952	94.13	gold quality
upper lobe of lung	UBERON:0008948	93.74	gold quality
pancreatic ductal cell	CL:0002079	93.28	gold quality
pericardium	UBERON:0002407	92.57	gold quality
lower lobe of lung	UBERON:0008949	92.03	gold quality
lung	UBERON:0002048	91.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.22	gold quality
omental fat pad	UBERON:0010414	91.19	gold quality
peritoneum	UBERON:0002358	91.14	gold quality
islet of Langerhans	UBERON:0000006	90.74	gold quality
descending thoracic aorta	UBERON:0002345	90.66	gold quality
vermiform appendix	UBERON:0001154	90.49	gold quality
left uterine tube	UBERON:0001303	90.09	gold quality
type B pancreatic cell	CL:0000169	89.99	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.80	gold quality
olfactory bulb	UBERON:0002264	89.70	silver quality
colonic epithelium	UBERON:0000397	89.62	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	6009.92
E-HCAD-36	yes	4159.82
E-MTAB-6678	yes	3850.47
E-HCAD-15	yes	2599.38
E-MTAB-7407	yes	1980.82
E-MTAB-9435	yes	1851.95
E-CURD-122	yes	1556.80
E-HCAD-4	yes	190.40
E-HCAD-1	yes	92.49
E-MTAB-6701	yes	74.44
E-MTAB-8142	yes	38.56
E-GEOD-84465	yes	36.88
E-MTAB-10553	yes	36.66
E-MTAB-9467	yes	36.15
E-MTAB-10287	yes	33.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF1, CTNNB1, DNMT1, E2F1, EGR1, EPAS1, ERP29, ETV4, FOS, FOSL1, FOSL2, FOXM1, FOXP2, HIF1A, JUN, JUNB, JUND, KLF4, MYC, NFATC1, NFKB1, NFKB, RELA, SP1, SP3, SPDEF, TCF7L2, TFAP2A, TFAP2B, TFAP2C, TP53, ZHX2

miRNA regulators (miRDB)

15 targeting PLAUR, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-5008-5P	98.42	65.87	1019

Literature-anchored findings (GeneRIF, showing 40)

• uPA regulates uPAR expression at a post-transcriptional level, by promoting the binding of uPAR mRNA to a stabilizing factor. (PMID:11728456)
• uPA-dependent VSMC adhesion is a function of selective Vn phosphorylation by the ectoprotein kinase CK2 (PMID:11756447)
• oxidative stress in AD and microglial activation establish a possible involvement of uPAR in AD pathogenesis. (PMID:11814408)
• Investigation of the role of Endo180/urokinase-type plasminogen activator receptor-associated protein as a collagenase 3 (matrix metalloproteinase 13) receptor (PMID:11903048)
• Amino acid substitutions at serine residues in UPA prevent signaling through UPAR, and prevents physical association of UPAR with alphavbeta5 vitronectin receptor, which is required for MCF-7 urokinase-dependent cell migration. (PMID:11928806)
• UPA receptor is weakly upregulated by bFGF in normal muscle satellite cells, while it is strongly up-regulated by TGFbeta, mainly in dystrophic myoblasts. (PMID:11928807)
• Coculture of monocytes and vascular smooth muscle results in increased expression of cell surface-associated uPAR in VSMC and up-regulation of UPA in monocytes, resulting in VSMC migration. (PMID:11928816)
• REVIEW: The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility. (PMID:11928822)
• Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT. (PMID:11959893)
• uPA receptor is expressed in benign and malignant thyroid tumors. (PMID:12017319)
• essential role in acute inflammation as well as in chronic degenerative vascular processes such as atherosclerosis (PMID:12023845)
• Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy. Review. (PMID:12023847)
• Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression (PMID:12070711)
• interaction with urokinase 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)
• Human breast adenocarcinoma cell lines promote angiogenesis by providing cells with uPA-PAI-1 and by enhancing their expression. (PMID:12124797)
• prognostic biomarker for endometrial cancer (PMID:12130664)
• MCP-1, MCP-2 & MCP-3 increased uPAR mRNA levels in time-dependent & dose-dependent manners. Up-regulation of uPAR in target cells might be an important and common feature of chemoattractants. (PMID:12138365)
• circulating UPA is not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (PMID:12174885)
• Bikunin downregulates constitutive & PMA-stimulated uPAR mRNA & protein Through suppression of upstream ERK cascade targets, whether cells were treated with exogenous bikunin or transfected with bikunin gene. (PMID:12180971)
• Mutation of NFKB1 protein’s promoter binding site (-45 bp) impaired the ability of ITGB3BP to downregulate this protein. (PMID:12244126)
• uPA-mediated uPAR cleavage and D1 removal, occurring on the cell surface of several cell types, can play a fundamental role in the regulation of multiple uPAR functions (PMID:12297505)
• seprase and the urokinase plasminogen activator receptor (uPAR), co-localize in the plasma membrane of LOX malignant melanoma cells (PMID:12376466)
• 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)
• Urokinase receptor surface expression regulates monocyte adhesion in acute myocardial infarction (PMID:12393744)
• correlates with cox2 expression levels and is responsible for poor prognosis of colorectal cancer (PMID:12405290)
• The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells, showing that specific CD87 binding is one factor important in the sensitivity of patient’s leukemic blasts to DTAT (PMID:12479856)
• uPAR up-regulated the Mac-1 adhesion to fibrinogen, and focal adhesion kinase and MAPK were involved in this regulation (PMID:12665127)
• the interaction between uPAR and Man-6-P/IGF2R is a low percentage binding event and that suPAR and full-length uPAR bind the Man-6-P/IGF2R by different mechanisms. (PMID:12665524)
• uPAR expression in lung cancer is regulated at a posttranscriptional level by uPA (PMID:12704669)
• The expression of uPAR was significantly correlated with gastric tumor size, depth, lymph node involvement, differentiation & vascular invasion. (PMID:12708473)
• Plasma uPAR levels are greater in those with bladder cancer than in healthy subjects (P <0.001) and greatest in patients with metastases to distant lymph nodes (P = 0.042). (PMID:12736046)
• urokinase receptor D2 contains two distinct ligand binding sites for urokinase-type plasminogen activator and vitronectin (PMID:12761227)
• data indicating that the structure of the kringle as well as its interaction with the growth factor domain govern urokinase binding to the urokinase receptor (PMID:12881310)
• Results suggest that uPAR can engage distinct signaling pathways involving different partner proteins that are functionally and physically segregated from one another in both lipid raft and non-raft domains of the plasma membrane. (PMID:12933356)
• Results suggest that Endo180 is a crucial link between urokinase-type plasminogen activator and its receptor and setting of the internal cellular compass. (PMID:12952933)
• predictors of human immunodeficiency virus (HIV) disease progression (review) (PMID:12960238)
• signaling for the uPAR response, as mediated by B. burgdorferi, proceeds with CD14 and TLR2 as partial contributors (PMID:14500474)
• Significant increases in uPAR were found in pretreatment determinations of patients with advanced small-cell lung cancer or non-small-cell lung cancer. (PMID:14507113)
• urokinase and urokinase receptor mRNAs are stabilized by HuR linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2 (PMID:14517288)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plaur	ENSMUSG00000046223
rattus_norvegicus	Plaur	ENSRNOG00000037931

Paralogs (2): LYPD3 (ENSG00000124466), LYPD5 (ENSG00000159871)

Protein

Protein identifiers

Urokinase plasminogen activator surface receptor — Q03405 (reviewed: Q03405)

Alternative names: Monocyte activation antigen Mo3

All UniProt accessions (10): Q03405, M0QX27, M0QYR6, M0QYS6, M0R0H5, M0R0L1, M0R0Y4, M0R1I2, M0R2E9, M0R383

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.

Subunit / interactions. Monomer. Interacts with MRC2. Interacts (via the UPAR/Ly6 domains) with SRPX2. Interacts with FAP (seprase); the interaction occurs at the cell surface of invadopodia membrane. Interacts with SORL1 (via N-terminal ectodomain); this interaction decreases PLAUR internalization. The ternary complex composed of PLAUR-PLAU-SERPINE1 also interacts with SORL1. Interacts with CD82; this interaction prevents PLAUR from binding to its high affinity ligand PLAU.

Subcellular location. Cell membrane. Cell projection. Invadopodium membrane Cell membrane Secreted.

Tissue specificity. Expressed in neurons of the rolandic area of the brain (at protein level). Expressed in the brain.

Isoforms (3)

UniProt ID	Names	Canonical?
Q03405-1	1, uPAR1, GPI-anchored	yes
Q03405-2	2, uPAR2, Secreted
Q03405-3	3

RefSeq proteins (4): NP_001005376, NP_001005377, NP_001287966, NP_002650* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR018363	CD59_antigen_CS	Conserved_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00021

UniProt features (77 total): strand 22, disulfide bond 14, sequence variant 7, turn 7, sequence conflict 6, glycosylation site 5, helix 4, splice variant 3, domain 3, site 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
2FD6	X-RAY DIFFRACTION	1.9
3U74	X-RAY DIFFRACTION	2.39
3BT2	X-RAY DIFFRACTION	2.5
1YWH	X-RAY DIFFRACTION	2.7
2I9B	X-RAY DIFFRACTION	2.8
3BT1	X-RAY DIFFRACTION	2.8
7V63	X-RAY DIFFRACTION	2.91
9YC5	ELECTRON MICROSCOPY	2.94
7E17	X-RAY DIFFRACTION	2.96
4QTI	X-RAY DIFFRACTION	3
3U73	X-RAY DIFFRACTION	3.19
4K24	X-RAY DIFFRACTION	4.5
9YC6	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03405-F1	81.56	0.61

Antibody-complex structures (SAbDab): 4 — 2FD6, 3BT2, 4K24, 4QTI

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 (2): 105–106 (cleavage; by u-pa); 111–112 (cleavage; by u-pa)

Post-translational modifications (1): 305

Disulfide bonds (14): 25–46, 28–34, 39–67, 93–98, 117–144, 120–127, 137–169, 175–192, 193–198, 216–244, 219–227, 237–263, 269–287, 288–293

Glycosylation sites (5): 184, 194, 222, 255, 74

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-162791	Attachment of GPI anchor to uPAR
R-HSA-6798695	Neutrophil degranulation
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-9855719	Regulation of FXIIa and plasma kallikrein activity
R-HSA-9970672	FXIIa activates plasma kallikrein-kinin system

MSigDB gene sets: 547 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, HARRIS_HYPOXIA, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, MODULE_64, GOCC_CELL_SURFACE, MODULE_16, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, NAGASHIMA_NRG1_SIGNALING_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP

GO Biological Process (15): positive regulation of protein phosphorylation (GO:0001934), chemotaxis (GO:0006935), signal transduction (GO:0007165), blood coagulation (GO:0007596), regulation of plasminogen activation (GO:0010755), regulation of cell adhesion (GO:0030155), regulation of proteolysis (GO:0030162), positive regulation of homotypic cell-cell adhesion (GO:0034112), urokinase plasminogen activator signaling pathway (GO:0038195), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA binding (GO:0043388), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), regulation of fibrinolysis (GO:0051917), positive regulation of release of cytochrome c from mitochondria (GO:0090200), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243)

GO Molecular Function (6): signaling receptor binding (GO:0005102), enzyme binding (GO:0019899), protein domain specific binding (GO:0019904), urokinase plasminogen activator receptor activity (GO:0030377), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (15): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extrinsic component of membrane (GO:0019898), specific granule membrane (GO:0035579), cell projection (GO:0042995), protein complex involved in cell-matrix adhesion (GO:0098637), serine-type endopeptidase complex (GO:1905370), anchoring junction (GO:0070161), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Innate Immune System	2
Post-translational modification: synthesis of GPI-anchored proteins	1
Hemostasis	1
FXIIa activates plasma kallikrein-kinin system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	3
membrane	3
regulation of cellular process	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
hemostasis	1
wound healing	1
coagulation	1
plasminogen activation	1
regulation of protein processing	1
cell adhesion	1
proteolysis	1
regulation of protein metabolic process	1
positive regulation of cell-cell adhesion	1
homotypic cell-cell adhesion	1
regulation of homotypic cell-cell adhesion	1
cell surface receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA binding	1
positive regulation of binding	1
regulation of DNA binding	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
fibrinolysis	1
release of cytochrome c from mitochondria	1
positive regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1

Protein interactions and networks

STRING

2808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAUR	PLAU	P00749	999
PLAUR	VTN	P01141	996
PLAUR	SERPINE1	P05121	984
PLAUR	PLG	P00747	898
PLAUR	EGFR	P00533	896
PLAUR	SRPX2	O60687	877
PLAUR	SERPINB2	P05120	864
PLAUR	MRC2	Q9UBG0	851
PLAUR	PLAT	P00750	826
PLAUR	SPACA4	Q8TDM5	820
PLAUR	ITGB2	P05107	814
PLAUR	GAPDH	P00354	804
PLAUR	FPR2	P25090	790
PLAUR	ITGAM	P11215	787
PLAUR	CD177	Q8N6Q3	750

IntAct

20 interactions, top by confidence:

A	B	Type	Score
ANG	PLAUR	psi-mi:“MI:0915”(physical association)	0.570
ANG	PLAUR	psi-mi:“MI:2364”(proximity)	0.570
ANG	PLAUR	psi-mi:“MI:0403”(colocalization)	0.570
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
ANG	ANXA2	psi-mi:“MI:0914”(association)	0.480
ANG	S100A10	psi-mi:“MI:0403”(colocalization)	0.480
PLAU	ANG	psi-mi:“MI:0915”(physical association)	0.400
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
CST11	PLXNB2	psi-mi:“MI:0914”(association)	0.350
PSCA	GPAA1	psi-mi:“MI:0914”(association)	0.350
S100A10	PLAUR	psi-mi:“MI:0403”(colocalization)	0.270
DYRK1A	PLAUR	psi-mi:“MI:0915”(physical association)	0.000
PLAUR	EEF1A1	psi-mi:“MI:0915”(physical association)	0.000
SUMO2	PLAUR	psi-mi:“MI:0915”(physical association)	0.000
PLAUR	PFN2	psi-mi:“MI:0915”(physical association)	0.000
PLAUR	SURF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (240): PLAUR (Affinity Capture-Western), PLAU (Affinity Capture-Western), TEX101 (Affinity Capture-Western), TUBB3 (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), LARGE (Affinity Capture-MS), PKN1 (Affinity Capture-MS), PXDN (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), DNA2 (Affinity Capture-MS), TAZ (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNB3, A0JNL5, A6NC86, H3BJG9, H3BQJ8, O55186, O94772, O95867, P05533, P0CW02, P0CW03, P0DTL4, P13987, P35456, P35459, P35460, P35461, P46657, P47777, P49616, P57096, P58019, Q03405, Q05588, Q14210, Q148C3, Q28216, Q28785, Q32PB3, Q4R5M8, Q5R510, Q63317, Q64253, Q6UWN5, Q6UX82, Q80ZQ0, Q8K1T6, Q8SQ46, Q8TDM5, Q924B5

Diamond homologs: A6NC86, C0STK9, P0DUK6, P35456, P49616, P60591, P82143, Q03405, Q05588, Q78CF9, Q7LZI2, Q90358, Q9GK78, Q9GK79, Q9GK80, Q9I8P7, Q9PWI3, Q9GK77

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PLAU	up-regulates	PLAUR	binding
PLAUR	“up-regulates activity”	KRT1	binding
PLAUR	“up-regulates activity”	ITGB3	binding
NFATC1	“up-regulates quantity by expression”	PLAUR	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1069 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43652221:TCAC:T	donor_loss	1.0000
19:43652222:CA:C	donor_loss	1.0000
19:43652223:A:AG	donor_loss	1.0000
19:43652372:C:CC	acceptor_gain	1.0000
19:43652373:T:C	acceptor_gain	1.0000
19:43652373:T:TC	acceptor_gain	1.0000
19:43652385:C:CT	acceptor_gain	1.0000
19:43652385:C:T	acceptor_gain	1.0000
19:43652386:A:T	acceptor_gain	1.0000
19:43655432:T:A	donor_gain	1.0000
19:43655437:A:AC	donor_gain	1.0000
19:43655438:C:CC	donor_gain	1.0000
19:43655570:CGCC:C	acceptor_gain	1.0000
19:43655572:CC:C	acceptor_gain	1.0000
19:43655572:CCC:C	acceptor_loss	1.0000
19:43655572:CCCTA:C	acceptor_gain	1.0000
19:43655573:CC:C	acceptor_gain	1.0000
19:43655574:C:CA	acceptor_loss	1.0000
19:43655574:C:CC	acceptor_gain	1.0000
19:43655575:T:A	acceptor_loss	1.0000
19:43655584:C:CT	acceptor_gain	1.0000
19:43655585:A:T	acceptor_gain	1.0000
19:43656473:GCTCA:G	donor_loss	1.0000
19:43656475:TCACC:T	donor_loss	1.0000
19:43656478:C:CA	donor_loss	1.0000
19:43656478:CCTT:C	donor_gain	1.0000
19:43656490:T:A	donor_gain	1.0000
19:43656636:CCGGC:C	acceptor_gain	1.0000
19:43656637:CGGC:C	acceptor_gain	1.0000
19:43656637:CGGCC:C	acceptor_gain	1.0000

AlphaMissense

2200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43656520:C:G	C144S	0.998
19:43656521:A:T	C144S	0.998
19:43656541:C:G	C137S	0.998
19:43656542:A:T	C137S	0.998
19:43656601:C:G	C117S	0.998
19:43656602:A:G	C117R	0.998
19:43656602:A:T	C117S	0.998
19:43667610:C:G	C46S	0.998
19:43667611:A:T	C46S	0.998
19:43656521:A:G	C144R	0.997
19:43656592:C:G	C120S	0.997
19:43656592:C:T	C120Y	0.997
19:43656593:A:T	C120S	0.997
19:43656600:G:C	C117W	0.997
19:43665333:C:G	C98S	0.997
19:43665334:A:T	C98S	0.997
19:43665426:C:G	C67S	0.997
19:43665427:A:T	C67S	0.997
19:43667609:G:C	C46W	0.997
19:43655540:C:G	C169S	0.996
19:43655541:A:T	C169S	0.996
19:43656519:G:C	C144W	0.996
19:43656542:A:G	C137R	0.996
19:43656571:C:G	C127S	0.996
19:43656572:A:T	C127S	0.996
19:43656593:A:G	C120R	0.996
19:43667610:C:T	C46Y	0.996
19:43667611:A:G	C46R	0.996
19:43667673:C:G	C25S	0.996
19:43667674:A:T	C25S	0.996

dbSNP variants (sampled 300 via entrez): RS1000165827 (19:43663971 C>A,T), RS1000416994 (19:43669998 T>C), RS1000480779 (19:43652482 A>G), RS1000802063 (19:43657254 A>C), RS1001095928 (19:43661323 G>GT), RS1001196665 (19:43645816 G>A), RS1001200003 (19:43654746 C>A), RS1001467953 (19:43655398 C>A,T), RS1001630124 (19:43654505 C>A), RS1001975432 (19:43671438 C>G), RS1002025619 (19:43658805 G>A,C), RS1002043690 (19:43667238 G>A), RS1002098944 (19:43667425 G>C), RS1002278049 (19:43665054 C>T), RS1002281936 (19:43655305 G>GATACTCCCATTTTTCAGA)

Disease associations

OMIM: gene MIM:173391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004608_138	Granulocyte percentage of myeloid white cells	1.000000e-37
GCST004609_151	Monocyte percentage of white cells	6.000000e-27
GCST004610_93	White blood cell count	5.000000e-59
GCST004613_74	Sum neutrophil eosinophil counts	5.000000e-67
GCST004614_76	Granulocyte count	1.000000e-66
GCST004620_38	Sum basophil neutrophil counts	5.000000e-68
GCST004623_36	Neutrophil percentage of granulocytes	1.000000e-09
GCST004626_159	Myeloid white cell count	2.000000e-63
GCST004629_45	Neutrophil count	1.000000e-68
GCST004632_23	Lymphocyte percentage of white cells	9.000000e-23
GCST004633_127	Neutrophil percentage of white cells	2.000000e-33
GCST010242_338	HDL cholesterol levels	4.000000e-13
GCST90002379_154	Basophil count	1.000000e-11
GCST90002382_467	Eosinophil percentage of white cells	5.000000e-11
GCST90002388_370	Lymphocyte count	3.000000e-16
GCST90002389_406	Lymphocyte percentage of white cells	6.000000e-37
GCST90002394_559	Monocyte percentage of white cells	2.000000e-47
GCST90002398_89	Neutrophil count	9.000000e-136
GCST90002399_437	Neutrophil percentage of white cells	1.000000e-58
GCST90002400_286	Plateletcrit	1.000000e-16
GCST90002407_626	White blood cell count	2.000000e-121

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883324 (PROTEIN-PROTEIN INTERACTION), CHEMBL4883 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 188,481 (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
CHEMBL21731	MAPROTILINE	4	19,686
CHEMBL23	DILTIAZEM	4	54,676
CHEMBL472	GLYBURIDE	4	53,236
CHEMBL54	HALOPERIDOL	4	60,883

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

Binding affinities (BindingDB)

42 measured of 42 human assays (42 total across all organisms); most potent 42 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
IPR-2260 (45)	KI	400 nM
IPR-1609 (46)	KI	600 nM
IPR-1110 (1)	KI	700 nM
IPR-1607 (44)	KI	800 nM
IPR-1168 (39)	KI	900 nM
IPR-1201 (4)	KI	1000 nM
IPR-1178 (7)	KI	1100 nM
IPR-1174 (23)	KI	1200 nM
IPR-1171 (13)	KI	1300 nM
IPR-1182 (17)	KI	1300 nM
IPR-1195 (15)	KI	1600 nM
IPR-1185 (9)	KI	1700 nM
IPR-1193 (11)	KI	1700 nM
IPR-1192 (10)	KI	1900 nM
IPR-1176 (22)	KI	1900 nM
IPR-1160 (36)	KI	1900 nM
IPR-1175 (12)	KI	2000 nM
IPR-1188 (26)	KI	2000 nM
IPR-1186 (16)	KI	2100 nM
IPR-1191 (29)	KI	2100 nM
IPR-1158 (34)	KI	2300 nM
IPR-1167 (38)	KI	2300 nM
IPR-1187 (8)	KI	2500 nM
IPR-1190 (28)	KI	2600 nM
IPR-1200 (5)	KI	2700 nM
IPR-1196 (18)	KI	3600 nM
IPR-1172 (40)	KI	3700 nM
IPR-1181 (6)	KI	3800 nM
IPR-1194 (14)	KI	4500 nM
IPR-1153 (32)	KI	4500 nM
IPR-1197 (42)	KI	5500 nM
IPR-1173 (41)	KI	7700 nM
IPR-1119 (20)	KI	8600 nM
IPR-1189 (27)	KI	11800 nM
IPR-1183 (21)	KI	13300 nM
IPR-1179 (24)	KI	15900 nM
IPR-1157 (33)	KI	17600 nM
IPR-1161 (37)	KI	18600 nM
IPR-1151 (31)	KI	31700 nM
IPR-1154 (47)	KI	33500 nM
IPR-1198 (43)	KI	55300 nM
IPR-1152 (19)	KI	95200 nM

ChEMBL bioactivities

48 potent at pChembl≥5 of 81 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.96	Ki	0.011	nM	CHEMBL2206698
10.92	Ki	0.012	nM	CHEMBL2206697
10.48	Ki	0.0333	nM	CHEMBL2206687
9.53	Ki	0.296	nM	CHEMBL2206686
9.10	IC50	0.8	nM	CHEMBL1767118
8.88	Ki	1.33	nM	CHEMBL2206682
8.54	IC50	2.9	nM	CHEMBL1767120
7.68	Ki	20.8	nM	CHEMBL1652555
7.48	IC50	33	nM	CHEMBL1767119
7.40	IC50	40	nM	CHEMBL412236
7.30	IC50	50	nM	CHEMBL405302
7.22	IC50	60	nM	CHEMBL405999
7.10	IC50	80	nM	CHEMBL263158
6.70	IC50	200	nM	CHEMBL385968
6.51	Kd	310	nM	CHEMBL3621951
6.30	IC50	500	nM	CHEMBL4753144
6.30	IC50	500	nM	CHEMBL4791246
6.16	Ki	700	nM	CHEMBL5175734
6.16	IC50	700	nM	CHEMBL412223
6.05	IC50	900	nM	CHEMBL264653
5.66	IC50	2200	nM	CHEMBL4752534
5.66	IC50	2200	nM	CHEMBL4748577
5.66	Ki	2200	nM	CHEMBL5169692
5.61	IC50	2450	nM	CHEMBL5169692
5.60	Ki	2500	nM	CHEMBL5182189
5.59	Ki	2560	nM	CHEMBL5186118
5.56	Ki	2750	nM	CHEMBL5183489
5.54	IC50	2850	nM	CHEMBL5186118
5.51	IC50	3060	nM	CHEMBL5183489
5.51	IC50	3060	nM	CHEMBL5199716
5.31	IC50	4900	nM	CHEMBL4791246
5.30	IC50	5000	nM	CHEMBL2206354
5.24	IC50	5800	nM	CHEMBL4748144
5.21	IC50	6200	nM	CHEMBL4742729
5.21	Ki	6200	nM	CHEMBL5199716
5.16	IC50	7000	nM	CHEMBL2205795
5.12	IC50	7500	nM	CHEMBL4753144
5.12	Ki	7500	nM	CHEMBL5169901
5.08	IC50	8350	nM	CHEMBL5169901
5.07	IC50	8600	nM	CHEMBL4791246
5.07	IC50	8500	nM	CHEMBL4760716
5.07	IC50	8500	nM	CHEMBL4740414
5.03	IC50	9300	nM	CHEMBL4790155
5.02	IC50	9500	nM	CHEMBL4748584
5.01	IC50	9800	nM	CHEMBL4757892
5.00	IC50	1e+04	nM	CHEMBL2206358
5.00	IC50	1e+04	nM	CHEMBL2205797
5.00	IC50	1e+04	nM	CHEMBL3621951

PubChem BioAssay actives

95 with measured affinity, of 248 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
2-amino-1-(4-chlorophenyl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-1-(3-chlorophenyl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-1-(4-bromophenyl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-1-(1H-benzimidazol-2-ylmethyl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
6-(1H-benzimidazol-2-ylmethyl)-11H-quinoxalino[2,3-b][1,4]benzodiazepin-13-one	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-1-(1H-benzimidazol-2-ylmethyl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-5-phenyl-1-pyridin-2-ylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-1-(3-chlorophenyl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
6-[(1-prop-2-enylbenzimidazol-2-yl)methyl]-11H-quinoxalino[2,3-b][1,4]benzodiazepin-13-one	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-1-(1H-benzimidazol-2-yl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-5-phenyl-1-pyridin-4-ylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-5-phenyl-1-pyridin-4-ylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-1-(4-bromophenyl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
ethyl 2-[2-[(13-oxo-11H-quinoxalino[2,3-b][1,4]benzodiazepin-6-yl)methyl]benzimidazol-1-yl]acetate	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-5-phenyl-1-pyridin-2-ylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-1-(3-bromophenyl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
1,3-bis(1H-benzimidazol-2-yl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
3-(1H-benzimidazol-2-yl)-1-(4-chlorophenyl)-5-phenylpyrrol-2-amine	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-amino-1-(3-bromophenyl)-5-phenylpyrrole-3-carbonitrile	718393: Binding affinity to uPAR	ki	<0.0001	uM
2-phenacylpropanedinitrile	718393: Binding affinity to uPAR	ki	0.0003	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
6,11-dihydroquinoxalino[2,3-b][1,4]benzodiazepin-13-one	718393: Binding affinity to uPAR	ki	0.0013	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
3-amino-1H-quinoxalin-2-one	718393: Binding affinity to uPAR	ki	0.0208	uM
N-[2-[(2-amino-2-oxoethyl)-[2-[bis(4-methoxyphenyl)methylamino]-2-oxoethyl]amino]-2-oxoethyl]-N-naphthalen-2-yl-2-(prop-2-ynylamino)acetamide;hydrochloride	593717: Inhibition of [125I]-labelled EGF-like domain of urokinase-type plasminogen activator binding to uPAR expressed in human DU-145 cells by radioligand competition binding assay	ic50	0.0330	uM
(2S)-4-amino-2-[[(3S,6R,9S,12R,15S,18R,21R,26R,29R)-21-amino-18-(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-9-(1H-imidazol-5-ylmethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20,28-octaoxo-3-propan-2-yl-23,24-dithia-1,4,7,10,13,16,19,27-octazabicyclo[27.3.0]dotriacontane-26-carbonyl]amino]-4-oxobutanoic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.0400	uM
(2S)-4-amino-2-[[(3S,6R,9S,12R,15S,18R,21R,26R,29R)-21-amino-18-(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-9-(1H-imidazol-5-ylmethyl)-12-(naphthalen-1-ylmethyl)-2,5,8,11,14,17,20,28-octaoxo-3-propan-2-yl-23,24-dithia-1,4,7,10,13,16,19,27-octazabicyclo[27.3.0]dotriacontane-26-carbonyl]amino]-4-oxobutanoic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.0500	uM
(2S)-4-amino-2-[[(3S,6R,9S,12R,15S,18R,21R,26R,29R)-21-amino-18-(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-butyl-9-(1H-imidazol-5-ylmethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20,28-octaoxo-3-propan-2-yl-23,24-dithia-1,4,7,10,13,16,19,27-octazabicyclo[27.3.0]dotriacontane-26-carbonyl]amino]-4-oxobutanoic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.0600	uM
(2S)-4-amino-2-[[(3S,6R,9S,12R,15S,18R,21R,26R,29R)-21-amino-18-(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-9-(1H-imidazol-5-ylmethyl)-12-(naphthalen-2-ylmethyl)-2,5,8,11,14,17,20,28-octaoxo-3-propan-2-yl-23,24-dithia-1,4,7,10,13,16,19,27-octazabicyclo[27.3.0]dotriacontane-26-carbonyl]amino]-4-oxobutanoic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.0800	uM
(3S,6R,9S,12R,15S,18R,21S,27R,32S,35R,38S,41R)-27-amino-18,35-bis(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-21,38-bis(hydroxymethyl)-9-(1H-imidazol-5-ylmethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20,23,26,34,37,40-dodecaoxo-3-propan-2-yl-29,30-dithia-1,4,7,10,13,16,19,22,25,33,36,39-dodecazabicyclo[39.3.0]tetratetracontane-32-carboxylic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.2000	uM
methyl 3-[4-[(3E)-3-[(4-chlorophenyl)-hydroxymethylidene]-2-(3-fluorophenyl)-4,5-dioxopyrrolidin-1-yl]phenyl]benzoate	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	0.4000	uM
[2-(3-fluorophenyl)-8-thiophen-2-ylquinolin-4-yl]-morpholin-4-ylmethanone	1684977: Binding affinity to recombinant soluble form urokinase-type plasminogen activator receptor (unknown origin) expressed in S2 cells assessed as inhibition of uPAR-uPA ATF protein-protein interaction measured after 30 mins by ELISA	ic50	0.5000	uM
morpholin-4-yl-(2-phenyl-8-thiophen-2-ylquinolin-4-yl)methanone	1684977: Binding affinity to recombinant soluble form urokinase-type plasminogen activator receptor (unknown origin) expressed in S2 cells assessed as inhibition of uPAR-uPA ATF protein-protein interaction measured after 30 mins by ELISA	ic50	0.5000	uM
(4E)-4-[(3-chlorophenyl)-hydroxymethylidene]-1-[2-(3,4-dichlorophenyl)ethyl]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	0.6000	uM
(3S,6R,9S,12R,15S,18R,21S,27S,32S,35R,38S,41R)-27-amino-18,35-bis(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-21,38-bis(hydroxymethyl)-9-(1H-imidazol-5-ylmethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20,23,26,34,37,40-dodecaoxo-3-propan-2-yl-29,30-dithia-1,4,7,10,13,16,19,22,25,33,36,39-dodecazabicyclo[39.3.0]tetratetracontane-32-carboxylic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.7000	uM
(4E)-1-(3-bromo-4-methylphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	0.7000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)-1-(4-phenylphenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	0.8000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-1-[2-(3,4-dichlorophenyl)ethyl]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	0.9000	uM
(2S)-4-amino-2-[[(3S,6R,9S,12R,15S,18R,21S,26S,29R)-21-amino-18-(2-amino-2-oxoethyl)-6-(3-amino-3-oxopropyl)-15-(2-carboxyethyl)-9-(1H-imidazol-5-ylmethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20,28-octaoxo-3-propan-2-yl-23,24-dithia-1,4,7,10,13,16,19,27-octazabicyclo[27.3.0]dotriacontane-26-carbonyl]amino]-4-oxobutanoic acid	215817: Inhibitory activity against human Urokinase plasminogen activator receptor (uPAR) was determined	ic50	0.9000	uM
(4E)-1-(3-bromo-4-methylphenyl)-4-[(4-chloro-3-methylphenyl)-hydroxymethylidene]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.0000	uM
(4E)-1-(3-bromo-4-methylphenyl)-5-(3-chlorophenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.1000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)-1-(3-hexoxy-4-methylphenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.2000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)-1-(3-iodo-4-methylphenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.3000	uM
(4E)-1-(3-chloro-4-methoxyphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.3000	uM
(4E)-1-(4-tert-butylphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.6000	uM
(4E)-1-(3-bromo-4-methylphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(2,6-difluoro-3-pyridinyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.7000	uM
(4E)-5-(1,3-benzodioxol-5-yl)-1-(3-bromo-4-methylphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.7000	uM
(4E)-1-(3-bromo-4-methylphenyl)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(2-fluorophenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.9000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)-1-(4-hexoxyphenyl)pyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.9000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-5-(3-fluorophenyl)-1-quinolin-6-ylpyrrolidine-2,3-dione	1802602: Fluorescence Polarization Assay from Article 10.1021/acs.biochem.6b01039: “Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.”	ki	1.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	8
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects splicing	7
Estradiol	decreases reaction, increases expression, affects expression, affects cotreatment, decreases expression	6
Arsenic Trioxide	decreases expression, increases reaction	5
Cisplatin	affects cotreatment, decreases expression, increases expression	3
Silicon Dioxide	increases expression	3
Asbestos, Crocidolite	increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression	3
sodium bichromate	decreases expression, increases expression, increases stability	2
nickel sulfate	decreases expression	2
perfluorooctane sulfonic acid	decreases reaction, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, decreases reaction	2
(+)-JQ1 compound	decreases expression, affects cotreatment	2
Resveratrol	decreases expression	2
Fulvestrant	decreases reaction, increases expression, decreases expression	2
Aerosols	increases expression	2
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Cadmium	affects reaction, decreases reaction, increases expression	2
Dexamethasone	decreases expression	2
Lipopolysaccharides	increases expression, increases reaction	2
Nicotine	decreases reaction, increases expression	2
Quercetin	increases expression, decreases expression, decreases phosphorylation, decreases reaction	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Asbestos, Serpentine	increases expression	2
Okadaic Acid	increases expression	2
beta-Naphthoflavone	increases expression, decreases expression	2
Raloxifene Hydrochloride	decreases expression	2
aristolochic acid I	increases expression	1

ChEMBL screening assays

29 unique, capped per target: 29 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1767810	Binding	Inhibition of [125I]-labelled urokinase-type plasminogen activator binding to uPAR in human DU-145 cells by radioligand competition binding assay	Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1TZ	Abcam U-87MG PLAUR KO	Cancer cell line	Male
CVCL_D1YE	Abcam A-549 PLAUR KO	Cancer cell line	Male
CVCL_D2CK	Abcam HCT 116 PLAUR KO	Cancer cell line	Male
CVCL_D2NX	Abcam THP-1 PLAUR KO	Cancer cell line	Male
CVCL_TE18	HAP1 PLAUR (-) 1	Cancer cell line	Male
CVCL_TE19	HAP1 PLAUR (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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