PCSK4

Summary

PCSK4 (proprotein convertase subtilisin/kexin type 4, HGNC:8746) is a protein-coding gene on chromosome 19p13.3, encoding Proprotein convertase subtilisin/kexin type 4 (Q6UW60). Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues.

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II.

Source: NCBI Gene 54760 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 176 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_017573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8746
Approved symbol	PCSK4
Name	proprotein convertase subtilisin/kexin type 4
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PC4, SPC5, DKFZp434B217, MGC34749
Ensembl gene	ENSG00000115257
Ensembl biotype	protein_coding
OMIM	600487
Entrez	54760

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 retained_intron, 3 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000300954, ENST00000441747, ENST00000586002, ENST00000586074, ENST00000586616, ENST00000587784, ENST00000588195, ENST00000588671, ENST00000590057, ENST00000591201, ENST00000591303, ENST00000591687, ENST00000614078, ENST00000883590

RefSeq mRNA: 2 — MANE Select: NM_017573 NM_001395257, NM_017573

CCDS: CCDS12069

Canonical transcript exons

ENST00000300954 — 15 exons

Exon	Start	End
ENSE00001337899	1487603	1487691
ENSE00003468728	1486853	1487065
ENSE00003497897	1481428	1482207
ENSE00003521809	1482896	1483020
ENSE00003535811	1487964	1488092
ENSE00003558988	1483838	1483941
ENSE00003561637	1482353	1482475
ENSE00003582531	1487785	1487861
ENSE00003591008	1487141	1487313
ENSE00003614119	1483284	1483463
ENSE00003615289	1484027	1484127
ENSE00003619357	1489793	1489897
ENSE00003635106	1488188	1488280
ENSE00003639753	1483650	1483767
ENSE00003978115	1490158	1490350

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 98.22.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3987 / max 135.3255, expressed in 716 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178022	1.2382	681
178023	0.0961	22
178024	0.0644	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.22	gold quality
right testis	UBERON:0004534	98.16	gold quality
testis	UBERON:0000473	94.84	gold quality
right uterine tube	UBERON:0001302	92.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.06	gold quality
adenohypophysis	UBERON:0002196	86.50	gold quality
pituitary gland	UBERON:0000007	84.05	gold quality
pancreatic ductal cell	CL:0002079	81.97	silver quality
right lobe of liver	UBERON:0001114	81.90	gold quality
ileal mucosa	UBERON:0000331	80.86	silver quality
metanephros cortex	UBERON:0010533	79.19	gold quality
right frontal lobe	UBERON:0002810	79.11	gold quality
right lobe of thyroid gland	UBERON:0001119	79.06	gold quality
left lobe of thyroid gland	UBERON:0001120	78.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.80	gold quality
hypothalamus	UBERON:0001898	77.78	gold quality
tibialis anterior	UBERON:0001385	77.40	silver quality
thyroid gland	UBERON:0002046	77.33	gold quality
anterior cingulate cortex	UBERON:0009835	76.96	gold quality
lower esophagus mucosa	UBERON:0035834	76.79	gold quality
stromal cell of endometrium	CL:0002255	76.55	gold quality
mucosa of transverse colon	UBERON:0004991	76.44	gold quality
nucleus accumbens	UBERON:0001882	75.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.94	gold quality
caudate nucleus	UBERON:0001873	75.93	gold quality
transverse colon	UBERON:0001157	75.23	gold quality
right adrenal gland	UBERON:0001233	75.02	gold quality
amygdala	UBERON:0001876	74.81	gold quality
right adrenal gland cortex	UBERON:0035827	74.81	gold quality
body of stomach	UBERON:0001161	74.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting PCSK4, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4315	94.78	64.86	112
HSA-MIR-7108-3P	94.37	64.79	183

Literature-anchored findings (GeneRIF, showing 2)

• abnormal processing of IGF-II by PC4 may represent a previously uncharacterized mechanism involved in the pathophysiology of fetoplacental growth restriction (PMID:16040806)
• Maturation by propeptide removal occurs very inefficiently when rat or human proPCSK4 is overexpressed in HEK293 cells where it interacts with BiP. (PMID:21080038)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcsk4	ENSMUSG00000020131
rattus_norvegicus	Pcsk4	ENSRNOG00000016405
drosophila_melanogaster	Fur2	FBGN0004598
caenorhabditis_elegans	kpc-1	WBGENE00002232

Paralogs (9): PCSK5 (ENSG00000099139), PCSK2 (ENSG00000125851), TPP2 (ENSG00000134900), PCSK6 (ENSG00000140479), FURIN (ENSG00000140564), MBTPS1 (ENSG00000140943), PCSK7 (ENSG00000160613), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Protein

Protein identifiers

Proprotein convertase subtilisin/kexin type 4 — Q6UW60 (reviewed: Q6UW60)

Alternative names: Proprotein convertase 4

All UniProt accessions (4): Q6UW60, A0A140VJQ9, K7EJB6, K7EN14

UniProt curated annotations — full annotation on UniProt →

Function. Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida. Also plays a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2. May also participate in folliculogenesis in the ovaries.

Subunit / interactions. The proPCSK4 form interacts with HSPA5; the interaction takes place at the endoplasmic reticulum.

Subcellular location. Membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

Tissue specificity. Placenta.

Post-translational modifications. N-glycosylated. Synthesized in the endoplasmic reticulum as a zymogen, is matured by autocatalytic cleavage between the prodomain and the catalytic domain.

Similarity. Belongs to the peptidase S8 family. Furin subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UW60-1	1	yes
Q6UW60-2	2

RefSeq proteins (2): NP_001382186, NP_060043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000209	Peptidase_S8/S53_dom	Domain
IPR002884	P_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR015500	Peptidase_S8_subtilisin-rel	Family
IPR022398	Peptidase_S8_His-AS	Active_site
IPR023827	Peptidase_S8_Asp-AS	Active_site
IPR023828	Peptidase_S8_Ser-AS	Active_site
IPR032815	S8_pro-domain	Domain
IPR034182	Kexin/furin	Domain
IPR036852	Peptidase_S8/S53_dom_sf	Homologous_superfamily
IPR038466	S8_pro-domain_sf	Homologous_superfamily

Pfam: PF00082, PF01483, PF16470

Enzyme classification (BRENDA):

• EC 3.4.21.B24 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)
• EC 3.4.21.B25 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (15 total): active site 3, glycosylation site 2, domain 2, signal peptide 1, propeptide 1, splice variant 1, sequence variant 1, mutagenesis site 1, sequence conflict 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW60-F1	84.68	0.65

Functional residue map

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

Catalytic / active sites (3): 158 (charge relay system); 199 (charge relay system); 373 (charge relay system)

Glycosylation sites (2): 629, 475

Mutagenesis-validated functional residues (1):

Position	Phenotype
373	no effect on interaction with hspa5.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_SINGLE_FERTILIZATION, E2F_Q4_01, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_PROTEIN_MATURATION, GOCC_TRANS_GOLGI_NETWORK, E2F_Q3, UEDA_PERIFERAL_CLOCK, AML_Q6, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (8): binding of sperm to zona pellucida (GO:0007339), acrosome reaction (GO:0007340), fertilization (GO:0009566), protein processing (GO:0016485), peptide hormone processing (GO:0016486), reproductive process (GO:0022414), sperm capacitation (GO:0048240), proteolysis (GO:0006508)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (7): Golgi membrane (GO:0000139), acrosomal vesicle (GO:0001669), acrosomal membrane (GO:0002080), trans-Golgi network (GO:0005802), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
reproductive process	2
cellular anatomical structure	2
sperm-egg recognition	1
membrane fusion involved in acrosome reaction	1
single fertilization	1
acrosomal vesicle exocytosis	1
sexual reproduction	1
proteolysis	1
protein maturation	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
biological_process	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
secretory granule	1
acrosomal vesicle	1
secretory granule membrane	1
Golgi apparatus subcompartment	1
vacuole	1
plasma membrane	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCSK4	MBTPS1	Q14703	640
PCSK4	LRRC8D	Q7L1W4	629
PCSK4	CFD	P00746	593
PCSK4	IGF2	P01344	522
PCSK4	TNFRSF18	Q9Y5U5	521
PCSK4	IGF2BP3	O00425	497
PCSK4	IHH	Q14623	496
PCSK4	AMH	P03971	495
PCSK4	ACRBP	Q8NEB7	492
PCSK4	IGF2BP2	Q9Y6M1	491
PCSK4	INS-IGF2	F8WCM5	480
PCSK4	SCG5	P01164	460
PCSK4	ADAM2	P78326	448
PCSK4	GDF11	O95390	443
PCSK4	GPC3	P51654	439

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ASPH	PCSK4	psi-mi:“MI:0915”(physical association)	0.560
PCSK4	ABCF1	psi-mi:“MI:0915”(physical association)	0.400
ASPH	PCSK4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): ASPH (Two-hybrid), ABCF1 (Proximity Label-MS), PCSK4 (Negative Genetic), PCSK4 (Protein-RNA), IGF2 (Biochemical Activity)

ESM2 similar proteins: A2AJ76, A8T644, A8T650, A8T655, A8T658, A8T662, A8T666, A8T672, A8T677, A8T682, A8T688, A8T695, A8T6A1, A8T6A6, D3Z7H8, O75173, O95450, O95479, P04088, P21709, P29121, P34820, P34821, P55103, P55104, P56201, P59996, P79331, Q0V8J4, Q13219, Q16549, Q5RFQ8, Q60750, Q61139, Q62849, Q6UW60, Q78EH2, Q7Z5Y6, Q80W65, Q8BNJ2

Diamond homologs: A0A044RE18, G5ECN9, O13359, O17798, P09231, P09958, P13134, P16519, P21661, P23188, P23377, P26016, P28840, P28841, P29119, P29120, P29121, P29122, P29141, P29145, P29146, P30430, P30432, P41413, P42781, P51559, P63239, P63240, P91863, Q03333, Q04592, Q09175, Q16549, Q28193, Q5REC2, Q61139, Q62849, Q63415, Q6UW60, Q78EH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	154
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1073440	NC_000019.9:g.(?1486852)(1491383_?)del	Pathogenic

SpliceAI

2133 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1482351:AC:A	donor_gain	1.0000
19:1482352:CC:C	donor_gain	1.0000
19:1482471:CGTCC:C	acceptor_gain	1.0000
19:1482498:C:CT	acceptor_gain	1.0000
19:1482500:C:CT	acceptor_gain	1.0000
19:1482501:A:T	acceptor_gain	1.0000
19:1482894:AC:A	donor_gain	1.0000
19:1482895:CC:C	donor_gain	1.0000
19:1482911:AGC:A	donor_gain	1.0000
19:1483280:TCAC:T	donor_loss	1.0000
19:1483282:ACC:A	donor_loss	1.0000
19:1483459:TGGGG:T	acceptor_gain	1.0000
19:1483681:T:TA	donor_gain	1.0000
19:1483764:CTCA:C	acceptor_gain	1.0000
19:1483766:CA:C	acceptor_gain	1.0000
19:1483768:C:CC	acceptor_gain	1.0000
19:1483938:CGGG:C	acceptor_gain	1.0000
19:1483942:C:CC	acceptor_gain	1.0000
19:1484025:A:AC	donor_gain	1.0000
19:1484026:C:CC	donor_gain	1.0000
19:1486849:TCACG:T	donor_loss	1.0000
19:1486851:A:AC	donor_gain	1.0000
19:1486851:ACGAT:A	donor_gain	1.0000
19:1486852:C:CA	donor_gain	1.0000
19:1486852:CG:C	donor_gain	1.0000
19:1486852:CGA:C	donor_gain	1.0000
19:1486852:CGAT:C	donor_gain	1.0000
19:1486852:CGATC:C	donor_gain	1.0000
19:1487136:CTCA:C	donor_loss	1.0000
19:1487137:TCA:T	donor_loss	1.0000

AlphaMissense

4869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1482936:C:A	W552C	0.998
19:1482936:C:G	W552C	0.998
19:1482938:A:G	W552R	0.998
19:1482938:A:T	W552R	0.998
19:1483319:G:C	S512R	0.998
19:1483319:G:T	S512R	0.998
19:1483321:T:G	S512R	0.998
19:1487222:G:C	S258R	0.998
19:1487222:G:T	S258R	0.998
19:1487224:T:G	S258R	0.998
19:1483338:A:G	L506P	0.997
19:1483348:G:T	R503S	0.997
19:1486907:G:C	C338W	0.997
19:1486908:C:T	C338Y	0.997
19:1486909:A:G	C338R	0.997
19:1486997:G:C	C308W	0.997
19:1487219:C:A	W259C	0.997
19:1487219:C:G	W259C	0.997
19:1487228:G:C	S256R	0.997
19:1487228:G:T	S256R	0.997
19:1487230:T:G	S256R	0.997
19:1487262:A:G	L245P	0.997
19:1482960:C:A	W544C	0.996
19:1482960:C:G	W544C	0.996
19:1483763:G:C	S426R	0.996
19:1483763:G:T	S426R	0.996
19:1483765:T:G	S426R	0.996
19:1486998:C:T	C308Y	0.996
19:1487847:G:C	S177R	0.996
19:1487847:G:T	S177R	0.996

dbSNP variants (sampled 300 via entrez): RS1000365572 (19:1486026 G>A), RS1000498097 (19:1488582 ATT>A,ATTT), RS1000527412 (19:1486526 G>A), RS1000564210 (19:1489588 T>C), RS1000646947 (19:1484807 C>A,T), RS1000811607 (19:1486294 T>C), RS1000962379 (19:1492752 C>T), RS1000987404 (19:1481860 C>T), RS1001348060 (19:1491841 C>T), RS1001558808 (19:1490522 G>A), RS1001852475 (19:1483821 G>A,C), RS1001874630 (19:1482236 G>A,C), RS1002538418 (19:1484290 C>A,G), RS1002648083 (19:1482840 C>G,T), RS1002821734 (19:1484038 C>T)

Disease associations

OMIM: gene MIM:600487 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4861 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S8: Subtilisin

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

Ligand	Action	Affinity	Parameter
furin inhibitor peptide	Inhibition	6.36	pKi

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.36	Ki	441	nM	CHEMBL502642
6.29	Ki	515	nM	CHEMBL455792
6.25	Ki	562	nM	CHEMBL525748
6.21	Ki	624	nM	CHEMBL499438
6.11	Ki	772	nM	CHEMBL500184
6.02	Ki	952	nM	CHEMBL503520

PubChem BioAssay actives

6 with measured affinity, of 6 total; 6 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
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carboxamide	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.4410	uM
(2S,3R)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoic acid	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.5150	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carboxamide	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.5620	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.6240	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoic acid	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.7720	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	360136: Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.9520	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
afuresertib	increases expression	1
kojic acid	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Diazinon	increases methylation	1
Estradiol	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008223	Binding	Inhibition of human recombinant PC4 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. — J Biol Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8S3	Ubigene HCT 116 PCSK4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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