PCSK6

Summary

PCSK6 (proprotein convertase subtilisin/kexin type 6, HGNC:8569) is a protein-coding gene on chromosome 15q26.3, encoding Proprotein convertase subtilisin/kexin type 6 (P29122). Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif.

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 the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 5046 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (No Known Disease Relationship, ClinGen)
• GWAS associations: 19
• Clinical variants (ClinVar): 41 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8569
Approved symbol	PCSK6
Name	proprotein convertase subtilisin/kexin type 6
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	SPC4
Ensembl gene	ENSG00000140479
Ensembl biotype	protein_coding
OMIM	167405
Entrez	5046

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 16 protein_coding, 6 protein_coding_CDS_not_defined, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000331826, ENST00000398185, ENST00000557794, ENST00000558154, ENST00000558433, ENST00000558864, ENST00000558951, ENST00000559417, ENST00000559430, ENST00000559499, ENST00000559605, ENST00000560785, ENST00000560902, ENST00000611716, ENST00000611967, ENST00000615296, ENST00000618548, ENST00000619160, ENST00000622483, ENST00000632686, ENST00000676494, ENST00000676598, ENST00000677364, ENST00000677528, ENST00000677962, ENST00000677996, ENST00000678381, ENST00000678918, ENST00000679007

RefSeq mRNA: 7 — MANE Select: NM_002570 NM_001291309, NM_002570, NM_138319, NM_138322, NM_138323, NM_138324, NM_138325

CCDS: CCDS73789, CCDS73790, CCDS73791, CCDS73792, CCDS73793

Canonical transcript exons

ENST00000611716 — 22 exons

Exon	Start	End
ENSE00003475463	101307213	101307325
ENSE00003490765	101318319	101318422
ENSE00003495471	101324850	101325046
ENSE00003510630	101322520	101322607
ENSE00003527136	101431990	101432100
ENSE00003529392	101398404	101398576
ENSE00003543108	101331852	101332031
ENSE00003569124	101431320	101431463
ENSE00003572649	101326377	101326479
ENSE00003574443	101443556	101443660
ENSE00003580864	101389464	101389564
ENSE00003591853	101429987	101430063
ENSE00003598814	101382092	101382209
ENSE00003611389	101366196	101366332
ENSE00003638070	101370335	101370523
ENSE00003663998	101393212	101393424
ENSE00003664147	101331651	101331689
ENSE00003683572	101427892	101427980
ENSE00003688728	101313376	101313505
ENSE00003737067	101489374	101489707
ENSE00003742027	101303933	101305355
ENSE00003786201	101384322	101384425

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1392 / max 884.4632, expressed in 1124 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151831	19.0645	1122
151822	0.0609	35
151830	0.0138	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.84	gold quality
liver	UBERON:0002107	97.40	gold quality
spinal cord	UBERON:0002240	97.34	gold quality
right lobe of liver	UBERON:0001114	97.31	gold quality
middle frontal gyrus	UBERON:0002702	97.04	gold quality
corpus callosum	UBERON:0002336	96.46	gold quality
spleen	UBERON:0002106	95.99	gold quality
inferior vagus X ganglion	UBERON:0005363	95.54	gold quality
inferior olivary complex	UBERON:0002127	95.28	gold quality
synovial joint	UBERON:0002217	94.48	gold quality
subthalamic nucleus	UBERON:0001906	93.87	gold quality
adrenal tissue	UBERON:0018303	93.58	gold quality
pons	UBERON:0000988	93.10	gold quality
medial globus pallidus	UBERON:0002477	92.94	gold quality
globus pallidus	UBERON:0001875	92.74	gold quality
substantia nigra	UBERON:0002038	92.11	gold quality
midbrain	UBERON:0001891	91.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.49	gold quality
apex of heart	UBERON:0002098	91.31	gold quality
medulla oblongata	UBERON:0001896	91.13	gold quality
endometrium epithelium	UBERON:0004811	89.90	gold quality
lateral globus pallidus	UBERON:0002476	89.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.35	gold quality
superior vestibular nucleus	UBERON:0007227	88.20	gold quality
monocyte	CL:0000576	87.37	gold quality
heart right ventricle	UBERON:0002080	87.37	gold quality
substantia nigra pars compacta	UBERON:0001965	87.27	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.85	gold quality
rectum	UBERON:0001052	86.79	gold quality
mononuclear cell	CL:0000842	86.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	53.67
E-GEOD-137537	yes	5.70
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, ASCL2, ATOH1, CTNNB1, E2F1, E2F2, E2F3, ETS1, NEUROD6, NEUROG1, NEUROG2, NEUROG3, TCF3

miRNA regulators (miRDB)

73 targeting PCSK6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-17-3P	99.55	66.77	1311

Literature-anchored findings (GeneRIF, showing 36)

• a unique SPC family protease that anchors heparan sulfate proteoglycans at the extracellular matrix; distribution in human placenta (PMID:12535616)
• reduction of PACE4 expression in ovarian cancer cells is caused, in part, by DNA hypermethylation and histone deacetylation (PMID:12805404)
• These results suggest that PACE4 expression is down-regulated by Hash-2/Mash-2 in both human and rat placenta and that many bioactive proteins might be regulated by PACE4 activity. (PMID:14561729)
• RB1CC1 and PACE4 genes might be the DNA targets of sodium arsenite treatment in human lymphoblastoid cells. (PMID:17707572)
• upregulation of the expression of PACE4 by E2F (PMID:17825503)
• Overexpression in a stable manner of the prosegment ppPACE4 in MDA-MB-231 breast cancer cells resulted in increased matrix metalloproteinase (MMP)-9 (but not MMP-2) activity and a reduced secretion of tissue inhibitor of metalloproteinase 1 (TIMP-1). (PMID:17909005)
• PACE4 is a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage; posttranslational activation of ADAMTS-4 and ADAMTS-5 in the extracellular milieu of cartilage results in aggrecan degradation (PMID:18671934)
• Data show that Cripto binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface. (PMID:18772886)
• PC1 and PC2 were primarily expressed in neurons, whereas PACE4 appeared to be largely restricted to glia. Thus, elevated PACE4 may modulate the bioactivity of proteins secreted in the ONH and retina. (PMID:19339735)
• In a genome-wide association study of handedness in patients with dyslexia, PCSK6 was the most highly associated marker. (PMID:21051773)
• PCSK6 as a novel glioma invasion-associated candidate gene that likely contribute to the invasive phenotype of malignant gliomas. (PMID:21722156)
• A variant in PCSK6 is strongly associated with protection against pain in knee osteoarthritis. (PMID:22440827)
• PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer. (PMID:23226097)
• Results provide evidence for the role of PCSK6 as candidate for involvement in the biological mechanisms that underlie the establishment of normal brain lateralization and thus handedness and support the assumption that the degree of handedness, instead the direction, may be the more appropriate indicator of cerebral organization. (PMID:23826248)
• PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. (PMID:23908247)
• PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFbeta2. (PMID:24860148)
• miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway. (PMID:24913567)
• PCSK6 is upregulated in the synovial tissues of patients with rheumatoid arthritis and has a genetic effect on the risk of rheumatoid arthritis. Inhibition of PCSK6 may play a protective role in the development of rheumatoid arthritis. (PMID:25433529)
• PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells. (PMID:26114115)
• identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient (PMID:26259032)
• PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways (PMID:26604689)
• In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in second heart field for atrial septation, providing a molecular framework for understanding the role of Tbx5 in congenital heart disease ontogeny. (PMID:26744331)
• Variants in non-coding sequences of PCSK6 gene is associated with handedness. (PMID:26908617)
• These results implicate PCSK6 in mediation of brain developmental pathways that jointly impact upon handedness, autism and aspects of schizotypy (PMID:26921480)
• Our results suggest that PACE4 is a promising target for estrogen-receptor-positive breast cancer. (PMID:28347547)
• PACE4 pre-mRNA undergoes DNA methylation-sensitive alternative splicing of its terminal exon 3’ untranslated region, generating an oncogenic, C-terminally modified isoform (PACE4-altCT). (PMID:28993410)
• Data suggest that soluble corin lacking transmembrane domain is activated by PCSK6 in conditioned medium or in cell-free system but not intracellularly; cell membrane association is unnecessary for PCSK6 to activate corin; soluble corin and PCSK6 are secreted by cardiomyocytes (or HEK293 cells) via different intracellular pathways. (PCSK6 = proprotein convertase subtilisin/kexin type-6) (PMID:29180304)
• PCSK6, a gene that has been implicated in the ontogenesis of bodily asymmetries by regulating the nodal cascade, is also relevant for structural asymmetries in the human brain. (PMID:31115778)
• PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling. (PMID:31893970)
• Upregulation of PACE4 in prostate cancer is not dependent on E2F transcription factors. (PMID:32119574)
• Paired Basic Amino Acid-cleaving Enzyme 4 (PCSK6): An Emerging New Target Molecule in Human Melanoma. (PMID:32449780)
• Up-regulation of PCSK6 by lipid oxidation products: A possible role in atherosclerosis. (PMID:33359561)
• Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome. (PMID:34301174)
• PACE4-altCT isoform of proprotein convertase PACE4 as tissue and plasmatic biomarker for prostate cancer. (PMID:35410344)
• PCSK6 and Survival in Idiopathic Pulmonary Fibrosis. (PMID:36780644)
• PCSK6 exacerbates Alzheimer’s disease pathogenesis by promoting MT5-MMP maturation. (PMID:38216110)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcsk6	ENSDARG00000104574
mus_musculus	Pcsk6	ENSMUSG00000030513
rattus_norvegicus	Pcsk6	ENSRNOG00000011526
drosophila_melanogaster	Fur2	FBGN0004598
caenorhabditis_elegans	kpc-1	WBGENE00002232

Paralogs (9): PCSK5 (ENSG00000099139), PCSK4 (ENSG00000115257), PCSK2 (ENSG00000125851), TPP2 (ENSG00000134900), FURIN (ENSG00000140564), MBTPS1 (ENSG00000140943), PCSK7 (ENSG00000160613), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Protein

Protein identifiers

Proprotein convertase subtilisin/kexin type 6 — P29122 (reviewed: P29122)

Alternative names: Paired basic amino acid cleaving enzyme 4, Subtilisin-like proprotein convertase 4, Subtilisin/kexin-like protease PACE4

All UniProt accessions (14): A0A087WY68, A0A087WZR0, A0A0J9YW51, A0A7I2V2Z7, A0A7I2V3M4, A0A7I2V3T2, A0A7I2YQH5, P29122, H0Y3Q0, H0YKK2, H0YKZ4, H0YLC8, H0YMW5, H7BXT3

UniProt curated annotations — full annotation on UniProt →

Function. Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues.

Subunit / interactions. The PACE4A-I precursor protein seems to exist in the reticulum endoplasmic as both a monomer and a dimer-sized complex whereas mature PACE4A-I exists only as a monomer, suggesting that propeptide cleavage affects its tertiary or quaternary structure. Interacts (immature form including the propeptide) with RCN3; probably involved in the maturation and the secretion of PCSK6.

Subcellular location. Secreted Secreted Endoplasmic reticulum Endoplasmic reticulum Endomembrane system Endomembrane system Secreted.

Tissue specificity. Each PACE4 isoform exhibits a unique restricted distribution. Isoform PACE4A-I is expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, but at comparatively higher levels in the liver. Isoform PACE4A-II is at least expressed in placenta. Isoform PACE4B was only found in the embryonic kidney cell line from which it was isolated. Isoform PACE4C and isoform PACE4D are expressed in placenta. Isoform PACE4E-I is expressed in cerebellum, placenta and pituitary. Isoform PACE4E-II is at least present in cerebellum.

Domain organisation. The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum. Isoform PACE4D lacks the propeptide domain.

Miscellaneous. Probably enzymatically inactive. Probably enzymatically inactive. Probably enzymatically inactive. Probably enzymatically inactive.

Similarity. Belongs to the peptidase S8 family.

Isoforms (8)

UniProt ID	Names	Canonical?
P29122-1	PACE4A-I, PACE4	yes
P29122-2	PACE4A-II
P29122-3	PACE4B, PACE4.1
P29122-4	PACE4C
P29122-5	PACE4CS
P29122-6	PACE4D
P29122-7	PACE4E-I
P29122-8	PACE4E-II

RefSeq proteins (7): NP_001278238, NP_002561, NP_612192, NP_612195, NP_612196, NP_612197, NP_612198 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000209	Peptidase_S8/S53_dom	Domain
IPR000742	EGF	Domain
IPR002884	P_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR010909	PLAC	Domain
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
IPR032778	GF_recep_IV	Domain
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, PF08686, PF14843, PF16470

Enzyme classification (BRENDA):

• EC 3.4.21.61 — Kexin (BRENDA: 9 organisms, 84 substrates, 175 inhibitors, 9 Km, 8 kcat entries)
• EC 3.4.21.B25 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AC-AYKK 4-METHYLCOUMARIN 7-AMIDE	0.35	1
AC-NLE-TYR-LYS-ARG 4-METHYLCOUMARIN 7-AMIDE	0.001	1
AC-NLE-YKK 4-METHYLCOUMARIN 7-AMIDE	0.038	1
AC-NLE-YKR 4-METHYLCOUMARIN 7-AMIDE	0.001	1
BENZYLOXYCARBONYL-ALA-TYR-LYS-LYS 4-METHYLCOUMAR	0.023	1
D-AC-NLE-TYR-LYS-ARG 4-METHYLCOUMARIN 7-AMIDE	0.001	1
T-BUTYLOXYCARBONYL-QGR 4-METHYLCOUMARIN 7-AMIDE	0.32	1
T-BUTYLOXYCARBONYL-EKK 4-METHYLCOUMARIN 7-AMIDE	—	0

UniProt features (37 total): splice variant 11, repeat 5, domain 3, region of interest 3, active site 3, glycosylation site 3, compositionally biased region 2, signal peptide 1, propeptide 1, short sequence motif 1, chain 1, site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29122-F1	81.84	0.50

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): 205 (charge relay system); 246 (charge relay system); 420 (charge relay system); 149–150 (cleavage; by autolysis)

Glycosylation sites (3): 259, 914, 932

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-167060	NGF processing
R-HSA-6809371	Formation of the cornified envelope
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 226 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_AXIS_SPECIFICATION, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, ATGTTAA_MIR302C, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_SPECIFICATION_OF_SYMMETRY, MARTINEZ_RB1_TARGETS_UP, GOBP_PROTEIN_MATURATION

GO Biological Process (10): zygotic determination of anterior/posterior axis, embryo (GO:0007354), determination of left/right symmetry (GO:0007368), glycoprotein metabolic process (GO:0009100), protein processing (GO:0016485), peptide hormone processing (GO:0016486), regulation of BMP signaling pathway (GO:0030510), nerve growth factor production (GO:0032902), secretion by cell (GO:0032940), plasma lipoprotein particle remodeling (GO:0034369), proteolysis (GO:0006508)

GO Molecular Function (8): endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), heparin binding (GO:0008201), nerve growth factor binding (GO:0048406), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), extracellular matrix (GO:0031012), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Developmental Biology	1
Expression and Processing of Neurotrophins	1
Keratinization	1
Plasma lipoprotein remodeling	1
Regulation of CDH1 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein metabolic process	2
peptidase activity	2
anterior/posterior axis specification, embryo	1
determination of bilateral symmetry	1
left/right pattern formation	1
carbohydrate derivative metabolic process	1
proteolysis	1
protein maturation	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
BMP signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to growth factor stimulus	1
neurotrophin production	1
secretion	1
export from cell	1
protein-lipid complex remodeling	1
plasma lipoprotein particle organization	1
regulation of plasma lipoprotein particle levels	1
endopeptidase activity	1
serine-type peptidase activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
neurotrophin binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCSK6	MBTPS1	Q14703	835
PCSK6	ESRRB	O95718	683
PCSK6	CORIN	Q9Y5Q5	615
PCSK6	PCSK9	Q8NBP7	599
PCSK6	CFD	P00746	572
PCSK6	ALPP	P05187	550
PCSK6	AMH	P03971	507
PCSK6	LRRTM1	Q86UE6	500
PCSK6	HYOU1	Q9Y4L1	500
PCSK6	LEFTY1	O75610	491
PCSK6	EOMES	O95936	482
PCSK6	PTH1R	Q03431	479
PCSK6	PDIA4	P13667	479
PCSK6	HSPA5	P11021	476
PCSK6	DNAJB1	P25685	462
PCSK6	CDX2	Q99626	462

IntAct

58 interactions, top by confidence:

A	B	Type	Score
PCSK5	PCSK6	psi-mi:“MI:0915”(physical association)	0.560
PCSK6	ZNF441	psi-mi:“MI:0915”(physical association)	0.560
PCSK6	PCSK5	psi-mi:“MI:0915”(physical association)	0.560
	PLOD2	psi-mi:“MI:0914”(association)	0.530
PCSK6	VDAC1	psi-mi:“MI:0915”(physical association)	0.400
PCSK6	CACNA1A	psi-mi:“MI:0915”(physical association)	0.370
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
TMEM87A	POTEF	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	RTCA	psi-mi:“MI:0914”(association)	0.350
IDS	RTCA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
C1QB	MANBA	psi-mi:“MI:0914”(association)	0.350
KLK2	MANBA	psi-mi:“MI:0914”(association)	0.350
TRGV3	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350
EPHA7	PLOD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-RNA), PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Two-hybrid), ZNF441 (Two-hybrid), PCSK6 (Proximity Label-MS), PCSK6 (Proximity Label-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Proximity Label-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS)

ESM2 similar proteins: A0A044RE18, B4F6N6, B5DF27, E1C3U7, F1QQC3, G5ECN9, O17798, O35548, O64481, P09231, P09958, P13134, P16519, P21661, P23188, P23377, P28840, P28841, P29119, P29120, P29122, P29145, P29146, P30432, P41413, P51512, P51559, P58022, P63239, P63240, P91863, Q03333, Q04592, Q08B63, Q09175, Q28193, Q5REC2, Q63415, Q8QGP3, Q8SQJ3

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

2 interactions.

A	Effect	B	Mechanism
PCSK6	“up-regulates activity”	INSR	cleavage
PCSK6	“up-regulates activity”	VWF	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	2
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
253543	GRCh37/hg19 15q26.2-26.3(chr15:98458265-102354857)x1	Pathogenic
980643	GRCh37/hg19 15q26.2-26.3(chr15:98275761-102358202)x1	Pathogenic

SpliceAI

6770 predictions. Top by Δscore:

Variant	Effect	Δscore
15:101293021:GT:G	donor_loss	1.0000
15:101293022:TA:T	donor_loss	1.0000
15:101293023:A:AC	donor_gain	1.0000
15:101293024:C:CA	donor_loss	1.0000
15:101293024:C:CC	donor_gain	1.0000
15:101293169:TACC:T	acceptor_gain	1.0000
15:101293170:ACCC:A	acceptor_loss	1.0000
15:101293171:CC:C	acceptor_gain	1.0000
15:101293171:CCCTA:C	acceptor_gain	1.0000
15:101293172:CC:C	acceptor_gain	1.0000
15:101293173:C:CC	acceptor_gain	1.0000
15:101293173:CTAT:C	acceptor_loss	1.0000
15:101293174:T:A	acceptor_loss	1.0000
15:101293180:A:AC	acceptor_gain	1.0000
15:101293180:A:C	acceptor_gain	1.0000
15:101295092:CTCA:C	donor_loss	1.0000
15:101295093:TCACC:T	donor_loss	1.0000
15:101295094:CACC:C	donor_loss	1.0000
15:101295095:A:AC	donor_gain	1.0000
15:101295095:AC:A	donor_gain	1.0000
15:101295095:ACC:A	donor_gain	1.0000
15:101295095:ACCCC:A	donor_loss	1.0000
15:101295096:C:CC	donor_gain	1.0000
15:101295096:C:CT	donor_loss	1.0000
15:101295096:CC:C	donor_gain	1.0000
15:101295096:CCC:C	donor_gain	1.0000
15:101305365:C:CT	acceptor_gain	1.0000
15:101305365:C:T	acceptor_gain	1.0000
15:101305370:C:CT	acceptor_gain	1.0000
15:101305371:A:T	acceptor_gain	1.0000

AlphaMissense

6347 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:101389539:C:G	C412S	1.000
15:101389540:A:G	C412R	1.000
15:101389540:A:T	C412S	1.000
15:101398482:C:A	W306C	1.000
15:101398482:C:G	W306C	1.000
15:101398484:A:G	W306R	1.000
15:101398484:A:T	W306R	1.000
15:101398570:C:G	R277P	1.000
15:101427926:G:C	C263W	1.000
15:101427965:A:C	C250W	1.000
15:101431360:T:A	D206V	1.000
15:101431360:T:G	D206A	1.000
15:101431363:T:A	D205V	1.000
15:101305285:G:C	C961W	0.999
15:101305286:C:T	C961Y	0.999
15:101305287:A:G	C961R	0.999
15:101305313:C:G	C952S	0.999
15:101305314:A:T	C952S	0.999
15:101305340:C:G	C943S	0.999
15:101305340:C:T	C943Y	0.999
15:101305341:A:T	C943S	0.999
15:101366250:A:G	W602R	0.999
15:101366250:A:T	W602R	0.999
15:101370389:A:G	L556P	0.999
15:101389538:A:C	C412W	0.999
15:101389539:C:T	C412Y	0.999
15:101398481:C:G	G307R	0.999
15:101398481:C:T	G307R	0.999
15:101398485:G:C	S305R	0.999
15:101398485:G:T	S305R	0.999

dbSNP variants (sampled 300 via entrez): RS1000016290 (15:101474065 T>C,G), RS1000020129 (15:101407914 T>C), RS1000072109 (15:101441894 C>T), RS1000094276 (15:101370944 T>A), RS1000129995 (15:101401873 C>T), RS1000137226 (15:101443018 T>C), RS1000155512 (15:101356959 G>A), RS1000159116 (15:101456616 T>C), RS1000172325 (15:101316682 C>A,G,T), RS1000186302 (15:101371609 A>G), RS1000237264 (15:101357155 C>A), RS1000237691 (15:101422887 C>G), RS1000285540 (15:101322069 G>A), RS1000293032 (15:101431839 C>T), RS1000294535 (15:101317216 G>A,C)

Disease associations

OMIM: gene MIM:167405 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	No Known Disease Relationship	UD

Mondo (1): congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000868_1	Handedness in dyslexia	2.000000e-08
GCST002183_3	Relative hand skill in reading disability	9.000000e-09
GCST004432_26	Platelet-derived growth factor BB levels	6.000000e-24
GCST006613_117	Triglycerides	3.000000e-08
GCST007221_2	Type 2 diabetes	2.000000e-08
GCST007231_6	Tuberculosis	2.000000e-06
GCST008839_357	Height	6.000000e-12
GCST009243_5	Cytokine levels	1.000000e-26
GCST009243_9	Cytokine levels	7.000000e-07
GCST009244_12	Cytokine network levels (multivariate analysis)	2.000000e-58
GCST009244_3	Cytokine network levels (multivariate analysis)	4.000000e-17
GCST010241_419	Apolipoprotein A1 levels	1.000000e-12
GCST010243_73	Apolipoprotein B levels	5.000000e-08
GCST010244_332	Triglyceride levels	4.000000e-14
GCST010244_366	Triglyceride levels	5.000000e-11
GCST011564_1	Severe coronary stenosis (young age of onset interaction)	7.000000e-10
GCST90000584_14	Inflammatory biomarkers (multivariate analysis)	1.000000e-54
GCST90000584_15	Inflammatory biomarkers (multivariate analysis)	3.000000e-69
GCST90002403_651	Red blood cell count	8.000000e-10

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness
EFO:0004530	triglyceride measurement
EFO:0004750	interleukin 10 measurement
EFO:0004753	interleukin 12 measurement
EFO:0004810	interleukin-6 measurement
EFO:0008165	interferon gamma measurement
EFO:0008174	interleukin 17 measurement
EFO:0008184	interleukin 4 measurement
EFO:0008293	stromal cell-derived factor 1 alpha measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004847	age at onset
EFO:0004872	inflammatory biomarker measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2951 (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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide	Inhibition	9.22	pKi
peptide 18 [PMID: 24350995]	Inhibition	8.51	pKi
multi-Leu (ML)-peptide	Inhibition	7.74	pKi
furin inhibitor peptide	Inhibition	6.79	pKi

ChEMBL bioactivities

156 potent at pChembl≥5 of 158 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Ki	0.2	nM	CHEMBL4089819
9.52	Ki	0.3	nM	CHEMBL4065072
9.47	Ki	0.34	nM	CHEMBL2179430
9.40	Ki	0.4	nM	CHEMBL2179835
9.40	Ki	0.4	nM	CHEMBL4084457
9.40	Ki	0.4	nM	CHEMBL4091099
9.30	Ki	0.5	nM	CHEMBL4100996
9.22	Ki	0.6	nM	CHEMBL4104777
9.22	Ki	0.6	nM	CHEMBL566340
9.05	Ki	0.9	nM	CHEMBL4070237
9.00	Ki	1	nM	CHEMBL4083310
9.00	Ki	1	nM	CHEMBL4064275
8.96	Ki	1.1	nM	CHEMBL2179836
8.89	Ki	1.3	nM	CHEMBL2179429
8.89	Ki	1.3	nM	CHEMBL4073661
8.82	Ki	1.5	nM	CHEMBL4094478
8.77	Ki	1.7	nM	CHEMBL4099961
8.74	Ki	1.8	nM	CHEMBL4097940
8.70	Ki	2	nM	CHEMBL2179431
8.70	Ki	2	nM	CHEMBL4063327
8.70	Ki	2	nM	CHEMBL4096348
8.70	Ki	2	nM	CHEMBL4101342
8.70	Ki	2	nM	CHEMBL4087970
8.70	Ki	2	nM	CHEMBL4103443
8.70	Ki	2	nM	CHEMBL4085824
8.70	Ki	2	nM	CHEMBL4093570
8.68	Ki	2.1	nM	CHEMBL4075692
8.66	Ki	2.2	nM	CHEMBL4072949
8.62	Ki	2.4	nM	CHEMBL569918
8.60	Ki	2.5	nM	CHEMBL4065627
8.59	Ki	2.6	nM	CHEMBL4286124
8.55	Ki	2.8	nM	CHEMBL4059801
8.55	Ki	2.8	nM	CHEMBL4084913
8.52	Ki	3	nM	CHEMBL4093266
8.52	Ki	3	nM	CHEMBL4063219
8.52	Ki	3	nM	CHEMBL4067772
8.52	Ki	3	nM	CHEMBL4089913
8.52	Ki	3	nM	CHEMBL4080551
8.52	Ki	3	nM	CHEMBL568525
8.51	Ki	3.1	nM	CHEMBL3115771
8.44	Ki	3.6	nM	CHEMBL3126388
8.43	Ki	3.7	nM	CHEMBL4076965
8.40	Ki	4	nM	CHEMBL4063459
8.40	Ki	4	nM	CHEMBL4077533
8.40	Ki	4	nM	CHEMBL4092088
8.40	Ki	4	nM	CHEMBL4060537
8.40	Ki	4	nM	CHEMBL4101304
8.40	Ki	4	nM	CHEMBL4066994
8.40	Ki	4	nM	CHEMBL4097058
8.39	Ki	4.1	nM	CHEMBL4091172

PubChem BioAssay actives

156 with measured affinity, of 163 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0002	uM
(2S)-2-acetamido-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0003	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	709448: Competitive inhibition of human recombinant PACE4 expressed in Drosophila S2 cells using pyroGlu-Arg-Val-Lys-Arg-methyl-coumaryl-7-amide as substrate at pH 6.5 after 60 mins by spectrofluorometric analysis	ki	0.0003	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-aminopropanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	709448: Competitive inhibition of human recombinant PACE4 expressed in Drosophila S2 cells using pyroGlu-Arg-Val-Lys-Arg-methyl-coumaryl-7-amide as substrate at pH 6.5 after 60 mins by spectrofluorometric analysis	ki	0.0004	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0004	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0004	uM
(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0005	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0006	uM
(2S)-N-[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-5-(diaminomethylideneamino)-2-[(2-phenylacetyl)amino]pentanamide	446386: Inhibition of human PACE4 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.0006	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0009	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0010	uM
(2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0010	uM
(4S)-4-amino-5-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid	709448: Competitive inhibition of human recombinant PACE4 expressed in Drosophila S2 cells using pyroGlu-Arg-Val-Lys-Arg-methyl-coumaryl-7-amide as substrate at pH 6.5 after 60 mins by spectrofluorometric analysis	ki	0.0011	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0013	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	709448: Competitive inhibition of human recombinant PACE4 expressed in Drosophila S2 cells using pyroGlu-Arg-Val-Lys-Arg-methyl-coumaryl-7-amide as substrate at pH 6.5 after 60 mins by spectrofluorometric analysis	ki	0.0013	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0015	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]butanediamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0017	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0018	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0020	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	709448: Competitive inhibition of human recombinant PACE4 expressed in Drosophila S2 cells using pyroGlu-Arg-Val-Lys-Arg-methyl-coumaryl-7-amide as substrate at pH 6.5 after 60 mins by spectrofluorometric analysis	ki	0.0020	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0021	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-6-amino-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0022	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-5-(diaminomethylideneamino)pentanamide	446386: Inhibition of human PACE4 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.0024	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0025	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(6-carbamimidoyl-3-pyridinyl)methyl]hexanamide	1415228: Inhibition of recombinant human PACE4 using pGlu-Arg-Thr-Lys-Arg-AMC peptide as substrate by spectrofluorometry	ki	0.0026	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0028	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0028	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-acetamidoacetyl)amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0030	uM
(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0030	uM
(2S)-1-acetyl-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0030	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0030	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0030	uM
N-[(2S)-1-[[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]decanamide	446386: Inhibition of human PACE4 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.0030	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1067777: Inhibition of human recombinant PACE4 expressed in drosophila schneider 2 cells using pyroGlu-Arg-Thr-Lys-Arg-AMC as substrate after 1 hr	ki	0.0031	uM
137630787	1628274: Inhibition of recombinant C-terminal truncated human SPC4 expressed in drosophila Schneider 2 cells after 1 hr by spectrofluorometry	ki	0.0036	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0037	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-1-[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]butanediamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0040	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[(4-carbamimidoylphenyl)methylamino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide	1481481: Inhibition of recombinant human PACE4 expressed in drosophila S2 cells using pyrGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin as substrate after 60 mins by spectrofluorometry method	ki	0.0041	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	5
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
Particulate Matter	increases abundance, increases expression, decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression, affects methylation	3
Progesterone	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Smoke	decreases expression, decreases reaction, increases expression	2
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
glycidamide	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	decreases expression, decreases reaction	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1049701	Binding	Inhibition of human PACE4 expressed in Drosophila schneider 2 cells by fluorescence assay	Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC55	HAP1 PCSK6 (-) 1	Cancer cell line	Male
CVCL_TC56	HAP1 PCSK6 (-) 2	Cancer cell line	Male
CVCL_TC57	HAP1 PCSK6 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE