1. 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
2. Our results suggest that PACE4 is a promising target for estrogen-receptor-positive breast cancer. PMID: 28347547
3. 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
4. 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
5. Variants in non-coding sequences of PCSK6 gene is associated with handedness. PMID: 26908617
6. These results implicate PCSK6 in mediation of brain developmental pathways that jointly impact upon handedness, autism and aspects of schizotypy PMID: 26921480
7. 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
8. PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways PMID: 26604689
9. 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
10. identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient PMID: 26259032
11. 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
12. PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFbeta2. PMID: 24860148
13. miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway. PMID: 24913567
14. 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
15. PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer. PMID: 23226097
16. A variant in PCSK6 is strongly associated with protection against pain in knee osteoarthritis. PMID: 22440827
17. PCSK6 as a novel glioma invasion-associated candidate gene that likely contribute to the invasive phenotype of malignant gliomas. PMID: 21722156
18. In a genome-wide association study of handedness in patients with dyslexia, PCSK6 was the most highly associated marker. PMID: 21051773
19. a unique SPC family protease that anchors heparan sulfate proteoglycans at the extracellular matrix; distribution in human placenta PMID: 12535616
20. reduction of PACE4 expression in ovarian cancer cells is caused, in part, by DNA hypermethylation and histone deacetylation PMID: 12805404
21. 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
22. RB1CC1 and PACE4 genes might be the DNA targets of sodium arsenite treatment in human lymphoblastoid cells. PMID: 17707572
23. upregulation of the expression of PACE4 by E2F PMID: 17825503
24. 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
25. 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
26. Data show that Cripto binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface. PMID: 18772886
27. 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

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[Isoform PACE4A-I]: Secreted.; [Isoform PACE4A-II]: Secreted.; [Isoform PACE4C]: Endoplasmic reticulum. Note=Not secreted, remains probably in zymogen form in endoplasmic reticulum.; [Isoform PACE4CS]: Endoplasmic reticulum. Note=Not secreted, remains probably in zymogen form in endoplasmic reticulum.; [Isoform PACE4E-I]: Endomembrane system; Peripheral membrane protein. Note=Retained intracellularly probably through a hydrophobic cluster in their C-terminus.; [Isoform PACE4E-II]: Endomembrane system; Peripheral membrane protein. Note=Retained intracellularly probably through a hydrophobic cluster in their C-terminus.; [Isoform PACE4B]: Secreted.

Peptidase S8 family

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 pla

HGNC: 8569

OMIM: 167405

KEGG: hsa:5046

STRING: 9606.ENSP00000305056

UniGene: Hs.498494