Property Summary

NCBI Gene PubMed Count 54
PubMed Score 212.08
PubTator Score 90.78

Knowledge Summary


No data available


  Differential Expression (21)

Disease log2 FC p
gastric cancer 1.100 2.0e-03
pancreatic cancer 1.400 4.8e-04
malignant mesothelioma 3.900 7.1e-09
psoriasis 1.200 7.1e-10
osteosarcoma -1.245 4.6e-03
group 4 medulloblastoma -1.800 1.8e-03
adrenocortical carcinoma 1.685 3.5e-02
pancreatic ductal adenocarcinoma liver m... -2.971 8.1e-04
intraductal papillary-mucinous neoplasm ... 1.900 7.3e-03
colon cancer -2.000 3.0e-02
lung cancer -2.300 1.6e-03
fibroadenoma 1.300 2.3e-04
posterior fossa group A ependymoma -1.100 6.7e-05
pancreatic carcinoma 1.400 4.8e-04
subependymal giant cell astrocytoma -2.087 5.0e-02
mucosa-associated lymphoid tissue lympho... 1.002 2.3e-02
ulcerative colitis -1.200 2.1e-03
ovarian cancer 1.100 4.2e-05
pituitary cancer -2.200 5.5e-06
Down syndrome 1.100 9.0e-03
facioscapulohumeral dystrophy -1.700 2.4e-02

Protein-protein Interaction (1)

Gene RIF (33)

26604689 PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways
26283733 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
26259032 identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient
26114115 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.
25433529 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.
24913567 miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway.
24860148 PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFbeta2.
23908247 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.
23226097 PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer.
22440827 A variant in PCSK6 is strongly associated with protection against pain in knee osteoarthritis.
21722156 PCSK6 as a novel glioma invasion-associated candidate gene that likely contribute to the invasive phenotype of malignant gliomas.
21051773 In a genome-wide association study of handedness in patients with dyslexia, PCSK6 was the most highly associated marker.
21051773 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19339735 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.
18976975 Knockdown of proprotein convertase subtilisin/kexin type 6 (PCSK6) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells
18772886 Data show that Cripto binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface.
18671934 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
18061232 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
17909005 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).
17825503 upregulation of the expression of PACE4 by E2F
17707572 RB1CC1 and PACE4 genes might be the DNA targets of sodium arsenite treatment in human lymphoblastoid cells.
15043778 Observational study of gene-disease association. (HuGE Navigator)
14561729 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.
12805404 reduction of PACE4 expression in ovarian cancer cells is caused, in part, by DNA hypermethylation and histone deacetylation
12535616 a unique SPC family protease that anchors heparan sulfate proteoglycans at the extracellular matrix; distribution in human placenta
11063880 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
9521771 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
8995442 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
8940009 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1
8670066 Vpr processing by soluble PCSK6 (PACE4) DOES NOT involve PAR1

AA Sequence


Text Mined References (54)

PMID Year Title
26908617 2016 The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts.
26604689 2015 PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways.
26259032 2015 PCSK6-mediated corin activation is essential for normal blood pressure.
26114115 2015 Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity.
25433529 2015 Inhibition of PCSK6 may play a protective role in the development of rheumatoid arthritis.
24913567 2014 miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway.
24860148 2014 PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGF?2.
24068947 2013 Common variants in left/right asymmetry genes and pathways are associated with relative hand skill.
23908247 2013 Profiling of atherosclerotic lesions by gene and tissue microarrays reveals PCSK6 as a novel protease in unstable carotid atherosclerosis.
23775089 2013 The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.
23226097 2012 Role of proprotein convertases in prostate cancer progression.
22679642 2012 The biology and therapeutic targeting of the proprotein convertases.
22440827 2012 A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype.
21805237 2011 The proprotein convertases, 20 years later.
21805236 2011 The prohormone theory and the proprotein convertases: it is all about serendipity.
21722156 2012 Identification and functional validation of CDH11, PCSK6 and SH3GL3 as novel glioma invasion-associated candidate genes.
21051773 2011 PCSK6 is associated with handedness in individuals with dyslexia.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19339735 2009 Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head.
18772886 2008 Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation.
18671934 2008 Proprotein convertase activation of aggrecanases in cartilage in situ.
18343183 2008 The activation and physiological functions of the proprotein convertases.
17909005 2007 Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1.
17825503 2007 Transcriptional regulation of subtilisin-like proprotein convertase PACE4 by E2F: possible role of E2F-mediated upregulation of PACE4 in tumor progression.
17707572 2007 Use of RAPD to detect sodium arsenite-induced DNA damage in human lymphoblastoid cells.
16433634 2006 A proteomic approach reveals transient association of reticulocalbin-3, a novel member of the CREC family, with the precursor of subtilisin-like proprotein convertase, PACE4.
15043778 2004 The association between paired basic amino acid cleaving enzyme 4 gene haplotype and diastolic blood pressure.
14561729 2003 The expression of proprotein convertase PACE4 is highly regulated by Hash-2 in placenta: possible role of placenta-specific basic helix-loop-helix transcription factor, human achaete-scute homologue-2.
12805404 2003 Epigenetic regulation of proprotein convertase PACE4 gene expression in human ovarian cancer cells.
12787574 2003 Neurotrophin secretion: current facts and future prospects.
12535616 2003 Secretory proprotein convertases PACE4 and PC6A are heparin-binding proteins which are localized in the extracellular matrix. Potential role of PACE4 in the activation of proproteins in the extracellular matrix.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12463163 2002 Precursor convertases in the secretory pathway, cytosol and extracellular milieu.
11736660 2001 Proprotein convertase PACE4 is down-regulated by the basic helix-loop-helix transcription factor hASH-1 and MASH-1.
11380615 2001 Proprotein convertase expression and localization in epidermis: evidence for multiple roles and substrates.
10900462 2000 The proprotein convertases furin and PACE4 play a significant role in tumor progression.
10467177 1999 Inactivation of proprotein convertase, PACE4, by alpha1-antitrypsin Portland (alpha1-PDX), a blocker of proteolytic activation of bone morphogenetic protein during embryogenesis: evidence that PACE4 is able to form an SDS-stable acyl intermediate with alpha1-PDX.
10467164 1999 Human subtilisin-like proprotein convertase, PACE4 (SPC4) gene expression is highly regulated through E-box elements in HepG2 and GH4C1 cells.
10409610 1999 Proteolytic processing in the secretory pathway.
10215603 1999 Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain.
10050053 1999 Subtilisin-like proprotein convertases, PACE4 and PC8, as well as furin, are endogenous proalbumin convertases in HepG2 cells.
10037747 1999 Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals.
9738469 1998 Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4).
9378725 1997 Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease.
9242664 1997 Processing of prothyrotropin-releasing hormone by the family of prohormone convertases.
9192737 1997 A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus.
8906861 1996 Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoform.
8615794 1996 Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases.
8218226 1993 PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE.
8179631 1994 Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.
7980617 1994 "Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.".
1741956 1991 Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15.