3.4.21.B25: PACE4 proprotein convertase
This is an abbreviated version!
For detailed information about PACE4 proprotein convertase, go to the full flat file.
Word Map on EC 3.4.21.B25
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3.4.21.B25
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convertases
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furin
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prohormone
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endoproteases
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furin-deficient
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furin-like
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alpha1-pdx
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dibasic
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pro-proteins
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alpha1-antitrypsin
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portland
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endoproteolysis
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diagnostics
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kexin
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kexin-like
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ski-1
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cys-rich
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medicine
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subtilisin-related
- 3.4.21.B25
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convertases
- furin
-
prohormone
- endoproteases
-
furin-deficient
-
furin-like
- alpha1-pdx
-
dibasic
-
pro-proteins
- alpha1-antitrypsin
- portland
-
endoproteolysis
- diagnostics
- kexin
-
kexin-like
- ski-1
-
cys-rich
- medicine
-
subtilisin-related
Reaction
releases mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys =
Synonyms
PACE 4, PACE-4, PACE4, PACE4/SPC4, paired basic amino acid cleaving enzyme 4, paired basic amino acid-cleaving enzyme 4, paired basic amino-acid-cleaving enzyme-4, PC7, proprotein convertase PACE4, S08.075, SPC4, subtilisin-like proprotein convertase, subtilisin-like proprotein convertase 4, subtilisin-like proprotein convertase PACE4, XPACE4
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General Information on EC 3.4.21.B25 - PACE4 proprotein convertase
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
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the enzyme belongs to the subtilisin-like proprotein convertase (SPC) family
malfunction
metabolism
insulin receptor requires the proteolytic cleavage of its proform by intra-Golgi furin-like activity. In mammalian cells, insulin receptor is expressed as two isoforms B and A that are responsible for insulin action, but only isozyme A transmits the growth-promoting and mitogenic effects of insulin-like growth factor 2. The two insulin receptor isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, insulin receptor proforms move to the cell surface where the proprotein convertase PACE4 selectively supports insulin receptor B maturation
physiological function
malfunction
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the expression of myosin light chain mRNA transcript is markedly reduced in PACE4 knockdown cells
malfunction
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silencing of PACE4 causes the suppression of branching morphogenesis and aquaporin 5 expression in rat embryonic submandibular gland rudiments culture system
malfunction
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enzyme PACE4 knockdown causes blockage of chondrogenic differentiation through downregulation of proBMP6 activation
malfunction
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the PACE4 gene-knockdown cells show a drastic decrease in mineralization even in the presence of any estrogen stimulus
malfunction
when the PACE4 gene is silenced by small interfering RNA the knockdown of human breast cancer MDA-MB-231 cells shows significantly reduced proliferation, migration and invasion rates
physiological function
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PACE4 plays a critical role in myogenic differentiation of C2C12 cells through its association with the insulin-like growth factor-II pathway
physiological function
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PACE4 regulates submandibular gland development via the activation of proproteins involved in salivary branching and/or salivary acinar differentiation
physiological function
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Pace4 activates Nodal in the epiblast to maintain pluripotency. Secreted Pace4 stimulates mesoderm and endoderm formation. Expression of Pace4 in the extraembryonic ectoderm suppresses neural differentiation
physiological function
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PACE4 plays an important role in submandibular gland development
physiological function
the enzyme is involved in the maturation of insulin receptor isoform B, thereby reducing the specific insulin receptor-dependent effects of insulin-like growth factor 2, IGF2
physiological function
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the enzyme is required for chondrogenic differentiation, e.g. for differentiation of ATDC-5 cells into type II collagen-expressing chondrocytes, type X collagen-expressing hypertrophic chondrocytes, and mineralizing chondrocytes
physiological function
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the enzyme participates in bone formation at least in osteoblast differentiation, estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells. Downregulators of the enzyme, e.g. equol or daidzein, restore the differentiation of MC3T3-E1 cells
physiological function
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morula compaction and inner cell mass formation depend on PC7 and the related proteases Furin and Pace4. These proteases jointly regulate cell-cell adhesion mediated by E-cadherin processing during blastocyst formation
physiological function
the enzyme participate in the post-translational activation of inactive proteins, leading to mature, biologically active proteins. It regulates proliferation, migration and invasion in human breast cancer MDA-MB-231 cells
physiological function
the enzyme play an important role in prostate cancer cell proliferation
physiological function
the enzyme regulates apoptosis in human pancreatic cancer PANC-1 cells via the mitochondrial signaling pathway
physiological function
the enzyme regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways
