Application | Comment | Organism |
---|---|---|
additional information | 1G08 fragment antigen binding represents a useful new tool for delineating the mechanism of PCSK9 uptake and low density lipoprotein receptor degradation | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
full-length and mutant PCSK9-V5-His proteins expressed in HEK-293 cells. Truncated PCSK9DELTAC (Gln-31-Ala-451) proteins with a C-terminal His tag expressed in Escherichia coli BL21 cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
E607A/K609A/E612N | mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding | Homo sapiens |
additional information | 1G08 fragment antigen binding fails to bind a truncated form of PCSK9 lacking the C-terminal domain. Lack of the C-terminal domain compromises the ability of PCSK9 to internalize into cells, and to inhibit low density lipoprotein uptake | Homo sapiens |
R549A | mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding | Homo sapiens |
R580A/R582A | mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | in HEK-293 and Hep-G2 cells, 1G08 fragment antigen binding reduces 50% the PCSK9-dependent inhibitory effects on low density lipoprotein uptake. 1G08 fragment antigen binding does not affect the PCSK9-low density lipoprotein receptor interaction but inhibits the internalization of PCSK9 in these cells. 1G08 fragment antigen binding binds a region of beta-strands encompassing Arg-549, Arg-580, Arg-582, Glu-607, Lys-609, and Glu-612 in the PCSK9 C-terminal domain. The membrane associated protein Annexin A2 does not affect 1G08-PCSK9 binding | Homo sapiens |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
75979 | - |
1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8NBP7 | - |
- |
Purification (Comment) | Organism |
---|---|
gel filtration | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
low density lipoprotein receptor | - |
Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
monomer | 1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
PCSK9 | - |
Homo sapiens |
proprotein convertase subtilisin-like/kexin type 9 | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
additional information | - |
at 20°C in 0.05 ml of buffer containing 10 mM Hepes, pH 7.4, 150 mM NaCl, 0.1 mM CaCl2, and 0.05% (w/v) bovine serum albumin: 0.0000048 mM with 1G08 fragment antigen binding, when wild-type expressed in HEK-293 cells, 0.0000150 mM with 1G08 fragment antigen binding, when wild-type expressed in Hep-G2 cells, 0.001 mM with 1G08 fragment antigen binding, when mutant R549A , mutant R580A/R582A and mutant E607A/K609A/E612N expressed in HEK-293 cells | Homo sapiens | additional information |
General Information | Comment | Organism |
---|---|---|
physiological function | PCSK9 binds to the low density lipoprotein receptor and leads to low density lipoprotein receptor degradation and inhibition of plasma low density lipoprotein cholesterol clearance. PCSK9 C-terminal domain contributes to its inhibition of low density lipoprotein receptor function mainly through its role in the cellular uptake of PCSK9 and low-density lipoprotein receptor complex | Homo sapiens |