Gene description for PCSK9
Gene name proprotein convertase subtilisin/kexin type 9
Gene symbol PCSK9
Other names/aliases FH3
HCHOLA3
LDLCQ1
NARC-1
NARC1
PC9
Species Homo sapiens
 Database cross references - PCSK9
ExoCarta ExoCarta_255738
Vesiclepedia VP_255738
Entrez Gene 255738
HGNC 20001
MIM 607786
UniProt Q8NBP7  
 PCSK9 identified in sEVs derived from the following tissue/cell type
Colorectal cancer cells 19837982    
Colorectal cancer cells 25890246    
Colorectal cancer cells 25890246    
Colorectal cancer cells 34887515    
Colorectal cancer cells 34887515    
Lung cancer cells 34887515    
Squamous carcinoma cells 20124223    
 Gene ontology annotations for PCSK9
Molecular Function
    RNA binding GO:0003723 HDA
    serine-type endopeptidase activity GO:0004252 IBA
    serine-type endopeptidase activity GO:0004252 IDA
    protein binding GO:0005515 IPI
    sodium channel inhibitor activity GO:0019871 IDA
    low-density lipoprotein particle binding GO:0030169 ISS
    signaling receptor inhibitor activity GO:0030547 IDA
    apolipoprotein binding GO:0034185 ISS
    very-low-density lipoprotein particle binding GO:0034189 ISS
    apolipoprotein receptor binding GO:0034190 IDA
    low-density lipoprotein particle receptor binding GO:0050750 IDA
    low-density lipoprotein particle receptor binding GO:0050750 IPI
    very-low-density lipoprotein particle receptor binding GO:0070326 IDA
Biological Process
    kidney development GO:0001822 ISS
    liver development GO:0001889 ISS
    negative regulation of receptor recycling GO:0001920 IDA
    negative regulation of receptor internalization GO:0002091 IDA
    positive regulation of receptor internalization GO:0002092 IDA
    triglyceride metabolic process GO:0006641 IEA
    phospholipid metabolic process GO:0006644 IEA
    apoptotic process GO:0006915 IEA
    lysosomal transport GO:0007041 IDA
    cholesterol metabolic process GO:0008203 IEA
    cellular response to starvation GO:0009267 ISS
    regulation of signaling receptor activity GO:0010469 IDA
    negative regulation of low-density lipoprotein particle clearance GO:0010989 IDA
    protein autoprocessing GO:0016540 IDA
    neurogenesis GO:0022008 ISS
    neuron differentiation GO:0030182 ISS
    low-density lipoprotein particle receptor catabolic process GO:0032802 IDA
    positive regulation of low-density lipoprotein particle receptor catabolic process GO:0032805 IDA
    cellular response to insulin stimulus GO:0032869 ISS
    lipoprotein metabolic process GO:0042157 IEA
    cholesterol homeostasis GO:0042632 IMP
    regulation of neuron apoptotic process GO:0043523 ISS
    positive regulation of neuron apoptotic process GO:0043525 IMP
    negative regulation of low-density lipoprotein particle receptor binding GO:1905596 IDA
    negative regulation of low-density lipoprotein receptor activity GO:1905598 IDA
    negative regulation of receptor-mediated endocytosis involved in cholesterol transport GO:1905601 IDA
    negative regulation of sodium ion transmembrane transporter activity GO:2000650 IDA
Subcellular Localization
    extracellular region GO:0005576 TAS
    extracellular space GO:0005615 IBA
    extracellular space GO:0005615 IDA
    cytoplasm GO:0005737 IDA
    lysosome GO:0005764 IDA
    lysosomal membrane GO:0005765 TAS
    early endosome GO:0005769 IDA
    late endosome GO:0005770 IDA
    endoplasmic reticulum GO:0005783 IDA
    endoplasmic reticulum lumen GO:0005788 TAS
    Golgi apparatus GO:0005794 IDA
    plasma membrane GO:0005886 IDA
    cell surface GO:0009986 IDA
    COPII-coated ER to Golgi transport vesicle GO:0030134 IEA
    extrinsic component of external side of plasma membrane GO:0031232 IC
    endolysosome membrane GO:0036020 TAS
    perinuclear region of cytoplasm GO:0048471 IDA
    PCSK9-LDLR complex GO:1990666 IDA
    PCSK9-AnxA2 complex GO:1990667 IDA
    PCSK9-AnxA2 complex GO:1990667 IPI
 Experiment description of studies that identified PCSK9 in sEVs
1
Experiment ID 21
MISEV standards
✔
EM|IEM
Biophysical techniques
✔
Alix|TSG101|HSP70|CD63
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method
Mass spectrometry   
PubMed ID 19837982    
Organism Homo sapiens
Experiment description Proteomic and bioinformatic analysis of immunoaffinity-purified exosomes derived from the human colon tumor cell line LIM1215.
Authors "Suresh Mathivanan, Justin W.E. Lim, Bow J. Tauro, Hong Ji, Robert L. Moritz and Richard J. Simpson"
Journal name MCP
Publication year 2009
Sample Colorectal cancer cells
Sample name LIM1215
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.10-1.12 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry [Orbitrap]
Western blotting
2
Experiment ID 282
MISEV standards
✔
CEM
Biophysical techniques
✔
Alix|TSG101|CD63|CD81|EpCAM
Enriched markers
✘ Negative markers
✔
DLS
Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25890246    
Organism Homo sapiens
Experiment description Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct.
Authors "Xu R, Greening DW, Rai A, Ji H, Simpson RJ."
Journal name Methods
Publication year 2015
Sample Colorectal cancer cells
Sample name LIM1863 - Ultracentrifugation - Rep 1
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Centrifugal concentration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
Western blotting
3
Experiment ID 283
MISEV standards
✔
CEM
Biophysical techniques
✔
Alix|TSG101|CD63|CD81|EpCAM
Enriched markers
✘ Negative markers
✔
DLS
Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25890246    
Organism Homo sapiens
Experiment description Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct.
Authors "Xu R, Greening DW, Rai A, Ji H, Simpson RJ."
Journal name Methods
Publication year 2015
Sample Colorectal cancer cells
Sample name LIM1863 - Ultracentrifugation - Rep 2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Centrifugal concentration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
Western blotting
4
Experiment ID 1202
MISEV standards
✘ Biophysical techniques
✔
SDCBP|CD9|FLOT1
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Western blotting
PubMed ID 34887515    
Organism Homo sapiens
Experiment description Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Authors "Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ."
Journal name Nat Cell Biol
Publication year 2021
Sample Colorectal cancer cells
Sample name LIM1215
Isolation/purification methods Differential centrifugation
Filtration
Centrifugal ultrafiltration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
5
Experiment ID 1203
MISEV standards
✔
EM
Biophysical techniques
✔
SDCBP|FLOT1|CD9|CD81|CD63|EPCAM|GAPDH|LAMP1|TFRC|CD151|CD82|LAMP2|RAB35|TSG101|FLOT2|RAB5B|ICAM1|RAB5A
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Western blotting
PubMed ID 34887515    
Organism Homo sapiens
Experiment description Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Authors "Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ."
Journal name Nat Cell Biol
Publication year 2021
Sample Colorectal cancer cells
Sample name DiFi
Isolation/purification methods Differential centrifugation
Filtration
Centrifugal ultrafiltration
Ultracentrifugation
OptiPrep density gradient centrifugation
Flotation density -
Molecules identified in the study Protein
miRNA
Methods used in the study Western blotting
Mass spectrometry
RNA sequencing
6
Experiment ID 1203
MISEV standards
✔
EM
Biophysical techniques
✔
SDCBP|FLOT1|CD9|CD81|CD63|EPCAM|GAPDH|LAMP1|TFRC|CD151|CD82|LAMP2|RAB35|TSG101|FLOT2|RAB5B|ICAM1|RAB5A
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 34887515    
Organism Homo sapiens
Experiment description Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Authors "Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ."
Journal name Nat Cell Biol
Publication year 2021
Sample Colorectal cancer cells
Sample name DiFi
Isolation/purification methods Differential centrifugation
Filtration
Centrifugal ultrafiltration
Ultracentrifugation
OptiPrep density gradient centrifugation
Flotation density -
Molecules identified in the study Protein
miRNA
Methods used in the study Western blotting
Mass spectrometry
RNA sequencing
7
Experiment ID 1201
MISEV standards
✘ Biophysical techniques
✔
SDCBP|CD9|FLOT1
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Western blotting
PubMed ID 34887515    
Organism Homo sapiens
Experiment description Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets
Authors "Zhang Q, Jeppesen DK, Higginbotham JN, Graves-Deal R, Trinh VQ, Ramirez MA, Sohn Y, Neininger AC, Taneja N, McKinley ET, Niitsu H, Cao Z, Evans R, Glass SE, Ray KC, Fissell WH, Hill S, Rose KL, Huh WJ, Washington MK, Ayers GD, Burnette DT, Sharma S, Rome LH, Franklin JL, Lee YA, Liu Q, Coffey RJ."
Journal name Nat Cell Biol
Publication year 2021
Sample Lung cancer cells
Sample name Calu-3
Isolation/purification methods Differential centrifugation
Filtration
Centrifugal ultrafiltration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
8
Experiment ID 191
MISEV standards
✘ Biophysical techniques
✔
Alix|CD81|CD9
Enriched markers
✘ Negative markers
✘ Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 20124223    
Organism Homo sapiens
Experiment description Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes.
Authors "Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK."
Journal name Mol Cell Proteomics
Publication year 2010
Sample Squamous carcinoma cells
Sample name Squamous carcinoma cell (A431)
Isolation/purification methods Differential centrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
 Protein-protein interactions for PCSK9
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 LY86  
Affinity Capture-MS Homo sapiens
2 DNASE1L1 1774
Affinity Capture-MS Homo sapiens
3 RHOT1 55288
Affinity Capture-MS Homo sapiens
4 BIRC2  
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
Biochemical Activity Homo sapiens
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
5 INHBE 83729
Affinity Capture-MS Homo sapiens
6 FCGR3B  
Affinity Capture-MS Homo sapiens
7 ELSPBP1  
Affinity Capture-MS Homo sapiens
8 CA6 765
Affinity Capture-MS Homo sapiens
9 ADAMTS4  
Affinity Capture-MS Homo sapiens
10 TRAF2 7186
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
11 CLGN 1047
Affinity Capture-MS Homo sapiens
12 SLC25A12 8604
Affinity Capture-MS Homo sapiens
13 FAM20C 56975
Affinity Capture-MS Homo sapiens
14 PRG3  
Affinity Capture-MS Homo sapiens
15 TMEM87A 25963
Affinity Capture-MS Homo sapiens
16 RPL28 6158
Affinity Capture-MS Homo sapiens
17 TCTN1  
Affinity Capture-MS Homo sapiens
18 PGRMC1 10857
Affinity Capture-MS Homo sapiens
19 FSTL4  
Affinity Capture-MS Homo sapiens
20 CDIPT 10423
Affinity Capture-MS Homo sapiens
21 BACE1  
Biochemical Activity Homo sapiens
Reconstituted Complex Homo sapiens
22 TAZ  
Affinity Capture-MS Homo sapiens
23 PSCA 8000
Affinity Capture-MS Homo sapiens
24 GGH 8836
Affinity Capture-MS Homo sapiens
25 DPEP2  
Affinity Capture-MS Homo sapiens
26 PDGFRA 5156
Affinity Capture-MS Homo sapiens
27 SLC25A10 1468
Affinity Capture-MS Homo sapiens
28 PRG2  
Affinity Capture-MS Homo sapiens
29 PI15  
Affinity Capture-MS Homo sapiens
30 PDIA4 9601
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
31 CBLN4  
Affinity Capture-MS Homo sapiens
32 SLC25A1 6576
Affinity Capture-MS Homo sapiens
33 HSPB1 3315
Affinity Capture-MS Homo sapiens
34 LYZL1  
Affinity Capture-MS Homo sapiens
35 FCN3 8547
Affinity Capture-MS Homo sapiens
36 CLEC4C  
Affinity Capture-MS Homo sapiens
37 NCR3  
Affinity Capture-MS Homo sapiens
38 IL5RA  
Affinity Capture-MS Homo sapiens
39 RCN1 5954
Affinity Capture-MS Homo sapiens
40 KLK2  
Affinity Capture-MS Homo sapiens
41 TUBB6 84617
Affinity Capture-MS Homo sapiens
42 NXF1 10482
Affinity Capture-RNA Homo sapiens
43 EPHA7 2045
Affinity Capture-MS Homo sapiens
44 MSTN  
Affinity Capture-MS Homo sapiens
45 UGGT1 56886
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
46 ARMC6 93436
Affinity Capture-MS Homo sapiens
47 IGLL5 100423062
Affinity Capture-MS Homo sapiens
48 C1QB 713
Affinity Capture-MS Homo sapiens
49 STUB1 10273
Affinity Capture-MS Homo sapiens
50 IDS  
Affinity Capture-MS Homo sapiens
51 SDF2L1 23753
Affinity Capture-MS Homo sapiens
52 FIBIN  
Affinity Capture-MS Homo sapiens
53 CRISP2  
Affinity Capture-MS Homo sapiens
54 C1orf54  
Affinity Capture-MS Homo sapiens
55 TRGV3  
Affinity Capture-MS Homo sapiens
56 ALPP 250
Affinity Capture-MS Homo sapiens
57 DNAJA1 3301
Affinity Capture-MS Homo sapiens
Affinity Capture-Western Homo sapiens
58 DNAJA2 10294
Affinity Capture-MS Homo sapiens
59 DNAJC10 54431
Affinity Capture-MS Homo sapiens
60 LDLR 3949
Affinity Capture-Western Homo sapiens
61 EDN3  
Affinity Capture-MS Homo sapiens
62 NXPH3  
Affinity Capture-MS Homo sapiens
63 TDGF1  
Affinity Capture-MS Homo sapiens
64 SEC11C 90701
Affinity Capture-MS Homo sapiens
65 ADAM18  
Affinity Capture-MS Homo sapiens
66 DNAJA3 9093
Affinity Capture-MS Homo sapiens
67 PTCH1  
Affinity Capture-MS Homo sapiens
68 LYPD4  
Affinity Capture-MS Homo sapiens
69 ISLR 3671
Affinity Capture-MS Homo sapiens
70 IL12RB1  
Affinity Capture-MS Homo sapiens
71 DNAJB11 51726
Affinity Capture-MS Homo sapiens
72 AGK 55750
Affinity Capture-MS Homo sapiens
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