UniProtKB - Q8NBP7 (PCSK9_HUMAN)
Proprotein convertase subtilisin/kexin type 9
PCSK9
Functioni
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 186 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 226 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 386 | Charge relay systemPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- apolipoprotein binding Source: UniProtKB
- apolipoprotein receptor binding Source: BHF-UCL
- low-density lipoprotein particle binding Source: UniProtKB
- low-density lipoprotein particle receptor binding Source: HGNC-UCL
- protein self-association Source: UniProtKB
- receptor inhibitor activity Source: BHF-UCL
- RNA binding Source: UniProtKB
- serine-type endopeptidase activity Source: HGNC-UCL
- sodium channel inhibitor activity Source: UniProtKB
- very-low-density lipoprotein particle binding Source: UniProtKB
- very-low-density lipoprotein particle receptor binding Source: BHF-UCL
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cellular protein metabolic process Source: Reactome
- cellular response to insulin stimulus Source: HGNC-UCL
- cellular response to starvation Source: HGNC-UCL
- cholesterol homeostasis Source: HGNC-UCL
- cholesterol metabolic process Source: UniProtKB-KW
- kidney development Source: HGNC-UCL
- lipoprotein metabolic process Source: Ensembl
- liver development Source: HGNC-UCL
- low-density lipoprotein particle clearance Source: Reactome
- low-density lipoprotein particle receptor catabolic process Source: UniProtKB
- lysosomal transport Source: BHF-UCL
- negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
- negative regulation of low-density lipoprotein particle receptor binding Source: BHF-UCL
- negative regulation of low-density lipoprotein receptor activity Source: BHF-UCL
- negative regulation of receptor-mediated endocytosis involved in cholesterol transport Source: BHF-UCL
- negative regulation of receptor recycling Source: BHF-UCL
- negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
- neurogenesis Source: HGNC-UCL
- neuron differentiation Source: HGNC-UCL
- phospholipid metabolic process Source: Ensembl
- positive regulation of low-density lipoprotein particle receptor catabolic process Source: BHF-UCL
- positive regulation of neuron apoptotic process Source: HGNC-UCL
- positive regulation of receptor internalization Source: BHF-UCL
- post-translational protein modification Source: Reactome
- protein autoprocessing Source: HGNC-UCL
- regulation of neuron apoptotic process Source: UniProtKB
- regulation of signaling receptor activity Source: BHF-UCL
- triglyceride metabolic process Source: Ensembl
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Biological process | Apoptosis, Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism |
Ligand | Calcium |
Enzyme and pathway databases
BRENDAi | 3.4.21.61 2681 |
Reactomei | R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8866427 VLDLR internalisation and degradation R-HSA-8957275 Post-translational protein phosphorylation R-HSA-8964038 LDL clearance |
SignaLinki | Q8NBP7 |
SIGNORi | Q8NBP7 |
Protein family/group databases
MEROPSi | S08.039 |
Names & Taxonomyi
Protein namesi | Recommended name: Proprotein convertase subtilisin/kexin type 9 (EC:3.4.21.-)Alternative name(s): Neural apoptosis-regulated convertase 1 Short name: NARC-1 Proprotein convertase 9 Short name: PC9 Subtilisin/kexin-like protease PC9 |
Gene namesi | Name:PCSK9 Synonyms:NARC1 ORF Names:PSEC0052 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20001 PCSK9 |
MIMi | 607786 gene |
neXtProti | NX_Q8NBP7 |
Subcellular locationi
Lysosome
Endosome
Endoplasmic reticulum
Extracellular region or secreted
Golgi apparatus
Other locations
Note: Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum lumen Source: Reactome
- rough endoplasmic reticulum Source: Ensembl
Endosome
- early endosome Source: UniProtKB
- endolysosome membrane Source: Reactome
- late endosome Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: HGNC-UCL
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Lysosome
- endolysosome membrane Source: Reactome
- lysosomal membrane Source: Reactome
- lysosome Source: UniProtKB
Plasma Membrane
- extrinsic component of external side of plasma membrane Source: BHF-UCL
- plasma membrane Source: BHF-UCL
Other locations
- cell surface Source: UniProtKB
- COPII-coated ER to Golgi transport vesicle Source: Ensembl
- cytoplasm Source: UniProtKB
- PCSK9-AnxA2 complex Source: BHF-UCL
- PCSK9-LDLR complex Source: BHF-UCL
- perinuclear region of cytoplasm Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, SecretedPathology & Biotechi
Involvement in diseasei
Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017199 | 127 | S → R in HCHOLA3. 1 PublicationCorresponds to variant dbSNP:rs28942111EnsemblClinVar. | 1 | |
Natural variantiVAR_058524 | 129 | D → G in HCHOLA3. Corresponds to variant dbSNP:rs1553135971EnsemblClinVar. | 1 | |
Natural variantiVAR_058526 | 215 | R → H in HCHOLA3. Corresponds to variant dbSNP:rs794728683EnsemblClinVar. | 1 | |
Natural variantiVAR_017200 | 216 | F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 PublicationCorresponds to variant dbSNP:rs28942112EnsemblClinVar. | 1 | |
Natural variantiVAR_058527 | 218 | R → S in HCHOLA3; complete loss of cleavage by furin and PCSK5; reduces glycosylation levels; no effect on protein sulfation and phosphorylation; no effect on protein sulfation but inhibits phosphorylation when associated with Y-374; highly reduces LDL uptake when associated with Y-374. 2 PublicationsCorresponds to variant dbSNP:rs970575319EnsemblClinVar. | 1 | |
Natural variantiVAR_058530 | 357 | R → H in HCHOLA3. Corresponds to variant dbSNP:rs370507566EnsemblClinVar. | 1 | |
Natural variantiVAR_058531 | 374 | D → H in HCHOLA3. Corresponds to variant dbSNP:rs137852912EnsemblClinVar. | 1 | |
Natural variantiVAR_058532 | 374 | D → Y in HCHOLA3; partial loss of cleavage by furin and PCSK5; no effect on protein sulfation but inhibits phosphorylation when associated with S-218; highly increases LDL uptake when associated with S-218. 2 PublicationsCorresponds to variant dbSNP:rs137852912EnsemblClinVar. | 1 | |
Natural variantiVAR_058534 | 496 | R → W in HCHOLA3. Corresponds to variant dbSNP:rs374603772EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 67 | C → A: Does not affect multimerization or zymogen processing. 1 Publication | 1 | |
Mutagenesisi | 226 | H → A: Remains in the endoplasmic reticulum and is not secreted. 1 Publication | 1 | |
Mutagenesisi | 533 | N → A: 1.5 kDa decrease of the apparent molecular mass of pro-PCSK9 and PCSK9 and no effect on processing and secretion. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 255738 |
GeneReviewsi | PCSK9 |
MalaCardsi | PCSK9 |
MIMi | 603776 phenotype |
OpenTargetsi | ENSG00000169174 |
Orphaneti | 391665 Homozygous familial hypercholesterolemia 426 NON RARE IN EUROPE: Familial hypobetalipoproteinemia 406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia |
PharmGKBi | PA38617 |
Miscellaneous databases
Pharosi | Q8NBP7 |
Chemistry databases
ChEMBLi | CHEMBL2929 |
DrugBanki | DB09302 Alirocumab DB09303 Evolocumab |
DrugCentrali | Q8NBP7 |
GuidetoPHARMACOLOGYi | 2388 |
Polymorphism and mutation databases
BioMutai | PCSK9 |
DMDMi | 317373487 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 30 | 1 PublicationAdd BLAST | 30 | |
PropeptideiPRO_0000027120 | 31 – 152 | 1 PublicationAdd BLAST | 122 | |
ChainiPRO_0000027121 | 153 – 692 | Proprotein convertase subtilisin/kexin type 9Add BLAST | 540 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 38 | Sulfotyrosine1 Publication | 1 | |
Modified residuei | 47 | Phosphoserine; by FAM20C2 Publications | 1 | |
Disulfide bondi | 223 ↔ 255 | Sequence analysis | ||
Disulfide bondi | 323 ↔ 358 | Sequence analysis | ||
Disulfide bondi | 457 ↔ 527 | Sequence analysis | ||
Disulfide bondi | 477 ↔ 526 | Sequence analysis | ||
Disulfide bondi | 486 ↔ 509 | Sequence analysis | ||
Glycosylationi | 533 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 534 ↔ 601 | Sequence analysis | ||
Disulfide bondi | 552 ↔ 600 | Sequence analysis | ||
Disulfide bondi | 562 ↔ 588 | Sequence analysis | ||
Disulfide bondi | 608 ↔ 679 | Sequence analysis | ||
Disulfide bondi | 626 ↔ 678 | Sequence analysis | ||
Disulfide bondi | 635 ↔ 654 | Sequence analysis | ||
Modified residuei | 688 | Phosphoserine; by FAM20CCombined sources2 Publications | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 152 – 153 | Cleavage; by autolysis1 Publication | 2 | |
Sitei | 218 – 219 | Cleavage; by furin and PCSK51 Publication | 2 |
Keywords - PTMi
Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation, ZymogenProteomic databases
EPDi | Q8NBP7 |
jPOSTi | Q8NBP7 |
MassIVEi | Q8NBP7 |
MaxQBi | Q8NBP7 |
PaxDbi | Q8NBP7 |
PeptideAtlasi | Q8NBP7 |
PRIDEi | Q8NBP7 |
ProteomicsDBi | 72807 [Q8NBP7-1] 72808 [Q8NBP7-2] |
PTM databases
iPTMneti | Q8NBP7 |
PhosphoSitePlusi | Q8NBP7 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000169174 Expressed in 85 organ(s), highest expression level in right lobe of liver |
Genevisiblei | Q8NBP7 HS |
Interactioni
Subunit structurei
Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers.
Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR.
Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR (PubMed:18799458).
9 PublicationsBinary interactionsi
GO - Molecular functioni
- apolipoprotein binding Source: UniProtKB
- apolipoprotein receptor binding Source: BHF-UCL
- low-density lipoprotein particle receptor binding Source: HGNC-UCL
- protein self-association Source: UniProtKB
- very-low-density lipoprotein particle binding Source: UniProtKB
- very-low-density lipoprotein particle receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGridi | 129116, 27 interactors |
ComplexPortali | CPX-128 LDLR-PCSK9 complex CPX-130 ANXA2-PCSK9 complex |
DIPi | DIP-29694N |
IntActi | Q8NBP7, 5 interactors |
MINTi | Q8NBP7 |
STRINGi | 9606.ENSP00000303208 |
Chemistry databases
BindingDBi | Q8NBP7 |
Structurei
Secondary structure
3D structure databases
SMRi | Q8NBP7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8NBP7 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 77 – 149 | Inhibitor I9Sequence analysisAdd BLAST | 73 | |
Domaini | 155 – 461 | Peptidase S8PROSITE-ProRule annotationAdd BLAST | 307 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 450 – 692 | C-terminal domainAdd BLAST | 243 |
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG1153 Eukaryota COG1404 LUCA |
GeneTreei | ENSGT00490000043472 |
HOGENOMi | HOG000049267 |
InParanoidi | Q8NBP7 |
KOi | K13050 |
OMAi | FAQSVPW |
OrthoDBi | 921536at2759 |
PhylomeDBi | Q8NBP7 |
TreeFami | TF106271 |
Family and domain databases
CDDi | cd04077 Peptidases_S8_PCSK9_ProteinaseK_like, 1 hit |
Gene3Di | 3.30.70.80, 1 hit 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR041254 PCSK9_C IPR041052 PCSK9_C2 IPR041051 PCSK9_C3 IPR034193 PCSK9_ProteinaseK-like IPR000209 Peptidase_S8/S53_dom IPR036852 Peptidase_S8/S53_dom_sf IPR015500 Peptidase_S8_subtilisin-rel IPR010259 S8pro/Inhibitor_I9 IPR037045 S8pro/Inhibitor_I9_sf |
Pfami | View protein in Pfam PF05922 Inhibitor_I9, 1 hit PF18459 PCSK9_C1, 1 hit PF18464 PCSK9_C2, 1 hit PF18463 PCSK9_C3, 1 hit PF00082 Peptidase_S8, 1 hit |
PRINTSi | PR00723 SUBTILISIN |
SUPFAMi | SSF52743 SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51892 SUBTILASE, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGTVSSRRSW WPLPLLLLLL LLLGPAGARA QEDEDGDYEE LVLALRSEED
60 70 80 90 100
GLAEAPEHGT TATFHRCAKD PWRLPGTYVV VLKEETHLSQ SERTARRLQA
110 120 130 140 150
QAARRGYLTK ILHVFHGLLP GFLVKMSGDL LELALKLPHV DYIEEDSSVF
160 170 180 190 200
AQSIPWNLER ITPPRYRADE YQPPDGGSLV EVYLLDTSIQ SDHREIEGRV
210 220 230 240 250
MVTDFENVPE EDGTRFHRQA SKCDSHGTHL AGVVSGRDAG VAKGASMRSL
260 270 280 290 300
RVLNCQGKGT VSGTLIGLEF IRKSQLVQPV GPLVVLLPLA GGYSRVLNAA
310 320 330 340 350
CQRLARAGVV LVTAAGNFRD DACLYSPASA PEVITVGATN AQDQPVTLGT
360 370 380 390 400
LGTNFGRCVD LFAPGEDIIG ASSDCSTCFV SQSGTSQAAA HVAGIAAMML
410 420 430 440 450
SAEPELTLAE LRQRLIHFSA KDVINEAWFP EDQRVLTPNL VAALPPSTHG
460 470 480 490 500
AGWQLFCRTV WSAHSGPTRM ATAVARCAPD EELLSCSSFS RSGKRRGERM
510 520 530 540 550
EAQGGKLVCR AHNAFGGEGV YAIARCCLLP QANCSVHTAP PAEASMGTRV
560 570 580 590 600
HCHQQGHVLT GCSSHWEVED LGTHKPPVLR PRGQPNQCVG HREASIHASC
610 620 630 640 650
CHAPGLECKV KEHGIPAPQE QVTVACEEGW TLTGCSALPG TSHVLGAYAV
660 670 680 690
DNTCVVRSRD VSTTGSTSEG AVTAVAICCR SRHLAQASQE LQ
The sequence of this isoform differs from the canonical sequence as follows:
1-174: MGTVSSRRSW...RYRADEYQPP → MSPWK
333-365: VITVGATNAQDQPVTLGTLGTNFGRCVDLFAPG → GRTSLVPPATAAPALCHRVGHHRLLPTWLALQP
366-692: Missing.
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 423 | V → A in BAC11572 (PubMed:14702039).Curated | 1 |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021336 | 23 | L → LL This polymoprhism seems to have a modifier effect on LDLR mutation and familial hypercholesterolemia. 4 Publications | 1 | |
Natural variantiVAR_017197 | 46 | R → L Polymorphism; associated with lower plasma levels of low-density lipoprotein cholesterol; reduced phosphorylation at Ser-47. 4 PublicationsCorresponds to variant dbSNP:rs11591147EnsemblClinVar. | 1 | |
Natural variantiVAR_017198 | 53 | A → V Polymorphism; associated with reduced phosphorylation at Ser-47. 4 PublicationsCorresponds to variant dbSNP:rs11583680EnsemblClinVar. | 1 | |
Natural variantiVAR_025451 | 57 | E → K1 PublicationCorresponds to variant dbSNP:rs145886902EnsemblClinVar. | 1 | |
Natural variantiVAR_058520 | 77 | T → I. Corresponds to variant dbSNP:rs756060557Ensembl. | 1 | |
Natural variantiVAR_058521 | 93 | R → C. Corresponds to variant dbSNP:rs151193009EnsemblClinVar. | 1 | |
Natural variantiVAR_058522 | 106 | G → R. | 1 | |
Natural variantiVAR_058523 | 114 | V → A. Corresponds to variant dbSNP:rs775988212EnsemblClinVar. | 1 | |
Natural variantiVAR_017199 | 127 | S → R in HCHOLA3. 1 PublicationCorresponds to variant dbSNP:rs28942111EnsemblClinVar. | 1 | |
Natural variantiVAR_058524 | 129 | D → G in HCHOLA3. Corresponds to variant dbSNP:rs1553135971EnsemblClinVar. | 1 | |
Natural variantiVAR_058525 | 157 | N → K. Corresponds to variant dbSNP:rs143117125EnsemblClinVar. | 1 | |
Natural variantiVAR_067351 | 174 | P → S Found in patients with familial hypercholesterolemia carrying a homozygous LDLR mutation; acts as a disease modifier resulting in a mild phenotype. 1 PublicationCorresponds to variant dbSNP:rs533273863EnsemblClinVar. | 1 | |
Natural variantiVAR_058526 | 215 | R → H in HCHOLA3. Corresponds to variant dbSNP:rs794728683EnsemblClinVar. | 1 | |
Natural variantiVAR_017200 | 216 | F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 PublicationCorresponds to variant dbSNP:rs28942112EnsemblClinVar. | 1 | |
Natural variantiVAR_058527 | 218 | R → S in HCHOLA3; complete loss of cleavage by furin and PCSK5; reduces glycosylation levels; no effect on protein sulfation and phosphorylation; no effect on protein sulfation but inhibits phosphorylation when associated with Y-374; highly reduces LDL uptake when associated with Y-374. 2 PublicationsCorresponds to variant dbSNP:rs970575319EnsemblClinVar. | 1 | |
Natural variantiVAR_058528 | 219 | Q → E. Corresponds to variant dbSNP:rs778617372EnsemblClinVar. | 1 | |
Natural variantiVAR_025452 | 237 | R → W1 PublicationCorresponds to variant dbSNP:rs148195424EnsemblClinVar. | 1 | |
Natural variantiVAR_058529 | 239 | A → D. | 1 | |
Natural variantiVAR_025453 | 253 | L → F Polymorphism; associated with lower plasma levels of low-density lipoprotein cholesterol. 1 PublicationCorresponds to variant dbSNP:rs72646508EnsemblClinVar. | 1 | |
Natural variantiVAR_058530 | 357 | R → H in HCHOLA3. Corresponds to variant dbSNP:rs370507566EnsemblClinVar. | 1 | |
Natural variantiVAR_058531 | 374 | D → H in HCHOLA3. Corresponds to variant dbSNP:rs137852912EnsemblClinVar. | 1 | |
Natural variantiVAR_058532 | 374 | D → Y in HCHOLA3; partial loss of cleavage by furin and PCSK5; no effect on protein sulfation but inhibits phosphorylation when associated with S-218; highly increases LDL uptake when associated with S-218. 2 PublicationsCorresponds to variant dbSNP:rs137852912EnsemblClinVar. | 1 | |
Natural variantiVAR_025454 | 391 | H → N1 PublicationCorresponds to variant dbSNP:rs146471967EnsemblClinVar. | 1 | |
Natural variantiVAR_067282 | 394 | G → S Found in a patient associated with autosomal dominant hypercholesterolemia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs368257906EnsemblClinVar. | 1 | |
Natural variantiVAR_025455 | 417 | H → Q1 PublicationCorresponds to variant dbSNP:rs143275858EnsemblClinVar. | 1 | |
Natural variantiVAR_021337 | 425 | N → S2 PublicationsCorresponds to variant dbSNP:rs28362261EnsemblClinVar. | 1 | |
Natural variantiVAR_021338 | 443 | A → T Polymorphism; associated with lower plasma levels of low-density lipoprotein cholesterol; more extensive cleavage by furin and PCSK5. 2 PublicationsCorresponds to variant dbSNP:rs28362263EnsemblClinVar. | 1 | |
Natural variantiVAR_058533 | 452 | G → D. | 1 | |
Natural variantiVAR_025456 | 469 | R → W1 PublicationCorresponds to variant dbSNP:rs141502002EnsemblClinVar. | 1 | |
Natural variantiVAR_021339 | 474 | V → I8 PublicationsCorresponds to variant dbSNP:rs562556EnsemblClinVar. | 1 | |
Natural variantiVAR_025457 | 482 | E → G1 PublicationCorresponds to variant dbSNP:rs141995194Ensembl. | 1 | |
Natural variantiVAR_073657 | 482 | E → Q No effect on interaction with ANXA2. 1 Publication | 1 | |
Natural variantiVAR_058534 | 496 | R → W in HCHOLA3. Corresponds to variant dbSNP:rs374603772EnsemblClinVar. | 1 | |
Natural variantiVAR_025458 | 515 | F → L1 PublicationCorresponds to variant dbSNP:rs1356131564Ensembl. | 1 | |
Natural variantiVAR_058535 | 522 | A → T. Corresponds to variant dbSNP:rs777300852Ensembl. | 1 | |
Natural variantiVAR_021340 | 553 | H → R2 PublicationsCorresponds to variant dbSNP:rs28362270EnsemblClinVar. | 1 | |
Natural variantiVAR_025459 | 554 | Q → E Increases interaction with ANXA2. 2 PublicationsCorresponds to variant dbSNP:rs149311926EnsemblClinVar. | 1 | |
Natural variantiVAR_058536 | 616 | P → L. Corresponds to variant dbSNP:rs755750316Ensembl. | 1 | |
Natural variantiVAR_021341 | 619 | Q → P2 PublicationsCorresponds to variant dbSNP:rs28362277EnsemblClinVar. | 1 | |
Natural variantiVAR_058537 | 668 | S → R. Corresponds to variant dbSNP:rs762298323EnsemblClinVar. | 1 | |
Natural variantiVAR_017201 | 670 | G → E8 PublicationsCorresponds to variant dbSNP:rs505151EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008844 | 1 – 174 | MGTVS…EYQPP → MSPWK in isoform 2. 1 PublicationAdd BLAST | 174 | |
Alternative sequenceiVSP_008845 | 333 – 365 | VITVG…LFAPG → GRTSLVPPATAAPALCHRVG HHRLLPTWLALQP in isoform 2. 1 PublicationAdd BLAST | 33 | |
Alternative sequenceiVSP_008846 | 366 – 692 | Missing in isoform 2. 1 PublicationAdd BLAST | 327 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AX127530 mRNA Translation: CAC38896.1 EF692496 mRNA Translation: ABV59216.1 AK075365 mRNA Translation: BAC11572.1 Frameshift. AK124635 mRNA Translation: BAC85910.1 AY829011 Genomic DNA Translation: AAV67948.1 FJ525880 Genomic DNA Translation: ACN81318.1 AC091609 Genomic DNA No translation available. AL589790 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06660.1 |
CCDSi | CCDS603.1 [Q8NBP7-1] |
RefSeqi | NP_777596.2, NM_174936.3 [Q8NBP7-1] |
Genome annotation databases
Ensembli | ENST00000302118; ENSP00000303208; ENSG00000169174 [Q8NBP7-1] |
GeneIDi | 255738 |
KEGGi | hsa:255738 |
UCSCi | uc001cyf.3 human [Q8NBP7-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AX127530 mRNA Translation: CAC38896.1 EF692496 mRNA Translation: ABV59216.1 AK075365 mRNA Translation: BAC11572.1 Frameshift. AK124635 mRNA Translation: BAC85910.1 AY829011 Genomic DNA Translation: AAV67948.1 FJ525880 Genomic DNA Translation: ACN81318.1 AC091609 Genomic DNA No translation available. AL589790 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06660.1 |
CCDSi | CCDS603.1 [Q8NBP7-1] |
RefSeqi | NP_777596.2, NM_174936.3 [Q8NBP7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2P4E | X-ray | 1.98 | A/P | 1-692 | [»] | |
2PMW | X-ray | 2.30 | A | 31-152 | [»] | |
B | 153-692 | [»] | ||||
2QTW | X-ray | 1.90 | A | 29-152 | [»] | |
B | 153-692 | [»] | ||||
2W2M | X-ray | 2.40 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
2W2N | X-ray | 2.30 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
2W2O | X-ray | 2.62 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
2W2P | X-ray | 2.62 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
2W2Q | X-ray | 2.33 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
2XTJ | X-ray | 2.70 | A | 153-451 | [»] | |
P | 53-152 | [»] | ||||
3BPS | X-ray | 2.41 | A | 153-692 | [»] | |
P | 53-152 | [»] | ||||
3GCW | X-ray | 2.70 | A | 153-692 | [»] | |
P | 53-152 | [»] | ||||
3GCX | X-ray | 2.70 | A | 153-692 | [»] | |
P | 53-152 | [»] | ||||
3H42 | X-ray | 2.30 | A | 31-152 | [»] | |
B | 153-692 | [»] | ||||
3M0C | X-ray | 7.01 | A | 29-152 | [»] | |
B | 153-692 | [»] | ||||
3P5B | X-ray | 3.30 | A | 153-692 | [»] | |
P | 61-152 | [»] | ||||
3P5C | X-ray | 4.20 | A | 153-692 | [»] | |
P | 61-152 | [»] | ||||
3SQO | X-ray | 2.70 | A | 153-692 | [»] | |
P | 31-152 | [»] | ||||
4K8R | X-ray | 3.22 | A | 61-152 | [»] | |
B | 153-692 | [»] | ||||
4NE9 | X-ray | 2.60 | A/B | 153-692 | [»] | |
C/P | 1-152 | [»] | ||||
4NMX | X-ray | 1.85 | A | 31-152 | [»] | |
B | 153-452 | [»] | ||||
4OV6 | X-ray | 2.69 | A/D | 60-152 | [»] | |
B/E | 153-446 | [»] | ||||
5OCA | X-ray | 2.30 | A | 31-152 | [»] | |
B | 153-692 | [»] | ||||
5VL7 | X-ray | 3.50 | A | 31-152 | [»] | |
B | 153-692 | [»] | ||||
5VLA | X-ray | 2.40 | A | 1-452 | [»] | |
5VLH | X-ray | 2.86 | A | 1-452 | [»] | |
5VLK | X-ray | 2.20 | A | 1-452 | [»] | |
5VLL | X-ray | 2.37 | A | 1-452 | [»] | |
5VLP | X-ray | 2.90 | A | 1-692 | [»] | |
6E4Y | X-ray | 2.24 | P | 32-53 | [»] | |
6E4Z | X-ray | 2.20 | P | 32-53 | [»] | |
6F5G | X-ray | 2.20 | A | 1-692 | [»] | |
6MV5 | X-ray | 2.10 | P | 32-53 | [»] | |
6OLZ | electron microscopy | 3.90 | A | 9-34 | [»] | |
6OM0 | electron microscopy | 3.10 | y | 9-34 | [»] | |
6OM7 | electron microscopy | 3.70 | y | 9-34 | [»] | |
SMRi | Q8NBP7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGridi | 129116, 27 interactors |
ComplexPortali | CPX-128 LDLR-PCSK9 complex CPX-130 ANXA2-PCSK9 complex |
DIPi | DIP-29694N |
IntActi | Q8NBP7, 5 interactors |
MINTi | Q8NBP7 |
STRINGi | 9606.ENSP00000303208 |
Chemistry databases
BindingDBi | Q8NBP7 |
ChEMBLi | CHEMBL2929 |
DrugBanki | DB09302 Alirocumab DB09303 Evolocumab |
DrugCentrali | Q8NBP7 |
GuidetoPHARMACOLOGYi | 2388 |
Protein family/group databases
MEROPSi | S08.039 |
PTM databases
iPTMneti | Q8NBP7 |
PhosphoSitePlusi | Q8NBP7 |
Polymorphism and mutation databases
BioMutai | PCSK9 |
DMDMi | 317373487 |
Proteomic databases
EPDi | Q8NBP7 |
jPOSTi | Q8NBP7 |
MassIVEi | Q8NBP7 |
MaxQBi | Q8NBP7 |
PaxDbi | Q8NBP7 |
PeptideAtlasi | Q8NBP7 |
PRIDEi | Q8NBP7 |
ProteomicsDBi | 72807 [Q8NBP7-1] 72808 [Q8NBP7-2] |
Protocols and materials databases
ABCDi | Q8NBP7 |
DNASUi | 255738 |
Genome annotation databases
Ensembli | ENST00000302118; ENSP00000303208; ENSG00000169174 [Q8NBP7-1] |
GeneIDi | 255738 |
KEGGi | hsa:255738 |
UCSCi | uc001cyf.3 human [Q8NBP7-1] |
Organism-specific databases
CTDi | 255738 |
DisGeNETi | 255738 |
GeneCardsi | PCSK9 |
GeneReviewsi | PCSK9 |
HGNCi | HGNC:20001 PCSK9 |
MalaCardsi | PCSK9 |
MIMi | 603776 phenotype 607786 gene |
neXtProti | NX_Q8NBP7 |
OpenTargetsi | ENSG00000169174 |
Orphaneti | 391665 Homozygous familial hypercholesterolemia 426 NON RARE IN EUROPE: Familial hypobetalipoproteinemia 406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia |
PharmGKBi | PA38617 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1153 Eukaryota COG1404 LUCA |
GeneTreei | ENSGT00490000043472 |
HOGENOMi | HOG000049267 |
InParanoidi | Q8NBP7 |
KOi | K13050 |
OMAi | FAQSVPW |
OrthoDBi | 921536at2759 |
PhylomeDBi | Q8NBP7 |
TreeFami | TF106271 |
Enzyme and pathway databases
BRENDAi | 3.4.21.61 2681 |
Reactomei | R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8866427 VLDLR internalisation and degradation R-HSA-8957275 Post-translational protein phosphorylation R-HSA-8964038 LDL clearance |
SignaLinki | Q8NBP7 |
SIGNORi | Q8NBP7 |
Miscellaneous databases
EvolutionaryTracei | Q8NBP7 |
GeneWikii | PCSK9 |
GenomeRNAii | 255738 |
Pharosi | Q8NBP7 |
PROi | PR:Q8NBP7 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000169174 Expressed in 85 organ(s), highest expression level in right lobe of liver |
Genevisiblei | Q8NBP7 HS |
Family and domain databases
CDDi | cd04077 Peptidases_S8_PCSK9_ProteinaseK_like, 1 hit |
Gene3Di | 3.30.70.80, 1 hit 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR041254 PCSK9_C IPR041052 PCSK9_C2 IPR041051 PCSK9_C3 IPR034193 PCSK9_ProteinaseK-like IPR000209 Peptidase_S8/S53_dom IPR036852 Peptidase_S8/S53_dom_sf IPR015500 Peptidase_S8_subtilisin-rel IPR010259 S8pro/Inhibitor_I9 IPR037045 S8pro/Inhibitor_I9_sf |
Pfami | View protein in Pfam PF05922 Inhibitor_I9, 1 hit PF18459 PCSK9_C1, 1 hit PF18464 PCSK9_C2, 1 hit PF18463 PCSK9_C3, 1 hit PF00082 Peptidase_S8, 1 hit |
PRINTSi | PR00723 SUBTILISIN |
SUPFAMi | SSF52743 SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51892 SUBTILASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PCSK9_HUMAN | |
Accessioni | Q8NBP7Primary (citable) accession number: Q8NBP7 Secondary accession number(s): A8T640 Q5SZQ2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 7, 2003 |
Last sequence update: | January 11, 2011 | |
Last modified: | November 13, 2019 | |
This is version 186 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references