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Q8NBP7

- PCSK9_HUMAN

UniProt

Q8NBP7 - PCSK9_HUMAN

Protein

Proprotein convertase subtilisin/kexin type 9

Gene

PCSK9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 3 (11 Jan 2011)
      Previous versions | rss
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    Functioni

    Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na+ channel (ENaC)-mediated Na+ absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.7 Publications

    Cofactori

    Calcium.Curated

    Enzyme regulationi

    Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei152 – 1532Cleavage; by autolysis
    Active sitei186 – 1861Charge relay systemBy similarity
    Sitei218 – 2192Cleavage; by furin and PCSK5
    Active sitei226 – 2261Charge relay systemBy similarity
    Active sitei386 – 3861Charge relay systemBy similarity

    GO - Molecular functioni

    1. apolipoprotein binding Source: UniProtKB
    2. apolipoprotein receptor binding Source: BHF-UCL
    3. low-density lipoprotein particle binding Source: UniProtKB
    4. low-density lipoprotein particle receptor binding Source: HGNC
    5. poly(A) RNA binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. protein self-association Source: UniProtKB
    8. serine-type endopeptidase activity Source: HGNC
    9. sodium channel inhibitor activity Source: UniProtKB
    10. very-low-density lipoprotein particle binding Source: UniProtKB
    11. very-low-density lipoprotein particle receptor binding Source: BHF-UCL

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cellular response to insulin stimulus Source: HGNC
    3. cellular response to starvation Source: HGNC
    4. cholesterol homeostasis Source: HGNC
    5. cholesterol metabolic process Source: UniProtKB-KW
    6. kidney development Source: HGNC
    7. lipoprotein metabolic process Source: Ensembl
    8. liver development Source: HGNC
    9. low-density lipoprotein particle receptor catabolic process Source: UniProtKB
    10. lysosomal transport Source: BHF-UCL
    11. negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
    12. negative regulation of receptor recycling Source: BHF-UCL
    13. neurogenesis Source: HGNC
    14. neuron differentiation Source: HGNC
    15. phospholipid metabolic process Source: Ensembl
    16. positive regulation of neuron apoptotic process Source: HGNC
    17. positive regulation of receptor internalization Source: BHF-UCL
    18. protein autoprocessing Source: HGNC
    19. proteolysis Source: RefGenome
    20. regulation of low-density lipoprotein particle receptor catabolic process Source: Ensembl
    21. regulation of neuron apoptotic process Source: UniProtKB
    22. regulation of receptor activity Source: BHF-UCL
    23. triglyceride metabolic process Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Apoptosis, Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

    Keywords - Ligandi

    Calcium

    Enzyme and pathway databases

    SignaLinkiQ8NBP7.

    Protein family/group databases

    MEROPSiS08.039.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:20001. PCSK9.

    Subcellular locationi

    Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus
    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.

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. early endosome Source: UniProtKB
    4. endoplasmic reticulum Source: UniProtKB
    5. extracellular space Source: HGNC
    6. extrinsic component of external side of plasma membrane Source: BHF-UCL
    7. Golgi apparatus Source: UniProtKB
    8. late endosome Source: UniProtKB
    9. lysosome Source: UniProtKB
    10. perinuclear region of cytoplasm Source: BHF-UCL
    11. plasma membrane Source: BHF-UCL
    12. rough endoplasmic reticulum Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3) [MIM:603776]: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti127 – 1271S → R in HCHOLA3. 1 Publication
    Corresponds to variant rs28942111 [ dbSNP | Ensembl ].
    VAR_017199
    Natural varianti129 – 1291D → G in HCHOLA3.
    VAR_058524
    Natural varianti215 – 2151R → H in HCHOLA3.
    VAR_058526
    Natural varianti216 – 2161F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 Publication
    Corresponds to variant rs28942112 [ dbSNP | Ensembl ].
    VAR_017200
    Natural varianti218 – 2181R → S in HCHOLA3; complete loss of cleavage by furin and PCSK5.
    VAR_058527
    Natural varianti357 – 3571R → H in HCHOLA3.
    VAR_058530
    Natural varianti374 – 3741D → H in HCHOLA3.
    VAR_058531
    Natural varianti374 – 3741D → Y in HCHOLA3; partial loss of cleavage by furin and PCSK5.
    VAR_058532
    Natural varianti496 – 4961R → W in HCHOLA3.
    VAR_058534

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi67 – 671C → A: Does not affect multimerization or zymogen processing. 1 Publication
    Mutagenesisi226 – 2261H → A: Remains in the endoplasmic reticulum and is not secreted. 1 Publication
    Mutagenesisi533 – 5331N → A: 1.5 kDa decrease of the apparent molecular mass of pro-PCSK9 and PCSK9 and no effect on processing and secretion. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi603776. phenotype.
    Orphaneti426. Familial hypobetalipoproteinemia.
    406. Heterozygous familial hypercholesterolemia.
    391665. Homozygous familial hypercholesterolemia.
    PharmGKBiPA38617.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 30301 PublicationAdd
    BLAST
    Propeptidei31 – 1521221 PublicationPRO_0000027120Add
    BLAST
    Chaini153 – 692540Proprotein convertase subtilisin/kexin type 9PRO_0000027121Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei38 – 381Sulfotyrosine1 Publication
    Modified residuei47 – 471Phosphoserine1 Publication
    Disulfide bondi223 ↔ 255Sequence Analysis
    Disulfide bondi323 ↔ 358Sequence Analysis
    Disulfide bondi457 ↔ 527Sequence Analysis
    Disulfide bondi477 ↔ 526Sequence Analysis
    Disulfide bondi486 ↔ 509Sequence Analysis
    Glycosylationi533 – 5331N-linked (GlcNAc...)1 Publication
    Disulfide bondi534 ↔ 601Sequence Analysis
    Disulfide bondi552 ↔ 600Sequence Analysis
    Disulfide bondi562 ↔ 588Sequence Analysis
    Disulfide bondi608 ↔ 679Sequence Analysis
    Disulfide bondi626 ↔ 678Sequence Analysis
    Disulfide bondi635 ↔ 654Sequence Analysis
    Modified residuei688 – 6881Phosphoserine4 Publications

    Post-translational modificationi

    Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.
    Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein.1 Publication
    Phosphorylation protects the propeptide against proteolysis.4 Publications

    Keywords - PTMi

    Autocatalytic cleavage, Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation, Zymogen

    Proteomic databases

    MaxQBiQ8NBP7.
    PaxDbiQ8NBP7.
    PRIDEiQ8NBP7.

    PTM databases

    PhosphoSiteiQ8NBP7.

    Expressioni

    Tissue specificityi

    Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.

    Gene expression databases

    ArrayExpressiQ8NBP7.
    BgeeiQ8NBP7.
    CleanExiHS_PCSK9.
    GenevestigatoriQ8NBP7.

    Organism-specific databases

    HPAiCAB025575.

    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.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ANXA2P073557EBI-7539251,EBI-352622
    LDLRP011309EBI-7539251,EBI-988319

    Protein-protein interaction databases

    BioGridi129116. 2 interactions.
    DIPiDIP-29694N.
    IntActiQ8NBP7. 2 interactions.
    MINTiMINT-3041747.
    STRINGi9606.ENSP00000303208.

    Structurei

    Secondary structure

    1
    692
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi63 – 653
    Helixi70 – 723
    Beta strandi73 – 8210
    Helixi88 – 10417
    Beta strandi110 – 1156
    Beta strandi117 – 1193
    Beta strandi121 – 1255
    Helixi128 – 1303
    Helixi131 – 1355
    Beta strandi140 – 15112
    Helixi156 – 1605
    Helixi168 – 1703
    Beta strandi181 – 1877
    Turni194 – 1996
    Beta strandi200 – 2067
    Beta strandi212 – 2143
    Turni218 – 2203
    Turni221 – 2244
    Helixi225 – 23511
    Turni237 – 2393
    Beta strandi241 – 2444
    Beta strandi246 – 2516
    Beta strandi257 – 2604
    Helixi261 – 27717
    Beta strandi283 – 2875
    Beta strandi289 – 2924
    Helixi295 – 30612
    Beta strandi310 – 3145
    Beta strandi317 – 3215
    Helixi322 – 3243
    Turni327 – 3293
    Beta strandi333 – 3397
    Beta strandi343 – 3453
    Beta strandi349 – 3524
    Beta strandi355 – 3584
    Beta strandi361 – 3644
    Beta strandi366 – 3727
    Beta strandi373 – 3753
    Beta strandi378 – 3825
    Helixi385 – 40218
    Helixi408 – 41710
    Beta strandi419 – 4224
    Helixi426 – 4283
    Helixi431 – 4333
    Turni434 – 4363
    Beta strandi440 – 4423
    Beta strandi456 – 4616
    Beta strandi467 – 4704
    Beta strandi472 – 4754
    Beta strandi482 – 4898
    Beta strandi491 – 4933
    Beta strandi495 – 5039
    Beta strandi506 – 5138
    Beta strandi521 – 5288
    Beta strandi533 – 5397
    Beta strandi544 – 5463
    Beta strandi548 – 5514
    Beta strandi558 – 5658
    Beta strandi567 – 5693
    Beta strandi587 – 5904
    Beta strandi594 – 6029
    Beta strandi606 – 61510
    Beta strandi621 – 6255
    Beta strandi631 – 6377
    Beta strandi644 – 6507
    Beta strandi653 – 6586
    Beta strandi672 – 68110

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2P4EX-ray1.98A/P1-692[»]
    2PMWX-ray2.30A31-152[»]
    B153-692[»]
    2QTWX-ray1.90A29-152[»]
    B153-692[»]
    2W2MX-ray2.40A153-451[»]
    P53-152[»]
    2W2NX-ray2.30A153-451[»]
    P53-152[»]
    2W2OX-ray2.62A153-451[»]
    P53-152[»]
    2W2PX-ray2.62A153-451[»]
    P53-152[»]
    2W2QX-ray2.33A153-451[»]
    P53-152[»]
    2XTJX-ray2.70A153-451[»]
    P53-152[»]
    3BPSX-ray2.41A153-692[»]
    P53-152[»]
    3GCWX-ray2.70A153-692[»]
    P53-152[»]
    3GCXX-ray2.70A153-692[»]
    P53-152[»]
    3H42X-ray2.30A31-152[»]
    B153-692[»]
    3M0CX-ray7.01A29-152[»]
    B153-692[»]
    3P5BX-ray3.30A153-692[»]
    P61-152[»]
    3P5CX-ray4.20A153-692[»]
    P61-152[»]
    3SQOX-ray2.70A153-692[»]
    P31-152[»]
    4K8RX-ray3.22A61-152[»]
    B153-692[»]
    4NMXX-ray1.85A31-152[»]
    B153-452[»]
    ProteinModelPortaliQ8NBP7.
    SMRiQ8NBP7. Positions 61-682.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8NBP7.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini182 – 424243Peptidase S8Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni450 – 692243C-terminal domainAdd
    BLAST

    Domaini

    The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities.1 Publication
    The catalytic domain is responsible for mediating its self-association.1 Publication

    Sequence similaritiesi

    Belongs to the peptidase S8 family.Curated
    Contains 1 peptidase S8 domain.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG1404.
    HOGENOMiHOG000049267.
    HOVERGENiHBG053530.
    InParanoidiQ8NBP7.
    KOiK13050.
    OMAiHVLTGCS.
    OrthoDBiEOG79PJNT.
    PhylomeDBiQ8NBP7.
    TreeFamiTF106271.

    Family and domain databases

    Gene3Di3.40.50.200. 1 hit.
    InterProiIPR010259. Inhibitor_I9.
    IPR000209. Peptidase_S8/S53_dom.
    IPR015500. Peptidase_S8_subtilisin-rel.
    IPR009020. Prot_inh_propept.
    [Graphical view]
    PANTHERiPTHR10795. PTHR10795. 1 hit.
    PfamiPF05922. Inhibitor_I9. 1 hit.
    PF00082. Peptidase_S8. 1 hit.
    [Graphical view]
    PRINTSiPR00723. SUBTILISIN.
    SUPFAMiSSF52743. SSF52743. 1 hit.
    SSF54897. SSF54897. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8NBP7-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGTVSSRRSW WPLPLLLLLL LLLGPAGARA QEDEDGDYEE LVLALRSEED    50
    GLAEAPEHGT TATFHRCAKD PWRLPGTYVV VLKEETHLSQ SERTARRLQA 100
    QAARRGYLTK ILHVFHGLLP GFLVKMSGDL LELALKLPHV DYIEEDSSVF 150
    AQSIPWNLER ITPPRYRADE YQPPDGGSLV EVYLLDTSIQ SDHREIEGRV 200
    MVTDFENVPE EDGTRFHRQA SKCDSHGTHL AGVVSGRDAG VAKGASMRSL 250
    RVLNCQGKGT VSGTLIGLEF IRKSQLVQPV GPLVVLLPLA GGYSRVLNAA 300
    CQRLARAGVV LVTAAGNFRD DACLYSPASA PEVITVGATN AQDQPVTLGT 350
    LGTNFGRCVD LFAPGEDIIG ASSDCSTCFV SQSGTSQAAA HVAGIAAMML 400
    SAEPELTLAE LRQRLIHFSA KDVINEAWFP EDQRVLTPNL VAALPPSTHG 450
    AGWQLFCRTV WSAHSGPTRM ATAVARCAPD EELLSCSSFS RSGKRRGERM 500
    EAQGGKLVCR AHNAFGGEGV YAIARCCLLP QANCSVHTAP PAEASMGTRV 550
    HCHQQGHVLT GCSSHWEVED LGTHKPPVLR PRGQPNQCVG HREASIHASC 600
    CHAPGLECKV KEHGIPAPQE QVTVACEEGW TLTGCSALPG TSHVLGAYAV 650
    DNTCVVRSRD VSTTGSTSEG AVTAVAICCR SRHLAQASQE LQ 692
    Length:692
    Mass (Da):74,286
    Last modified:January 11, 2011 - v3
    Checksum:i9BCB9418B90AEE23
    GO
    Isoform 2 (identifier: Q8NBP7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-174: MGTVSSRRSW...RYRADEYQPP → MSPWK
         333-365: VITVGATNAQDQPVTLGTLGTNFGRCVDLFAPG → GRTSLVPPATAAPALCHRVGHHRLLPTWLALQP
         366-692: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:196
    Mass (Da):20,827
    Checksum:i6073DFE87E84FA15
    GO

    Sequence cautioni

    The sequence BAC11572.1 differs from that shown. Reason: Frameshift at position 494.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti423 – 4231V → A in BAC11572. (PubMed:14702039)Curated

    Polymorphismi

    Variant Leu-23 ins polymorphism in PCSK9 might have a modifier effect on LDLR mutation and familial hypercholesterolemia.
    Genetic variations in PCSK9 define the low density lipoprotein cholesterol level quantitative trait locus 1 (LDLCQ1) [MIMi:603776].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti23 – 231L → LL This polymoprhism seems to have a modifier effect on LDLR mutation and familial hypercholesterolemia. 4 Publications
    VAR_021336
    Natural varianti46 – 461R → L Polymorphism associated with lower plasma levels of low-density lipoprotein cholesterol and reduced phosphorylation at Ser-47. 4 Publications
    Corresponds to variant rs11591147 [ dbSNP | Ensembl ].
    VAR_017197
    Natural varianti53 – 531A → V Polymorphism associated with reduced phosphorylation at Ser-47. 4 Publications
    Corresponds to variant rs11583680 [ dbSNP | Ensembl ].
    VAR_017198
    Natural varianti57 – 571E → K.1 Publication
    VAR_025451
    Natural varianti77 – 771T → I.
    VAR_058520
    Natural varianti93 – 931R → C.
    Corresponds to variant rs151193009 [ dbSNP | Ensembl ].
    VAR_058521
    Natural varianti106 – 1061G → R.
    VAR_058522
    Natural varianti114 – 1141V → A.
    VAR_058523
    Natural varianti127 – 1271S → R in HCHOLA3. 1 Publication
    Corresponds to variant rs28942111 [ dbSNP | Ensembl ].
    VAR_017199
    Natural varianti129 – 1291D → G in HCHOLA3.
    VAR_058524
    Natural varianti157 – 1571N → K.
    VAR_058525
    Natural varianti174 – 1741P → S Found in patients with familial hypercholesterolemia carrying a homozygous LDLR mutation; acts as a disease modifier resulting in a mild phenotype. 1 Publication
    VAR_067351
    Natural varianti215 – 2151R → H in HCHOLA3.
    VAR_058526
    Natural varianti216 – 2161F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 Publication
    Corresponds to variant rs28942112 [ dbSNP | Ensembl ].
    VAR_017200
    Natural varianti218 – 2181R → S in HCHOLA3; complete loss of cleavage by furin and PCSK5.
    VAR_058527
    Natural varianti219 – 2191Q → E.
    VAR_058528
    Natural varianti237 – 2371R → W.1 Publication
    VAR_025452
    Natural varianti239 – 2391A → D.
    VAR_058529
    Natural varianti253 – 2531L → F Polymorphism associated with lower plasma levels of low-density lipoprotein cholesterol. 1 Publication
    Corresponds to variant rs28362270 [ dbSNP | Ensembl ].
    VAR_025453
    Natural varianti357 – 3571R → H in HCHOLA3.
    VAR_058530
    Natural varianti374 – 3741D → H in HCHOLA3.
    VAR_058531
    Natural varianti374 – 3741D → Y in HCHOLA3; partial loss of cleavage by furin and PCSK5.
    VAR_058532
    Natural varianti391 – 3911H → N.1 Publication
    VAR_025454
    Natural varianti394 – 3941G → S Found in a patient associated with autosomal dominant hypercholesterolemia; unknown pathological significance. 1 Publication
    VAR_067282
    Natural varianti417 – 4171H → Q.1 Publication
    Corresponds to variant rs143275858 [ dbSNP | Ensembl ].
    VAR_025455
    Natural varianti425 – 4251N → S.2 Publications
    Corresponds to variant rs28362261 [ dbSNP | Ensembl ].
    VAR_021337
    Natural varianti443 – 4431A → T Polymorphism associated with lower plasma levels of low-density lipoprotein cholesterol; more extensive cleavage by furin and PCSK5. 2 Publications
    Corresponds to variant rs28362263 [ dbSNP | Ensembl ].
    VAR_021338
    Natural varianti452 – 4521G → D.
    VAR_058533
    Natural varianti469 – 4691R → W.1 Publication
    Corresponds to variant rs141502002 [ dbSNP | Ensembl ].
    VAR_025456
    Natural varianti474 – 4741V → I.8 Publications
    Corresponds to variant rs562556 [ dbSNP | Ensembl ].
    VAR_021339
    Natural varianti482 – 4821E → G.1 Publication
    VAR_025457
    Natural varianti496 – 4961R → W in HCHOLA3.
    VAR_058534
    Natural varianti515 – 5151F → L.1 Publication
    VAR_025458
    Natural varianti522 – 5221A → T.
    VAR_058535
    Natural varianti553 – 5531H → R.2 Publications
    Corresponds to variant rs28362270 [ dbSNP | Ensembl ].
    VAR_021340
    Natural varianti554 – 5541Q → E.1 Publication
    Corresponds to variant rs149311926 [ dbSNP | Ensembl ].
    VAR_025459
    Natural varianti616 – 6161P → L.
    VAR_058536
    Natural varianti619 – 6191Q → P.2 Publications
    Corresponds to variant rs28362277 [ dbSNP | Ensembl ].
    VAR_021341
    Natural varianti668 – 6681S → R.
    VAR_058537
    Natural varianti670 – 6701G → E.8 Publications
    Corresponds to variant rs505151 [ dbSNP | Ensembl ].
    VAR_017201

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 174174MGTVS…EYQPP → MSPWK in isoform 2. 1 PublicationVSP_008844Add
    BLAST
    Alternative sequencei333 – 36533VITVG…LFAPG → GRTSLVPPATAAPALCHRVG HHRLLPTWLALQP in isoform 2. 1 PublicationVSP_008845Add
    BLAST
    Alternative sequencei366 – 692327Missing in isoform 2. 1 PublicationVSP_008846Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    AL589790, AC091609 Genomic DNA. Translation: CAI17845.1.
    CH471059 Genomic DNA. Translation: EAX06660.1.
    CCDSiCCDS603.1. [Q8NBP7-1]
    RefSeqiNP_777596.2. NM_174936.3. [Q8NBP7-1]
    UniGeneiHs.18844.

    Genome annotation databases

    EnsembliENST00000302118; ENSP00000303208; ENSG00000169174. [Q8NBP7-1]
    GeneIDi255738.
    KEGGihsa:255738.
    UCSCiuc001cyf.2. human. [Q8NBP7-1]

    Polymorphism databases

    DMDMi317373487.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    AL589790 , AC091609 Genomic DNA. Translation: CAI17845.1 .
    CH471059 Genomic DNA. Translation: EAX06660.1 .
    CCDSi CCDS603.1. [Q8NBP7-1 ]
    RefSeqi NP_777596.2. NM_174936.3. [Q8NBP7-1 ]
    UniGenei Hs.18844.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    4NMX X-ray 1.85 A 31-152 [» ]
    B 153-452 [» ]
    ProteinModelPortali Q8NBP7.
    SMRi Q8NBP7. Positions 61-682.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 129116. 2 interactions.
    DIPi DIP-29694N.
    IntActi Q8NBP7. 2 interactions.
    MINTi MINT-3041747.
    STRINGi 9606.ENSP00000303208.

    Chemistry

    BindingDBi Q8NBP7.
    ChEMBLi CHEMBL2929.

    Protein family/group databases

    MEROPSi S08.039.

    PTM databases

    PhosphoSitei Q8NBP7.

    Polymorphism databases

    DMDMi 317373487.

    Proteomic databases

    MaxQBi Q8NBP7.
    PaxDbi Q8NBP7.
    PRIDEi Q8NBP7.

    Protocols and materials databases

    DNASUi 255738.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302118 ; ENSP00000303208 ; ENSG00000169174 . [Q8NBP7-1 ]
    GeneIDi 255738.
    KEGGi hsa:255738.
    UCSCi uc001cyf.2. human. [Q8NBP7-1 ]

    Organism-specific databases

    CTDi 255738.
    GeneCardsi GC01P055505.
    GeneReviewsi PCSK9.
    H-InvDB HIX0023558.
    HGNCi HGNC:20001. PCSK9.
    HPAi CAB025575.
    MIMi 603776. phenotype.
    607786. gene.
    neXtProti NX_Q8NBP7.
    Orphaneti 426. Familial hypobetalipoproteinemia.
    406. Heterozygous familial hypercholesterolemia.
    391665. Homozygous familial hypercholesterolemia.
    PharmGKBi PA38617.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1404.
    HOGENOMi HOG000049267.
    HOVERGENi HBG053530.
    InParanoidi Q8NBP7.
    KOi K13050.
    OMAi HVLTGCS.
    OrthoDBi EOG79PJNT.
    PhylomeDBi Q8NBP7.
    TreeFami TF106271.

    Enzyme and pathway databases

    SignaLinki Q8NBP7.

    Miscellaneous databases

    EvolutionaryTracei Q8NBP7.
    GeneWikii PCSK9.
    GenomeRNAii 255738.
    NextBioi 92626.
    PROi Q8NBP7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8NBP7.
    Bgeei Q8NBP7.
    CleanExi HS_PCSK9.
    Genevestigatori Q8NBP7.

    Family and domain databases

    Gene3Di 3.40.50.200. 1 hit.
    InterProi IPR010259. Inhibitor_I9.
    IPR000209. Peptidase_S8/S53_dom.
    IPR015500. Peptidase_S8_subtilisin-rel.
    IPR009020. Prot_inh_propept.
    [Graphical view ]
    PANTHERi PTHR10795. PTHR10795. 1 hit.
    Pfami PF05922. Inhibitor_I9. 1 hit.
    PF00082. Peptidase_S8. 1 hit.
    [Graphical view ]
    PRINTSi PR00723. SUBTILISIN.
    SUPFAMi SSF52743. SSF52743. 1 hit.
    SSF54897. SSF54897. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Nucleic acid molecules derived from rat brain and programmed cell death models."
      Chiang L.W.
      Patent number WO0131007, 03-MAY-2001
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ILE-474 AND GLU-670.
    2. "Evidence for positive selection in the C-terminal domain of the cholesterol metabolism gene PCSK9 based on phylogenetic analysis in 14 primate species."
      Ding K., McDonough S.J., Kullo I.J.
      PLoS ONE 2:E1098-E1098(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ILE-474 AND GLU-670.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-474.
      Tissue: Cerebellum and Teratocarcinoma.
    4. SeattleSNPs variation discovery resource
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-23 INS; LEU-46; VAL-53; SER-425; THR-443; ILE-474; ARG-553; PRO-619 AND GLU-670.
    5. NHLBI resequencing and genotyping service (RS&G)
      Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-23 INS; ILE-474 AND GLU-670.
    6. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ILE-474 AND GLU-670.
    8. "The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation."
      Seidah N.G., Benjannet S., Wickham L., Marcinkiewicz J., Jasmin S.B., Stifani S., Basak A., Prat A., Chretien M.
      Proc. Natl. Acad. Sci. U.S.A. 100:928-933(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF N-TERMINUS, CHARACTERIZATION, MUTAGENESIS OF CYS-67; HIS-226 AND ASN-533.
    9. Cited for: AUTOCATALYTIC CLEAVAGE SITE.
    10. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    11. "The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications."
      Benjannet S., Rhainds D., Hamelin J., Nassoury N., Seidah N.G.
      J. Biol. Chem. 281:30561-30572(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-533, SULFATION AT TYR-38, CLEAVAGE AT ARG-218 BY FURIN AND PCSK5.
    12. "The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR."
      Nassoury N., Blasiole D.A., Tebon Oler A., Benjannet S., Hamelin J., Poupon V., McPherson P.S., Attie A.D., Prat A., Seidah N.G.
      Traffic 8:718-732(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LDLR.
    13. "Self-association of human PCSK9 correlates with its LDLR-degrading activity."
      Fan D., Yancey P.G., Qiu S., Ding L., Weeber E.J., Linton M.F., Fazio S.
      Biochemistry 47:1631-1639(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    14. "PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1."
      Jonas M.C., Costantini C., Puglielli L.
      EMBO Rep. 9:916-922(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH BACE1.
    15. "PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans."
      Dewpura T., Raymond A., Hamelin J., Seidah N.G., Mbikay M., Chretien M., Mayne J.
      FEBS J. 275:3480-3493(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-47 AND SER-688, IDENTIFICATION BY MASS SPECTROMETRY.
    16. "The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2."
      Poirier S., Mayer G., Benjannet S., Bergeron E., Marcinkiewicz J., Nassoury N., Mayer H., Nimpf J., Prat A., Seidah N.G.
      J. Biol. Chem. 283:2363-2372(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VLDLR AND LRP8/APOER2.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    18. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    19. "Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation."
      Chen Y., Wang H., Yu L., Yu X., Qian Y.W., Cao G., Wang J.
      Biochem. Biophys. Res. Commun. 415:515-518(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    20. "A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor."
      Yamamoto T., Lu C., Ryan R.O.
      J. Biol. Chem. 286:5464-5470(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LDLR.
    21. "Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein."
      Du F., Hui Y., Zhang M., Linton M.F., Fazio S., Fan D.
      J. Biol. Chem. 286:43054-43061(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN C-TERMINAL.
    22. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    23. "Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor."
      Sun H., Samarghandi A., Zhang N., Yao Z., Xiong M., Teng B.B.
      Arterioscler. Thromb. Vasc. Biol. 32:1585-1595(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH APOB.
    24. Cited for: REVIEW.
    25. Cited for: REVIEW.
    26. "The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis."
      Mousavi S.A., Berge K.E., Leren T.P.
      J. Intern. Med. 266:507-519(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    27. "PCSK9: a convertase that coordinates LDL catabolism."
      Horton J.D., Cohen J.C., Hobbs H.H.
      J. Lipid Res. 50:S172-S177(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    28. "Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition."
      Tibolla G., Norata G.D., Artali R., Meneghetti F., Catapano A.L.
      Nutr. Metab. Cardiovasc. Dis. 21:835-843(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    29. "Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease."
      Abifadel M., Rabes J.P., Devillers M., Munnich A., Erlich D., Junien C., Varret M., Boileau C.
      Hum. Mutat. 30:520-529(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    30. "Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients."
      Slimani A., Jelassi A., Jguirim I., Najah M., Rebhi L., Omezzine A., Maatouk F., Hamda K.B., Kacem M., Rabes J.P., Abifadel M., Boileau C., Rouis M., Slimane M.N., Varret M.
      Atherosclerosis 222:158-166(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN LDLCQ1, VARIANT SER-174.
    31. "Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9)."
      Sharotri V., Collier D.M., Olson D.R., Zhou R., Snyder P.M.
      J. Biol. Chem. 287:19266-19274(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.
    32. "The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol."
      Piper D.E., Jackson S., Liu Q., Romanow W.G., Shetterly S., Thibault S.T., Shan B., Walker N.P.
      Structure 15:545-552(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 31-692.
    33. Cited for: VARIANTS HCHOLA3 ARG-127 AND LEU-216, VARIANTS LEU-46; VAL-53 AND GLU-670.
    34. "A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol."
      Kotowski I.K., Pertsemlidis A., Luke A., Cooper R.S., Vega G.L., Cohen J.C., Hobbs H.H.
      Am. J. Hum. Genet. 78:410-422(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LEU-46; VAL-53; LYS-57; TRP-237; PHE-253; ASN-391; GLN-417; SER-425; THR-443; TRP-469; ILE-474; GLY-482; LEU-515; ARG-553; GLU-554; PRO-619 AND GLU-670.
    35. "The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene."
      Abifadel M., Rabes J.-P., Jambart S., Halaby G., Gannage-Yared M.-H., Sarkis A., Beaino G., Varret M., Salem N., Corbani S., Aydenian H., Junien C., Munnich A., Boileau C.
      Hum. Mutat. 30:E682-E691(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN LDLCQ1, VARIANT LEU-23 INS, IMPACT ON FAMILIAL HYPERCHOLESTEROLEMIA.
    36. "Genetic variation in APOB, PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels."
      Huijgen R., Sjouke B., Vis K., de Randamie J.S., Defesche J.C., Kastelein J.J., Hovingh G.K., Fouchier S.W.
      Hum. Mutat. 33:448-455(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN LDLCQ1, VARIANTS LEU-23 INS; LEU-46; VAL-53; SER-394; ILE-474 AND GLU-670.

    Entry informationi

    Entry nameiPCSK9_HUMAN
    AccessioniPrimary (citable) accession number: Q8NBP7
    Secondary accession number(s): A8T640
    , C0JYY9, Q5PSM5, Q5SZQ2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 7, 2003
    Last sequence update: January 11, 2011
    Last modified: October 1, 2014
    This is version 135 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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 proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3