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Q8NBP7

- PCSK9_HUMAN

UniProt

Q8NBP7 - PCSK9_HUMAN

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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

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

Ca2+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 self-association Source: UniProtKB
  7. serine-type endopeptidase activity Source: HGNC
  8. sodium channel inhibitor activity Source: UniProtKB
  9. very-low-density lipoprotein particle binding Source: UniProtKB
  10. 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
Complete GO annotation...

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. ER to Golgi transport vesicle Source: Ensembl
  6. extracellular space Source: HGNC
  7. extrinsic component of external side of plasma membrane Source: BHF-UCL
  8. Golgi apparatus Source: UniProtKB
  9. late endosome Source: UniProtKB
  10. lysosome Source: UniProtKB
  11. perinuclear region of cytoplasm Source: BHF-UCL
  12. plasma membrane Source: BHF-UCL
  13. rough endoplasmic reticulum Source: Ensembl
Complete GO annotation...

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

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 – 653Combined sources
Helixi70 – 723Combined sources
Beta strandi73 – 8210Combined sources
Beta strandi84 – 863Combined sources
Helixi88 – 10417Combined sources
Beta strandi110 – 1156Combined sources
Beta strandi117 – 1193Combined sources
Beta strandi121 – 1255Combined sources
Helixi128 – 1303Combined sources
Helixi131 – 1355Combined sources
Beta strandi140 – 15112Combined sources
Helixi156 – 1605Combined sources
Helixi168 – 1703Combined sources
Beta strandi181 – 1877Combined sources
Turni194 – 1996Combined sources
Beta strandi200 – 2067Combined sources
Beta strandi212 – 2143Combined sources
Turni218 – 2203Combined sources
Turni221 – 2244Combined sources
Helixi225 – 23511Combined sources
Turni237 – 2393Combined sources
Beta strandi241 – 2444Combined sources
Beta strandi246 – 2516Combined sources
Beta strandi257 – 2604Combined sources
Helixi261 – 27717Combined sources
Beta strandi283 – 2875Combined sources
Beta strandi289 – 2924Combined sources
Helixi295 – 30612Combined sources
Beta strandi310 – 3145Combined sources
Beta strandi317 – 3215Combined sources
Helixi322 – 3243Combined sources
Turni327 – 3293Combined sources
Beta strandi333 – 3397Combined sources
Beta strandi343 – 3453Combined sources
Beta strandi349 – 3524Combined sources
Beta strandi355 – 3584Combined sources
Beta strandi361 – 3644Combined sources
Beta strandi366 – 3727Combined sources
Beta strandi373 – 3753Combined sources
Beta strandi378 – 3825Combined sources
Helixi385 – 40218Combined sources
Helixi408 – 41710Combined sources
Beta strandi419 – 4224Combined sources
Helixi426 – 4283Combined sources
Helixi431 – 4333Combined sources
Turni434 – 4363Combined sources
Beta strandi440 – 4423Combined sources
Beta strandi456 – 4616Combined sources
Beta strandi467 – 4704Combined sources
Beta strandi472 – 4754Combined sources
Beta strandi482 – 4898Combined sources
Beta strandi491 – 4933Combined sources
Beta strandi495 – 5039Combined sources
Beta strandi506 – 5138Combined sources
Beta strandi521 – 5288Combined sources
Beta strandi533 – 5397Combined sources
Beta strandi544 – 5463Combined sources
Beta strandi548 – 5514Combined sources
Beta strandi558 – 5658Combined sources
Beta strandi568 – 5703Combined sources
Beta strandi587 – 5904Combined sources
Beta strandi594 – 6029Combined sources
Beta strandi606 – 61510Combined sources
Beta strandi621 – 6255Combined sources
Beta strandi631 – 6377Combined sources
Beta strandi644 – 6507Combined sources
Beta strandi653 – 6586Combined sources
Beta strandi672 – 68110Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4NE9X-ray2.60A/B153-692[»]
C/P1-152[»]
4NMXX-ray1.85A31-152[»]
B153-452[»]
4OV6X-ray2.69A/D60-152[»]
B/E153-446[»]
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.
GeneTreeiENSGT00490000043472.
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

        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
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. Curated

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:
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.
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:
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 .
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:
PDBei
RCSB PDBi
PDBji
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 [» ]
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 [» ]
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

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.
GeneTreei ENSGT00490000043472.
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

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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 137 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