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UniProtKB - Q8NBP7 (PCSK9_HUMAN)

Protein

Proprotein convertase subtilisin/kexin type 9

Gene

PCSK9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:18039658). 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 (PubMed:18799458, PubMed:17461796, PubMed:18197702, PubMed:22074827). 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 (PubMed:18660751). 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.8 Publications

Cofactori

Ca2+Curated

Activity 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)DescriptionActionsGraphical viewLength
Active sitei186Charge relay systemBy similarity1
Active sitei226Charge relay systemBy similarity1
Active sitei386Charge relay systemBy similarity1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis, Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism
LigandCalcium

Enzyme and pathway databases

BRENDAi3.4.21.61 2681
ReactomeiR-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
SignaLinkiQ8NBP7
SIGNORiQ8NBP7

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000169174.10
HGNCiHGNC:20001 PCSK9
MIMi607786 gene
neXtProtiNX_Q8NBP7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.
See also OMIM:603776
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017199127S → R in HCHOLA3. 1 PublicationCorresponds to variant dbSNP:rs28942111EnsemblClinVar.1
Natural variantiVAR_058524129D → G in HCHOLA3. 1
Natural variantiVAR_058526215R → H in HCHOLA3. Corresponds to variant dbSNP:rs794728683EnsemblClinVar.1
Natural variantiVAR_017200216F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 PublicationCorresponds to variant dbSNP:rs28942112EnsemblClinVar.1
Natural variantiVAR_058527218R → 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_058530357R → H in HCHOLA3. Corresponds to variant dbSNP:rs370507566EnsemblClinVar.1
Natural variantiVAR_058531374D → H in HCHOLA3. Corresponds to variant dbSNP:rs137852912EnsemblClinVar.1
Natural variantiVAR_058532374D → 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_058534496R → W in HCHOLA3. Corresponds to variant dbSNP:rs374603772EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67C → A: Does not affect multimerization or zymogen processing. 1 Publication1
Mutagenesisi226H → A: Remains in the endoplasmic reticulum and is not secreted. 1 Publication1
Mutagenesisi533N → A: 1.5 kDa decrease of the apparent molecular mass of pro-PCSK9 and PCSK9 and no effect on processing and secretion. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi255738
GeneReviewsiPCSK9
MalaCardsiPCSK9
MIMi603776 phenotype
OpenTargetsiENSG00000169174
Orphaneti391665 Homozygous familial hypercholesterolemia
426 NON RARE IN EUROPE: Familial hypobetalipoproteinemia
406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia
PharmGKBiPA38617

Chemistry databases

ChEMBLiCHEMBL2929
DrugBankiDB09302 Alirocumab
DB09303 Evolocumab
GuidetoPHARMACOLOGYi2388

Polymorphism and mutation databases

BioMutaiPCSK9
DMDMi317373487

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 301 PublicationAdd BLAST30
PropeptideiPRO_000002712031 – 1521 PublicationAdd BLAST122
ChainiPRO_0000027121153 – 692Proprotein convertase subtilisin/kexin type 9Add BLAST540

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38Sulfotyrosine1 Publication1
Modified residuei47Phosphoserine; by FAM20C2 Publications1
Disulfide bondi223 ↔ 255Sequence analysis
Disulfide bondi323 ↔ 358Sequence analysis
Disulfide bondi457 ↔ 527Sequence analysis
Disulfide bondi477 ↔ 526Sequence analysis
Disulfide bondi486 ↔ 509Sequence analysis
Glycosylationi533N-linked (GlcNAc...) asparagine1 Publication1
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 residuei688Phosphoserine; by FAM20CCombined sources2 Publications1

Post-translational modificationi

Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.1 Publication
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei152 – 153Cleavage; by autolysis1 Publication2
Sitei218 – 219Cleavage; by furin and PCSK51 Publication2

Keywords - PTMi

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

Proteomic databases

EPDiQ8NBP7
MaxQBiQ8NBP7
PaxDbiQ8NBP7
PeptideAtlasiQ8NBP7
PRIDEiQ8NBP7
ProteomicsDBi72807
72808 [Q8NBP7-2]

PTM databases

iPTMnetiQ8NBP7
PhosphoSitePlusiQ8NBP7

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000169174 Expressed in 85 organ(s), highest expression level in right lobe of liver
CleanExiHS_PCSK9
GenevisibleiQ8NBP7 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 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi129116, 27 interactors
ComplexPortaliCPX-128 LDLR-PCSK9 complex
CPX-130 ANXA2-PCSK9 complex
DIPiDIP-29694N
IntActiQ8NBP7, 5 interactors
MINTiQ8NBP7
STRINGi9606.ENSP00000303208

Chemistry databases

BindingDBiQ8NBP7

Structurei

Secondary structure

1692
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8NBP7
SMRiQ8NBP7
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8NBP7

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini182 – 424Peptidase S8Add BLAST243

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni450 – 692C-terminal domainAdd BLAST243

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1153 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00490000043472
HOGENOMiHOG000049267
HOVERGENiHBG053530
InParanoidiQ8NBP7
KOiK13050
OMAiKCDSHGT
OrthoDBiEOG091G067E
PhylomeDBiQ8NBP7
TreeFamiTF106271

Family and domain databases

CDDicd04077 Peptidases_S8_PCSK9_Proteinase, 1 hit
Gene3Di3.30.70.80, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
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
PfamiView protein in Pfam
PF05922 Inhibitor_I9, 1 hit
PF00082 Peptidase_S8, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF52743 SSF52743, 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. AlignAdd to basket
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 differs from that shown. Reason: Frameshift at position 494.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti423V → A in BAC11572 (PubMed:14702039).Curated1

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].3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02133623L → LL This polymoprhism seems to have a modifier effect on LDLR mutation and familial hypercholesterolemia. 4 Publications1
Natural variantiVAR_01719746R → 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_01719853A → V Polymorphism; associated with reduced phosphorylation at Ser-47. 4 PublicationsCorresponds to variant dbSNP:rs11583680EnsemblClinVar.1
Natural variantiVAR_02545157E → K1 PublicationCorresponds to variant dbSNP:rs145886902EnsemblClinVar.1
Natural variantiVAR_05852077T → I. Corresponds to variant dbSNP:rs756060557Ensembl.1
Natural variantiVAR_05852193R → C. Corresponds to variant dbSNP:rs151193009EnsemblClinVar.1
Natural variantiVAR_058522106G → R. 1
Natural variantiVAR_058523114V → A. Corresponds to variant dbSNP:rs775988212Ensembl.1
Natural variantiVAR_017199127S → R in HCHOLA3. 1 PublicationCorresponds to variant dbSNP:rs28942111EnsemblClinVar.1
Natural variantiVAR_058524129D → G in HCHOLA3. 1
Natural variantiVAR_058525157N → K. Corresponds to variant dbSNP:rs143117125Ensembl.1
Natural variantiVAR_067351174P → 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_058526215R → H in HCHOLA3. Corresponds to variant dbSNP:rs794728683EnsemblClinVar.1
Natural variantiVAR_017200216F → L in HCHOLA3; partial loss of cleavage by furin and PCSK5. 1 PublicationCorresponds to variant dbSNP:rs28942112EnsemblClinVar.1
Natural variantiVAR_058527218R → 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_058528219Q → E. Corresponds to variant dbSNP:rs778617372EnsemblClinVar.1
Natural variantiVAR_025452237R → W1 PublicationCorresponds to variant dbSNP:rs148195424EnsemblClinVar.1
Natural variantiVAR_058529239A → D. 1
Natural variantiVAR_025453253L → F Polymorphism; associated with lower plasma levels of low-density lipoprotein cholesterol. 1 PublicationCorresponds to variant dbSNP:rs72646508EnsemblClinVar.1
Natural variantiVAR_058530357R → H in HCHOLA3. Corresponds to variant dbSNP:rs370507566EnsemblClinVar.1
Natural variantiVAR_058531374D → H in HCHOLA3. Corresponds to variant dbSNP:rs137852912EnsemblClinVar.1
Natural variantiVAR_058532374D → 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_025454391H → N1 PublicationCorresponds to variant dbSNP:rs146471967EnsemblClinVar.1
Natural variantiVAR_067282394G → S Found in a patient associated with autosomal dominant hypercholesterolemia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs368257906EnsemblClinVar.1
Natural variantiVAR_025455417H → Q1 PublicationCorresponds to variant dbSNP:rs143275858EnsemblClinVar.1
Natural variantiVAR_021337425N → S2 PublicationsCorresponds to variant dbSNP:rs28362261EnsemblClinVar.1
Natural variantiVAR_021338443A → 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_058533452G → D. 1
Natural variantiVAR_025456469R → W1 PublicationCorresponds to variant dbSNP:rs141502002EnsemblClinVar.1
Natural variantiVAR_021339474V → I8 PublicationsCorresponds to variant dbSNP:rs562556EnsemblClinVar.1
Natural variantiVAR_025457482E → G1 PublicationCorresponds to variant dbSNP:rs141995194Ensembl.1
Natural variantiVAR_073657482E → Q No effect on interaction with ANXA2. 1 Publication1
Natural variantiVAR_058534496R → W in HCHOLA3. Corresponds to variant dbSNP:rs374603772EnsemblClinVar.1
Natural variantiVAR_025458515F → L1 PublicationCorresponds to variant dbSNP:rs1356131564Ensembl.1
Natural variantiVAR_058535522A → T. Corresponds to variant dbSNP:rs777300852Ensembl.1
Natural variantiVAR_021340553H → R2 PublicationsCorresponds to variant dbSNP:rs28362270EnsemblClinVar.1
Natural variantiVAR_025459554Q → E Increases interaction with ANXA2. 2 PublicationsCorresponds to variant dbSNP:rs149311926EnsemblClinVar.1
Natural variantiVAR_058536616P → L. Corresponds to variant dbSNP:rs755750316Ensembl.1
Natural variantiVAR_021341619Q → P2 PublicationsCorresponds to variant dbSNP:rs28362277EnsemblClinVar.1
Natural variantiVAR_058537668S → R. Corresponds to variant dbSNP:rs762298323EnsemblClinVar.1
Natural variantiVAR_017201670G → E8 PublicationsCorresponds to variant dbSNP:rs505151EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0088441 – 174MGTVS…EYQPP → MSPWK in isoform 2. 1 PublicationAdd BLAST174
Alternative sequenceiVSP_008845333 – 365VITVG…LFAPG → GRTSLVPPATAAPALCHRVG HHRLLPTWLALQP in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_008846366 – 692Missing in isoform 2. 1 PublicationAdd BLAST327

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
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.3 human [Q8NBP7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS603.1 [Q8NBP7-1]
RefSeqiNP_777596.2, NM_174936.3 [Q8NBP7-1]
UniGeneiHs.18844

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5OCAX-ray2.30A31-152[»]
B153-692[»]
5VL7X-ray3.50A31-152[»]
B153-692[»]
5VLAX-ray2.40A1-452[»]
5VLHX-ray2.86A1-452[»]
5VLKX-ray2.20A1-452[»]
5VLLX-ray2.37A1-452[»]
5VLPX-ray2.90A1-692[»]
ProteinModelPortaliQ8NBP7
SMRiQ8NBP7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi129116, 27 interactors
ComplexPortaliCPX-128 LDLR-PCSK9 complex
CPX-130 ANXA2-PCSK9 complex
DIPiDIP-29694N
IntActiQ8NBP7, 5 interactors
MINTiQ8NBP7
STRINGi9606.ENSP00000303208

Chemistry databases

BindingDBiQ8NBP7
ChEMBLiCHEMBL2929
DrugBankiDB09302 Alirocumab
DB09303 Evolocumab
GuidetoPHARMACOLOGYi2388

Protein family/group databases

MEROPSiS08.039

PTM databases

iPTMnetiQ8NBP7
PhosphoSitePlusiQ8NBP7

Polymorphism and mutation databases

BioMutaiPCSK9
DMDMi317373487

Proteomic databases

EPDiQ8NBP7
MaxQBiQ8NBP7
PaxDbiQ8NBP7
PeptideAtlasiQ8NBP7
PRIDEiQ8NBP7
ProteomicsDBi72807
72808 [Q8NBP7-2]

Protocols and materials databases

DNASUi255738
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302118; ENSP00000303208; ENSG00000169174 [Q8NBP7-1]
GeneIDi255738
KEGGihsa:255738
UCSCiuc001cyf.3 human [Q8NBP7-1]

Organism-specific databases

CTDi255738
DisGeNETi255738
EuPathDBiHostDB:ENSG00000169174.10
GeneCardsiPCSK9
GeneReviewsiPCSK9
H-InvDBiHIX0023558
HGNCiHGNC:20001 PCSK9
MalaCardsiPCSK9
MIMi603776 phenotype
607786 gene
neXtProtiNX_Q8NBP7
OpenTargetsiENSG00000169174
Orphaneti391665 Homozygous familial hypercholesterolemia
426 NON RARE IN EUROPE: Familial hypobetalipoproteinemia
406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia
PharmGKBiPA38617
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1153 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00490000043472
HOGENOMiHOG000049267
HOVERGENiHBG053530
InParanoidiQ8NBP7
KOiK13050
OMAiKCDSHGT
OrthoDBiEOG091G067E
PhylomeDBiQ8NBP7
TreeFamiTF106271

Enzyme and pathway databases

BRENDAi3.4.21.61 2681
ReactomeiR-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
SignaLinkiQ8NBP7
SIGNORiQ8NBP7

Miscellaneous databases

EvolutionaryTraceiQ8NBP7
GeneWikiiPCSK9
GenomeRNAii255738
PROiPR:Q8NBP7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169174 Expressed in 85 organ(s), highest expression level in right lobe of liver
CleanExiHS_PCSK9
GenevisibleiQ8NBP7 HS

Family and domain databases

CDDicd04077 Peptidases_S8_PCSK9_Proteinase, 1 hit
Gene3Di3.30.70.80, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
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
PfamiView protein in Pfam
PF05922 Inhibitor_I9, 1 hit
PF00082 Peptidase_S8, 1 hit
PRINTSiPR00723 SUBTILISIN
SUPFAMiSSF52743 SSF52743, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPCSK9_HUMAN
AccessioniPrimary (citable) accession number: Q8NBP7
Secondary accession number(s): A8T640
, C0JYY9, Q5PSM5, Q5SZQ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 176 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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