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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

PCSK9 Gene

protein-coding GIFtS: 64
GCID: GC01P055505

proprotein convertase subtilisin/kexin type 9

(Previous names: hypercholesterolemia, autosomal dominant 3 )
(Previous symbol: HCHOLA3)

Explore 30 diseases affiliated with
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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Proprotein Convertase Subtilisin/Kexin Type 9¹ ²		Hypercholesterolemia, Autosomal Dominant 3¹
NARC-1¹ ² ³		Convertase Subtilisin/Kexin Type 9 Preproprotein²
FH3¹ ² ⁵		Neural Apoptosis Regulated Convertase 1²
HCHOLA3¹ ² ⁵		EC 3.4.21.-³
NARC1² ³ ⁵		Neural Apoptosis-Regulated Convertase 1³
Subtilisin/Kexin-Like Protease PC9² ³		Proprotein Convertase 9³
PC9² ³		EC 3.4.21⁸
LDLCQ1² ⁵		EC 3.4.21.111⁸

External Ids:	HGNC: 20001¹	Entrez Gene: 255738²	Ensembl: ENSG00000169174⁷	OMIM: 607786⁵	UniProtKB: Q8NBP7³

Export aliases for PCSK9 gene to outside databases

Previous GC identifers: GC01P054862 GC01P054875 GC01P055217 GC01P055277 GC01P053618

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for PCSK9:

This gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family.

The encoded protein is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the

endoplasmic reticulum. The protein may function as a proprotein convertase. This protein plays a role in cholesterol

homeostasis and may have a role in the differentiation of cortical neurons. Mutations in this gene have been

associated with a third form of autosomal dominant familial hypercholesterolemia (HCHOLA3). (provided by RefSeq, Jul

2008)

UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7

Function: 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

Gene Wiki entry for PCSK9

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000001.10 NC_018912.1 NT_032977.9

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the PCSK9 gene promoter:
RFX1 HOXA3 NCX/Ncx HNF-3beta Cdc5 HNF-1A PPAR-alpha HNF-1 ZID Msx-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: PCSK9 promoter sequence

Search SABiosciences Chromatin IP Primers for PCSK9

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PCSK9

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p32.3 Ensembl cytogenetic band: 1p32.3 HGNC cytogenetic band: 1p34.1-p32

PCSK9 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PCSK9 gene location

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01P055505: view genomic region (about GC identifiers)

Start:	55,505,149 bp from pter	End:	55,530,526 bp from pter
Size:	25,378 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7 (See protein sequence)

Recommended Name: Proprotein convertase subtilisin/kexin type 9 precursor

Size: 692 amino acids; 74286 Da

Cofactor: Calcium (Probable)

Subunit: 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

Subcellular location: 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 co-localizes 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

Sequence caution: Sequence=BAC11572.1; Type=Frameshift; Positions=494;

6/17 PDB 3D structures from and Proteopedia for PCSK9 (see all 17):

2P4E (3D)

2PMW (3D)

2QTW (3D)

2W2M (3D)

2W2N (3D)

2W2O (3D)

Secondary accessions: A8T640 C0JYY9 Q5PSM5 Q5SZQ2

Alternative splicing: 2 isoforms: Q8NBP7-1 Q8NBP7-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for PCSK9: NX_Q8NBP7

Post-translational modifications:

Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation¹

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

protein¹

Phosphorylation protects the propeptide against proteolysis¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q8NBP7

4/33 DME Specific Peptides for PCSK9 (Q8NBP7) (see all 33)

GWTLTGC

AHNAFGG

WRLPGTY

YSPASAP

PCSK9 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_777596.2

ENSEMBL proteins:

ENSP00000303208 ENSP00000401598 ENSP00000441859

Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for PCSK9 (Proprotein Convertase 9/PCSK9)
	Enzo Life Sciences proteins for PCSK9
	OriGene Purified Protein: PCSK9 OriGene Protein Over-expression Lysate: PCSK9 OriGene Custom Protein Services for PCSK9
	GenScript Custom Purified and Recombinant Proteins Services for PCSK9
	Novus Biologicals PCSK9 Lysate
	Sino Biological Recombinant Protein for PCSK9
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for PCSK9

Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	--	--
GO:0005615	extracellular space	IDA	12552133
GO:0005737	cytoplasm	IDA	--
GO:0005764	lysosome	IDA	18039658
GO:0005769	early endosome	IDA	17461796

PCSK9 for ontologies About GeneDecksing

PCSK9 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of PCSK9
	R&D Systems Antibodies for PCSK9 (Proprotein Convertase 9/PCSK9)
	OriGene Antibodies: PCSK9 OriGene Custom Antibody Services for PCSK9
	GenScript Custom Superior Antibodies Services for PCSK9
	Novus Biologicals PCSK9 Antibodies
	Abcam antibodies for PCSK9
	Uscn Antibodies for PCSK9
	ThermoFisher Antibodies for PCSK9

Assay Products for PCSK9:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for PCSK9 (Proprotein Convertase 9/PCSK9) (see all)
	GenScript Custom Assay Services for PCSK9
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for PCSK9

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

PCSK9 for domains About GeneDecksing

4 InterPro domains/families:

IPR000209 Peptidase_S8/S53_dom

IPR015500 Peptidase_S8_subtilisin-rel

IPR010259 Inhibitor_I9

IPR009020 Prot_inh_propept

Graphical View of Domain Structure for InterPro Entry Q8NBP7

ProtoNet protein and cluster: Q8NBP7

1 Blocks protein family: IPB000209 Subtilisin serine protease family (S8) signature

UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7

Domain: The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities (PubMed:22027821)

Domain: The catalytic domain is responsible for mediating its self-association

Similarity: Belongs to the peptidase S8 family

Similarity: Contains 1 peptidase S8 domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: