Pcsk9 proprotein convertase subtilisin/kexin type 9 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pcsk9provided by MGI
Official Full Name: proprotein convertase subtilisin/kexin type 9provided by MGI
Primary source: MGI:MGI:2140260
See related: Ensembl:ENSMUSG00000044254 AllianceGenome:MGI:2140260
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: FH3; PC9; Narc1; HCHOLA3
Summary: Enables apolipoprotein binding activity; lipoprotein particle binding activity; and low-density lipoprotein particle receptor binding activity. Involved in several processes, including cellular response to insulin stimulus; liver development; and regulation of neuron apoptotic process. Acts upstream of or within several processes, including cholesterol metabolic process; low-density lipoprotein receptor particle metabolic process; and regulation of low-density lipoprotein particle receptor catabolic process. Located in COPII-coated ER to Golgi transport vesicle; endoplasmic reticulum; and extracellular space. Is expressed in several structures, including alimentary system; cerebellum; genitourinary system; liver; and telencephalon. Human ortholog(s) of this gene implicated in familial hypercholesterolemia and hypobetalipoproteinemia. Orthologous to human PCSK9 (proprotein convertase subtilisin/kexin type 9). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in liver E18 (RPKM 43.5), liver E14.5 (RPKM 36.7) and 7 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 C7; 4 49.67 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (106299531..106321522, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (106442334..106464325, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Knock-Out of IKKepsilon Ameliorates Atherosclerosis and Fatty Liver Disease by Alterations of Lipid Metabolism in the PCSK9 Model in Mice.
Title: Knock-Out of IKKepsilon Ameliorates Atherosclerosis and Fatty Liver Disease by Alterations of Lipid Metabolism in the PCSK9 Model in Mice.
Roles of PCSK9 in the Pathogenesis of Periodontal Disease.
Title: Roles of PCSK9 in the Pathogenesis of Periodontal Disease.
The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.
Title: The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.
miR-181d-5p ameliorates hypercholesterolemia by targeting PCSK9.
Title: miR-181d-5p ameliorates hypercholesterolemia by targeting PCSK9.
E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.
Title: E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.
PCSK9 aggravated carotid artery stenosis in ApoE[-/-] mice by promoting the expression of tissue factors in endothelial cells via the TLR4/NF-kappaB pathway.
Title: PCSK9 aggravated carotid artery stenosis in ApoE(-/-) mice by promoting the expression of tissue factors in endothelial cells via the TLR4/NF-κB pathway.
Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin-Mediated Mitophagy.
Title: Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin-Mediated Mitophagy.
PCSK9 inhibition ameliorates experimental autoimmune myocarditis by reducing Th17 cell differentiation through LDLR/STAT-3/ROR-gammat pathway.
Title: PCSK9 inhibition ameliorates experimental autoimmune myocarditis by reducing Th17 cell differentiation through LDLR/STAT-3/ROR-γt pathway.
Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome.
Title: Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome.
PCSK9 causes inflammation and cGAS/STING pathway activation in diabetic nephropathy.
Title: PCSK9 causes inflammation and cGAS/STING pathway activation in diabetic nephropathy.

Submit: New GeneRIF Correction See all GeneRIFs (152)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (14)
Targeted (8) 1 citation

General gene information

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Markers

AI415265 (e-PCR)
- UniSTS:159266

AI747682 (e-PCR)
- UniSTS:179038

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables apolipoprotein binding	IDA Inferred from Direct Assay more info	PubMed
enables apolipoprotein receptor binding	IEA Inferred from Electronic Annotation more info
enables apolipoprotein receptor binding	ISO Inferred from Sequence Orthology more info
enables low-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables signaling receptor inhibitor activity	IEA Inferred from Electronic Annotation more info
enables signaling receptor inhibitor activity	ISO Inferred from Sequence Orthology more info
enables sodium channel inhibitor activity	IEA Inferred from Electronic Annotation more info
enables sodium channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables very-low-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables very-low-density lipoprotein particle receptor binding	IEA Inferred from Electronic Annotation more info
enables very-low-density lipoprotein particle receptor binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to insulin stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to starvation	ISO Inferred from Sequence Orthology more info
involved_in cholesterol homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within cholesterol metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in kidney development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within lipoprotein metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in liver development	IEP Inferred from Expression Pattern more info	PubMed
involved_in low-density lipoprotein particle receptor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in low-density lipoprotein particle receptor catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within low-density lipoprotein receptor particle metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in lysosomal transport	IEA Inferred from Electronic Annotation more info
involved_in lysosomal transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of low-density lipoprotein particle clearance	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of low-density lipoprotein particle clearance	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of low-density lipoprotein particle receptor binding	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of low-density lipoprotein receptor activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of receptor recycling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of receptor recycling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of receptor-mediated endocytosis involved in cholesterol transport	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of receptor-mediated endocytosis involved in cholesterol transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in neurogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in neuron differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phospholipid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of low-density lipoprotein particle receptor catabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of low-density lipoprotein particle receptor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of receptor internalization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in protein autoprocessing	ISO Inferred from Sequence Orthology more info
involved_in protein autoprocessing	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in protein processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of low-density lipoprotein particle receptor catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of signaling receptor activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within triglyceride metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in COPII-coated ER to Golgi transport vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
part_of PCSK9-AnxA2 complex	ISO Inferred from Sequence Orthology more info
part_of PCSK9-AnxA2 complex	ISS Inferred from Sequence or Structural Similarity more info
part_of PCSK9-LDLR complex	ISO Inferred from Sequence Orthology more info
part_of PCSK9-LDLR complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in early endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in late endosome	ISO Inferred from Sequence Orthology more info
located_in late endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: proprotein convertase subtilisin/kexin type 9

Names: NARC-1; convertase subtilisin; neural apoptosis regulated convertase 1; proprotein convertase 9; proprotein convertase PC9; subtilisin/kexin-like protease PC9

NP_705793.1

EC 3.4.21.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_153565.2 → NP_705793.1 proprotein convertase subtilisin/kexin type 9 precursor

See identical proteins and their annotated locations for NP_705793.1

Status: VALIDATED

Source sequence(s)

AV027564, BC038085

Consensus CDS

CCDS18418.1

UniProtKB/Swiss-Prot

B1AZI4, Q3UEH7, Q80W65, Q8BXW9, Q8CFT6

Related

ENSMUSP00000055757.6, ENSMUST00000049507.6

Conserved Domains (3) summary

cd04077
Location:159 → 424

Peptidases_S8_PCSK9_ProteinaseK_like; Peptidase S8 family domain in ProteinaseK-like proteins

pfam00082
Location:183 → 420

Peptidase_S8; Subtilase family

pfam05922
Location:80 → 152

Inhibitor_I9; Peptidase inhibitor I9