This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sort... See more...

Aliases for PCSK2 Gene

Aliases for PCSK2 Gene

  • Proprotein Convertase Subtilisin/Kexin Type 2 2 3 5
  • Neuroendocrine Convertase 2 2 3 4
  • KEX2-Like Endoprotease 2 2 3 4
  • Prohormone Convertase 2 3 4
  • EC 3.4.21.94 4 52
  • NEC 2 3 4
  • NEC2 3 4
  • PC2 3 4
  • Proprotein Convertase 2 4
  • EC 3.4.21 52
  • NEC-2 3
  • SPC2 3

External Ids for PCSK2 Gene

Previous HGNC Symbols for PCSK2 Gene

  • NEC2

Previous GeneCards Identifiers for PCSK2 Gene

  • GC20P017195
  • GC20P017202
  • GC20P017155
  • GC20P017206
  • GC20P017170

Summaries for PCSK2 Gene

Entrez Gene Summary for PCSK2 Gene

  • This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]

GeneCards Summary for PCSK2 Gene

PCSK2 (Proprotein Convertase Subtilisin/Kexin Type 2) is a Protein Coding gene. Diseases associated with PCSK2 include Polycystic Kidney Disease 1 With Or Without Polycystic Liver Disease and Insulinoma. Among its related pathways are Peptide hormone metabolism and Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers. Gene Ontology (GO) annotations related to this gene include endopeptidase activity. An important paralog of this gene is FURIN.

UniProtKB/Swiss-Prot Summary for PCSK2 Gene

  • Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.

Gene Wiki entry for PCSK2 Gene

Additional gene information for PCSK2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PCSK2 Gene

Genomics for PCSK2 Gene

GeneHancer (GH) Regulatory Elements for PCSK2 Gene

Promoters and enhancers for PCSK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20J017226 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.7 686 1.2 EP300 ZIC2 REST ZBTB10 ZBTB26 SAP30 ATF2 POLR2A EZH2 SIN3A ENSG00000287241 PCSK2 piR-31534-410
GH20J017227 Enhancer 0.6 ENCODE 500.7 +1.7 1684 0.2 REST SAP30 HDAC2 SIN3A ZNF263 MXI1 YY1 ZNF366 MNT ZNF143 ENSG00000287241 PCSK2 piR-31534-410
GH20J017170 Enhancer 0.7 Ensembl 52.1 -56.3 -56306 0.4 TCF7 SAP130 POLR2A FOXP1 SMAD4 BCL6 FOXP2 RARA THRB SMARCA4 PCSK2 piR-31534-409 L13714-281 LOC105372544
GH20J017344 Enhancer 0.8 Ensembl ENCODE CraniofacialAtlas 26.5 +118.3 118294 1.6 EP300 EZH2 SMARCA4 POLR2A PCSK2 LOC105372546 piR-59297-398
GH20J017023 Enhancer 0.8 Ensembl ENCODE 8.5 -201.6 -201606 3 EP300 USF1 SAP30 RFX1 HDAC2 PKNOX1 SIN3A NFE2L2 JUND TFAP4 ENSG00000212165 PCSK2 piR-41525-394 piR-41525-395
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PCSK2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PCSK2

Top Transcription factor binding sites by QIAGEN in the PCSK2 gene promoter:
  • aMEF-2
  • Hlf
  • HNF-1
  • HNF-1A
  • MEF-2A
  • NRSF form 1
  • NRSF form 2
  • Spz1

Genomic Locations for PCSK2 Gene

Genomic Locations for PCSK2 Gene
chr20:17,226,107-17,484,578
(GRCh38/hg38)
Size:
258,472 bases
Orientation:
Plus strand
chr20:17,206,752-17,465,223
(GRCh37/hg19)
Size:
258,472 bases
Orientation:
Plus strand

Genomic View for PCSK2 Gene

Genes around PCSK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PCSK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PCSK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PCSK2 Gene

Proteins for PCSK2 Gene

  • Protein details for PCSK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P16519-NEC2_HUMAN
    Recommended name:
    Neuroendocrine convertase 2
    Protein Accession:
    P16519
    Secondary Accessions:
    • B1ANH9
    • B4DFQ3
    • Q14927
    • Q5JYQ1
    • Q8IWA8
    • Q9NQG3
    • Q9NUG1
    • Q9UJC6

    Protein attributes for PCSK2 Gene

    Size:
    638 amino acids
    Molecular mass:
    70565 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for PCSK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PCSK2 Gene

Selected DME Specific Peptides for PCSK2 Gene

P16519:
  • TVNATRRGDLNINMTSPMGTKSILLSRRPR
  • LTWRDMQHL
  • VLTLTTDACEGKENFVRYLEHVQAV
  • LFCVMVFASAERPVFTNHFLVELH
  • HGTRCAGE
  • SKVAGIR
  • GYTGKGV
  • RKKRGYRDINEIDIN
  • GTSAAAP
  • TGKLVLTL
  • SWGPTDNGK
  • TISINSA
  • KVGFDKWPFMTTHTWGEDARGTW
  • ARQVAAEHGFGVRKLPFAEGLYHFYHNGLAKA
  • CGVGVAY
  • YTGKGVTIG
  • KGRGGKGSI
  • ALQQEGF

Post-translational modifications for PCSK2 Gene

  • Glycosylation at Asn375, Asn514, and Asn524
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for PCSK2 Gene

Domains & Families for PCSK2 Gene

Gene Families for PCSK2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for PCSK2 Gene

Suggested Antigen Peptide Sequences for PCSK2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ54929, highly similar to Neuroendocrine convertase 2 (EC 3.4.21.94) (B4DFQ3_HUMAN)
  • Proprotein convertase 2 (NEC2_HUMAN)
  • cDNA, FLJ92660, Homo sapiens proprotein convertase subtilisin/kexin type 2 (PCSK2),mRNA (Q5JYQ1_HUMAN)
  • PCSK2 protein (Q8IWA8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P16519

UniProtKB/Swiss-Prot:

NEC2_HUMAN :
  • Belongs to the peptidase S8 family. Furin subfamily.
Family:
  • Belongs to the peptidase S8 family. Furin subfamily.
genes like me logo Genes that share domains with PCSK2: view

Function for PCSK2 Gene

Molecular function for PCSK2 Gene

UniProtKB/Swiss-Prot Function:
Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg- - bonds.; EC=3.4.21.94;.
GENATLAS Biochemistry:
proprotein convertase subtilisin,kexin like 2,primarily expressed in tissues and cells containing secretory granules

Enzyme Numbers (IUBMB) for PCSK2 Gene

Phenotypes From GWAS Catalog for PCSK2 Gene

Gene Ontology (GO) - Molecular Function for PCSK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IDA 7626024
GO:0005515 protein binding IPI 7913882
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PCSK2: view
genes like me logo Genes that share phenotypes with PCSK2: view

Animal Models for PCSK2 Gene

MGI Knock Outs for PCSK2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PCSK2

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PCSK2 Gene

Localization for PCSK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PCSK2 Gene

Cytoplasmic vesicle, secretory vesicle. Secreted. Note=Localized in the secretion granules.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PCSK2 gene
Compartment Confidence
extracellular 5
nucleus 4
golgi apparatus 4
plasma membrane 2
endoplasmic reticulum 2
cytoskeleton 1
mitochondrion 1
endosome 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PCSK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 9020868
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005802 trans-Golgi network IBA 21873635
genes like me logo Genes that share ontologies with PCSK2: view

Pathways & Interactions for PCSK2 Gene

genes like me logo Genes that share pathways with PCSK2: view

Pathways by source for PCSK2 Gene

1 Cell Signaling Technology pathway for PCSK2 Gene

SIGNOR curated interactions for PCSK2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for PCSK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IDA 7626024
GO:0007399 nervous system development IEA --
GO:0016485 protein processing IBA 21873635
GO:0016486 peptide hormone processing IDA 28719828
GO:0016540 protein autoprocessing IEA --
genes like me logo Genes that share ontologies with PCSK2: view

Drugs & Compounds for PCSK2 Gene

(15) Drugs for PCSK2 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Insulin human Approved, Investigational Pharma Enzyme, activator 0
Insulin pork Approved Pharma Target 0

(13) Additional Compounds for PCSK2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PCSK2: view

Transcripts for PCSK2 Gene

mRNA/cDNA for PCSK2 Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PCSK2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PCSK2 Gene

No ASD Table

Relevant External Links for PCSK2 Gene

GeneLoc Exon Structure for
PCSK2

Expression for PCSK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PCSK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PCSK2 Gene

This gene is overexpressed in Thyroid (x9.0), Brain - Frontal Cortex (BA9) (x5.1), and Brain - Anterior cingulate cortex (BA24) (x5.0).

Protein differential expression in normal tissues from HIPED for PCSK2 Gene

This gene is overexpressed in Adrenal (42.3), Vitreous humor (12.0), and Islet of Langerhans (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PCSK2 Gene



Protein tissue co-expression partners for PCSK2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PCSK2

SOURCE GeneReport for Unigene cluster for PCSK2 Gene:

Hs.315186

Evidence on tissue expression from TISSUES for PCSK2 Gene

  • Nervous system(5)
  • Pancreas(4.2)
  • Lung(4.1)
  • Adrenal gland(2.2)
genes like me logo Genes that share expression patterns with PCSK2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PCSK2 Gene

Orthologs for PCSK2 Gene

This gene was present in the common ancestor of animals.

Orthologs for PCSK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PCSK2 31 30
  • 99.63 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PCSK2 31 30
  • 92.11 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PCSK2 31
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pcsk2 30
  • 90.11 (n)
oppossum
(Monodelphis domestica)
Mammalia PCSK2 31
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pcsk2 17 31 30
  • 89.59 (n)
cow
(Bos Taurus)
Mammalia PCSK2 31 30
  • 89.18 (n)
OneToOne
chicken
(Gallus gallus)
Aves PCSK2 31 30
  • 79.29 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PCSK2 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pcsk2 30
  • 75.18 (n)
Str.12201 30
African clawed frog
(Xenopus laevis)
Amphibia pcsk2-A 30
zebrafish
(Danio rerio)
Actinopterygii pcsk2 31 30
  • 75.96 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta amon 31 32 30
  • 62.98 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002176 30
  • 62.91 (n)
worm
(Caenorhabditis elegans)
Secernentea egl-3 31 32 30
  • 59.57 (n)
OneToOne
bli-4 32
  • 43 (a)
aex-5 32
  • 34 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6212 31
  • 62 (a)
OneToOne
Species where no ortholog for PCSK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PCSK2 Gene

ENSEMBL:
Gene Tree for PCSK2 (if available)
TreeFam:
Gene Tree for PCSK2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PCSK2: view image

Paralogs for PCSK2 Gene

Paralogs for PCSK2 Gene

(6) SIMAP similar genes for PCSK2 Gene using alignment to 1 proteins:

  • NEC2_HUMAN
genes like me logo Genes that share paralogs with PCSK2: view

Variants for PCSK2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PCSK2 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
714814 Benign: not provided 17,481,830(+) G/A SYNONYMOUS_VARIANT
777519 Benign: not provided 17,465,559(+) TG/T INTRON_VARIANT
rs780820865 A colorectal cancer sample p.Asp424Asn
rs139619496 - p.Met525Val
rs144151196 - p.Ala267Thr

Additional dbSNP identifiers (rs#s) for PCSK2 Gene

Structural Variations from Database of Genomic Variants (DGV) for PCSK2 Gene

Variant ID Type Subtype PubMed ID
dgv21e197 CNV deletion 19546169
esv1992600 CNV deletion 18987734
esv2659718 CNV deletion 23128226
esv2758787 CNV loss 17122850
esv2760670 CNV gain 21179565
esv3535 CNV loss 18987735
esv3645421 CNV loss 21293372
nsv1123458 CNV deletion 24896259
nsv1136509 CNV deletion 24896259
nsv1138925 CNV deletion 24896259
nsv179945 CNV deletion 16902084
nsv3308 CNV insertion 18451855
nsv3309 CNV insertion 18451855
nsv517986 CNV loss 19592680
nsv520899 CNV loss 19592680

Variation tolerance for PCSK2 Gene

Residual Variation Intolerance Score: 13.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.19; 24.05% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PCSK2 Gene

Human Gene Mutation Database (HGMD)
PCSK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PCSK2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PCSK2 Gene

Disorders for PCSK2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for PCSK2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
polycystic kidney disease 1 with or without polycystic liver disease
  • pkd1
insulinoma
  • islet cell tumor
wolfram syndrome
  • wfs
hyperproinsulinemia
  • hpri
myocardial infarction
  • myocardial infarction, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search PCSK2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PCSK2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PCSK2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PCSK2 Gene

Publications for PCSK2 Gene

  1. [Analysis of the gene encoding human PC2, a prohormone processing enzyme]. (PMID: 7983775) Ohagi S … Nanjo K (Nihon rinsho. Japanese journal of clinical medicine 1994) 3 4 23 54
  2. Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. (PMID: 1594602) Ohagi S … Steiner DF (Proceedings of the National Academy of Sciences of the United States of America 1992) 3 4 23 54
  3. Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2. (PMID: 2154467) Smeekens SP … Steiner DF (The Journal of biological chemistry 1990) 3 4 23 54
  4. Functional analysis of PCSK2 coding variants: A founder effect in the Old Order Amish population. (PMID: 28719828) Winters A … Lindberg I (Diabetes research and clinical practice 2017) 3 4 54
  5. Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. (PMID: 21546767) Murea M … Freedman BI (American journal of nephrology 2011) 3 41 54

Products for PCSK2 Gene

Sources for PCSK2 Gene