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PCSK2 proprotein convertase subtilisin/kexin type 2 [ Homo sapiens (human) ]

Gene ID: 5126, updated on 5-Mar-2024

Summary

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Official Symbol
PCSK2provided by HGNC
Official Full Name
proprotein convertase subtilisin/kexin type 2provided by HGNC
Primary source
HGNC:HGNC:8744
See related
Ensembl:ENSG00000125851 MIM:162151; AllianceGenome:HGNC:8744
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PC2; NEC2; SPC2; NEC 2; NEC-2
Summary
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]
Expression
Biased expression in adrenal (RPKM 14.5), brain (RPKM 10.5) and 9 other tissues See more
Orthologs
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Genomic context

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See PCSK2 in Genome Data Viewer
Location:
20p12.1
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (17226107..17484578)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (17276847..17535278)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (17206752..17465223)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372545 Neighboring gene RNA, U1 small nuclear 131, pseudogene Neighboring gene uncharacterized LOC105372546 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:17411563-17412069 Neighboring gene NANOG hESC enhancer GRCh37_chr20:17430829-17431354 Neighboring gene dynein light chain Tctex-type 3 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:17485157-17485680 Neighboring gene hESC enhancers GRCh37_chr20:17511284-17511824 and GRCh37_chr20:17511825-17512364 Neighboring gene beaded filament structural protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17564 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12688 Neighboring gene MPRA-validated peak4154 silencer Neighboring gene RPS27A pseudogene 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:17537881-17538596 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:17549683-17550250 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12689 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12690 Neighboring gene RN7SK pseudogene 69 Neighboring gene destrin, actin depolymerizing factor

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin. Remes SM, et al. APMIS, 2020 Nov. PMID 32794589, Free PMC Article
  2. Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population. Chang TJ, et al. Sci Rep, 2015 Nov 26. PMID 26607656, Free PMC Article
  3. Effect of a common variant of the PCSK2 gene on reduced insulin secretion. Jonsson A, et al. Diabetologia, 2012 Dec. PMID 23011353
  4. Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population. Zheng X, et al. Mol Biol Rep, 2012 Jan. PMID 21437630
  5. Possible relevance between prohormone convertase 2 expression and tumor growth in human adrenocorticotropin-producing pituitary adenoma. Iino K, et al. J Clin Endocrinol Metab, 2010 Aug. PMID 20501680

See all (65) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Revisiting Proinsulin Processing: Evidence That Human beta-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2.
    Title: Revisiting Proinsulin Processing: Evidence That Human β-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2.
  2. PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
    Title: PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
  3. PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes.
    Title: Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population.
  4. FAM20C plays a role in 7B2-mediated proPC2 activation by phosphorylating residue Thr111; and that 7B2 function is regulated by alternative splicing.
    Title: Phosphorylation and Alternative Splicing of 7B2 Reduce Prohormone Convertase 2 Activation.
  5. in the processing of hypothalamic neuropeptides in huntington disease may partially arise from decreased PC1/3 and PC2 expressions.
    Title: Decreased hypothalamic prohormone convertase expression in huntington disease patients.
  6. variant of the PCSK2 gene was associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes
    Title: Effect of a common variant of the PCSK2 gene on reduced insulin secretion.
  7. The association of risk allele rs2021785 at PCSK2 with type 2 diabetes exists in a Han Chinese population
    Title: Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
  8. differential gene expression profiles revealed more abundant mRNA expression in ectopic ACTH syndrome than in Cushing disease of proprotein convertase-2
    Title: Differential gene expression profiles of POMC-related enzymes, transcription factors and receptors between non-pituitary and pituitary ACTH-secreting tumors.
  9. PC1/3 governs the endocrine, and PC2 the neuronal processing, of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22.
    Title: The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6.
  10. SEMA3F, CLEC16A, LAMA3, and PCSK2 variants have roles in myocardial infarction in Japanese individuals
    Title: Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association meta-analysis of preschool internalizing problems.
EBI GWAS Catalog
Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes.
EBI GWAS Catalog
Genome-wide association study of biochemical traits in Korcula Island, Croatia.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
EBI GWAS Catalog
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in enkephalin processing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in insulin processing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in islet amyloid polypeptide processing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in peptide hormone processing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in peptide hormone processing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autoprocessing IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in dendrite IEA
Inferred from Electronic Annotation
more info
  
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 intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
located_in secretory granule IEA
Inferred from Electronic Annotation
more info
  
located_in transport vesicle IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
neuroendocrine convertase 2
Names
KEX2-like endoprotease 2
prohormone convertase 2
NP_001188457.1
NP_001188458.1
NP_002585.2

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)

  1. NM_001201528.2 → NP_001188457.1  neuroendocrine convertase 2 isoform 3

    See identical proteins and their annotated locations for NP_001188457.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AL031664, BC001905, BC040546
    Consensus CDS
    CCDS56180.1
    UniProtKB/Swiss-Prot
    P16519
    Related
    ENSP00000367131.1, ENST00000377899.5
    Conserved Domains (4) summary
    cd04059
    Location:103 → 399
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:139 → 416
    Peptidase_S8; Subtilase family
    pfam01483
    Location:485 → 572
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:14 → 90
    S8_pro-domain; Peptidase S8 pro-domain

  2. NM_001201529.3 → NP_001188458.1  neuroendocrine convertase 2 isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_001188458.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AK294200, AL031664, AL359511, BC040546
    Consensus CDS
    CCDS56179.1
    UniProtKB/Swiss-Prot
    P16519
    Related
    ENSP00000437458.1, ENST00000536609.1
    Conserved Domains (4) summary
    cd04059
    Location:87 → 383
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:123 → 400
    Peptidase_S8; Subtilase family
    pfam01483
    Location:469 → 556
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33 → 74
    S8_pro-domain; Peptidase S8 pro-domain

  3. NM_002594.5 → NP_002585.2  neuroendocrine convertase 2 isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_002585.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC001905, BC005815, BC040546, BP384064, CD519990, DA148468, HY137524
    Consensus CDS
    CCDS13125.1
    UniProtKB/Swiss-Prot
    B1ANH9, B4DFQ3, P16519, Q14927, Q5JYQ1, Q8IWA8, Q9NQG3, Q9NUG1, Q9UJC6
    Related
    ENSP00000262545.2, ENST00000262545.7
    Conserved Domains (4) summary
    cd04059
    Location:122 → 418
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:158 → 435
    Peptidase_S8; Subtilase family
    pfam01483
    Location:504 → 591
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33 → 109
    S8_pro-domain; Peptidase S8 pro-domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    17226107..17484578
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    17276847..17535278
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P16519.2 GenPept UniProtKB/Swiss-Prot:P16519

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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