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

Summary

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: mouse all
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Genomic context

Location:: 20p12.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (17226107..17484578)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (17276847..17535278)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (17206752..17465223)

Chromosome 20 - NC_000020.11 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11928 (e-PCR)
- UniSTS:6402

RH65786 (e-PCR)
- UniSTS:44327

PCSK2 (e-PCR)
- UniSTS:253994

D20S431 (e-PCR)
- UniSTS:66092

GDB:215832 (e-PCR)
- UniSTS:156204

Z94716 (e-PCR)
- UniSTS:27694

MARC_42817-42818:1094748518:1 (e-PCR)
- UniSTS:471608

WI-22195 (e-PCR)
- UniSTS:25657

D20S112 (e-PCR), detects polymorphism
- UniSTS:29245

D20S112 (e-PCR), detects polymorphism
- UniSTS:83785

RH66076 (e-PCR)
- UniSTS:54356

MARC_46539-42818:1108157929:1 (e-PCR)
- UniSTS:471647

D20S48 (e-PCR)
- UniSTS:66159

A005D19 (e-PCR)
- UniSTS:50312

SHGC-152681 (e-PCR)
- UniSTS:177582

D20S47 (e-PCR)
- UniSTS:146871

D20S1060 (e-PCR)
- UniSTS:12751

D20S778 (e-PCR)
- UniSTS:61392

RH64144 (e-PCR)
- UniSTS:37592

D20S112 (e-PCR), detects polymorphism
- UniSTS:19944

SGC32415 (e-PCR)
- UniSTS:99820

D20S114 (e-PCR), detects polymorphism
- UniSTS:31983

D20S733 (e-PCR)
- UniSTS:35059

D20S470 (e-PCR)
- UniSTS:34041

D20S114 (e-PCR), detects polymorphism
- UniSTS:74749

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

EC 3.4.21.94

NP_001188458.1

EC 3.4.21.94

NP_002585.2

EC 3.4.21.94

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_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
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
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