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

Gene ID: 5126, updated on 15-Jun-2019

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
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

Genomic context

See PCSK2 in Genome Data Viewer
Location:
20p12.1
Exon count:
13
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 20 NC_000020.11 (17226107..17484578)
105 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 dynein light chain Tctex-type 3 pseudogene 1 Neighboring gene beaded filament structural protein 1 Neighboring gene ribosomal protein S27a pseudogene 2 Neighboring gene RN7SK pseudogene 69 Neighboring gene destrin, actin depolymerizing factor

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • Insulin processing, organism-specific biosystem (from REACTOME)
    Insulin processing, organism-specific biosystemThe generation of insulin-containing secretory granules from proinsulin in the lumen of the endoplasmic reticulum (ER) can be described in 4 steps: formation of intramolecular disulfide bonds, format...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
    Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

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

General protein information

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)

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_001201528.1NP_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:103399
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:139416
    Peptidase_S8; Subtilase family
    pfam01483
    Location:485572
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:1490
    S8_pro-domain; Peptidase S8 pro-domain
  2. NM_001201529.3NP_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:87383
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:123400
    Peptidase_S8; Subtilase family
    pfam01483
    Location:469556
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:3374
    S8_pro-domain; Peptidase S8 pro-domain
  3. NM_002594.5NP_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
    P16519
    Related
    ENSP00000262545.2, ENST00000262545.7
    Conserved Domains (4) summary
    cd04059
    Location:122418
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:158435
    Peptidase_S8; Subtilase family
    pfam01483
    Location:504591
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33109
    S8_pro-domain; Peptidase S8 pro-domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

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