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PCSK1 proprotein convertase subtilisin/kexin type 1 [ Homo sapiens (human) ]

Gene ID: 5122, updated on 2-Nov-2024

Summary

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Official Symbol
PCSK1provided by HGNC
Official Full Name
proprotein convertase subtilisin/kexin type 1provided by HGNC
Primary source
HGNC:HGNC:8743
See related
Ensembl:ENSG00000175426 MIM:162150; AllianceGenome:HGNC:8743
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
PC1; PC3; NEC1; SPC3; PC1/3; BMIQ12
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 encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The 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. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
Expression
Biased expression in brain (RPKM 13.3), adrenal (RPKM 3.9) and 6 other tissues See more
Orthologs
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Genomic context

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See PCSK1 in Genome Data Viewer
Location:
5q15
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (96390333..96433248, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (96891318..96934221, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (95726037..95768952, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929710 Neighboring gene calpastatin Neighboring gene uncharacterized LOC124901032 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22814 Neighboring gene uncharacterized LOC107986365 Neighboring gene uncharacterized LOC124901034 Neighboring gene Sharpr-MPRA regulatory region 7163 Neighboring gene NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like Neighboring gene Sharpr-MPRA regulatory region 11450 Neighboring gene MPRA-validated peak5360 silencer Neighboring gene MPRA-validated peak5361 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22815 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:95992448-95993647 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:95997733-95998234 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16194 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:96038749-96039248 Neighboring gene uncharacterized LOC107986363

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 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. The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status. Gjesing AP, et al. PLoS One, 2011. PMID 21935364, Free PMC Article
  2. Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters. Kulanuwat S, et al. Southeast Asian J Trop Med Public Health, 2014 Jan. PMID 24964673
  3. Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph. Blanco EH, et al. Endocrinology, 2014 Sep. PMID 24932808, Free PMC Article
  4. A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity. Philippe J, et al. Int J Obes (Lond), 2015 Feb. PMID 24890885
  5. Epistasis between polymorphisms in PCSK1 and DBH is associated with premature ovarian failure. Pyun JA, et al. Menopause, 2014 Nov. PMID 24618767

See all (126) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children.
    Title: Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children.
  2. The N221D variant in PCSK1 is highly prevalent in childhood obesity and can influence the metabolic profile.
    Title: The N221D variant in PCSK1 is highly prevalent in childhood obesity and can influence the metabolic profile.
  3. Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults.
    Title: Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults.
  4. Functional characterization of all missense variants in LEPR, PCSK1, and POMC genes arising from single-nucleotide variants.
    Title: Functional characterization of all missense variants in LEPR, PCSK1, and POMC genes arising from single-nucleotide variants.
  5. Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study.
    Title: Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study.
  6. Rare Heterozygous <i>PCSK1</i> Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.
    Title: Rare Heterozygous PCSK1 Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.
  7. Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.
    Title: Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.
  8. GLP-1 receptor signaling increases PCSK1 and beta cell features in human alpha cells.
    Title: GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells.
  9. 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.
  10. PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.
    Title: PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.
Submit: New GeneRIF Correction See all GeneRIFs (69)

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

Associated conditions

Description Tests
Body mass index quantitative trait locus 12
MedGen: C2676498 OMIM: 612362 GeneReviews: Not available
Compare labs
Obesity due to prohormone convertase I deficiency
MedGen: C1833053 OMIM: 600955 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
EBI GWAS Catalog
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
EBI GWAS Catalog
Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
EBI GWAS Catalog
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
EBI GWAS Catalog
Meta-analysis identifies common variants associated with body mass index in east Asians.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
EBI GWAS Catalog
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
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)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env PC1, one of the subtilisin/kexin family convertases, cleaves HIV-1 gp160 into gp120 and gp41 at amino acids 511-512 PubMed

Go to the HIV-1, Human Interaction Database

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 identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in insulin processing IEA
Inferred from Electronic Annotation
more info
  
involved_in neurogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in pancreas development IEA
Inferred from Electronic Annotation
more info
  
involved_in peptide biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in peptide hormone processing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in pituitary gland development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of protein secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in protein autoprocessing IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to axon injury IEA
Inferred from Electronic Annotation
more info
  
involved_in response to calcium ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to chlorate IEA
Inferred from Electronic Annotation
more info
  
involved_in response to fatty acid IEA
Inferred from Electronic Annotation
more info
  
involved_in response to glucocorticoid IEA
Inferred from Electronic Annotation
more info
  
involved_in response to glucose IEA
Inferred from Electronic Annotation
more info
  
involved_in response to interleukin-1 IEA
Inferred from Electronic Annotation
more info
  
involved_in response to lipopolysaccharide IEA
Inferred from Electronic Annotation
more info
  
involved_in response to nutrient levels IEA
Inferred from Electronic Annotation
more info
  
involved_in response to peptide hormone IEA
Inferred from Electronic Annotation
more info
  
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in axon terminus IEA
Inferred from Electronic Annotation
more info
  
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 
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in secretory granule lumen TAS
Traceable Author Statement
more info
  
located_in trans-Golgi network 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 1
Names
prohormone convertase 1
prohormone convertase 3
proprotein convertase 1/3
NP_000430.3
NP_001171346.1

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.

Genomic

  1. NG_021161.1 RefSeqGene

    Range
    5034..47949
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000439.5 → NP_000430.3  neuroendocrine convertase 1 isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_000430.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).
    Source sequence(s)
    AC008951, DA192592, X64810
    Consensus CDS
    CCDS4081.1
    UniProtKB/Swiss-Prot
    B7Z8T7, E9PHA1, P29120, P78478, Q92532
    UniProtKB/TrEMBL
    A1L3V6
    Related
    ENSP00000308024.2, ENST00000311106.8
    Conserved Domains (5) summary
    cd04059
    Location:121 → 415
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:158 → 432
    Peptidase_S8; Subtilase family
    pfam01483
    Location:504 → 591
    P_proprotein; Proprotein convertase P-domain
    pfam12177
    Location:715 → 751
    Proho_convert; Prohormone convertase enzyme
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  2. NM_001177875.2 → NP_001171346.1  neuroendocrine convertase 1 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, and initiates translation at an alternate start codon compared to variant 1. The resulting isoform (2) is shorter and has a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC008951, AC108107, AK303888
    Consensus CDS
    CCDS54881.1
    UniProtKB/TrEMBL
    Q59H85
    Related
    ENSP00000421600.1, ENST00000508626.5
    Conserved Domains (5) summary
    cd04059
    Location:74 → 368
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:111 → 385
    Peptidase_S8; Subtilase family
    pfam01483
    Location:457 → 544
    P_proprotein; Proprotein convertase P-domain
    pfam12177
    Location:668 → 704
    Proho_convert; Prohormone convertase enzyme
    pfam16470
    Location:8 → 63
    S8_pro-domain; Peptidase S8 pro-domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    96390333..96433248 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    96891318..96934221 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001177876.1: Suppressed sequence

    Description
    NM_001177876.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P29120.2 GenPept UniProtKB/Swiss-Prot:P29120

Gene LinkOut

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

Chemical Information
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