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

Gene ID: 5122, updated on 21-Apr-2019

Summary

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
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; 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

Genomic context

See PCSK1 in Genome Data Viewer
Location:
5q15
Exon count:
15
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (96390336..96433281, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (95726040..95768985, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929710 Neighboring gene MIR583 host gene Neighboring gene RNA, U6 small nuclear 524, pseudogene Neighboring gene uncharacterized LOC107986365 Neighboring gene NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 pseudogene Neighboring gene uncharacterized LOC107986362 Neighboring gene uncharacterized LOC107986364 Neighboring gene calpastatin

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

Associated conditions

Description Tests
Body mass index quantitative trait locus 12
MedGen: C2676498 OMIM: 612362 GeneReviews: Not available
Compare labs
Proprotein convertase 1/3 deficiency
MedGen: C1833053 OMIM: 600955 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

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

HIV-1 interactions

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 BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
identical protein binding IEA
Inferred from Electronic Annotation
more info
 
serine-type endopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
peptide biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
peptide hormone processing TAS
Traceable Author Statement
more info
 
proteolysis TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
secretory granule lumen TAS
Traceable Author Statement
more info
 
transport vesicle IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
neuroendocrine convertase 1
Names
prohormone convertase 1
prohormone convertase 3
NP_000430.3
NP_001171346.1

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.

Genomic

  1. NG_021161.1 RefSeqGene

    Range
    5001..47946
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000439.5NP_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
    P29120
    Related
    ENSP00000308024.2, ENST00000311106.8
    Conserved Domains (5) summary
    cd04059
    Location:121415
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:158432
    Peptidase_S8; Subtilase family
    pfam01483
    Location:504591
    P_proprotein; Proprotein convertase P-domain
    pfam12177
    Location:715751
    Proho_convert; Prohormone convertase enzyme
    pfam16470
    Location:34110
    S8_pro-domain; Peptidase S8 pro-domain
  2. NM_001177875.1NP_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, AK303888
    Consensus CDS
    CCDS54881.1
    UniProtKB/Swiss-Prot
    P29120
    Related
    ENSP00000421600.1, ENST00000508626.5
    Conserved Domains (5) summary
    cd04059
    Location:74368
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:111385
    Peptidase_S8; Subtilase family
    pfam01483
    Location:457544
    P_proprotein; Proprotein convertase P-domain
    pfam12177
    Location:668704
    Proho_convert; Prohormone convertase enzyme
    pfam16470
    Location:863
    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.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    96390336..96433281 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.
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