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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
    mouse all
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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)

    Genotypes

    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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    NEW Try the new Transcript table

    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.

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