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

    Gene ID: 5122, updated on 11-May-2012

    Summary

    Official Symbol
    PCSK1provided by HGNC
    Official Full Name
    proprotein convertase subtilisin/kexin type 1provided by HGNC
    Primary source
    HGNC:8743
    See related
    Ensembl:ENSG00000175426; HPRD:01201; MIM:162150; Vega:OTTHUMG00000122089
    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
    The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a type I proinsulin-processing enzyme that plays a key role in regulating insulin biosynthesis. It is also known to cleave proopiomelanocortin, prorenin, proenkephalin, prodynorphin, prosomatostatin and progastrin. Mutations in this gene are thought to cause obesity. This encoded protein is associated with carcinoid tumors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

    Genomic context

    Location :
    5q15-q21
    Sequence :
    Chromosome: 5; NC_000005.9 (95726040..95768985, complement)
    See PCSK1 in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene fatty acid binding protein 5 pseudogene 5 Neighboring gene microRNA 583 Neighboring gene calpastatin Neighboring gene endoplasmic reticulum aminopeptidase 1 Neighboring gene endoplasmic reticulum aminopeptidase 2

    Genomic regions, transcripts, and products

    Bibliography

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    HIV-1 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 Protein Interaction Database

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P29120 P10997 IAPP    HPRD  PubMed  
    P29120 Q9UHG2 PCSK1N    HPRD  PubMed  
    P29120 P20382 PMCH    HPRD  PubMed  
    P29120 P00797 REN    HPRD  PubMed  
    BioGRID:111151 BioGRID:110445 AFF1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111151 BioGRID:107880 CTNNB1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111151 BioGRID:111719 PTK2    BioGRID  PubMed Affinity Capture-Western 

    General gene information

    Markers

    Homology

    Pathways from BioSystems

    • Diabetes pathways, organism-specific biosystem (from REACTOME)
      Diabetes pathways, organism-specific biosystemThis module groups several normal processes that have key roles in the synthesis and function of insulin, insulin-like growth factors and ghrelin, and whose derangement is thus central to the pathoge...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Incretin Synthesis, Secretion, and Inactivation, organism-specific biosystem (from REACTOME)
      Incretin Synthesis, Secretion, and Inactivation, organism-specific biosystemIncretins are peptide hormones produced by the gut that enhance the ability of glucose to stimulate insulin secretion from beta cells in the pancreas. Two incretins have been identified: Glucagon-lik...
    • Insulin Synthesis and Processing, organism-specific biosystem (from REACTOME)
      Insulin Synthesis and 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...
    • Integration of energy metabolism, organism-specific biosystem (from REACTOME)
      Integration of energy metabolism, organism-specific biosystemMany hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insul...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
      Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
    • Peptide hormone biosynthesis, organism-specific biosystem (from REACTOME)
      Peptide hormone biosynthesis, organism-specific biosystemPeptide hormones are peptides that are secreted directly into the blood stream (endocrine hormones). They are synthesized as precursors that require proteolytic processing (not discussed here) to gen...
    • Regulation of Insulin Secretion, organism-specific biosystem (from REACTOME)
      Regulation of Insulin Secretion, organism-specific biosystemPancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or in...
    • Synthesis, Secretion, and Deacylation of Ghrelin, organism-specific biosystem (from REACTOME)
      Synthesis, Secretion, and Deacylation of Ghrelin, organism-specific biosystemGhrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the ma...
    • Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1), organism-specific biosystem (from REACTOME)
      Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1), organism-specific biosystemIn L cells of the intestine the transcription factors TCF-4 (TCF7L2) and Beta-catenin form a heterodimer and bind the G2 enhancer of the Proglucagon gene GCG,activating its transcription to yield Pro...
    • Synthesis, Secretion, and Inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP), organism-specific biosystem (from REACTOME)
      Synthesis, Secretion, and Inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP), organism-specific biosystemIn K cells of the intestine the transcription factors PAX6 and PDX-1 activate transcription of the gene encoding Glucose-dependent Insulinotropic Polypeptide (GIP, first called Gastric Inhibitory Pep...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    chaperone binding IEA
    Inferred from Electronic Annotation
    more info
     
    endopeptidase activity TAS
    Traceable Author Statement
    more info
     
    insulin binding IEA
    Inferred from Electronic Annotation
    more info
     
    peptidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    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 
    cellular nitrogen compound metabolic process TAS
    Traceable Author Statement
    more info
     
    embryo development IEA
    Inferred from Electronic Annotation
    more info
     
    energy reserve metabolic process TAS
    Traceable Author Statement
    more info
     
    metabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    neurogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    pancreas development IEA
    Inferred from Electronic Annotation
    more info
     
    peptide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    peptide hormone processing TAS
    Traceable Author Statement
    more info
     
    pituitary gland development IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of protein secretion IEA
    Inferred from Electronic Annotation
    more info
     
    protein autoprocessing IEA
    Inferred from Electronic Annotation
    more info
     
    proteolysis IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of insulin secretion TAS
    Traceable Author Statement
    more info
     
    response to axon injury IEA
    Inferred from Electronic Annotation
    more info
     
    response to calcium ion IEA
    Inferred from Electronic Annotation
    more info
     
    response to chlorate IEA
    Inferred from Electronic Annotation
    more info
     
    response to drug IEA
    Inferred from Electronic Annotation
    more info
     
    response to fatty acid IEA
    Inferred from Electronic Annotation
    more info
     
    response to glucocorticoid stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    response to interleukin-1 IEA
    Inferred from Electronic Annotation
    more info
     
    response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    response to morphine IEA
    Inferred from Electronic Annotation
    more info
     
    response to nutrient levels IEA
    Inferred from Electronic Annotation
    more info
     
    response to organic cyclic compound IEA
    Inferred from Electronic Annotation
    more info
     
    response to peptide hormone stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    axon terminus IEA
    Inferred from Electronic Annotation
    more info
     
    cytoplasmic vesicle IEA
    Inferred from Electronic Annotation
    more info
     
    dendrite IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
     
    perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    rough endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
     
    secretory granule TAS
    Traceable Author Statement
    more info
     
    trans-Golgi network IEA
    Inferred from Electronic Annotation
    more info
     
    transport vesicle IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    neuroendocrine convertase 1
    Names
    neuroendocrine convertase 1
    NEC 1
    prohormone convertase 1
    prohormone convertase 3
    NP_000430.3
    NP_001171346.1
    NP_001171347.1

    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_000439.4NP_000430.3  neuroendocrine convertase 1 isoform 1 preproprotein

      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, OTTHUMP00000151175, ENST00000311106, OTTHUMT00000242851
      Conserved Domains (3) summary
      pfam12177
      Location:712752
      Blast Score: 213
      Proho_convert; Prohormone convertase enzyme
      cd04059
      Location:121415
      Blast Score: 1235
      Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
      pfam01483
      Location:504591
      Blast Score: 344
      P_proprotein; Proprotein convertase P-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 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/TrEMBL
      B7Z8T7
      UniProtKB/TrEMBL
      E9PHA1
      Related
      ENSP00000421600, OTTHUMP00000222725, ENST00000508626, OTTHUMT00000370538
      Conserved Domains (3) summary
      pfam12177
      Location:665705
      Blast Score: 210
      Proho_convert; Prohormone convertase enzyme
      cd04059
      Location:74368
      Blast Score: 1232
      Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
      pfam01483
      Location:457544
      Blast Score: 341
      P_proprotein; Proprotein convertase P-domain
    3. NM_001177876.1NP_001171347.1  neuroendocrine convertase 1 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC008951, AK308575
      Conserved Domains (3) summary
      pfam12177
      Location:402442
      Blast Score: 214
      Proho_convert; Prohormone convertase enzyme
      pfam01483
      Location:194281
      Blast Score: 343
      P_proprotein; Proprotein convertase P-domain
      cl10459
      Location:56105
      Blast Score: 256
      Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      95726040..95768985, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      90916038..90958959, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC008951.6 (4278..24742) None
    genomic AC108107.2 (58239..76407) None
    genomic CH471084.1 EAW96062.1
      EAW96063.1
    genomic D73407.2 BAA11133.1
    genomic U24128.1 AAA73788.1
    mRNA AB208874.1 BAD92111.1
    mRNA AK303888.1 BAH14073.1
    mRNA AK308575.1 None
    mRNA BC031211.1 None
    mRNA BC130295.1 AAI30296.1
    mRNA BC136486.1 AAI36487.1
    mRNA DA192592.1 None
    mRNA M90753.1 AAA59918.1
    mRNA X64810.1 CAA46031.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P29120.2 GenPept UniProtKB/Swiss-Prot:P29120
    Q59H85 GenPept UniProtKB/TrEMBL:Q59H85

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