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PCSK5 proprotein convertase subtilisin/kexin type 5 [ Homo sapiens (human) ]

Gene ID: 5125, updated on 7-Jun-2020

Summary

Official Symbol
PCSK5provided by HGNC
Official Full Name
proprotein convertase subtilisin/kexin type 5provided by HGNC
Primary source
HGNC:HGNC:8747
See related
Ensembl:ENSG00000099139 MIM:600488
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
PC5; PC6; PC6A; SPC6
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. It then sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. This encoded protein is widely expressed and one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It mediates posttranslational endoproteolytic processing for several integrin alpha subunits and is thought to process prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1 glycoprotein gp160. Alternative splicing results in multiple transcript variants, some of which encode distinct isoforms, including a protease packaged into dense core granules (PC5A) and a type 1 membrane bound protease (PC5B). [provided by RefSeq, May 2014]
Expression
Broad expression in small intestine (RPKM 6.4), duodenum (RPKM 5.8) and 20 other tissues See more
Orthologs

Genomic context

See PCSK5 in Genome Data Viewer
Location:
9q21.13
Exon count:
40
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (75890644..76362975)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (78505560..78977255)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene OTX2 pseudogene 1 Neighboring gene uncharacterized LOC105376091 Neighboring gene RNA binding motif protein 22 pseudogene 5 Neighboring gene Sharpr-MPRA regulatory region 10 Neighboring gene ribosomal protein SA pseudogene 9 Neighboring gene riboflavin kinase

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 Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
NHGRI GWA Catalog
Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
NHGRI GWA Catalog
Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.
NHGRI GWA Catalog
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.
NHGRI GWA Catalog
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
NHGRI GWA Catalog
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
NHGRI GWA Catalog
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env Kexin/subtilisin-related convertases such as furin, PACE4, PC1, PC2, PC5 and its isoform PC5/6-B can process HIV-1 gp160 to gp120/gp41 PubMed
Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of proprotein convertase subtilisin/kexin type 5 (PCSK5) in primary human brain microvascular endothelial cells PubMed
tat Proprotein convertase subtilisin/kexin type 5 (PCSK5) is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells PubMed
Vpr vpr Proprotein convertase PC5 cleaves extracellular HIV-1 Vpr between amino-acids 88-89 located within the functionally important C-terminal arginine-rich domain RQRR(88)V/A/G(89)R in Vpr PubMed
nucleocapsid gag Proprotein convertase subtilisin/kexin type 5 (PCSK5) is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ11149, FLJ13034, FLJ16215

Gene Ontology Provided by GOA

Function Evidence Code Pubs
endopeptidase activity EXP
Inferred from Experiment
more info
PubMed 
peptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
peptide binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
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
anterior/posterior pattern specification IMP
Inferred from Mutant Phenotype
more info
PubMed 
cardiac septum development IEA
Inferred from Electronic Annotation
more info
 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
coronary vasculature development IEA
Inferred from Electronic Annotation
more info
 
cytokine biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
determination of left/right symmetry IEA
Inferred from Electronic Annotation
more info
 
embryo implantation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
embryonic digestive tract development IMP
Inferred from Mutant Phenotype
more info
PubMed 
embryonic digestive tract development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
embryonic skeletal system development IMP
Inferred from Mutant Phenotype
more info
PubMed 
embryonic skeletal system development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
heart development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
kidney development IMP
Inferred from Mutant Phenotype
more info
PubMed 
kidney development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
limb morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
nerve growth factor processing TAS
Traceable Author Statement
more info
 
peptide biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
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 processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein processing IDA
Inferred from Direct Assay
more info
PubMed 
regulation of lipoprotein lipase activity TAS
Traceable Author Statement
more info
 
renin secretion into blood stream IEP
Inferred from Expression Pattern
more info
PubMed 
respiratory tube development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
signal peptide processing IDA
Inferred from Direct Assay
more info
PubMed 
viral life cycle IEP
Inferred from Expression Pattern
more info
PubMed 
viral life cycle ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
 
Golgi apparatus TAS
Traceable Author Statement
more info
PubMed 
Golgi lumen TAS
Traceable Author Statement
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
integral component of Golgi membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
secretory granule ISS
Inferred from Sequence or Structural Similarity
more info
 
trans-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
proprotein convertase subtilisin/kexin type 5
Names
prohormone convertase 5
proprotein convertase 6
protease PC6
subtilase
subtilisin/kexin-like protease PC5
NP_001177411.1
NP_001358972.1
NP_006191.2
XP_011517071.1
XP_011517072.1
XP_016870289.1

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_029445.1 RefSeqGene

    Range
    5001..476696
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001190482.1NP_001177411.1  proprotein convertase subtilisin/kexin type 5 isoform PC6B preproprotein

    See identical proteins and their annotated locations for NP_001177411.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform PC5B, alternatively referred to as the long form.
    Source sequence(s)
    AK122718, AL391868, AL589653, BC012064, DA992221, DT932737, DV080167, DY655633
    Consensus CDS
    CCDS55320.1
    UniProtKB/Swiss-Prot
    Q92824
    Related
    ENSP00000446280.1, ENST00000545128.5
    Conserved Domains (8) summary
    cd04059
    Location:126420
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:782823
    FU; Furin-like repeats
    cd00064
    Location:14701518
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00082
    Location:162445
    Peptidase_S8; Subtilase family
    pfam00757
    Location:845992
    Furin-like; Furin-like cysteine rich region
    pfam01483
    Location:505595
    P_proprotein; Proprotein convertase P-domain
    pfam14843
    Location:15691686
    GF_recep_IV; Growth factor receptor domain IV
    pfam16470
    Location:38114
    S8_pro-domain; Peptidase S8 pro-domain
  2. NM_001372043.1NP_001358972.1  proprotein convertase subtilisin/kexin type 5 isoform 3 precursor

    Status: REVIEWED

    Source sequence(s)
    AL353607, AL359253, AL391868, AL589653
    Related
    ENSP00000500971.1, ENST00000674117.1
  3. NM_006200.6NP_006191.2  proprotein convertase subtilisin/kexin type 5 isoform PC6A preproprotein

    See identical proteins and their annotated locations for NP_006191.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks several 3' exons but contains an alternate 3' terminal exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (PC5A, alternatively referred to as the short form) has a substantially shorter and distinct C-terminus, compared to isoform PC5B.
    Source sequence(s)
    AI379031, AK023096, BC012064, BM719207, CK023649, CN360310, DA992221, HY155058
    Consensus CDS
    CCDS6652.1
    UniProtKB/Swiss-Prot
    Q92824
    Related
    ENSP00000365943.4, ENST00000376752.8
    Conserved Domains (7) summary
    cd04059
    Location:126420
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:782823
    FU; Furin-like repeats
    cd00064
    Location:688738
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00082
    Location:162445
    Peptidase_S8; Subtilase family
    pfam01483
    Location:505595
    P_proprotein; Proprotein convertase P-domain
    pfam08686
    Location:886910
    PLAC; PLAC (protease and lacunin) domain
    pfam16470
    Location:38114
    S8_pro-domain; Peptidase S8 pro-domain

RNA

  1. NR_120409.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the central region, and also lacks several 3' exons but contains an alternate 3' terminal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AI379031, AK023096, AK225773, BM719207, CK023649, CN360310, DA992221, HY155058

RefSeqs of Annotated Genomes: Homo sapiens Updated 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_000009.12 Reference GRCh38.p13 Primary Assembly

    Range
    75890644..76362975
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011518769.3XP_011517071.1  proprotein convertase subtilisin/kexin type 5 isoform X2

    Conserved Domains (9) summary
    cd04059
    Location:126420
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:782823
    FU; Furin-like repeats
    cd00064
    Location:14961544
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00082
    Location:162445
    Peptidase_S8; Subtilase family
    pfam00757
    Location:845992
    Furin-like; Furin-like cysteine rich region
    pfam01483
    Location:505595
    P_proprotein; Proprotein convertase P-domain
    pfam14843
    Location:15951712
    GF_recep_IV; Growth factor receptor domain IV
    pfam15913
    Location:12361304
    Furin-like_2; Furin-like repeat, cysteine-rich
    pfam16470
    Location:38114
    S8_pro-domain; Peptidase S8 pro-domain
  2. XM_017014800.1XP_016870289.1  proprotein convertase subtilisin/kexin type 5 isoform X4

    Related
    ENSP00000411654.1, ENST00000424854.6
  3. XM_011518770.2XP_011517072.1  proprotein convertase subtilisin/kexin type 5 isoform X3

    Conserved Domains (7) summary
    pfam03302
    Location:8451130
    VSP; Giardia variant-specific surface protein
    smart00261
    Location:336377
    FU; Furin-like repeats
    cd00064
    Location:10511099
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00757
    Location:399546
    Furin-like; Furin-like cysteine rich region
    pfam01483
    Location:59149
    P_proprotein; Proprotein convertase P-domain
    pfam14843
    Location:11501267
    GF_recep_IV; Growth factor receptor domain IV
    pfam15913
    Location:791859
    Furin-like_2; Furin-like repeat, cysteine-rich

RNA

  1. XR_929807.2 RNA Sequence

  2. XR_929806.2 RNA Sequence

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