PCSK5 (Proprotein Convertase Subtilisin/Kexin Type 5)
2014-06-01 Majid Khatib , Béatrice Demoures AffiliationUniversity Bordeaux 1, INSERM U1029, Avenue des Facultes, Batiment B2, Talence 33405, France
Identity
HGNC
LOCATION
9q21.13
LOCUSID
ALIAS
PC5,PC6,PC6A,SPC6
FUSION GENES
DNA/RNA

Description
This gene can be found on chromosome 9 at location: 77695406-78164112.
Transcription
The DNA sequence contains 37 exons and the transcript length: 9538 bps translated to 1860 residues protein.
Proteins

Description
PCSK5 is a member of the family of subtilisin-like proprotein convertase (PCs) that process proteins at basic residues. This protease 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.
Expression
PCSK5 is widely expressed and encoded by two alternatively spliced mRNAs: PC5A (which encodes a soluble 913-amino acid protein) and PC5B (which encodes a type I membrane-bound 1860-amino acid enzyme). PC5A is mostly found in the adrenal gland, uterus, ovary, aorta, brain and lung. PC5B is more limited with high expression in the intestine (jejunum, duodenum, ileum, colon), the kidney and the liver.
Localisation
Isoform PC6A: Secreted.
Isoform PC6B: Endomembrane system: Type I membrane protein localized
Isoform PC6B: Endomembrane system: Type I membrane protein localized
Function
PCSK5 is capable of cleavage at the R-X-(K/R)-R consensus motif to release mature proteins from their proproteins. PCSK5 substrates include growth factors (GDF11, TGFb, BMP2, CALD1, NGF, PDGF-A, PDGF-B, VEGF-C), receptors (IGF-1R), prohormones (pro-renin), ECM proteins (N-cadherin, alpha-integrins), enzymes (phospholipase, pro-MT1-MMP, ADAM family), and viral protein (HIV-1 glycoprotein gp160). The activation/inactivation of these substrates implicated directly the latter to homeostatic balance, HDL metabolism, pregnancy establishment and development, and to cell adhesion, proliferation and migration.
Homology
The PCSK5 catalytic domain has a high percentage of homology with those of the other PCs: 65% between PCSK5 and Furin.
Implicated in
Entity name
Gastric cancer
Note
Studies have shown that mice developing adenocarcinomas along the small intestine exhibited more tumours when they lack PCSK5 in enterocytes.
Entity name
Currarino syndrome
Note
Exon sequencing of healthy individuals and patients with VACTERL malformations linked mutations in the human PCSK5 gene to this syndrome.
Entity name
Viral infection
Note
The human immunodeficiency virus HIV envelope glycoprotein gp160 is synthesized as an inactive precursor, which is processed into its fusiogenic form gp120/gp41 by host cell PCSK5 during its intracellular trafficking.
Article Bibliography
Other Information
Locus ID:
NCBI: 5125
MIM: 600488
HGNC: 8747
Ensembl: ENSG00000099139
Variants:
dbSNP: 5125
ClinVar: 5125
TCGA: ENSG00000099139
COSMIC: PCSK5
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
Citation
Majid Khatib ; Béatrice Demoures
PCSK5 (Proprotein Convertase Subtilisin/Kexin Type 5)
Atlas Genet Cytogenet Oncol Haematol. 2014-06-01
Online version: http://atlasgeneticsoncology.org/gene/52105/pcsk5-(proprotein-convertase-subtilisin-kexin-type-5)