PCSK4 (proprotein convertase subtilisin/kexin type 4)

2014-06-01   Majid Khatib , Béatrice Demoures 

University Bordeaux 1, INSERM U1029, Avenue des Facultes, Batiment B2, Talence 33405, France

Identity

HGNC
LOCATION
19p13.3
LOCUSID
ALIAS
PC4,SPC5
FUSION GENES

DNA/RNA

Atlas Image

Description

This gene can be found on chromosome 19 at location: at 1432427 and ends at 1441410.

Transcription

The DNA sequence contains 15 exons and the transcript length: 2661 bps translated to a 755 residues protein.

Proteins

Atlas Image

Description

PCSK4 is a member of the family of subtilisin-like proprotein convertase (PCs) that process protein at basic residues. This protein is produced in the inactive zymogen form and is activated by proteolytic removal of its prodomain in the N-terminal site.

Expression

PCSK4 is restricted to the reproductive tract and expressed primarily in testicular germ cells and sperm. Low levels of PCSK4 mRNA have also been detected in ovaries and the placenta.

Localisation

PCSK4 exact intracellular location has not yet been determined.

Function

PCSK4 cleaves synthetic peptide substrates after an Arg in a basic sequence context; most often after paired basic residues (K/R-X-K/R), to release mature proteins from their proproteins. PCSK4 substrates include growth factors (DEAF-1, proIGF2, proenkephalin, proNGF, proPACAP, HGFR), receptors (IGF-1R, HGFR), and members of the ADAM (a-disintegrin-and-metalloproteinase) family (ADAM-1, ADAM-2, ADAM-3, ADAM-5. The activation/inactivation of these substrates implicated directly the latter to the regulation of gonadal functions, sperm motility, and species specific reproduction.

Homology

The PCSK4 catalytic domain has a high percentage of homology with those of the other PCs: 70% between PCSK4 and Furin.

Implicated in

Entity name
Pregnancy difficulties
Note
An aberrant processing of IGF-II by PCSK4 plays a role in inadequate trophoblast migration and, thus, fetal growth restriction.
Entity name
Infertility
Note
The fertilizing ability of PCSK4 null spermatozoa was also found to be significantly reduced. Moreover, PCSK4 cleavages lead to sperm acquisition of fertilization competence.

Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 54760
MIM: 600487
HGNC: 8746
Ensembl: ENSG00000115257

Variants:

dbSNP: 54760
ClinVar: 54760
TCGA: ENSG00000115257
COSMIC: PCSK4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000115257ENST00000300954Q6UW60
ENSG00000115257ENST00000300954A0A140VJQ9
ENSG00000115257ENST00000588671K7EN14
ENSG00000115257ENST00000591201K7EJB6

Expression (GTEx)

0
50
100
150
200
250
300

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
160408062005Role of pro-IGF-II processing by proprotein convertase 4 in human placental development.21
206280862010Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.11
210800382011The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone.1

Citation

Majid Khatib ; Béatrice Demoures

PCSK4 (proprotein convertase subtilisin/kexin type 4)

Atlas Genet Cytogenet Oncol Haematol. 2014-06-01

Online version: http://atlasgeneticsoncology.org/gene/50716/gene-explorer/