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 subcellula... See more...

Aliases for PCSK4 Gene

Aliases for PCSK4 Gene

  • Proprotein Convertase Subtilisin/Kexin Type 4 2 3 4 5
  • PC4 2 3 4
  • SPC5 2 3
  • Testicular Tissue Protein Li 135 3
  • Proprotein Convertase 4 4
  • DKFZp434B217 2
  • EC 3.4.21.75 51
  • EC 3.4.21.93 51
  • EC 3.4.21.- 4
  • EC 3.4.21 51
  • MGC34749 2
  • PCSK4 5

External Ids for PCSK4 Gene

Previous GeneCards Identifiers for PCSK4 Gene

  • GC19U990073
  • GC19M001550
  • GC19M001421
  • GC19M001432
  • GC19M001256

Summaries for PCSK4 Gene

Entrez Gene Summary for PCSK4 Gene

  • 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. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]

GeneCards Summary for PCSK4 Gene

PCSK4 (Proprotein Convertase Subtilisin/Kexin Type 4) is a Protein Coding gene. Diseases associated with PCSK4 include Dilated Cardiomyopathy 1T. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is FURIN.

UniProtKB/Swiss-Prot Summary for PCSK4 Gene

  • Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity).

Gene Wiki entry for PCSK4 Gene

Additional gene information for PCSK4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PCSK4 Gene

Genomics for PCSK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PCSK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J001489 Promoter/Enhancer 2.5 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 618.4 -1.3 -1317 6 SP1 HNRNPL GATAD2A ATF7 PRDM10 ZNF629 TFE3 RFX1 LEF1 IKZF1 PCSK4 REEP6 lnc-PCSK4-1 SF3A2 GRIN3B CIRBP LMNB2 TMEM259 LSM7 TCF3
GH19J001442 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.2 +46.0 46018 4.3 CTCF HNRNPL PRDM10 ZNF629 REST TFE3 IKZF1 NFKBIZ ZNF692 RCOR2 APC2 SF3A2 FAM174C DAZAP1 C19orf25 PCSK4 REEP6 CIRBP GRIN3B SCAMP4
GH19J001506 Promoter/Enhancer 2 Ensembl ENCODE CraniofacialAtlas dbSUPER 11 -18.6 -18601 9.7 SP1 HNRNPL CREB1 CTCF ZNF629 LEF1 IKZF1 KDM1A ZNF692 RCOR2 ENSG00000267092 PLK5 PCSK4 REEP6 ADAMTSL5 ENSG00000261526 lnc-ADAMTSL5-1
GH19J001441 Enhancer 0.9 ENCODE dbSUPER 12.2 +48.7 48659 0.6 PRDM1 RBFOX2 PATZ1 POLR2A ZNF600 ZBTB44 BCL11A NCOR1 NFIC ARNT AB372681 ENSG00000268798 C19orf25 PCSK4 REEP6 APC2 RPS15
GH19J001502 Enhancer 1.1 ENCODE dbSUPER 9.2 -12.7 -12708 1.2 HNRNPL GATAD2A CTCF ZNF629 TFE3 IKZF1 ZNF692 BACH1 ZNF143 MTA2 REEP6 PCSK4 PLK5 piR-43097-028
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PCSK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PCSK4

Top Transcription factor binding sites by QIAGEN in the PCSK4 gene promoter:
  • AhR
  • AML1a
  • Arnt
  • LUN-1
  • Pax-5
  • Spz1
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c
  • YY1

Genomic Locations for PCSK4 Gene

Genomic Locations for PCSK4 Gene
chr19:1,481,428-1,490,874
(GRCh38/hg38)
Size:
9,447 bases
Orientation:
Minus strand
chr19:1,481,427-1,490,751
(GRCh37/hg19)
Size:
9,325 bases
Orientation:
Minus strand

Genomic View for PCSK4 Gene

Genes around PCSK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PCSK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PCSK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PCSK4 Gene

Proteins for PCSK4 Gene

  • Protein details for PCSK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6UW60-PCSK4_HUMAN
    Recommended name:
    Proprotein convertase subtilisin/kexin type 4
    Protein Accession:
    Q6UW60
    Secondary Accessions:
    • Q8IY88
    • Q9UF79

    Protein attributes for PCSK4 Gene

    Size:
    755 amino acids
    Molecular mass:
    82795 Da
    Quaternary structure:
    • The proPCSK4 form interacts with HSPA5; the interaction takes place at the endoplasmic reticulum.

    Alternative splice isoforms for PCSK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PCSK4 Gene

Selected DME Specific Peptides for PCSK4 Gene

Q6UW60:
  • VTTDLHH
  • HGTRCAGEVAA
  • LTWRDMQHL
  • HGTRCAGE
  • HTGTSASAP
  • ASYDFND
  • GGVRMLDG
  • IYSASWGPEDDG
  • YGYGLLDAG
  • CDGYTNSI
  • DGYTNSI
  • DPDPQPRYT
  • WASGNGG

Post-translational modifications for PCSK4 Gene

  • N-glycosylated.
  • Synthesized in the endoplasmic reticulum as a zymogen, is matured by autocatalytic cleavage between the prodomain and the catalytic domain.
  • Glycosylation at Asn629 and Asn475
  • Modification sites at PhosphoSitePlus

Domains & Families for PCSK4 Gene

Gene Families for PCSK4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for PCSK4 Gene

Suggested Antigen Peptide Sequences for PCSK4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ32673 fis, clone TESTI1000138, highly similar to Proprotein convertase subtilisin/kexin type 4 (EC 3.4.21.-) (B3KQ28_HUMAN)
  • Proprotein convertase 4 (PCSK4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6UW60

UniProtKB/Swiss-Prot:

PCSK4_HUMAN :
  • Belongs to the peptidase S8 family. Furin subfamily.
Family:
  • Belongs to the peptidase S8 family. Furin subfamily.
genes like me logo Genes that share domains with PCSK4: view

Function for PCSK4 Gene

Molecular function for PCSK4 Gene

UniProtKB/Swiss-Prot Function:
Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity).
GENATLAS Biochemistry:
proprotein convertase subtilisin,kexin like 4,only expressed in testicular germ cells

Enzyme Numbers (IUBMB) for PCSK4 Gene

Gene Ontology (GO) - Molecular Function for PCSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA,IBA 21873635
GO:0005515 protein binding IPI 11164898
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PCSK4: view
genes like me logo Genes that share phenotypes with PCSK4: view

Animal Models for PCSK4 Gene

MGI Knock Outs for PCSK4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PCSK4

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PCSK4 Gene

Localization for PCSK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PCSK4 Gene

Membrane. Single-pass membrane protein. Cytoplasmic vesicle, secretory vesicle, acrosome membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PCSK4 gene
Compartment Confidence
golgi apparatus 4
plasma membrane 2
extracellular 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
peroxisome 0
lysosome 0

Gene Ontology (GO) - Cellular Components for PCSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle ISS --
GO:0002080 acrosomal membrane ISS --
GO:0005802 trans-Golgi network IBA 21873635
GO:0016020 membrane IBA 21873635
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with PCSK4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PCSK4 Gene

Pathways & Interactions for PCSK4 Gene

PathCards logo

SuperPathways for PCSK4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for PCSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0007339 binding of sperm to zona pellucida ISS --
GO:0007340 acrosome reaction ISS --
GO:0009566 fertilization ISS --
GO:0016485 protein processing IBA,IDA 16040806
genes like me logo Genes that share ontologies with PCSK4: view

No data available for Pathways by source and SIGNOR curated interactions for PCSK4 Gene

Drugs & Compounds for PCSK4 Gene

(1) Drugs for PCSK4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with PCSK4: view

Transcripts for PCSK4 Gene

mRNA/cDNA for PCSK4 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PCSK4

Alternative Splicing Database (ASD) splice patterns (SP) for PCSK4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14a · 14b · 14c
SP1: -
SP2:
SP3:
SP4: - -
SP5:
SP6:

Relevant External Links for PCSK4 Gene

GeneLoc Exon Structure for
PCSK4

Expression for PCSK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PCSK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Testis (Reproductive System)

mRNA differential expression in normal tissues according to GTEx for PCSK4 Gene

This gene is overexpressed in Testis (x25.3).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PCSK4

SOURCE GeneReport for Unigene cluster for PCSK4 Gene:

Hs.46884

mRNA Expression by UniProt/SwissProt for PCSK4 Gene:

Q6UW60-PCSK4_HUMAN
Tissue specificity: Placenta.

Evidence on tissue expression from TISSUES for PCSK4 Gene

  • Muscle(2.1)
  • Skin(2)
genes like me logo Genes that share expression patterns with PCSK4: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PCSK4 Gene

Orthologs for PCSK4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PCSK4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PCSK4 30 31
  • 98.5 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PCSK4 30 31
  • 87.4 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PCSK4 30 31
  • 85.24 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pcsk4 30
  • 82.96 (n)
Mouse
(Mus musculus)
Mammalia Pcsk4 30 17 31
  • 82.72 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PCSK4 31
  • 67 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PCSK4 31
  • 64 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PCSK4 30 31
  • 68.09 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PCSK4 31
  • 66 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pcsk4 30
  • 59.8 (n)
Zebrafish
(Danio rerio)
Actinopterygii pcsk5a 31
  • 17 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Fur2 31
  • 19 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea bli-4 31
  • 31 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KEX2 30
  • 46.34 (n)
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_ABL203W 30
  • 45.9 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D19811g 30
  • 43.71 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU03219 30
  • 49.42 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes krp1 30
  • 45.88 (n)
Species where no ortholog for PCSK4 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PCSK4 Gene

ENSEMBL:
Gene Tree for PCSK4 (if available)
TreeFam:
Gene Tree for PCSK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PCSK4: view image

Paralogs for PCSK4 Gene

Paralogs for PCSK4 Gene

(6) SIMAP similar genes for PCSK4 Gene using alignment to 5 proteins:

  • PCSK4_HUMAN
  • K7EJB6_HUMAN
  • K7EKJ6_HUMAN
  • K7EMJ4_HUMAN
  • K7EN14_HUMAN
genes like me logo Genes that share paralogs with PCSK4: view

Variants for PCSK4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PCSK4 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs36123574 - p.Thr267Met

Additional dbSNP identifiers (rs#s) for PCSK4 Gene

Structural Variations from Database of Genomic Variants (DGV) for PCSK4 Gene

Variant ID Type Subtype PubMed ID
esv2758743 CNV gain+loss 17122850
esv32942 CNV gain+loss 17666407
esv3643399 CNV loss 21293372
nsv470105 CNV gain 18288195
nsv470106 CNV loss 18288195
nsv578279 CNV gain 21841781
nsv578295 CNV gain 21841781
nsv833705 CNV loss 17160897
nsv953942 CNV deletion 24416366

Variation tolerance for PCSK4 Gene

Residual Variation Intolerance Score: 86% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.38; 70.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PCSK4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PCSK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PCSK4 Gene

Disorders for PCSK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PCSK4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
dilated cardiomyopathy 1t
  • cmd1t
- elite association - COSMIC cancer census association via MalaCards
Search PCSK4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PCSK4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PCSK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PCSK4 Gene

Publications for PCSK4 Gene

  1. Role of pro-IGF-II processing by proprotein convertase 4 in human placental development. (PMID: 16040806) Qiu Q … Gruslin A (Proceedings of the National Academy of Sciences of the United States of America 2005) 3 4 23
  2. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human. (PMID: 7782070) Mbikay M … Simpson EM (Genomics 1995) 2 3 23
  3. The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone. (PMID: 21080038) Gyamera-Acheampong C … Mbikay M (Molecular and cellular biochemistry 2011) 3 4
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  5. Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review. (PMID: 19109312) Gyamera-Acheampong C … Mbikay M (Human reproduction update 2009) 3 23

Products for PCSK4 Gene

Sources for PCSK4 Gene