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Pcsk4 proprotein convertase subtilisin/kexin type 4 [ Mus musculus (house mouse) ]

Gene ID: 18551, updated on 2-Nov-2024

Summary

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Official Symbol
Pcsk4provided by MGI
Official Full Name
proprotein convertase subtilisin/kexin type 4provided by MGI
Primary source
MGI:MGI:97514
See related
Ensembl:ENSMUSG00000020131 AllianceGenome:MGI:97514
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
PC4; NEC3; SPC5; NEC 3
Summary
Predicted to enable serine-type endopeptidase activity. Involved in fertilization and sperm capacitation. Acts upstream of or within acrosome reaction and binding activity of sperm to zona pellucida. Located in acrosomal membrane. Is expressed in early conceptus; epididymis; gonad; and neural retina. Human ortholog(s) of this gene implicated in colorectal adenocarcinoma. Orthologous to human PCSK4 (proprotein convertase subtilisin/kexin type 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Biased expression in testis adult (RPKM 108.7), duodenum adult (RPKM 13.6) and 5 other tissues See more
Orthologs
human all
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Genomic context

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See Pcsk4 in Genome Data Viewer
Location:
10 C1; 10 39.72 cM
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 10 NC_000076.7 (80157117..80165583, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 10 NC_000076.6 (80321283..80329748, complement)

Chromosome 10 - NC_000076.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E5154 Neighboring gene ribosomal protein S15 Neighboring gene APC regulator of WNT signaling pathway 2 Neighboring gene STARR-positive B cell enhancer ABC_E8347 Neighboring gene RIKEN cDNA 2310011J03 gene Neighboring gene STARR-positive B cell enhancer ABC_E5155 Neighboring gene STARR-positive B cell enhancer ABC_E366 Neighboring gene predicted gene, 51809 Neighboring gene receptor accessory protein 6 Neighboring gene ADAMTS-like 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expression. Nakayama K, et al. J Biol Chem, 1992 Mar 25. PMID 1372895
  2. Cloning, nucleotide sequence and functions of XPR6, which codes for a dibasic processing endoprotease from the yeast Yarrowia lipolytica. Enderlin CS, et al. Yeast, 1994 Jan. PMID 8203153
  3. Structure of the gene for the testis-specific proprotein convertase 4 and of its alternate messenger RNA isoforms. Mbikay M, et al. Genomics, 1994 Mar 15. PMID 8020970
  4. In vitro regulatory effect of epididymal serpin CRES on protease activity of proprotein convertase PC4/PCSK4. Mishra P, et al. Curr Mol Med, 2012 Sep. PMID 22827436
  5. Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Mbikay M, et al. Proc Natl Acad Sci U S A, 1997 Jun 24. PMID 9192653, Free PMC Article

See all (40) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CRES may be a regulator of PC4 in sperm-egg interaction and fertilization.
    Title: In vitro regulatory effect of epididymal serpin CRES on protease activity of proprotein convertase PC4/PCSK4.
  2. Data suggest that the fertility defect in PCSK4 knockout mice is due, in part, to altered processing/proteolysis of ACRBP (proacrosin/acrosin binding protein sp32) as well as structural abnormalities in sperm heads and acrosomes.
    Title: Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice.
  3. thatADAM2may be a natural substrate of sperm PCSK4 and its cleavage by the enzyme during acrosome reaction may be relevant to the fertilization process.
    Title: Enzymatic activity of sperm proprotein convertase is important for mammalian fertilization.
  4. Efficient activation and trafficking of PCSK4 requires a special environment, which presumably exists in testicular germ cells where it is highly expressed, but not in somatic cells where it is not or is barely expressed.
    Title: The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone.
  5. Alterations in signal transduction and proteolytic processing during in vitro capacitation may underlie the fertilization incompetence of PCSK4-null sperm.
    Title: PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation.
  6. PCSK4-null sperm underwent capacitation at a faster rate; they were induced to acrosome react by lower concentrations of zona pellucida; and their egg-binding ability was only half that of wild-type sperm.
    Title: Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability.
Submit: New GeneRIF Correction

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC63195

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within acrosome reaction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within binding of sperm to zona pellucida IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in fertilization IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within fertilization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in fertilization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in peptide hormone processing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein processing ISO
Inferred from Sequence Orthology
more info
  
involved_in protein processing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in reproductive process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sperm capacitation IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within sperm capacitation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sperm capacitation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in Golgi membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in acrosomal membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in acrosomal vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
is_active_in trans-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
proprotein convertase subtilisin/kexin type 4
Names
KEX2-like endoprotease 3
neuroendocrine convertase 3
prohormone convertase 3

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

  1. NM_008793.3 → NP_032819.1  proprotein convertase subtilisin/kexin type 4 precursor

    See identical proteins and their annotated locations for NP_032819.1

    Status: VALIDATED

    Source sequence(s)
    AC152062
    Consensus CDS
    CCDS24018.1
    UniProtKB/Swiss-Prot
    P29121, Q62094
    Related
    ENSMUSP00000020340.9, ENSMUST00000020340.15
    Conserved Domains (4) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
    pfam00082
    Location:146 → 419
    Peptidase_S8; Subtilase family
    pfam01483
    Location:488 → 553
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

RNA

  1. NR_190479.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC152062

  2. NR_190480.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC152062

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000076.7 Reference GRCm39 C57BL/6J

    Range
    80157117..80165583 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006513364.5 → XP_006513427.1  proprotein convertase subtilisin/kexin type 4 isoform X7

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  2. XM_006513361.5 → XP_006513424.1  proprotein convertase subtilisin/kexin type 4 isoform X4

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  3. XM_006513362.5 → XP_006513425.1  proprotein convertase subtilisin/kexin type 4 isoform X5

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  4. XM_006513365.5 → XP_006513428.1  proprotein convertase subtilisin/kexin type 4 isoform X10

    Conserved Domains (3) summary
    pfam01483
    Location:320 → 385
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain
    cl10459
    Location:115 → 226
    Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

  5. XM_006513360.5 → XP_006513423.1  proprotein convertase subtilisin/kexin type 4 isoform X3

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  6. XM_006513359.5 → XP_006513422.1  proprotein convertase subtilisin/kexin type 4 isoform X2

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  7. XM_006513358.5 → XP_006513421.1  proprotein convertase subtilisin/kexin type 4 isoform X1

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:512 → 577
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  8. XM_006513369.5 → XP_006513432.1  proprotein convertase subtilisin/kexin type 4 isoform X12

    Conserved Domains (2) summary
    pfam01483
    Location:228 → 293
    P_proprotein; Proprotein convertase P-domain
    cl10459
    Location:70 → 120
    Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

  9. XM_036155689.1 → XP_036011582.1  proprotein convertase subtilisin/kexin type 4 isoform X9

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:459 → 524
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  10. XM_030244951.2 → XP_030100811.1  proprotein convertase subtilisin/kexin type 4 isoform X8

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:488 → 553
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  11. XM_006513363.5 → XP_006513426.1  proprotein convertase subtilisin/kexin type 4 isoform X6

    Conserved Domains (3) summary
    cd04059
    Location:115 → 404
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:459 → 524
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

  12. XM_006513368.3 → XP_006513431.1  proprotein convertase subtilisin/kexin type 4 isoform X11

    See identical proteins and their annotated locations for XP_006513431.1

    Conserved Domains (2) summary
    cd04059
    Location:115 → 387
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam16470
    Location:34 → 110
    S8_pro-domain; Peptidase S8 pro-domain

RNA

  1. XR_004936124.1 RNA Sequence

  2. XR_003948614.2 RNA Sequence

  3. XR_004936123.1 RNA Sequence

  4. XR_003948612.2 RNA Sequence

  5. XR_003948611.2 RNA Sequence

  6. XR_003948615.2 RNA Sequence

  7. XR_004936125.1 RNA Sequence

  8. XR_004936127.1 RNA Sequence

  9. XR_004936126.1 RNA Sequence

  10. XR_004936122.1 RNA Sequence

  11. XR_003948610.2 RNA Sequence

  12. XR_004936120.1 RNA Sequence

  13. XR_004936121.1 RNA Sequence

  14. XR_003948609.2 RNA Sequence

  15. XR_004936119.1 RNA Sequence

  16. XR_004936117.1 RNA Sequence

  17. XR_004936118.1 RNA Sequence

  18. XR_003948605.2 RNA Sequence

  19. XR_003948607.2 RNA Sequence

  20. XR_380374.3 RNA Sequence

  21. XR_380375.4 RNA Sequence

  22. XR_380371.4 RNA Sequence

  23. XR_380370.3 RNA Sequence

  24. XR_380372.3 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P29121.1 GenPept UniProtKB/Swiss-Prot:P29121

Gene LinkOut

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