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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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