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    Pcsk6 proprotein convertase subtilisin/kexin type 6 [ Mus musculus (house mouse) ]

    Gene ID: 18553, updated on 27-Nov-2024

    Summary

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    Official Symbol
    Pcsk6provided by MGI
    Official Full Name
    proprotein convertase subtilisin/kexin type 6provided by MGI
    Primary source
    MGI:MGI:102897
    See related
    Ensembl:ENSMUSG00000030513 AllianceGenome:MGI:102897
    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
    SPC4; Pace4; b2b2830Clo
    Summary
    Predicted to enable heparin binding activity; nerve growth factor binding activity; and serine-type endopeptidase activity. Acts upstream of or within determination of left/right symmetry; protein processing; and zygotic determination of anterior/posterior axis, embryo. Predicted to be active in several cellular components, including cell surface; collagen-containing extracellular matrix; and extracellular space. Is expressed in several structures, including central nervous system; early conceptus; genitourinary system; limb; and skeleton. Orthologous to human PCSK6 (proprotein convertase subtilisin/kexin type 6). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in liver adult (RPKM 17.9), cerebellum adult (RPKM 13.1) and 26 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Pcsk6 in Genome Data Viewer
    Location:
    7 C; 7 35.36 cM
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 7 NC_000073.7 (65511884..65700134)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 7 NC_000073.6 (65862136..66050386)

    Chromosome 7 - NC_000073.7Genomic Context describing neighboring genes Neighboring gene RIKEN cDNA 1810008I18 gene Neighboring gene STARR-seq mESC enhancer starr_19067 Neighboring gene STARR-seq mESC enhancer starr_19068 Neighboring gene STARR-seq mESC enhancer starr_19072 Neighboring gene predicted gene 20684 Neighboring gene STARR-seq mESC enhancer starr_19080 Neighboring gene predicted gene, 51486 Neighboring gene STARR-seq mESC enhancer starr_19081 Neighboring gene STARR-positive B cell enhancer ABC_E1088 Neighboring gene small nuclear ribonucleoprotein polypeptide A' Neighboring gene selenoprotein S

    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
    • 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. Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells. Mohammad AH, et al. PLoS One, 2023. PMID 37463144, Free PMC Article
    2. Subtilisin-like proprotein convertase paired basic amino acid-cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells. Yuasa K, et al. FEBS J, 2012 Nov. PMID 22925071
    3. Estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells. Kim H, et al. J Bone Miner Metab, 2015 Jan. PMID 24557631
    4. Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6). Bassi DE, et al. Mol Carcinog, 2015 Oct. PMID 24845697, Free PMC Article
    5. Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology. Mujoomdar ML, et al. Reproduction, 2011 Mar. PMID 21183657

    See all (84) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.
      Title: Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.
    2. PCSK6 mediates Th1 differentiation and promotes chronic colitis progression and mucosal barrier injury via STAT1.
      Title: PCSK6 mediates Th1 differentiation and promotes chronic colitis progression and mucosal barrier injury via STAT1.
    3. Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.
      Title: Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.
    4. Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice.
      Title: Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice.
    5. PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation.
      Title: PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation.
    6. Mice overexpressing PACE4 exhibited tumors of increased growth rate.
      Title: Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6).
    7. PACE4 participates in bone formation at least in osteoblast differentiation, and estrogen receptor-mediated stimuli induce osteoblast differentiation through the upregulation of PACE4 expression
      Title: Estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells.
    8. we observed an increased susceptibility to UV in single furin transgenic mice that was not substantially enhanced in the double furin/PACE4 transgenic mice.
      Title: Enhanced UV-induced skin carcinogenesis in transgenic mice overexpressing proprotein convertases.
    9. A variant in PCSK6 is strongly associated with protection against pain in knee osteoarthritis.
      Title: A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype.
    10. Furin and Pace4 are released by the extraembryonic microenvironment, and that they cleave a membrane-bound reporter substrate in adjacent epiblast cells and activate Nodal to maintain pluripotency
      Title: The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Chemically induced (ENU) (1) 
    • Endonuclease-mediated (2) 
    • Targeted (1)  1 citation

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables endopeptidase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables heparin binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables nerve growth factor binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within determination of left/right symmetry IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in glycoprotein metabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in nerve growth factor production ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in peptide hormone processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in peptide hormone processing ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within protein processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein processing ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in secretion by cell ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within zygotic determination of anterior/posterior axis, embryo IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within zygotic determination of anterior/posterior axis, embryo IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cell surface ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in collagen-containing extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in collagen-containing extracellular matrix ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    proprotein convertase subtilisin/kexin type 6 isoform 1
    Names
    paired basic amino acid cleaving system 4

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001291184.1 → NP_001278113.1  proprotein convertase subtilisin/kexin type 6 isoform 1 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC132595, AC148973, AC165968
      Consensus CDS
      CCDS71978.1
      UniProtKB/TrEMBL
      E9Q4D0, Q62030
      Related
      ENSMUSP00000095992.5, ENSMUST00000098391.11
      Conserved Domains (8) summary
      cd04059
      Location:150 → 444
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:720 → 766
      FU; Furin-like repeats
      cd00064
      Location:672 → 724
      FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
      pfam00082
      Location:186 → 469
      Peptidase_S8; Subtilase family
      pfam01483
      Location:529 → 619
      P_proprotein; Proprotein convertase P-domain
      pfam08686
      Location:919 → 942
      PLAC; PLAC (protease and lacunin) domain
      pfam15913
      Location:728 → 824
      Furin-like_2; Furin-like repeat, cysteine-rich
      pfam16470
      Location:65 → 141
      S8_pro-domain; Peptidase S8 pro-domain

    2. NM_011048.1 → NP_035178.1  proprotein convertase subtilisin/kexin type 6 isoform 1 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC132595, AC148973, AC165968
      Consensus CDS
      CCDS52267.1
      UniProtKB/TrEMBL
      F6XJP7, Q62030
      Related
      ENSMUSP00000053742.6, ENSMUST00000055576.12
      Conserved Domains (8) summary
      cd04059
      Location:150 → 444
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:733 → 779
      FU; Furin-like repeats
      cd00064
      Location:685 → 737
      FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
      pfam00082
      Location:186 → 469
      Peptidase_S8; Subtilase family
      pfam01483
      Location:529 → 619
      P_proprotein; Proprotein convertase P-domain
      pfam08686
      Location:932 → 955
      PLAC; PLAC (protease and lacunin) domain
      pfam15913
      Location:741 → 837
      Furin-like_2; Furin-like repeat, cysteine-rich
      pfam16470
      Location:65 → 141
      S8_pro-domain; Peptidase S8 pro-domain

    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_000073.7 Reference GRCm39 C57BL/6J

      Range
      65511884..65700134
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version

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