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

Gene ID: 18553, updated on 2-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 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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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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