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    MBTPS1 membrane bound transcription factor peptidase, site 1 [ Homo sapiens (human) ]

    Gene ID: 8720, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MBTPS1provided by HGNC
    Official Full Name
    membrane bound transcription factor peptidase, site 1provided by HGNC
    Primary source
    HGNC:HGNC:15456
    See related
    Ensembl:ENSG00000140943 MIM:603355; AllianceGenome:HGNC:15456
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    S1P; PCSK8; SEDKF; SKI-1
    Summary
    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 the cis/medial-Golgi where a second autocatalytic event takes place and the catalytic activity is acquired. It encodes a type 1 membrane bound protease which is ubiquitously expressed and regulates cholesterol or lipid homeostasis via cleavage of substrates at non-basic residues. Mutations in this gene may be associated with lysosomal dysfunction. [provided by RefSeq, Feb 2014]
    Expression
    Ubiquitous expression in thyroid (RPKM 38.5), ovary (RPKM 28.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MBTPS1 in Genome Data Viewer
    Location:
    16q23.3-q24.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (84053763..84116942, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (90119889..90190524, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (84087368..84150547, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene oxidative stress induced growth inhibitor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84007063-84007564 Neighboring gene Sharpr-MPRA regulatory region 13657 Neighboring gene N-terminal EF-hand calcium binding protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7773 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:84035929-84036711 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7774 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84050003-84050504 Neighboring gene solute carrier family 38 member 8 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84060729-84061230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84066580-84067080 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84075154-84075858 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84075859-84076562 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr16:84076563-84077267 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr16:84077268-84077971 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84078959-84079731 Neighboring gene RNA, 5S ribosomal pseudogene 432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:84082148-84083032 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:84088845-84089438 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:84089439-84090031 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7775 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr16:84125154-84126353 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7776 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11232 Neighboring gene MBTPS1 divergent transcript Neighboring gene polo like kinase 1 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins. Espenshade PJ, et al. J Biol Chem, 1999 Aug 6. PMID 10428864
    2. Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity. Al-Maskari M, et al. Sci Rep, 2018 Sep 25. PMID 30254311, Free PMC Article
    3. Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1. Carvalho DR, et al. Am J Med Genet A, 2020 Jul. PMID 32420688, Free PMC Article
    4. Genomic structure and chromosomal mapping of the human site-1 protease (S1P) gene. Nakajima T, et al. J Hum Genet, 2000. PMID 10944850
    5. Inhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces apoptosis in human melanoma cells. Weiß N, et al. J Invest Dermatol, 2014 Jan. PMID 23884247

    See all (82) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG.
      Title: Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG.
    2. The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells.
      Title: The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells.
    3. Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.
      Title: Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.
    4. Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.
      Title: Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.
    5. Sphingosine 1-phosphate alleviates radiation-induced ferroptosis in ovarian granulosa cells by upregulating glutathione peroxidase 4.
      Title: Sphingosine 1-phosphate alleviates radiation-induced ferroptosis in ovarian granulosa cells by upregulating glutathione peroxidase 4.
    6. Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM).
      Title: Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM).
    7. Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.
      Title: Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.
    8. Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
      Title: Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
    9. Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1.
      Title: Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1.
    10. Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity
      Title: Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity.
    Submit: New GeneRIF Correction See all GeneRIFs (30)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0091, MGC138711, MGC138712

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ATF6-mediated unfolded protein response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cholesterol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endoplasmic reticulum unfolded protein response TAS
    Traceable Author Statement
    more info
    		  
    involved_in lysosome organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in membrane protein intracellular domain proteolysis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in mitotic G2 DNA damage checkpoint signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein maturation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein maturation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cholesterol biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of vesicle-mediated transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to endoplasmic reticulum stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in Golgi membrane EXP
    Inferred from Experiment
    more info
    		 PubMed 
    is_active_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Golgi membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in Golgi stack IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    membrane-bound transcription factor site-1 protease
    Names
    endopeptidase S1P
    proprotein convertase subtilisin/kexin type 8
    site-1 protease
    subtilisin/kexin isozyme-1
    NP_003782.1
    XP_047290786.1
    XP_047290787.1
    XP_054170226.1
    XP_054170227.1

    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.

    Genomic

    1. NG_033017.1 RefSeqGene

      Range
      4971..68150
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003791.4 → NP_003782.1  membrane-bound transcription factor site-1 protease preproprotein

      See identical proteins and their annotated locations for NP_003782.1

      Status: REVIEWED

      Source sequence(s)
      BC114555, BM680126, BP364386, D42053
      Consensus CDS
      CCDS10941.1
      UniProtKB/Swiss-Prot
      A8K6V8, Q14703, Q24JQ2, Q9UF67
      UniProtKB/TrEMBL
      B4DR21, E7EM85
      Related
      ENSP00000344223.3, ENST00000343411.8
      Conserved Domains (3) summary
      cd07479
      Location:203 → 455
      Peptidases_S8_SKI-1_like; Peptidase S8 family domain in SKI-1-like proteins
      pfam00082
      Location:209 → 464
      Peptidase_S8; Subtilase family
      pfam14258
      Location:651 → 724
      DUF4350; Domain of unknown function (DUF4350)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      84053763..84116942 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047434831.1 → XP_047290787.1  membrane-bound transcription factor site-1 protease isoform X1

      UniProtKB/Swiss-Prot
      A8K6V8, Q14703, Q24JQ2, Q9UF67
      UniProtKB/TrEMBL
      B4DR21, E7EM85

    2. XM_047434830.1 → XP_047290786.1  membrane-bound transcription factor site-1 protease isoform X1

      UniProtKB/Swiss-Prot
      A8K6V8, Q14703, Q24JQ2, Q9UF67
      UniProtKB/TrEMBL
      B4DR21, E7EM85

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      90119889..90190524 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054314252.1 → XP_054170227.1  membrane-bound transcription factor site-1 protease isoform X1

      UniProtKB/Swiss-Prot
      A8K6V8, Q14703, Q24JQ2, Q9UF67
      UniProtKB/TrEMBL
      B4DR21, E7EM85

    2. XM_054314251.1 → XP_054170226.1  membrane-bound transcription factor site-1 protease isoform X1

      UniProtKB/Swiss-Prot
      A8K6V8, Q14703, Q24JQ2, Q9UF67
      UniProtKB/TrEMBL
      B4DR21, E7EM85

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_201268.1: Suppressed sequence

      Description
      NM_201268.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14703.1 GenPept UniProtKB/Swiss-Prot:Q14703

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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