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

Gene ID: 8720, updated on 3-Apr-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
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Genomic context

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Location:
16q23.3-q24.1
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (84053763..84116942, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (90119889..90190524, complement)
105.20220307 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

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. 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
  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. Site-1 protease and lysosomal homeostasis. Velho RV, et al. Biochim Biophys Acta Mol Cell Res, 2017 Nov. PMID 28693924
  4. Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1 protease. da Palma JR, et al. J Biol Chem, 2014 Dec 26. PMID 25378398, Free PMC Article
  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 (74) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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).
  6. 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.
  7. Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
    Title: Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
  8. 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.
  9. 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.
  10. rs11642644 associated with facial profile
    Title: Genetics of the human face: Identification of large-effect single gene variants.
Submit: New GeneRIF Correction See all GeneRIFs (29)

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)

Genotypes

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 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_2023_10

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

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

    UniProtKB/Swiss-Prot
    A8K6V8, Q14703, Q24JQ2, Q9UF67

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

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

    UniProtKB/Swiss-Prot
    A8K6V8, Q14703, Q24JQ2, Q9UF67

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

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