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

Summary

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

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_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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).
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.
Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
Title: Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta.
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.
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.
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

Associated conditions

Description	Tests
Spondyloepiphyseal dysplasia, kondo-fu type MedGen: C5193071 OMIM: 618392 GeneReviews: MBTPS1-Related Spondyloepimetaphyseal Dysplasia with Elevated Lysosomal Enzymes	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-60819 (e-PCR)
- UniSTS:53004

SHGC-146327 (e-PCR)
- UniSTS:175151

D16S2940 (e-PCR)
- UniSTS:23602

A009A27 (e-PCR)
- UniSTS:25162

SHGC-148572 (e-PCR)
- UniSTS:176471

SHGC-61039 (e-PCR)
- UniSTS:15203

D16S3012 (e-PCR)
- UniSTS:154231

RH25319 (e-PCR)
- UniSTS:84604

SHGC-60638 (e-PCR)
- UniSTS:57507

D16S2645 (e-PCR)
- UniSTS:152252

A009K43 (e-PCR)
- UniSTS:18111

G32629 (e-PCR)
- UniSTS:117212

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

EC 3.4.21.112

XP_047290786.1

EC 3.4.21.112

XP_047290787.1

EC 3.4.21.112

XP_054170226.1

EC 3.4.21.112

XP_054170227.1

EC 3.4.21.112

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

NG_033017.1 RefSeqGene

Range

4971..68150

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

84053763..84116942 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

A8K6V8, Q14703, Q24JQ2, Q9UF67
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

NC_060940.1 Alternate T2T-CHM13v2.0

Range

90119889..90190524 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

A8K6V8, Q14703, Q24JQ2, Q9UF67
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

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.