MBTPS2 membrane bound transcription factor peptidase, site 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MBTPS2provided by HGNC
Official Full Name: membrane bound transcription factor peptidase, site 2provided by HGNC
Primary source: HGNC:HGNC:15455
See related: Ensembl:ENSG00000012174 MIM:300294; AllianceGenome:HGNC:15455
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: S2P; IFAP; KFSD; OI19; KFSDX; OLMSX; BRESEK
Summary: This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009]
Expression: Ubiquitous expression in adrenal (RPKM 6.7), ovary (RPKM 6.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp22.12

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (21839617..21885423)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (21422918..21468735)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (21857735..21903541)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders.
Title: MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders.
MBTPS2 mutation is associated with Retinal venous tortuosity.
Title: Retinal venous tortuosity in a woman hemizygous for MBTPS2 mutation.
Study reports a novel missense mutation c.638C>T (p.Ser213Leu) in MBTPS2 in a large Chinese family with keratosis follicularis spinulosa decalvans.
Title: Novel mutation in MBTPS2 causes keratosis follicularis spinulosa decalvans in a large Chinese family.
Study reports a three-generation Chinese pedigree with a mild phenotype of ichthyosis follicularis with atrichia and photophobia syndrome caused by a novel hemizygous missense mutation c.1494G>T (p.Leu498Phe) in exon 11 of MBTPS2.
Title: Novel MBTPS2 mutation causes a mild phenotype of ichthyosis follicularis with atrichia and photophobia syndrome in a Chinese pedigree.
MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.
Title: MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.
This study identified a direct regulatory effect of MBTPS2 on TRPV3 which can partially contribute to the overlapping clinical features of IFAP and Olmsted syndromes under a common signaling pathway.
Title: Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3.
S2P is essential owing to its activation of the sterol regulatory element binding proteins (SREBPs); in the absence of exogenous lipid, cells lacking S2P cannot survive. (Review)
Title: The site-2 protease.
In male patients, a genotype-phenotype correlation has begun to emerge, linking the site of the mutation in MBTPS2 with the clinical outcome described as IFAP syndrome.
Title: Genotype-phenotype correlations emerging from the identification of missense mutations in MBTPS2.
We demonstrate a novel association between an MBTPS2 mutation and an X-linked form of Olmsted syndrome.
Title: A missense mutation in the MBTPS2 gene underlies the X-linked form of Olmsted syndrome.
We report a fourth pedigree affected with Keratosis Follicularis Spinulosa Decalvans resulting from a recurrent missense mutation in the MBTPS2 gene.
Title: MBTPS2 mutation in a British pedigree with keratosis follicularis spinulosa decalvans.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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
IFAP syndrome 1, with or without BRESHECK syndrome MedGen: C5399971 OMIM: 308205 GeneReviews: Not available	Compare labs
Keratosis follicularis spinulosa decalvans, X-linked MedGen: C3887525 OMIM: 308800 GeneReviews: Not available	Compare labs
Olmsted syndrome, X-linked MedGen: C3806745 OMIM: 300918 GeneReviews: Not available	Compare labs
Osteogenesis imperfecta, type 19 MedGen: C4746956 OMIM: 301014 GeneReviews: Not available	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

DXS7577 (e-PCR)
- UniSTS:154137

D8S2279 (e-PCR)
- UniSTS:473907

DXS7674 (e-PCR)
- UniSTS:62519

DXS8252 (e-PCR)
- UniSTS:57419

DXS7480 (e-PCR)
- UniSTS:40537

SGC30434 (e-PCR)
- UniSTS:40538

WI-17374 (e-PCR)
- UniSTS:912

Mbtps2 (e-PCR), detects polymorphism
- UniSTS:530588

DXS8242 (e-PCR)
- UniSTS:59069

DXS7157 (e-PCR)
- UniSTS:60375

A008R38 (e-PCR)
- UniSTS:41200

DXS6998E (e-PCR)
- UniSTS:48113

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	EXP Inferred from Experiment more info	PubMed
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription regulator activator activity	IGI Inferred from Genetic Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ATF6-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in bone maturation	IMP Inferred from Mutant Phenotype 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 membrane protein intracellular domain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane protein intracellular domain proteolysis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitotic G2 DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein maturation	EXP Inferred from Experiment more info	PubMed
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cholesterol biosynthetic process	TAS Traceable Author Statement more info
involved_in regulation of response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	IGI Inferred from Genetic Interaction 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 membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in Golgi membrane	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: membrane-bound transcription factor site-2 protease

Names: SREBPs intramembrane protease; endopeptidase S2P; keratosis follicularis spinulosa decalvans; membrane-bound transcription factor protease, site 2; site-2 protease; sterol regulatory element-binding proteins intramembrane protease

NP_056968.1

EC 3.4.24.85

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_012797.2 RefSeqGene

Range

5080..50886

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_015884.4 → NP_056968.1 membrane-bound transcription factor site-2 protease

See identical proteins and their annotated locations for NP_056968.1

Status: REVIEWED

Source sequence(s)

AF019612, AK056736, AK307143, AW204540, BX489533

Consensus CDS

CCDS14201.1

UniProtKB/Swiss-Prot

O43462, Q9UM70, Q9UMD3

UniProtKB/TrEMBL

A8KA68

Related

ENSP00000368798.5, ENST00000379484.10

Conserved Domains (3) summary

cd05709
Location:419 → 508

S2P-M50; Site-2 protease (S2P) class of zinc metalloproteases (MEROPS family M50) cleaves transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of this family use proteolytic ...

cd06162
Location:18 → 229

S2P-M50_PDZ_SREBP; Sterol regulatory element-binding protein (SREBP) Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50A), regulates intramembrane proteolysis (RIP) of SREBP and is part of a signal transduction mechanism involved in sterol and lipid ...

cl00117
Location:255 → 299

PDZ; PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). Many PDZ domains bind C-terminal polypeptides, though binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. ...