Human Gene MBTPS1 (uc002fhi.3) Description and Page Index
  Description: Homo sapiens membrane-bound transcription factor peptidase, site 1 (MBTPS1), mRNA.
RefSeq Summary (NM_003791): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660803.232414.1, SRR1803612.128417.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000343411.8/ ENSP00000344223.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr16:84,087,369-84,150,517 Size: 63,149 Total Exon Count: 23 Strand: -
Coding Region
   Position: hg19 chr16:84,088,054-84,135,388 Size: 47,335 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr16:84,087,369-84,150,517)mRNA (may differ from genome)Protein (1052 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Membrane-bound transcription factor site-1 protease; EC=; AltName: Full=Endopeptidase S1P; AltName: Full=Subtilisin/kexin-isozyme 1; Short=SKI-1; Flags: Precursor;
FUNCTION: Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs). Other known substrates are BDNF and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg-Ser-Val-Leu (SERBP-2), Arg-His- Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu.
CATALYTIC ACTIVITY: Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3.
COFACTOR: Calcium.
ENZYME REGULATION: Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Note=May sort to other organelles, including lysosomal and/or endosomal compartments.
TISSUE SPECIFICITY: Widely expressed.
INDUCTION: Down-regulated by sterols.
PTM: The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8kDa intermediates.
SIMILARITY: Belongs to the peptidase S8 family.
SEQUENCE CAUTION: Sequence=BAA07653.2; Type=Erroneous initiation;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MBTPS1
CDC HuGE Published Literature: MBTPS1

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 44.78 RPKM in Pituitary
Total median expression: 1103.99 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -187.10502-0.373 Picture PostScript Text
3' UTR -226.60685-0.331 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000209 - Peptidase_S8/S53
IPR022398 - Peptidase_S8_His-AS
IPR023828 - Peptidase_S8_Ser-AS
IPR015500 - Peptidase_S8_subtilisin-rel

Pfam Domains:
PF00082 - Subtilase family

SCOP Domains:
52743 - Subtilisin-like

ModBase Predicted Comparative 3D Structure on Q14703
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 Protein SequenceProtein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004222 metalloendopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0006508 proteolysis
GO:0006606 protein import into nucleus
GO:0006629 lipid metabolic process
GO:0007040 lysosome organization
GO:0008202 steroid metabolic process
GO:0008203 cholesterol metabolic process
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031293 membrane protein intracellular domain proteolysis
GO:0034976 response to endoplasmic reticulum stress
GO:0036500 ATF6-mediated unfolded protein response
GO:0043687 post-translational protein modification
GO:0044267 cellular protein metabolic process
GO:0045540 regulation of cholesterol biosynthetic process

Cellular Component:
GO:0000139 Golgi membrane
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005789 endoplasmic reticulum membrane
GO:0005794 Golgi apparatus
GO:0005795 Golgi stack
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  LP858664 - Sequence 15 from Patent WO2017141032.
D42053 - Homo sapiens KIAA0091 mRNA.
BC026330 - Homo sapiens membrane-bound transcription factor peptidase, site 1, mRNA (cDNA clone IMAGE:4816102).
AK299067 - Homo sapiens cDNA FLJ58156 complete cds, highly similar to Membrane-bound transcription factor site 1 protease precursor (EC 3.4.21.-).
AK291773 - Homo sapiens cDNA FLJ78678 complete cds, highly similar to Homo sapiens membrane-bound transcription factor peptidase, site 1 (MBTPS1), transcript variant 1, mRNA.
BC114555 - Homo sapiens membrane-bound transcription factor peptidase, site 1, transcript variant 1, mRNA (cDNA clone MGC:138712 IMAGE:40054075), complete cds.
BC114961 - Homo sapiens membrane-bound transcription factor peptidase, site 1, mRNA (cDNA clone MGC:138711 IMAGE:40054074), complete cds.
AL133583 - Homo sapiens mRNA; cDNA DKFZp434A219 (from clone DKFZp434A219).
AK091212 - Homo sapiens cDNA FLJ33893 fis, clone CTONG2007681, highly similar to Membrane-bound transcription factor site 1 protease precursor (EC 3.4.21.-).
AX746852 - Sequence 377 from Patent EP1308459.
AK054744 - Homo sapiens cDNA FLJ30182 fis, clone BRACE2001154, highly similar to Intraluminal subtilisin-like proteinase S1P.
JD141138 - Sequence 122162 from Patent EP1572962.
JD265381 - Sequence 246405 from Patent EP1572962.
JD340297 - Sequence 321321 from Patent EP1572962.
JD458901 - Sequence 439925 from Patent EP1572962.
JD055027 - Sequence 36051 from Patent EP1572962.
AB383745 - Synthetic construct DNA, clone: pF1KSDA0091, Homo sapiens MBTPS1 gene for membrane-bound transcription factor site-1 protease precursor, complete cds, without stop codon, in Flexi system.
JD034052 - Sequence 15076 from Patent EP1572962.
JD026077 - Sequence 7101 from Patent EP1572962.
KJ901904 - Synthetic construct Homo sapiens clone ccsbBroadEn_11298 MBTPS1 gene, encodes complete protein.
JD166015 - Sequence 147039 from Patent EP1572962.
JD084958 - Sequence 65982 from Patent EP1572962.
JD553381 - Sequence 534405 from Patent EP1572962.
JD048431 - Sequence 29455 from Patent EP1572962.
JD519067 - Sequence 500091 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_s1pPathway - SREBP control of lipid synthesis

Reactome (by CSHL, EBI, and GO)

Protein Q14703 (Reactome details) participates in the following event(s):

R-HSA-381135 MBTPS1 (S1P) cleaves ATF6 (ATF6-alpha)
R-HSA-1655842 S1P hydrolyzes SREBP1A,1C,2
R-HSA-8874186 MBTPS1 (S1P) cleaves CREB3L4
R-HSA-8874204 MBTPS1 (S1P) cleaves CREB3
R-HSA-8874205 MBTPS1 (S1P) cleaves CREB3L2
R-HSA-8874206 MBTPS1 (S1P) cleaves CREB3L3
R-HSA-8874212 MBTPS1 (S1P) cleaves CREB3L1
R-HSA-6784620 MBTPS1,2 cleaves CREB3L3 to CREB3L3(1-?) and CREB3L3(?-461)
R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-8874211 CREB3 factors activate genes
R-HSA-381119 Unfolded Protein Response (UPR)
R-HSA-8957322 Metabolism of steroids
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-392499 Metabolism of proteins
R-HSA-556833 Metabolism of lipids
R-HSA-8963899 Plasma lipoprotein remodeling
R-HSA-597592 Post-translational protein modification
R-HSA-1430728 Metabolism
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: KIAA0091, MBTP1_HUMAN, NM_003791, NP_003782, Q14703, Q24JQ2, Q9UF67, S1P, SKI1
UCSC ID: uc002fhi.3
RefSeq Accession: NM_003791
Protein: Q14703 (aka MBTP1_HUMAN or MS1P_HUMAN)
CCDS: CCDS10941.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_003791.2
exon count: 23CDS single in 3' UTR: no RNA size: 4354
ORF size: 3159CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6255.50frame shift in genome: no % Coverage: 99.82
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.