MBTP2_MOUSE
ID MBTP2_MOUSE Reviewed; 515 AA.
AC Q8CHX6; A2AC85;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Membrane-bound transcription factor site-2 protease;
DE EC=3.4.24.85 {ECO:0000250|UniProtKB:O43462};
DE AltName: Full=Endopeptidase S2P;
GN Name=Mbtps2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Zinc metalloprotease that mediates intramembrane proteolysis
CC of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2.
CC Catalyzes the second step in the proteolytic activation of the sterol
CC regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and
CC SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment,
CC thereby releasing the N-terminal segment with a portion of the
CC transmembrane segment attached. Mature N-terminal SREBP fragments
CC shuttle to the nucleus and activate gene transcription. Also mediates
CC the second step in the proteolytic activation of the cyclic AMP-
CC dependent transcription factor ATF-6 (ATF6 and ATF6B). Involved in
CC intramembrane proteolysis during bone formation.
CC {ECO:0000250|UniProtKB:O43462}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves several transcription factors that are type-2
CC transmembrane proteins within membrane-spanning domains. Known
CC substrates include sterol regulatory element-binding protein (SREBP)
CC -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2
CC is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The
CC residues Asn-Pro, 11 residues distal to the site of cleavage in the
CC membrane-spanning domain, are important for cleavage by S2P
CC endopeptidase. Replacement of either of these residues does not
CC prevent cleavage, but there is no cleavage if both of these residues
CC are replaced.; EC=3.4.24.85; Evidence={ECO:0000250|UniProtKB:O43462};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O43462};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O43462};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:O43462}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:O43462}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43462}.
CC -!- SIMILARITY: Belongs to the peptidase M50A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK148325; BAE28482.1; -; mRNA.
DR EMBL; AK164486; BAE37807.1; -; mRNA.
DR EMBL; AL663072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038343; AAH38343.1; -; mRNA.
DR CCDS; CCDS30498.1; -.
DR RefSeq; NP_758511.1; NM_172307.3.
DR AlphaFoldDB; Q8CHX6; -.
DR STRING; 10090.ENSMUSP00000059471; -.
DR MEROPS; M50.001; -.
DR GlyGen; Q8CHX6; 1 site.
DR iPTMnet; Q8CHX6; -.
DR PhosphoSitePlus; Q8CHX6; -.
DR MaxQB; Q8CHX6; -.
DR PaxDb; Q8CHX6; -.
DR PeptideAtlas; Q8CHX6; -.
DR PRIDE; Q8CHX6; -.
DR ProteomicsDB; 295810; -.
DR Antibodypedia; 483; 150 antibodies from 29 providers.
DR DNASU; 270669; -.
DR Ensembl; ENSMUST00000058098; ENSMUSP00000059471; ENSMUSG00000046873.
DR GeneID; 270669; -.
DR KEGG; mmu:270669; -.
DR UCSC; uc009usb.1; mouse.
DR CTD; 51360; -.
DR MGI; MGI:2444506; Mbtps2.
DR VEuPathDB; HostDB:ENSMUSG00000046873; -.
DR eggNOG; KOG2921; Eukaryota.
DR GeneTree; ENSGT00510000048066; -.
DR HOGENOM; CLU_032523_1_0_1; -.
DR InParanoid; Q8CHX6; -.
DR OMA; CMHYPYD; -.
DR OrthoDB; 1012405at2759; -.
DR PhylomeDB; Q8CHX6; -.
DR TreeFam; TF314478; -.
DR Reactome; R-MMU-1655829; Regulation of cholesterol biosynthesis by SREBP (SREBF).
DR Reactome; R-MMU-381033; ATF6 (ATF6-alpha) activates chaperones.
DR Reactome; R-MMU-8874211; CREB3 factors activate genes.
DR BioGRID-ORCS; 270669; 9 hits in 27 CRISPR screens.
DR ChiTaRS; Mbtps2; mouse.
DR PRO; PR:Q8CHX6; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8CHX6; protein.
DR Bgee; ENSMUSG00000046873; Expressed in superior cervical ganglion and 222 other tissues.
DR ExpressionAtlas; Q8CHX6; baseline and differential.
DR Genevisible; Q8CHX6; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISO:MGI.
DR GO; GO:0070977; P:bone maturation; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:1905897; P:regulation of response to endoplasmic reticulum stress; IBA:GO_Central.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001193; MBTPS2.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR008915; Peptidase_M50.
DR PANTHER; PTHR13325; PTHR13325; 1.
DR Pfam; PF02163; Peptidase_M50; 1.
DR PRINTS; PR01000; SREBPS2PTASE.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Cytoplasm; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..515
FT /note="Membrane-bound transcription factor site-2 protease"
FT /id="PRO_0000261592"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..74
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..140
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 141..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..442
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 443..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..488
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 489..509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 510..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 171
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 515 AA; 56960 MW; E7C3A93A58D17A21 CRC64;
MIPVSLLVVV VGGWTAVYLA DLVLKSSVYF KHSYEDWLEN NGLSISPFHI RWQTSIFNRA
FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SPYSSSSSSS
SSSSSSSSSS SSLHNEQVLQ VVVPGINLPV NQLTYFFAAV LISGVVHEIG HGIAAIREQV
RFNGFGIFLF IIYPGAFVDL FTTHLQLISP VQQLRIFCAG IWHNFVLALL GILALVLLPV
ILLPFYYTGV GVLITEVAED SPAIGPRGLF VGDLVTHLQD CPVTNVQDWN ECLDTIAYEP
QIGYCISAST LQQLSFPVRA YKRLDGSTEC CNNHSLTDVC FSYRNNFNKR LHTCLPARKA
VEATQVCRSN KDCKSGASSS FCIVPSLETH TRLIKVKHPP QIDMLYVGHP LHLHYTVSIT
SFIPRFNFLS IDLPVIVETF VKYLISLSGA LAIVNAVPCF ALDGQWILNS FLDATLTSVI
GDNDVKDLIG FFILLGGSVL LAANVTLGLW MVTAR
