LOCUS       NM_015884               4446 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens membrane bound transcription factor peptidase, site 2
            (MBTPS2), mRNA.
ACCESSION   NM_015884
VERSION     NM_015884.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4446)
  AUTHORS   Caengprasath,N., Theerapanon,T., Porntaveetus,T. and Shotelersuk,V.
  TITLE     MBTPS2, a membrane bound protease, underlying several distinct skin
            and bone disorders
  JOURNAL   J Transl Med 19 (1), 114 (2021)
   PUBMED   33743732
  REMARK    GeneRIF: MBTPS2, a membrane bound protease, underlying several
            distinct skin and bone disorders.
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4446)
  AUTHORS   Yang,Z., Xu,Z., Xing,H. and Ma,L.
  TITLE     Novel MBTPS2 mutation causes a mild phenotype of ichthyosis
            follicularis with atrichia and photophobia syndrome in a Chinese
            pedigree
  JOURNAL   J Dermatol 46 (4), e126-e128 (2019)
   PUBMED   30294811
  REMARK    GeneRIF: 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.
REFERENCE   3  (bases 1 to 4446)
  AUTHORS   Chen,C., Xu,C., Li,H., Jia,M. and Tang,S.
  TITLE     Novel mutation in MBTPS2 causes keratosis follicularis spinulosa
            decalvans in a large Chinese family
  JOURNAL   Int J Dermatol 58 (4), 493-496 (2019)
   PUBMED   29951998
  REMARK    GeneRIF: Study reports a novel missense mutation c.638C>T
            (p.Ser213Leu) in MBTPS2 in a large Chinese family with keratosis
            follicularis spinulosa decalvans.
REFERENCE   4  (bases 1 to 4446)
  AUTHORS   Khan,A.O. and Al Teneiji,A.M.
  TITLE     Retinal venous tortuosity in a woman hemizygous for MBTPS2 mutation
  JOURNAL   Ophthalmic Genet 40 (1), 69-70 (2019)
   PUBMED   30589367
  REMARK    GeneRIF: MBTPS2 mutation is associated with Retinal venous
            tortuosity.
REFERENCE   5  (bases 1 to 4446)
  AUTHORS   Nemer,G., Safi,R., Kreidieh,F., Usta,J., Bergqvist,C., Ballout,F.,
            Btadini,W., Hamzeh,N., Abbas,O., Kibbi,A.G., Shimomura,Y. and
            Kurban,M.
  TITLE     Understanding the phenotypic similarities between IFAP and Olmsted
            syndrome from a molecular perspective: the interaction of MBTPS2
            and TRPV3
  JOURNAL   Arch Dermatol Res 309 (8), 637-643 (2017)
   PUBMED   28717930
  REMARK    GeneRIF: 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.
REFERENCE   6  (bases 1 to 4446)
  AUTHORS   Oeffner,F., Fischer,G., Happle,R., Konig,A., Betz,R.C.,
            Bornholdt,D., Neidel,U., Boente Mdel,C., Redler,S.,
            Romero-Gomez,J., Salhi,A., Vera-Casano,A., Weirich,C. and
            Grzeschik,K.H.
  TITLE     IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane
            zinc metalloprotease essential for cholesterol homeostasis and ER
            stress response
  JOURNAL   Am J Hum Genet 84 (4), 459-467 (2009)
   PUBMED   19361614
  REMARK    GeneRIF: assign the IFAP syndrome locus to the 5.4 Mb region
            between DXS989 and DXS8019 on Xp22.11-p22.13 and provide evidence
            that missense mutations of membrane-bound transcription factor
            protease, site 2 (MBTPS2) are associated with this phenotype
REFERENCE   7  (bases 1 to 4446)
  AUTHORS   Ye,J., Rawson,R.B., Komuro,R., Chen,X., Dave,U.P., Prywes,R.,
            Brown,M.S. and Goldstein,J.L.
  TITLE     ER stress induces cleavage of membrane-bound ATF6 by the same
            proteases that process SREBPs
  JOURNAL   Mol Cell 6 (6), 1355-1364 (2000)
   PUBMED   11163209
REFERENCE   8  (bases 1 to 4446)
  AUTHORS   Ye,J., Dave,U.P., Grishin,N.V., Goldstein,J.L. and Brown,M.S.
  TITLE     Asparagine-proline sequence within membrane-spanning segment of
            SREBP triggers intramembrane cleavage by site-2 protease
  JOURNAL   Proc Natl Acad Sci U S A 97 (10), 5123-5128 (2000)
   PUBMED   10805775
REFERENCE   9  (bases 1 to 4446)
  AUTHORS   Zelenski,N.G., Rawson,R.B., Brown,M.S. and Goldstein,J.L.
  TITLE     Membrane topology of S2P, a protein required for intramembranous
            cleavage of sterol regulatory element-binding proteins
  JOURNAL   J Biol Chem 274 (31), 21973-21980 (1999)
   PUBMED   10419520
REFERENCE   10 (bases 1 to 4446)
  AUTHORS   Rawson,R.B., Zelenski,N.G., Nijhawan,D., Ye,J., Sakai,J.,
            Hasan,M.T., Chang,T.Y., Brown,M.S. and Goldstein,J.L.
  TITLE     Complementation cloning of S2P, a gene encoding a putative
            metalloprotease required for intramembrane cleavage of SREBPs
  JOURNAL   Mol Cell 1 (1), 47-57 (1997)
   PUBMED   9659902
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX489533.1, AF019612.1,
            AK307143.1, AK056736.1 and AW204540.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_015884.3.
            
            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].
            
            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 :: SRR1660809.202900.1,
                                           SRR1660809.65774.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000379484.10/ ENSP00000368798.5
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-19                BX489533.1         81-99
            20-1778             AF019612.1         1-1759
            1779-2406           AK307143.1         1032-1659
            2407-4439           AK056736.1         508-2540
            4440-4446           AW204540.1         17-23               c
FEATURES             Location/Qualifiers
     source          1..4446
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.12"
     gene            1..4446
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /note="membrane bound transcription factor peptidase, site
                     2"
                     /db_xref="GeneID:51360"
                     /db_xref="HGNC:HGNC:15455"
                     /db_xref="MIM:300294"
     exon            1..193
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     CDS             119..1678
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /EC_number="3.4.24.85"
                     /note="membrane-bound transcription factor protease, site
                     2; endopeptidase S2P; SREBPs intramembrane protease;
                     sterol regulatory element-binding proteins intramembrane
                     protease; keratosis follicularis spinulosa decalvans;
                     site-2 protease"
                     /codon_start=1
                     /product="membrane-bound transcription factor site-2
                     protease"
                     /protein_id="NP_056968.1"
                     /db_xref="CCDS:CCDS14201.1"
                     /db_xref="GeneID:51360"
                     /db_xref="HGNC:HGNC:15455"
                     /db_xref="MIM:300294"
                     /translation="MIPVSLVVVVVGGWTVVYLTDLVLKSSVYFKHSYEDWLENNGLS
                     ISPFHIRWQTAVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTL
                     AQMMADSPSSYSSSSSSSSSSSSSSSSSSSSSSSLHNEQVLQVVVPGINLPVNQLTYF
                     FTAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQL
                     RIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVG
                     DLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTEC
                     CNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKKSSSSSFCIIPSLE
                     THTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVVVETFVKYLIS
                     LSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAAN
                     VTLGLWMVTAR"
     exon            194..342
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            343..556
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            557..660
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            661..788
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            789..907
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            908..1088
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            1089..1183
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            1184..1379
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            1380..1455
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     exon            1456..4446
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4410..4415
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /note="hexamer: AATAAA"
     polyA_site      4446
                     /gene="MBTPS2"
                     /gene_synonym="BRESEK; IFAP; KFSD; KFSDX; OI19; OLMSX;
                     S2P"
                     /note="major polyA site"
ORIGIN      
        1 ggcggtagct tggttcctga gcggatgctg gggctgtaag gcgcgcgcgg tcagctgttg
       61 gcggtgcagg gaggaggacg ccggggctcg ccttccctcc tctgccgccg ctgccgccat
      121 gattccggtg tcgctggtgg tggtggtggt gggtggctgg actgtcgtct acctgaccga
      181 cttggtgctg aagtcatctg tctattttaa acattcttat gaagactggc tggaaaacaa
      241 cggactgagc atctcccctt tccacataag atggcaaact gctgttttca atcgtgcctt
      301 ttacagttgg ggacggcgga aagcaaggat gctttaccaa tggttcaatt ttggaatggt
      361 gtttggcgta attgccatgt ttagctcatt ttttctcctt ggaaaaacgc tgatgcagac
      421 tttggcacaa atgatggctg actctccctc ttcttattct tcctcctctt cttcctcttc
      481 ctcctcttct tcctcttcct cttcttcatc ttcttcctct tcctcgcttc acaatgaaca
      541 ggtgttacaa gttgtggttc ctggtataaa tttacccgtc aatcaactga cctatttctt
      601 cacggcagtt ctcattagtg gtgttgtaca tgaaattgga catgggatag cagctattag
      661 ggaacaagtt cgatttaatg gctttgggat ttttctcttc attatttatc ctggagcatt
      721 tgttgatctg ttcaccactc atttgcaact tatatcgcca gtccagcagc taaggatatt
      781 ttgtgcaggt atctggcata attttgtcct tgcactcttg ggtattttag ctcttgttct
      841 cctcccagta attctcttgc cattttacta cactggagtt ggggtgctca tcactgaagt
      901 tgctgaggac tctcctgcca ttggacccag aggccttttt gtgggagacc ttgtcaccca
      961 tctacaggat tgtcctgtta ctaatgtgca agattggaat gaatgtttag ataccatcgc
     1021 ctatgagccc caaattggtt actgtataag tgcatcaact ttacagcagt taagtttccc
     1081 agttagagca tacaaacgac tagatggttc aactgaatgc tgtaacaatc acagcctcac
     1141 agatgtgtgc ttttcctaca gaaataattt taataagcgt ttgcatacat gtcttcctgc
     1201 ccggaaagca gttgaagcaa ctcaagtttg cagaaccaat aaagactgta aaaaaagctc
     1261 aagttcaagt ttctgtataa taccttcttt ggaaactcac actcgcttaa taaaagtaaa
     1321 acacccacct cagattgata tgttatacgt aggacatcct ctgcatcttc actacacagt
     1381 gagcatcacc agttttatcc cacgttttaa ctttctaagc atagatctgc cagtggttgt
     1441 ggagacattt gtcaagtacc tgatttccct ctcaggagct ctggctattg ttaatgcagt
     1501 accctgcttt gctttggatg gacaatggat tctaaactct ttcttggatg ccacccttac
     1561 ctcagtgatt ggagacaatg atgtcaaaga tctaataggg tttttcatct tgctgggtgg
     1621 cagtgtactt ttggctgcca atgtgaccct gggactctgg atggttacag cacggtaatg
     1681 tttgcactca tctgacagaa tccctgagtt acagtataca gctatgtggt aatattcatt
     1741 gccattgaaa ttcttacttg gtatgaaata taaagtgttt ccttaaaatt acatcttagc
     1801 caacaaccct gagctcctcc catatccaga gtacccaaac tctgtggtag aagataagca
     1861 gaagaaatga aaggcatagt ccctgactat attctaattt aggactgaat gtacccagat
     1921 gcttgtggaa taatatctaa gcaagtgcaa attcatgtaa taccgttttg tctgattaca
     1981 tattgtgttg aaatagtata aaggagaaca gaactgggtg gaattaattg ggaaaaactt
     2041 cttacaaaag catcattaat caaaatttga aggagaccag actttggcca agtggaagga
     2101 tgaccattgt cttggcctgt atctcttgtc ctttgtcttg tttgaaaagt attttaaaac
     2161 ttaatggtgt attattttgt gctctgaaag ctgaggtctg attacaatta gtaaaattct
     2221 atagaagaat ctgctgacgt gaaagggaaa aatctttgtc aaatgatacc aaataaatga
     2281 acaaaacagg aagtagggcc tatgatatcg tgagacatgt tttgccccac aagagttgca
     2341 tcttttataa ggtgtctctg ccccctcata aagcagcact agctttgaca tccacggtga
     2401 gctgcaggaa gcatcacaca ccagcagcat gtgagcagag ggaggcagtt ggggttgaac
     2461 ttcggaacta ggccgggtct cctgacagat cacaagacac cccagaggat cttcagcagt
     2521 cctacttccc attctctata gagctttgaa gcttggaacc cttccagggt aaacattttc
     2581 tcttgtgctg ctcaggacat ctggggccta gctcctgggt tcctgtctcc aagaagcaat
     2641 gaccttaaac tctgagccat actctgtcct caccagcggc tcccatgttt ttctgtgtca
     2701 ggttattaag tacctagtcc ttgttttctg tctctctcct aagctacctc tctgggtcca
     2761 cagaagactt ggtagtatag tgagaatggc tatacgtgag tacaaacgtg gattttccag
     2821 ggcttgggaa ctgattcttg agcccagaag agccacgcct gctttgaggt cttttggagt
     2881 ggagatgcag ccctgggaaa tttggggagt cagcaggcca gtgtgaagct attggtccta
     2941 ggagtatatg agcttgctgt ttctttgatg gaaaatacat gcttctcttg tatactcaga
     3001 agtgactaag ggcaataact cattaatagc catctatcca acttctttac tgagtgatgt
     3061 attccatggg gttacctttt tcagattatt gagttgctct gtaagcacta aaacttttta
     3121 atcattttta agaaactttt tagattgtat tacaaatttg ccttaacagt aattagatgt
     3181 tgaatataat tttaacattt tattaatgac ttgggtcatc agttaatacc agtactaaaa
     3241 ccatacgaat tattggttta ttccagaaaa tacagtattt gttctatttt taggtagaca
     3301 atcatttggg atcagagtac attagcatag taatgctcag tcagacctgt tcaagtagta
     3361 gagcttggag aatgccatga aatacttata taattaattt gattgcatga actaagcaat
     3421 tttactaatg aaaaggttgt atatgtgcaa gtcacttttt taaaaaccaa gaaaaaactt
     3481 taatagagga aatcttattc attaatttat ttttctgagt aaaaaaacga aacccaaatc
     3541 tcattttatt tcaactgtta aacattttga tctgttgacc cataggatca ggatttggga
     3601 accactttac taggaaagag cagatcagta ccatttgtat aaaaccggcc tcattatgta
     3661 agaaagaaaa tgttacgtgt tttcttcttt agcttggttg tgggcacttc tacagcaagg
     3721 accatatcat attcatcttt gcatccctgg cacagtgcat gagacataag tacttaataa
     3781 atgcagttga atggataatg attagtgtta tttatggatt agaaaaagca tgtttctatt
     3841 taagtaagct gtaaaaagta ttattgaata tttactgtaa atatatgttc acataaaaaa
     3901 ataacttgga gggtctttgt gtccctggca tattatcatc ttcatggaaa gaatccactg
     3961 tggtttctgt agagtgattg gaaaaatgga ttattttgag gattgaagaa agtgttcttt
     4021 ctgcgttgtc actttgttca acagtaaaac tttattctca gtgttcctac tctgcattgt
     4081 ttacattttt gacagttttt tttaatcacc tacaatctgt aaagaatgta tatattcttt
     4141 tcagcatctc agtttgaaaa gacatgcagt taaacttgac cttttgataa tcgctcttac
     4201 aggtcattgt ctgttctaac agcaaattgt aaacatgtgc ttcatagata ttgtggctct
     4261 cagtcatcac tttgtcctat ggtatttatt gaatgttcac atactaatgg tgcacaggtg
     4321 tttttttcta taaatcttct gactgtcctg taattcattc ttaagcttta acttgaaggt
     4381 atcgtaattg ccggcatttg atgtttagca ataaaagaat aaatgtgtac cagcatttta
     4441 tgttta
//
