LOCUS       NM_015331               2822 bp    mRNA    linear   PRI 20-FEB-2024
DEFINITION  Homo sapiens nicastrin (NCSTN), transcript variant 1, mRNA.
ACCESSION   NM_015331
VERSION     NM_015331.3
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 2822)
  AUTHORS   He,Y., Wang,W., Ma,X., Duan,Z., Wang,B., Li,M. and Xu,H.
  TITLE     Discovery and Potential Functional Characterization of Long
            Noncoding RNAs Associated with Familial Acne Inversa with NCSTN
            Mutation
  JOURNAL   Dermatology 240 (1), 119-131 (2024)
   PUBMED   37490873
  REMARK    GeneRIF: Discovery and Potential Functional Characterization of
            Long Noncoding RNAs Associated with Familial Acne Inversa with
            NCSTN Mutation.
REFERENCE   2  (bases 1 to 2822)
  AUTHORS   de Oliveira,A.S.L.E., de Siqueira,R.C., Nait-Meddour,C.,
            Tricarico,P.M., Moura,R., Agrelli,A., d'Adamo,A.P., Jamain,S.,
            Crovella,S., de Fatima Medeiros Brito,M., Boniotto,M. and
            Brandao,L.A.C.
  TITLE     A loss-of-function NCSTN mutation associated with familial Dowling
            Degos disease and hidradenitis suppurativa
  JOURNAL   Exp Dermatol 32 (11), 1935-1945 (2023)
   PUBMED   37665193
  REMARK    GeneRIF: A loss-of-function NCSTN mutation associated with familial
            Dowling Degos disease and hidradenitis suppurativa.
REFERENCE   3  (bases 1 to 2822)
  AUTHORS   Zhang,Z., Zhang,B., Guo,Y., Chen,J., Zheng,S., Gao,X., Chen,H. and
            Xu,X.
  TITLE     A novel mutation of the NCSTN gene in a Chinese hidradenitis
            suppurativa family with familial comedones as the main clinical
            manifestation
  JOURNAL   Int J Dermatol 61 (8), e293-e294 (2022)
   PUBMED   34860362
  REMARK    GeneRIF: A novel mutation of the NCSTN gene in a Chinese
            hidradenitis suppurativa family with familial comedones as the main
            clinical manifestation.
REFERENCE   4  (bases 1 to 2822)
  AUTHORS   Hermasch,M.A., Janning,H., Perera,R.P., Schnabel,V., Rostam,N.,
            Ramos-Gomes,F., Muschalek,W., Bennemann,A., Alves,F., Ralser,D.J.,
            Betz,R.C., Schon,M.P., Dosch,R. and Frank,J.
  TITLE     Evolutionary distinct roles of gamma-secretase subunit nicastrin in
            zebrafish and humans
  JOURNAL   J Dermatol Sci 105 (2), 80-87 (2022)
   PUBMED   35016821
  REMARK    GeneRIF: Evolutionary distinct roles of gamma-secretase subunit
            nicastrin in zebrafish and humans.
REFERENCE   5  (bases 1 to 2822)
  AUTHORS   Mitsuda,N., Yamagata,H.D., Zhong,W., Aoto,M., Akatsu,H., Uekawa,N.,
            Kamino,K., Taguchi,K., Yamamoto,T., Maruyama,M., Kosaka,K.,
            Takeda,M., Kondo,I. and Miki,T.
  TITLE     A novel alternative splice variant of nicastrin and its implication
            in Alzheimer disease
  JOURNAL   Life Sci 78 (21), 2444-2448 (2006)
   PUBMED   16303145
  REMARK    GeneRIF: we have identified a novel alternatively spliced
            transcript of nicastrin in human brain tissue
REFERENCE   6  (bases 1 to 2822)
  AUTHORS   Chen,F., Yu,G., Arawaka,S., Nishimura,M., Kawarai,T., Yu,H.,
            Tandon,A., Supala,A., Song,Y.Q., Rogaeva,E., Milman,P., Sato,C.,
            Yu,C., Janus,C., Lee,J., Song,L., Zhang,L., Fraser,P.E. and St
            George-Hyslop,P.H.
  TITLE     Nicastrin binds to membrane-tethered Notch
  JOURNAL   Nat Cell Biol 3 (8), 751-754 (2001)
   PUBMED   11483961
REFERENCE   7  (bases 1 to 2822)
  AUTHORS   Satoh,J. and Kuroda,Y.
  TITLE     Nicastrin, a key regulator of presenilin function, is expressed
            constitutively in human neural cell lines
  JOURNAL   Neuropathology 21 (2), 115-122 (2001)
   PUBMED   11396676
REFERENCE   8  (bases 1 to 2822)
  AUTHORS   Fagan,R., Swindells,M., Overington,J. and Weir,M.
  TITLE     Nicastrin, a presenilin-interacting protein, contains an
            aminopeptidase/transferrin receptor superfamily domain
  JOURNAL   Trends Biochem Sci 26 (4), 213-214 (2001)
   PUBMED   11295540
REFERENCE   9  (bases 1 to 2822)
  AUTHORS   Yu,G., Nishimura,M., Arawaka,S., Levitan,D., Zhang,L., Tandon,A.,
            Song,Y.Q., Rogaeva,E., Chen,F., Kawarai,T., Supala,A., Levesque,L.,
            Yu,H., Yang,D.S., Holmes,E., Milman,P., Liang,Y., Zhang,D.M.,
            Xu,D.H., Sato,C., Rogaev,E., Smith,M., Janus,C., Zhang,Y.,
            Aebersold,R., Farrer,L.S., Sorbi,S., Bruni,A., Fraser,P. and St
            George-Hyslop,P.
  TITLE     Nicastrin modulates presenilin-mediated notch/glp-1 signal
            transduction and betaAPP processing
  JOURNAL   Nature 407 (6800), 48-54 (2000)
   PUBMED   10993067
REFERENCE   10 (bases 1 to 2822)
  AUTHORS   De Strooper,B., Annaert,W., Cupers,P., Saftig,P., Craessaerts,K.,
            Mumm,J.S., Schroeter,E.H., Schrijvers,V., Wolfe,M.S., Ray,W.J.,
            Goate,A. and Kopan,R.
  TITLE     A presenilin-1-dependent gamma-secretase-like protease mediates
            release of Notch intracellular domain
  JOURNAL   Nature 398 (6727), 518-522 (1999)
   PUBMED   10206645
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF240468.1, BC047621.1 and
            CN429672.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_015331.2.
            
            Summary: This gene encodes a type I transmembrane glycoprotein that
            is an integral component of the multimeric gamma-secretase complex.
            The encoded protein cleaves integral membrane proteins, including
            Notch receptors and beta-amyloid precursor protein, and may be a
            stabilizing cofactor required for gamma-secretase complex assembly.
            The cleavage of beta-amyloid precursor protein yields amyloid beta
            peptide, the main component of the neuritic plaque and the hallmark
            lesion in the brains of patients with Alzheimer's disease; however,
            the nature of the encoded protein's role in Alzheimer's disease is
            not known for certain. Mutations in this gene are associated with
            familial acne inversa. A pseudogene of this gene is present on
            chromosome 21. Alternatively spliced transcript variants of this
            gene have been described, but the full-length nature of some of
            these variants has not been determined. [provided by RefSeq, Feb
            2014].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            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 :: D87442.1, AY359120.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000294785.10/ ENSP00000294785.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2145              AF240468.1         129-2273
            2146-2154           BC047621.1         2352-2360
            2155-2821           AF240468.1         2283-2949
            2822-2822           CN429672.1         545-545
FEATURES             Location/Qualifiers
     source          1..2822
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q23.2"
     gene            1..2822
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /note="nicastrin"
                     /db_xref="GeneID:23385"
                     /db_xref="HGNC:HGNC:17091"
                     /db_xref="MIM:605254"
     exon            1..99
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     CDS             15..2144
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; anterior pharynx-defective 2"
                     /codon_start=1
                     /product="nicastrin isoform 1 precursor"
                     /protein_id="NP_056146.1"
                     /db_xref="CCDS:CCDS1203.1"
                     /db_xref="GeneID:23385"
                     /db_xref="HGNC:HGNC:17091"
                     /db_xref="MIM:605254"
                     /translation="MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPL
                     NKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKH
                     FTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCR
                     EIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLF
                     SHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVV
                     VAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGET
                     FDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRN
                     QVEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHN
                     KYYQSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFS
                     DTVQADPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYV
                     VQYALANLTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRST
                     ARLARALSPAFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIF
                     SLIVTYCINAKADVLFIAPREPGAVSY"
     exon            100..204
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            205..328
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            329..450
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            451..596
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            597..747
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            748..857
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            858..1010
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1011..1115
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1116..1193
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1194..1366
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1367..1469
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1470..1565
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1566..1653
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1654..1808
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            1809..2021
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     exon            2022..2822
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2802..2807
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /note="hexamer: ATTAAA"
     polyA_site      2822
                     /gene="NCSTN"
                     /gene_synonym="ATAG1874"
                     /note="major polyA site"
ORIGIN      
        1 agcagagagg caagatggct acggcagggg gtggctctgg ggctgacccg ggaagtcggg
       61 gtctccttcg ccttctgtct ttctgcgtcc tactagcagg tttgtgcagg ggaaactcag
      121 tggagaggaa gatatatatc cccttaaata aaacagctcc ctgtgttcgc ctgctcaacg
      181 ccactcatca gattggctgc cagtcttcaa ttagtggaga cacaggggtt atccacgtag
      241 tagagaaaga ggaggaccta cagtgggtat tgactgatgg ccccaacccc ccttacatgg
      301 ttctgctgga gagcaagcat tttaccaggg atttaatgga gaagctgaaa gggagaacca
      361 gccgaattgc tggtcttgca gtgtccttga ccaagcccag tcctgcctca ggcttctctc
      421 ctagtgtaca gtgcccaaat gatgggtttg gtgtttactc caattcctat gggccagagt
      481 ttgctcactg cagagaaata cagtggaatt cgctgggcaa tggtttggct tatgaagact
      541 ttagtttccc catctttctt cttgaagatg aaaatgaaac caaagtcatc aagcagtgct
      601 atcaagatca caacctgagt cagaatggct cagcaccaac cttcccacta tgtgccatgc
      661 agctcttttc acacatgcat gctgtcatca gcactgccac ctgcatgcgg cgcagctcca
      721 tccaaagcac cttcagcatc aacccagaaa tcgtctgtga ccccctgtct gattacaatg
      781 tgtggagcat gctaaagcct ataaatacaa ctgggacatt aaagcctgac gacagggttg
      841 tggttgctgc cacccggctg gatagtcgtt cctttttctg gaatgtggcc ccaggggctg
      901 aaagcgcagt ggcttccttt gtcacccagc tggctgctgc tgaagctttg caaaaggcac
      961 ctgatgtgac caccctgccc cgcaatgtca tgtttgtctt ctttcaaggg gaaacttttg
     1021 actacattgg cagctcgagg atggtctacg atatggagaa gggcaagttt cccgtgcagt
     1081 tagagaatgt tgactcattt gtggagctgg gacaggtggc cttaagaact tcattagagc
     1141 tttggatgca cacagatcct gtttctcaga aaaatgagtc tgtacggaac caggtggagg
     1201 atctcctggc cacattggag aagagtggtg ctggtgtccc tgctgtcatc ctcaggaggc
     1261 caaatcagtc ccagcctctc ccaccatctt ccctgcagcg atttcttcga gctcgaaaca
     1321 tctctggcgt tgttctggct gaccactctg gtgccttcca taacaaatat taccagagta
     1381 tttacgacac tgctgagaac attaatgtga gctatcccga atggctgagc cctgaagagg
     1441 acctgaactt tgtaacagac actgccaagg ccctggcaga tgtggccacg gtgctgggac
     1501 gtgctctgta tgagcttgca ggaggaacca acttcagcga cacagttcag gctgatcccc
     1561 aaacggttac ccgcctgctc tatgggttcc tgattaaagc caacaactca tggttccagt
     1621 ctatcctcag gcaggaccta aggtcctact tgggtgacgg gcctcttcaa cattacatcg
     1681 ctgtctccag ccccaccaac accacttatg ttgtacagta tgccttggca aatttgactg
     1741 gcacagtggt caacctcacc cgagagcagt gccaggatcc aagtaaagtc ccaagtgaaa
     1801 acaaggatct gtatgagtac tcatgggtcc agggcccttt gcattctaat gagacggacc
     1861 gactcccccg gtgtgtgcgt tctactgcac gattagccag ggccttgtct cctgcctttg
     1921 aactgagtca gtggagctct actgaatact ctacatggac tgagagccgc tggaaagata
     1981 tccgtgcccg gatatttctc atcgccagca aagagcttga gttgatcacc ctgacagtgg
     2041 gcttcggcat cctcatcttc tccctcatcg tcacctactg catcaatgcc aaagctgatg
     2101 tccttttcat tgctccccgg gagccaggag ctgtgtcata ctgaggagga ccccagcttt
     2161 tcttgccagc tcagcagttc acttcctaga gcatctgtcc cactgggaca caaccactaa
     2221 tttgtcactg gaacctccct gggcctgtct cagattggga ttaacataaa agagtggaac
     2281 tatccaaaag agacagggag aaataaataa attgcctccc ttcctccgct cccctttccc
     2341 atcacccctt ccccatttcc tcttccttct ctactcatgc cagattttgg gattacaaat
     2401 agaagcttct tgctcctgtt taactcccta gttacccacc ctaatttgcc cttcaggacc
     2461 cttctacttt ttccttcctg ccctgtacct ctctctgctc ctcaccccca cccctgtacc
     2521 cagccacctt cctgactggg aaggacataa aaggtttaat gtcagggtca aactacattg
     2581 agcccctgag gacaggggca tctctgggct gagcctactg tctccttccc actgtccttt
     2641 ctccaggccc tcagatggca cattagggtg ggcgtgctgc gggtgggtat cccacctcca
     2701 gcccacagtg ctcagttgta ctttttatta agctgtaata tctatttttg tttttgtctt
     2761 tttcctttat tctttttgta aatatatata taatgagttt cattaaaata gattatccca
     2821 ca
//
