LOCUS       NM_000447               2249 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens presenilin 2 (PSEN2), transcript variant 1, mRNA.
ACCESSION   NM_000447
VERSION     NM_000447.3
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 2249)
  AUTHORS   Sun,Y., Islam,S., Gao,Y., Nakamura,T., Tomita,T., Michikawa,M. and
            Zou,K.
  TITLE     Presenilin deficiency enhances tau phosphorylation and its
            secretion
  JOURNAL   J Neurochem 168 (9), 2956-2973 (2024)
   PUBMED   38946496
  REMARK    GeneRIF: Presenilin deficiency enhances tau phosphorylation and its
            secretion.
REFERENCE   2  (bases 1 to 2249)
  AUTHORS   Colijn,M.A. and Ismail,Z.
  TITLE     Presenilin Gene Mutation-associated Psychosis: Phenotypic
            Characteristics and Clinical Implications
  JOURNAL   Alzheimer Dis Assoc Disord 38 (1), 101-106 (2024)
   PUBMED   38227890
  REMARK    GeneRIF: Presenilin Gene Mutation-associated Psychosis: Phenotypic
            Characteristics and Clinical Implications.
            Review article
REFERENCE   3  (bases 1 to 2249)
  AUTHORS   Eccles,M.K., Main,N., Carlessi,R., Armstrong,A.M., Sabale,M.,
            Roberts-Mok,B., Tirnitz-Parker,J.E.E., Agostino,M., Groth,D.,
            Fraser,P.E. and Verdile,G.
  TITLE     Quantitative comparison of presenilin protein expression reveals
            greater activity of PS2-gamma-secretase
  JOURNAL   FASEB J 38 (1), e23396 (2024)
   PUBMED   38156414
  REMARK    GeneRIF: Quantitative comparison of presenilin protein expression
            reveals greater activity of PS2-gamma-secretase.
REFERENCE   4  (bases 1 to 2249)
  AUTHORS   Vanova,T., Sedmik,J., Raska,J., Amruz Cerna,K., Taus,P.,
            Pospisilova,V., Nezvedova,M., Fedorova,V., Kadakova,S., Klimova,H.,
            Capandova,M., Orviska,P., Fojtik,P., Bartova,S., Plevova,K.,
            Spacil,Z., Hribkova,H. and Bohaciakova,D.
  TITLE     Cerebral organoids derived from patients with Alzheimer's disease
            with PSEN1/2 mutations have defective tissue patterning and altered
            development
  JOURNAL   Cell Rep 42 (11), 113310 (2023)
   PUBMED   37864790
  REMARK    GeneRIF: Cerebral organoids derived from patients with Alzheimer's
            disease with PSEN1/2 mutations have defective tissue patterning and
            altered development.
REFERENCE   5  (bases 1 to 2249)
  AUTHORS   Rogaev,E.I., Sherrington,R., Rogaeva,E.A., Levesque,G., Ikeda,M.,
            Liang,Y., Chi,H., Lin,C., Holman,K., Tsuda,T. et al.
  TITLE     Familial Alzheimer's disease in kindreds with missense mutations in
            a gene on chromosome 1 related to the Alzheimer's disease type 3
            gene
  JOURNAL   Nature 376 (6543), 775-778 (1995)
   PUBMED   7651536
REFERENCE   6  (bases 1 to 2249)
  AUTHORS   Levy-Lahad,E., Wasco,W., Poorkaj,P., Romano,D.M., Oshima,J.,
            Pettingell,W.H., Yu,C.E., Jondro,P.D., Schmidt,S.D., Wang,K. et al.
  TITLE     Candidate gene for the chromosome 1 familial Alzheimer's disease
            locus
  JOURNAL   Science 269 (5226), 973-977 (1995)
   PUBMED   7638622
REFERENCE   7  (bases 1 to 2249)
  AUTHORS   Levy-Lahad,E., Wijsman,E.M., Nemens,E., Anderson,L., Goddard,K.A.,
            Weber,J.L., Bird,T.D. and Schellenberg,G.D.
  TITLE     A familial Alzheimer's disease locus on chromosome 1
  JOURNAL   Science 269 (5226), 970-973 (1995)
   PUBMED   7638621
REFERENCE   8  (bases 1 to 2249)
  AUTHORS   Hershberger,R.E. and Jordan,E.
  TITLE     Dilated Cardiomyopathy Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301486
REFERENCE   9  (bases 1 to 2249)
  AUTHORS   Bird,T.D.
  TITLE     Early-Onset Familial Alzheimer Disease - RETIRED CHAPTER, FOR
            HISTORICAL REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301414
REFERENCE   10 (bases 1 to 2249)
  AUTHORS   Bird,T.D.
  TITLE     Alzheimer Disease Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301340
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA198818.1, DA915823.1,
            BT006984.1 and L43964.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000447.2.
            
            Summary: Alzheimer's disease (AD) patients with an inherited form
            of the disease carry mutations in the presenilin proteins (PSEN1 or
            PSEN2) or the amyloid precursor protein (APP). These disease-linked
            mutations result in increased production of the longer form of
            amyloid-beta (main component of amyloid deposits found in AD
            brains). Presenilins are postulated to regulate APP processing
            through their effects on gamma-secretase, an enzyme that cleaves
            APP. Also, it is thought that the presenilins are involved in the
            cleavage of the Notch receptor such that, they either directly
            regulate gamma-secretase activity, or themselves act are protease
            enzymes. Two alternatively spliced transcript variants encoding
            different isoforms of PSEN2 have been identified. [provided by
            RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the longer 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 :: SRR1803611.189067.1,
                                           SRR1803613.35480.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000366783.8/ ENSP00000355747.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-451               DA198818.1         45-495
            452-758             DA915823.1         449-755
            759-1728            BT006984.1         376-1345
            1729-2249           L43964.1           1713-2233
FEATURES             Location/Qualifiers
     source          1..2249
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q42.13"
     gene            1..2249
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /note="presenilin 2"
                     /db_xref="GeneID:5664"
                     /db_xref="HGNC:HGNC:9509"
                     /db_xref="MIM:600759"
     exon            1..34
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            35..177
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            178..363
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            364..524
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     CDS             384..1730
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /note="isoform 1 is encoded by transcript variant 1; AD5;
                     E5-1; PS-2; AD3LP; STM-2; Alzheimer disease 4; Alzheimer
                     disease 3-like"
                     /codon_start=1
                     /product="presenilin-2 isoform 1"
                     /protein_id="NP_000438.2"
                     /db_xref="CCDS:CCDS1556.1"
                     /db_xref="GeneID:5664"
                     /db_xref="HGNC:HGNC:9509"
                     /db_xref="MIM:600759"
                     /translation="MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENT
                     AQWRSQENEEDGEEDPDRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVV
                     VATIKSVRFYTEKNGQLIYTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLY
                     KYRCYKFIHGWLIMSSLMLLFLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVC
                     IHWKGPLVLQQAYLIMISALMALVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRM
                     LVETAQERNEPIFPALIYSSAMVWTVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEP
                     SYPEVFEPPLTGYPGEELEEEEERGVKLGLGDFIFYSVLVGKAAATGSGDWNTTLACF
                     VAILIGLCLTLLLLAVFKKALPALPISITFGLIFYFSTDNLVRPFMDTLASHQLYI"
     exon            525..739
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            740..881
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            882..949
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            950..1170
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            1171..1269
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            1270..1353
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            1354..1455
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            1456..1574
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     exon            1575..2249
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2229..2234
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /note="hexamer: AATAGA"
     polyA_site      2249
                     /gene="PSEN2"
                     /gene_synonym="AD3L; AD4; CMD1V; PS2; STM2"
                     /note="major polyA site"
ORIGIN      
        1 gcgtaaactc cgctggagcg cggcggcaga gcaggcattt ccagcagtga ggagacagcc
       61 agaagcaagc ttttggagct gaaggaacct gagacagaag ctagtccccc ctctgaattt
      121 tactgatgaa gaaactgagg ccacagagct aaagtgactt ttcccaaggt cgcccagcga
      181 ggacgtggga cttctcagac gtcaggagag tgatgtgagg gagctgtgtg accatagaaa
      241 gtgacgtgtt aaaaaccagc gctgccctct ttgaaagcca gggagcatca ttcatttagc
      301 ctgctgagaa gaagaaacca agtgtccggg attcagacct ctctgcggcc ccaagtgttc
      361 gtggtgcttc cagaggcagg gctatgctca cattcatggc ctctgacagc gaggaagaag
      421 tgtgtgatga gcggacgtcc ctaatgtcgg ctgagagccc cacgccgcgc tcctgccagg
      481 agggcaggca gggcccagag gatggagaga acactgccca gtggagaagc caggagaacg
      541 aggaggacgg tgaggaggac cctgaccgct atgtctgtag tggggttccc gggcggccgc
      601 caggcctgga ggaagagctg accctcaaat acggagcgaa gcacgtgatc atgctgtttg
      661 tgcctgtcac tctgtgcatg atcgtggtgg tagccaccat caagtctgtg cgcttctaca
      721 cagagaagaa tggacagctc atctacacgc cattcactga ggacacaccc tcggtgggcc
      781 agcgcctcct caactccgtg ctgaacaccc tcatcatgat cagcgtcatc gtggttatga
      841 ccatcttctt ggtggtgctc tacaagtacc gctgctacaa gttcatccat ggctggttga
      901 tcatgtcttc actgatgctg ctgttcctct tcacctatat ctaccttggg gaagtgctca
      961 agacctacaa tgtggccatg gactacccca ccctcttgct gactgtctgg aacttcgggg
     1021 cagtgggcat ggtgtgcatc cactggaagg gccctctggt gctgcagcag gcctacctca
     1081 tcatgatcag tgcgctcatg gccctagtgt tcatcaagta cctcccagag tggtccgcgt
     1141 gggtcatcct gggcgccatc tctgtgtatg atctcgtggc tgtgctgtgt cccaaagggc
     1201 ctctgagaat gctggtagaa actgcccagg agagaaatga gcccatattc cctgccctga
     1261 tatactcatc tgccatggtg tggacggttg gcatggcgaa gctggacccc tcctctcagg
     1321 gtgccctcca gctcccctac gacccggaga tggaagaaga ctcctatgac agttttgggg
     1381 agccttcata ccccgaagtc tttgagcctc ccttgactgg ctacccaggg gaggagctgg
     1441 aggaagagga ggaaaggggc gtgaagcttg gcctcgggga cttcatcttc tacagtgtgc
     1501 tggtgggcaa ggcggctgcc acgggcagcg gggactggaa taccacgctg gcctgcttcg
     1561 tggccatcct cattggcttg tgtctgaccc tcctgctgct tgctgtgttc aagaaggcgc
     1621 tgcccgccct ccccatctcc atcacgttcg ggctcatctt ttacttctcc acggacaacc
     1681 tggtgcggcc gttcatggac accctggcct cccatcagct ctacatctga gggacatggt
     1741 gtgccacagg ctgcaagctg cagggaattt tcattggatg cagttgtata gttttacact
     1801 ctagtgccat atatttttaa gacttttctt tccttaaaaa ataaagtacg tgtttacttg
     1861 gtgaggagga ggcagaacca gctctttggt gccagctgtt tcatcaccag actttggctc
     1921 ccgctttggg gagcgcctcg cttcacggac aggaagcaca gcaggtttat ccagatgaac
     1981 tgagaaggtc agattagggc ggggagaaga gcatccggca tgagggctga gatgcgcaaa
     2041 gagtgtgctc gggagtggcc cctggcacct gggtgctctg gctggagagg aaaagccagt
     2101 tccctacgag gagtgttccc aatgctttgt ccatgatgtc cttgttattt tattgccttt
     2161 agaaactgag tcctgttctt gttacggcag tcacactgct gggaagtggc ttaatagtaa
     2221 tatcaataaa tagatgagtc ctgttagaa
//
