LOCUS       NM_000484               3583 bp    mRNA    linear   PRI 11-MAR-2025
DEFINITION  Homo sapiens amyloid beta precursor protein (APP), transcript
            variant 1, mRNA.
ACCESSION   NM_000484
VERSION     NM_000484.4
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 3583)
  AUTHORS   Majernikova,N., Marmolejo-Garza,A., Salinas,C.S., Luu,M.D.A.,
            Zhang,Y., Trombetta-Lima,M., Tomin,T., Birner-Gruenberger,R.,
            Lehtonen,S., Koistinaho,J., Wolters,J.C., Ayton,S., den
            Dunnen,W.F.A. and Dolga,A.M.
  TITLE     The link between amyloid beta and ferroptosis pathway in
            Alzheimer's disease progression
  JOURNAL   Cell Death Dis 15 (10), 782 (2024)
   PUBMED   39468028
  REMARK    GeneRIF: The link between amyloid beta and ferroptosis pathway in
            Alzheimer's disease progression.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3583)
  AUTHORS   Munch,N.S., Das,S. and Seeger,S.
  TITLE     Unveiling the effect of CaCl2 on amyloid beta aggregation via
            supercritical angle Raman and fluorescence spectroscopy and
            microscopy
  JOURNAL   Phys Chem Chem Phys 26 (41), 26266-26276 (2024)
   PUBMED   39371012
  REMARK    GeneRIF: Unveiling the effect of CaCl2 on amyloid beta aggregation
            via supercritical angle Raman and fluorescence spectroscopy and
            microscopy.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3583)
  AUTHORS   Kang,W., Lu,Y., Etaka,J.C., Salsbury,F.R. Jr. and Derreumaux,P.
  TITLE     Structural Insight into Melatonin's Influence on the Conformation
            of Abeta42 Dimer Studied by Molecular Dynamics Simulation
  JOURNAL   J Phys Chem B 128 (41), 9947-9958 (2024)
   PUBMED   39364725
  REMARK    GeneRIF: Structural Insight into Melatonin's Influence on the
            Conformation of Abeta42 Dimer Studied by Molecular Dynamics
            Simulation.
REFERENCE   4  (bases 1 to 3583)
  AUTHORS   Tsoy,A., Umbayev,B., Kassenova,A., Kaupbayeva,B. and Askarova,S.
  TITLE     Pathology of Amyloid-beta (Abeta) Peptide Peripheral Clearance in
            Alzheimer's Disease
  JOURNAL   Int J Mol Sci 25 (20), 10964 (2024)
   PUBMED   39456746
  REMARK    GeneRIF: Pathology of Amyloid-beta (Abeta) Peptide Peripheral
            Clearance in Alzheimer's Disease.
            Review article
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3583)
  AUTHORS   Soscia,S.J., Kirby,J.E., Washicosky,K.J., Tucker,S.M.,
            Ingelsson,M., Hyman,B., Burton,M.A., Goldstein,L.E., Duong,S.,
            Tanzi,R.E. and Moir,R.D.
  TITLE     The Alzheimer's disease-associated amyloid beta-protein is an
            antimicrobial peptide
  JOURNAL   PLoS One 5 (3), e9505 (2010)
   PUBMED   20209079
  REMARK    GeneRIF: Alzheimer's disease-associated amyloid beta-protein
            peptides display antimicrobial activity against C. albicans, E.
            coli, S. epidermidis, S. pneumoniae, S. aureus, L. monocytogenes,
            E. faecalis, and S. agalactiae.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3583)
  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   7  (bases 1 to 3583)
  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
REFERENCE   8  (bases 1 to 3583)
  AUTHORS   Mant,R., Asherson,P., Gill,M., McGuffin,P., Owen,M., Wert,S.E.,
            Gregory,R.J., Smith,A.E., Cohn,J.A., Wilson,J.M. et al.
  TITLE     Schizophrenia scepticism
  JOURNAL   Nat Genet 2 (1), 12 (1992)
   PUBMED   1303244
REFERENCE   9  (bases 1 to 3583)
  AUTHORS   Mullan,M., Crawford,F., Axelman,K., Houlden,H., Lilius,L.,
            Winblad,B. and Lannfelt,L.
  TITLE     A pathogenic mutation for probable Alzheimer's disease in the APP
            gene at the N-terminus of beta-amyloid
  JOURNAL   Nat Genet 1 (5), 345-347 (1992)
   PUBMED   1302033
REFERENCE   10 (bases 1 to 3583)
  AUTHORS   Hendriks,L., van Duijn,C.M., Cras,P., Cruts,M., Van Hul,W., van
            Harskamp,F., Warren,A., McInnis,M.G., Antonarakis,S.E., Martin,J.J.
            et al.
  TITLE     Presenile dementia and cerebral haemorrhage linked to a mutation at
            codon 692 of the beta-amyloid precursor protein gene
  JOURNAL   Nat Genet 1 (3), 218-221 (1992)
   PUBMED   1303239
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI559391.1, AK312326.1,
            BC065529.1 and BM876312.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000484.3.
            
            Summary: This gene encodes a cell surface receptor and
            transmembrane precursor protein that is cleaved by secretases to
            form a number of peptides. Some of these peptides are secreted and
            can bind to the acetyltransferase complex APBB1/TIP60 to promote
            transcriptional activation, while others form the protein basis of
            the amyloid plaques found in the brains of patients with Alzheimer
            disease. In addition, two of the peptides are antimicrobial
            peptides, having been shown to have bacteriocidal and antifungal
            activities. Mutations in this gene have been implicated in
            autosomal dominant Alzheimer disease and cerebroarterial
            amyloidosis (cerebral amyloid angiopathy). Multiple transcript
            variants encoding several different isoforms have been found for
            this gene. [provided by RefSeq, Aug 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a, also known as PreA4
            770).
            
            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 :: SRR11853560.19016.1,
                                           SRR14038194.1684132.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match                 :: ENST00000346798.8/
                                                  ENSP00000284981.4
            Protein has antimicrobial activity :: PMID: 20209079
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-149               BI559391.1         56-204
            150-1241            AK312326.1         65-1156
            1242-1242           BC065529.1         1166-1166
            1243-2463           AK312326.1         1158-2378
            2464-3580           BC065529.1         2388-3504
            3581-3583           BM876312.1         16-18               c
FEATURES             Location/Qualifiers
     source          1..3583
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="21"
                     /map="21q21.3"
     gene            1..3583
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="amyloid beta precursor protein"
                     /db_xref="GeneID:351"
                     /db_xref="HGNC:HGNC:620"
                     /db_xref="MIM:104760"
     exon            1..207
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     CDS             151..2463
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; peptidase nexin-II; cerebral vascular amyloid
                     peptide; protease nexin-II; amyloid beta A4 protein;
                     beta-amyloid peptide; alzheimer disease amyloid protein;
                     beta-amyloid peptide(1-40); beta-amyloid peptide(1-42);
                     amyloid precursor protein; beta-amyloid precursor protein;
                     testicular tissue protein Li 2; amyloid beta (A4)
                     precursor protein; alzheimer disease amyloid A4 protein
                     homolog"
                     /codon_start=1
                     /product="amyloid-beta precursor protein isoform a
                     precursor"
                     /protein_id="NP_000475.1"
                     /db_xref="CCDS:CCDS13576.1"
                     /db_xref="GeneID:351"
                     /db_xref="HGNC:HGNC:620"
                     /db_xref="MIM:104760"
                     /translation="MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMH
                     MNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGR
                     KQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSE
                     KSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYA
                     DGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTT
                     TTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTE
                     EYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQ
                     KAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANER
                     QQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHT
                     LKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELL
                     QKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSF
                     GADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYE
                     VHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDA
                     AVTPEERHLSKMQQNGYENPTYKFFEQMQN"
     exon            208..375
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            376..505
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            506..618
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            619..812
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            813..1015
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1016..1183
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1184..1240
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1241..1374
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1375..1449
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1450..1608
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1609..1737
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1738..1837
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1838..2059
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            2060..2113
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            2114..2214
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            2215..2361
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     exon            2362..3583
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3309..3314
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="hexamer: AATAAA"
     polyA_site      3327
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="major polyA site"
     regulatory      3560..3565
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="hexamer: AATAAA"
     polyA_site      3583
                     /gene="APP"
                     /gene_synonym="AAA; ABETA; ABPP; AD1; alpha-sAPP; APPI;
                     CTFgamma; CVAP; PN-II; PN2; preA4"
                     /note="major polyA site"
ORIGIN      
        1 gtcagtttcc tcggcagcgg taggcgagag cacgcggagg agcgtgcgcg ggggccccgg
       61 gagacggcgg cggtggcggc gcgggcagag caaggacgcg gcggatccca ctcgcacagc
      121 agcgcactcg gtgccccgcg cagggtcgcg atgctgcccg gtttggcact gctcctgctg
      181 gccgcctgga cggctcgggc gctggaggta cccactgatg gtaatgctgg cctgctggct
      241 gaaccccaga ttgccatgtt ctgtggcaga ctgaacatgc acatgaatgt ccagaatggg
      301 aagtgggatt cagatccatc agggaccaaa acctgcattg ataccaagga aggcatcctg
      361 cagtattgcc aagaagtcta ccctgaactg cagatcacca atgtggtaga agccaaccaa
      421 ccagtgacca tccagaactg gtgcaagcgg ggccgcaagc agtgcaagac ccatccccac
      481 tttgtgattc cctaccgctg cttagttggt gagtttgtaa gtgatgccct tctcgttcct
      541 gacaagtgca aattcttaca ccaggagagg atggatgttt gcgaaactca tcttcactgg
      601 cacaccgtcg ccaaagagac atgcagtgag aagagtacca acttgcatga ctacggcatg
      661 ttgctgccct gcggaattga caagttccga ggggtagagt ttgtgtgttg cccactggct
      721 gaagaaagtg acaatgtgga ttctgctgat gcggaggagg atgactcgga tgtctggtgg
      781 ggcggagcag acacagacta tgcagatggg agtgaagaca aagtagtaga agtagcagag
      841 gaggaagaag tggctgaggt ggaagaagaa gaagccgatg atgacgagga cgatgaggat
      901 ggtgatgagg tagaggaaga ggctgaggaa ccctacgaag aagccacaga gagaaccacc
      961 agcattgcca ccaccaccac caccaccaca gagtctgtgg aagaggtggt tcgagaggtg
     1021 tgctctgaac aagccgagac ggggccgtgc cgagcaatga tctcccgctg gtactttgat
     1081 gtgactgaag ggaagtgtgc cccattcttt tacggcggat gtggcggcaa ccggaacaac
     1141 tttgacacag aagagtactg catggccgtg tgtggcagcg ccatgtccca aagtttactc
     1201 aagactaccc aggaacctct tgcccgagat cctgttaaac ttcctacaac agcagccagt
     1261 acccctgatg ccgttgacaa gtatctcgag acacctgggg atgagaatga acatgcccat
     1321 ttccagaaag ccaaagagag gcttgaggcc aagcaccgag agagaatgtc ccaggtcatg
     1381 agagaatggg aagaggcaga acgtcaagca aagaacttgc ctaaagctga taagaaggca
     1441 gttatccagc atttccagga gaaagtggaa tctttggaac aggaagcagc caacgagaga
     1501 cagcagctgg tggagacaca catggccaga gtggaagcca tgctcaatga ccgccgccgc
     1561 ctggccctgg agaactacat caccgctctg caggctgttc ctcctcggcc tcgtcacgtg
     1621 ttcaatatgc taaagaagta tgtccgcgca gaacagaagg acagacagca caccctaaag
     1681 catttcgagc atgtgcgcat ggtggatccc aagaaagccg ctcagatccg gtcccaggtt
     1741 atgacacacc tccgtgtgat ttatgagcgc atgaatcagt ctctctccct gctctacaac
     1801 gtgcctgcag tggccgagga gattcaggat gaagttgatg agctgcttca gaaagagcaa
     1861 aactattcag atgacgtctt ggccaacatg attagtgaac caaggatcag ttacggaaac
     1921 gatgctctca tgccatcttt gaccgaaacg aaaaccaccg tggagctcct tcccgtgaat
     1981 ggagagttca gcctggacga tctccagccg tggcattctt ttggggctga ctctgtgcca
     2041 gccaacacag aaaacgaagt tgagcctgtt gatgcccgcc ctgctgccga ccgaggactg
     2101 accactcgac caggttctgg gttgacaaat atcaagacgg aggagatctc tgaagtgaag
     2161 atggatgcag aattccgaca tgactcagga tatgaagttc atcatcaaaa attggtgttc
     2221 tttgcagaag atgtgggttc aaacaaaggt gcaatcattg gactcatggt gggcggtgtt
     2281 gtcatagcga cagtgatcgt catcaccttg gtgatgctga agaagaaaca gtacacatcc
     2341 attcatcatg gtgtggtgga ggttgacgcc gctgtcaccc cagaggagcg ccacctgtcc
     2401 aagatgcagc agaacggcta cgaaaatcca acctacaagt tctttgagca gatgcagaac
     2461 tagacccccg ccacagcagc ctctgaagtt ggacagcaaa accattgctt cactacccat
     2521 cggtgtccat ttatagaata atgtgggaag aaacaaaccc gttttatgat ttactcatta
     2581 tcgccttttg acagctgtgc tgtaacacaa gtagatgcct gaacttgaat taatccacac
     2641 atcagtaatg tattctatct ctctttacat tttggtctct atactacatt attaatgggt
     2701 tttgtgtact gtaaagaatt tagctgtatc aaactagtgc atgaatagat tctctcctga
     2761 ttatttatca catagcccct tagccagttg tatattattc ttgtggtttg tgacccaatt
     2821 aagtcctact ttacatatgc tttaagaatc gatgggggat gcttcatgtg aacgtgggag
     2881 ttcagctgct tctcttgcct aagtattcct ttcctgatca ctatgcattt taaagttaaa
     2941 catttttaag tatttcagat gctttagaga gatttttttt ccatgactgc attttactgt
     3001 acagattgct gcttctgcta tatttgtgat ataggaatta agaggataca cacgtttgtt
     3061 tcttcgtgcc tgttttatgt gcacacatta ggcattgaga cttcaagctt ttcttttttt
     3121 gtccacgtat ctttgggtct ttgataaaga aaagaatccc tgttcattgt aagcactttt
     3181 acggggcggg tggggagggg tgctctgctg gtcttcaatt accaagaatt ctccaaaaca
     3241 attttctgca ggatgattgt acagaatcat tgcttatgac atgatcgctt tctacactgt
     3301 attacataaa taaattaaat aaaataaccc cgggcaagac ttttctttga aggatgacta
     3361 cagacattaa ataatcgaag taattttggg tggggagaag aggcagattc aattttcttt
     3421 aaccagtctg aagtttcatt tatgatacaa aagaagatga aaatggaagt ggcaatataa
     3481 ggggatgagg aaggcatgcc tggacaaacc cttcttttaa gatgtgtctt caatttgtat
     3541 aaaatggtgt tttcatgtaa ataaatacat tcttggagga gca
//
