LOCUS       NM_017439               3200 bp    mRNA    linear   PRI 01-JUN-2024
DEFINITION  Homo sapiens gamma-secretase activating protein (GSAP), transcript
            variant 1, mRNA.
ACCESSION   NM_017439 XM_374625 XM_379881 XM_499340 XM_499452
VERSION     NM_017439.4
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 3200)
  AUTHORS   Xu,P., Chang,J.C., Zhou,X., Wang,W., Bamkole,M., Wong,E.,
            Bettayeb,K., Jiang,L.L., Huang,T., Luo,W., Xu,H., Nairn,A.C.,
            Flajolet,M., Ip,N.Y., Li,Y.M. and Greengard,P.
  TITLE     GSAP regulates lipid homeostasis and mitochondrial function
            associated with Alzheimer's disease
  JOURNAL   J Exp Med 218 (8) (2021)
   PUBMED   34156424
  REMARK    GeneRIF: GSAP regulates lipid homeostasis and mitochondrial
            function associated with Alzheimer's disease.
REFERENCE   2  (bases 1 to 3200)
  AUTHORS   Perez,S.E., Nadeem,M., Malek-Ahmadi,M.H., He,B. and Mufson,E.J.
  TITLE     Frontal Cortex and Hippocampal gamma-Secretase Activating Protein
            Levels in Prodromal Alzheimer Disease
  JOURNAL   Neurodegener Dis 17 (6), 235-241 (2017)
   PUBMED   28743126
  REMARK    GeneRIF: These data demonstrate that GSAP proteins are
            differentially dysregulated in severe Alzheimer Disease, but only
            the full-length form was associated with cognitive test scores in
            Alzheimer Disease.
REFERENCE   3  (bases 1 to 3200)
  AUTHORS   Chu,J., Li,J.G., Hoffman,N.E., Stough,A.M., Madesh,M. and
            Pratico,D.
  TITLE     Regulation of gamma-secretase activating protein by the
            5Lipoxygenase: in vitro and in vivo evidence
  JOURNAL   Sci Rep 5, 11086 (2015)
   PUBMED   26076991
  REMARK    GeneRIF: GSAP cleavage via caspase-3 is regulated and depend upon
            the availability of 5-Lipoxygenase in Alzheimer's disease.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3200)
  AUTHORS   Zhu,M., Tao,Y., He,Q., Gao,H., Song,F., Sun,Y.M., Li,H.L., Wu,Z.Y.
            and Saffen,D.
  TITLE     Common GSAP promoter variant contributes to Alzheimer's disease
            liability
  JOURNAL   Neurobiol Aging 35 (11), 2656 (2014)
   PUBMED   25037285
  REMARK    GeneRIF: Its promoter variant contributes to Alzheimer's disease
            liability.
REFERENCE   5  (bases 1 to 3200)
  AUTHORS   Hussain,I., Fabregue,J., Anderes,L., Ousson,S., Borlat,F.,
            Eligert,V., Berger,S., Dimitrov,M., Alattia,J.R., Fraering,P.C. and
            Beher,D.
  TITLE     The role of gamma-secretase activating protein (GSAP) and imatinib
            in the regulation of gamma-secretase activity and amyloid-beta
            generation
  JOURNAL   J Biol Chem 288 (4), 2521-2531 (2013)
   PUBMED   23209290
  REMARK    GeneRIF: gamma-secretase activating protein (GSAP) and imatinib
            have roles in the regulation of gamma-secretase activity and
            amyloid-beta generation
REFERENCE   6  (bases 1 to 3200)
  AUTHORS   Deatherage,C.L., Hadziselimovic,A. and Sanders,C.R.
  TITLE     Purification and characterization of the human gamma-secretase
            activating protein
  JOURNAL   Biochemistry 51 (25), 5153-5159 (2012)
   PUBMED   22681044
  REMARK    GeneRIF: Protocols for recombinant bacterial expression and
            purification of potentially important protein GSAP are not
            successful in generating soluble forms of GSAP that contain
            well-ordered and homogeneous tertiary structure.
REFERENCE   7  (bases 1 to 3200)
  AUTHORS   Satoh,J., Tabunoki,H., Ishida,T., Saito,Y. and Arima,K.
  TITLE     Immunohistochemical characterization of gamma-secretase activating
            protein expression in Alzheimer's disease brains
  JOURNAL   Neuropathol Appl Neurobiol 38 (2), 132-141 (2012)
   PUBMED   21718343
  REMARK    GeneRIF: Aberrant regulation of gamma-secretase activating protein
            expression plays a key role in acceleration of gamma-cleavage of
            beta-secretase-cleaved C-terminal fragment of amyloid precursor
            protein and accumulation of Abeta in AD brains
REFERENCE   8  (bases 1 to 3200)
  AUTHORS   He,G., Luo,W., Li,P., Remmers,C., Netzer,W.J., Hendrick,J.,
            Bettayeb,K., Flajolet,M., Gorelick,F., Wennogle,L.P. and
            Greengard,P.
  TITLE     Gamma-secretase activating protein is a therapeutic target for
            Alzheimer's disease
  JOURNAL   Nature 467 (7311), 95-98 (2010)
   PUBMED   20811458
  REMARK    GeneRIF: A gamma-secretase activating protein (GSAP) that
            selectively increases amyloid-beta production via interactions with
            both gamma-secretase and its substrate, the amyloid precursor
            protein carboxy-terminal fragment.
REFERENCE   9  (bases 1 to 3200)
  AUTHORS   Oh,J.H., Yang,J.O., Hahn,Y., Kim,M.R., Byun,S.S., Jeon,Y.J.,
            Kim,J.M., Song,K.S., Noh,S.M., Kim,S., Yoo,H.S., Kim,Y.S. and
            Kim,N.S.
  TITLE     Transcriptome analysis of human gastric cancer
  JOURNAL   Mamm Genome 16 (12), 942-954 (2005)
   PUBMED   16341674
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BC110797.1, DB498013.1 and BM842423.1.
            
            On Nov 23, 2018 this sequence version replaced NM_017439.3.
            
            Summary: Accumulation of neurotoxic amyloid-beta is a major
            hallmark of Alzheimer disease (AD; MIM 104300). Formation of
            amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM
            104311), a protease with numerous substrates. PION, or GSAP,
            selectively increases amyloid-beta production through a mechanism
            involving its interaction with both gamma-secretase and its
            substrate, the amyloid-beta precursor protein (APP; MIM 104760)
            C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed
            20811458]).[supplied by OMIM, Nov 2010].
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC110797.1, SRR1803614.70689.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000257626.12/ ENSP00000257626.7
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-167               BC110797.1         52-218
            168-460             DB498013.1         212-504
            461-1341            BC110797.1         512-1392
            1342-1366           BM842423.1         235-259
            1367-3200           BC110797.1         1417-3250
FEATURES             Location/Qualifiers
     source          1..3200
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q11.23"
     gene            1..3200
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /note="gamma-secretase activating protein"
                     /db_xref="GeneID:54103"
                     /db_xref="HGNC:HGNC:28042"
                     /db_xref="MIM:613552"
     exon            1..137
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     CDS             29..2593
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /note="isoform a is encoded by transcript variant 1;
                     protein pigeon homolog"
                     /codon_start=1
                     /product="gamma-secretase-activating protein isoform a"
                     /protein_id="NP_059135.2"
                     /db_xref="CCDS:CCDS34672.2"
                     /db_xref="GeneID:54103"
                     /db_xref="HGNC:HGNC:28042"
                     /db_xref="MIM:613552"
                     /translation="MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYE
                     SLHVLNVERNGNIIYTYKDDKGNVVFGLYDCQTRQNELLYTFEKDLQVFSCSVNSERT
                     LLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVKVLKAVDSYIWVQFLYPHIES
                     HPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFVWAQWDMSE
                     QRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDK
                     FSKHLTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMT
                     KGITFLNLDYYVAVYLPGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSG
                     SLVLDCCSGKLYRALLSQSSLLQLLQNTCLDCEKMAALHCALYCGQGAQFLEAQIIQW
                     ISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHSSVLTWNTEIPGITLVTED
                     IALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEKTGKRRSA
                     AYVRNILDNAVKVISNLEARNLGPRLTPLLQEEDSHQRLLMGLMVSELKDHFLRHLQG
                     VEKKKIEQMVLDYISKLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTR
                     ILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDN
                     TEKNEKLKFSIIVRLPPLIGQKICRLWDHPMSSNIISRNHVTRLLQNYKKQPRNSMIN
                     KSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFVEEAALKHTAMLLGL"
     exon            138..214
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            215..271
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            272..341
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            342..395
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            396..484
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            485..554
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            555..604
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            605..709
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            710..769
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            770..813
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            814..899
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            900..977
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            978..1055
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1056..1148
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1149..1366
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1367..1436
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1437..1519
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1520..1573
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1574..1702
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1703..1761
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1762..1793
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1794..1855
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1856..1951
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            1952..2022
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2023..2117
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2118..2237
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2238..2299
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2300..2401
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2402..2501
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     exon            2502..3200
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3180..3185
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /note="hexamer: ATTAAA"
     polyA_site      3200
                     /gene="GSAP"
                     /gene_synonym="PION"
                     /note="major polyA site"
ORIGIN      
        1 agagccgccc ggtggtcgtg tccgggcgat ggctcttcgc ctggtcgccg acttcgacct
       61 cgggaaggac gtgctcccgt ggttgcgggc gcagcgggca gtgtcggagg ccagcggggc
      121 cggaagcggc ggcgcagatg ttttagaaaa cgattatgag agcttacatg tattaaatgt
      181 tgaaagaaat ggaaatatta tttataccta taaggatgat aagggaaatg tcgtctttgg
      241 attatatgat tgtcaaacca gacaaaatga gcttctatat acctttgaga aagacttgca
      301 agttttcagt tgctctgtca acagtgaaag gactttgctt gctgcaagtt tagttcagtc
      361 tactaaagaa ggaaaaagga acgaacttca accaggatca aagtgcttga ctttgttggt
      421 tgaaatccac cctgttaaca atgtgaaggt tctaaaggct gtggatagct atatttgggt
      481 tcagtttctc tacccacata ttgaaagtca tcctcttcca gagaaccatc tgttactgat
      541 ttcagaagag aaatatattg aacaatttcg tatccatgtc gcccaagaag atggaaatag
      601 agtggtgatt aaaaattctg gccatctccc aagagacaga atagctgagg atttcgtttg
      661 ggctcagtgg gatatgtcag aacagagatt atattacatt gacctgaaga aatcaaggag
      721 tatcttaaaa tgtatccagt tttatgctga tgagagctat aacttaatgt ttgaagtacc
      781 cttggacata tcattaagca actcaggatt taaacttgtc aactttggat gtgattatca
      841 tcaataccga gataaatttt ccaaacacct gactctgtgt gtttttacca accatacagg
      901 aagtttgtgt gtatgttaca gcccgaagtg tgcctcttgg ggacaaatca catattcagt
      961 gttttacatt cataaaggac acagcaagac cttcaccact tctcttgaga atgttgggtc
     1021 acacatgaca aagggcatta cttttctcaa ccttgactat tatgtggctg tttacttacc
     1081 tggtcatttc ttccacctac ttaatgttca acatccagac ctgatctgcc acaatctctt
     1141 tctgacagga aataatgaaa tgattgatat gctacctcat tgccctttac agtcattgtc
     1201 agggtccctg gtattggatt gttgttctgg aaagctctat agagcactgc tcagccagtc
     1261 gtctttatta cagcttctgc agaacacttg cttagactgt gagaagatgg ctgcgttgca
     1321 ctgcgcgctc tactgcggtc aaggtgcgca gttcctggaa gcccagatta ttcagtggat
     1381 ttctgagaat gtctctgcct gccattcatt tgacctcatt caggaattta taattgcttc
     1441 ttcatactgg agtgtatatt cagagacaag taacatggac aaactattgc cacattcctc
     1501 agtgctcact tggaatacag aaattcctgg aataactctt gtgacagaag acattgcatt
     1561 gcctcttatg aaggtgctca gctttaaggg ctactgggaa aaactgaact ccaacctaga
     1621 atatgttaag tacgccaagc cacacttcca ctataacaac agtgtggtca ggagagagtg
     1681 gcacaacctg atctctgaag agaaaacagg aaaaagaagg tctgcggcat acgtgaggaa
     1741 tattcttgat aatgcagtaa aggtgatttc taacctagaa gcaagaaatt tggggccaag
     1801 attaacaccc ctcctgcagg aggaagacag ccaccagcgg ctgctcatgg ggctgatggt
     1861 gtctgagcta aaagaccatt ttttgagaca cctacagggt gtagaaaaga agaaaattga
     1921 acagatggtt ctggactaca tttcaaaact gctggatctc atttgccaca tcgtagaaac
     1981 caattggagg aaacataatc ttcattcctg ggttctccac ttcaatagtc gtggcagtgc
     2041 tgctgaattt gcagtttttc acatcatgac caggattctg gaagctacaa acagtttgtt
     2101 tttacctctg cctcctggtt ttcatactct gcacaccatc ctcggggtcc agtgtctccc
     2161 tttgcataac ctgctgcatt gcattgacag tggagtgttg cttctcactg aaacagctgt
     2221 cataaggctc atgaaagatc tggataatac agagaaaaat gaaaaactga aattcagtat
     2281 cattgtgcgg cttcctccgc ttattgggca gaagatttgt agactttggg atcatcctat
     2341 gagttctaac atcatttcgc ggaaccacgt gacgcgactg cttcagaact ataagaaaca
     2401 gcctcggaat tctatgatta acaagtcatc gttcagtgta gaatttctgc ctctgaacta
     2461 cttcattgaa attctgacag atatagagtc ctccaatcaa gccctgtatc cttttgaagg
     2521 acatgacaat gtggatgcag aatttgtaga ggaagcagct ctgaaacaca ccgcgatgct
     2581 tttaggctta tgaaaaagaa aacgcaattg gatctgctgc tgccatttta atcttgctca
     2641 ttaaccttac tcctttgaga attctttaac aatatttaaa attggtaaca aaaatagttt
     2701 agccataatt gtttagccat gtgagtttca ggttggtaca cgttcagaca gaactgctgt
     2761 atcacattcc aattttgaat agccagtgag caatcaagtg tagagaaatg ataaatggcc
     2821 taagaaggca tacagtggca taaacgatgc tcttcctagt agcttaatag gccacaagct
     2881 agtttctgtt gcactctgaa ataaaatatg ctttaaaaat gtagggaaca gtgcttagaa
     2941 aagcaaaaac taggtgtgtc attgaaataa taggcataaa aattaaatgt tacataagaa
     3001 cactatttgg aaagagggtc cttttaaaaa ctgaatttgt actaaatcag atttgccatg
     3061 tccagtacag aataatttgt acttagtatt tgcagcaggg tttgtctttg tgaattcaga
     3121 tgaaacatat ttattttttt ttatttataa aaggttgatt taggaatatt ttgtcagtca
     3181 ttaaaaaacc tgaaaacata
//
