LOCUS       NM_146104               3215 bp    mRNA    linear   ROD 30-APR-2024
DEFINITION  Mus musculus aph1 homolog A, gamma secretase subunit (Aph1a),
            transcript variant 1, mRNA.
ACCESSION   NM_146104
VERSION     NM_146104.3
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 3215)
  AUTHORS   Adams,D.J., Barlas,B., McIntyre,R.E., Salguero,I., van der
            Weyden,L., Barros,A., Vicente,J.R., Karimpour,N., Haider,A.,
            Ranzani,M., Turner,G., Thompson,N.A., Harle,V., Olvera-Leon,R.,
            Robles-Espinoza,C.D., Speak,A.O., Geisler,N., Weninger,W.J.,
            Geyer,S.H., Hewinson,J., Karp,N.A., Fu,B., Yang,F., Kozik,Z.,
            Choudhary,J., Yu,L., van Ruiten,M.S., Rowland,B.D., Lelliott,C.J.,
            Del Castillo Velasco-Herrera,M., Verstraten,R., Bruckner,L.,
            Henssen,A.G., Rooimans,M.A., de Lange,J., Mohun,T.J., Arends,M.J.,
            Kentistou,K.A., Coelho,P.A., Zhao,Y., Zecchini,H., Perry,J.R.B.,
            Jackson,S.P. and Balmus,G.
  CONSRTM   Sanger Mouse Genetics Project
  TITLE     Genetic determinants of micronucleus formation in vivo
  JOURNAL   Nature 627 (8002), 130-136 (2024)
   PUBMED   38355793
REFERENCE   2  (bases 1 to 3215)
  AUTHORS   Ma,T., Tian,X., Zhang,B., Li,M., Wang,Y., Yang,C., Wu,J., Wei,X.,
            Qu,Q., Yu,Y., Long,S., Feng,J.W., Li,C., Zhang,C., Xie,C., Wu,Y.,
            Xu,Z., Chen,J., Yu,Y., Huang,X., He,Y., Yao,L., Zhang,L., Zhu,M.,
            Wang,W., Wang,Z.C., Zhang,M., Bao,Y., Jia,W., Lin,S.Y., Ye,Z.,
            Piao,H.L., Deng,X., Zhang,C.S. and Lin,S.C.
  TITLE     Low-dose metformin targets the lysosomal AMPK pathway through PEN2
  JOURNAL   Nature 603 (7899), 159-165 (2022)
   PUBMED   35197629
REFERENCE   3  (bases 1 to 3215)
  AUTHORS   Han,J., Hyun,J., Park,J., Jung,S., Oh,Y., Kim,Y., Ryu,S.H.,
            Kim,S.H., Jeong,E.I., Jo,D.G., Park,S.H. and Jung,Y.K.
  TITLE     Aberrant role of pyruvate kinase M2 in the regulation of
            gamma-secretase and memory deficits in Alzheimer's disease
  JOURNAL   Cell Rep 37 (10), 110102 (2021)
   PUBMED   34879266
  REMARK    GeneRIF: Aberrant role of pyruvate kinase M2 in the regulation of
            gamma-secretase and memory deficits in Alzheimer's disease.
REFERENCE   4  (bases 1 to 3215)
  AUTHORS   Wouters,R., Michiels,C., Sannerud,R., Kleizen,B., Dillen,K.,
            Vermeire,W., Ayala,A.E., Demedts,D., Schekman,R. and Annaert,W.
  TITLE     Assembly of gamma-secretase occurs through stable dimers after exit
            from the endoplasmic reticulum
  JOURNAL   J Cell Biol 220 (9) (2021)
   PUBMED   34292306
  REMARK    GeneRIF: Assembly of gamma-secretase occurs through stable dimers
            after exit from the endoplasmic reticulum.
REFERENCE   5  (bases 1 to 3215)
  AUTHORS   Jiang,D., Burger,C.A., Casasent,A.K., Albrecht,N.E., Li,F. and
            Samuel,M.A.
  TITLE     Spatiotemporal gene expression patterns reveal molecular
            relatedness between retinal laminae
  JOURNAL   J Comp Neurol 528 (5), 729-755 (2020)
   PUBMED   31609468
REFERENCE   6  (bases 1 to 3215)
  AUTHORS   Fraering,P.C., Ye,W., Strub,J.M., Dolios,G., LaVoie,M.J.,
            Ostaszewski,B.L., van Dorsselaer,A., Wang,R., Selkoe,D.J. and
            Wolfe,M.S.
  TITLE     Purification and characterization of the human gamma-secretase
            complex
  JOURNAL   Biochemistry 43 (30), 9774-9789 (2004)
   PUBMED   15274632
REFERENCE   7  (bases 1 to 3215)
  AUTHORS   Cheng,H.T., Miner,J.H., Lin,M., Tansey,M.G., Roth,K. and Kopan,R.
  TITLE     Gamma-secretase activity is dispensable for
            mesenchyme-to-epithelium transition but required for podocyte and
            proximal tubule formation in developing mouse kidney
  JOURNAL   Development 130 (20), 5031-5042 (2003)
   PUBMED   12952904
REFERENCE   8  (bases 1 to 3215)
  AUTHORS   Luo,W.J., Wang,H., Li,H., Kim,B.S., Shah,S., Lee,H.J.,
            Thinakaran,G., Kim,T.W., Yu,G. and Xu,H.
  TITLE     PEN-2 and APH-1 coordinately regulate proteolytic processing of
            presenilin 1
  JOURNAL   J Biol Chem 278 (10), 7850-7854 (2003)
   PUBMED   12522139
REFERENCE   9  (bases 1 to 3215)
  AUTHORS   Lee,S.F., Shah,S., Li,H., Yu,C., Han,W. and Yu,G.
  TITLE     Mammalian APH-1 interacts with presenilin and nicastrin and is
            required for intramembrane proteolysis of amyloid-beta precursor
            protein and Notch
  JOURNAL   J Biol Chem 277 (47), 45013-45019 (2002)
   PUBMED   12297508
REFERENCE   10 (bases 1 to 3215)
  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 BY264531.1, AK148400.1 and
            AC092855.39.
            
            On Jan 30, 2013 this sequence version replaced NM_146104.2.
            
            Summary: This gene encodes a subunit of the gamma-secretase
            complex, which is localized to the endoplasmic reticulum and golgi
            apparatus. Gamma-secretase is a multi-protein enzyme that catalyzes
            intramembraneous proteolysis of type I transmembrane proteins and
            is essential for many signaling pathways, including the Notch
            signaling pathway. Studies suggest that the protein encoded by this
            locus binds directly to substrates of the gamma-secretase complex,
            including the beta-amyloid precursor protein which is associated
            with Alzheimer disease progression. This gene is required for
            normal embryonic development and survival, and disruption is
            associated with defects in the yolk sack angiogenesis, neural tube
            formation, and somitogenesis. A pseudogene of this gene is located
            on chromosome 1. Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Jan 2013].
            
            Transcript Variant: This variant (1) differs in the 3' coding
            region and 3' UTR, compared to variant 2. The resulting isoform (1,
            also known as isoform S) is shorter and has a distinct C-terminus,
            compared to isoform 2.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript from the same
            strain was available for the full length of the gene. The extent of
            this transcript is supported by transcript alignments and
            orthologous data.The genomic coordinates used for the transcript
            record were based on alignments.
            
            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 :: BC012406.1, AK148400.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN00849374, SAMN00849375
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-48                BY264531.1         1-48
            49-1038             AK148400.1         2-991
            1039-3215           AC092855.39        73339-75515
FEATURES             Location/Qualifiers
     source          1..3215
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="3"
                     /map="3 41.47 cM"
     gene            1..3215
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="aph1 homolog A, gamma secretase subunit"
                     /db_xref="GeneID:226548"
                     /db_xref="MGI:MGI:2385110"
     exon            1..363
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     CDS             251..994
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="isoform 1 is encoded by transcript variant 1;
                     gamma-secretase subunit APH-1A; aph-1alpha; anterior
                     pharynx defective 1a homolog"
                     /codon_start=1
                     /product="gamma-secretase subunit APH-1A isoform 1"
                     /protein_id="NP_666216.1"
                     /db_xref="CCDS:CCDS17624.1"
                     /db_xref="GeneID:226548"
                     /db_xref="MGI:MGI:2385110"
                     /translation="MGAAVFFGCTFVAFGPAFSLFLITVAGDPLRVIILVAGAFFWLV
                     SLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLA
                     SLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTS
                     AFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIY
                     AVTVSMGLWAFITAGGSLRSIQRSLSCKD"
     exon            364..534
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     exon            535..608
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     exon            609..731
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     exon            732..859
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     exon            860..3215
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2069..2074
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="hexamer: AATAAA"
     polyA_site      2092
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="major polyA site"
     regulatory      3194..3199
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="hexamer: ATTAAA"
     polyA_site      3213
                     /gene="Aph1a"
                     /gene_synonym="APH-1a"
                     /note="major polyA site"
ORIGIN      
        1 gaattagatg ggaggtggcc atggggcagc gaccgggggt tgttccctct tcggcttccg
       61 tagacgaggt cgggcggacc ttcgtccggg gtttcggcac ccccccttcc ccttccccgg
      121 ggtccggggg tgacattgca ccgcgcccct cctggggttg cgtcctcgcc ccacgcggac
      181 tccccctcgg cgcgcagctc cctttcgcct tccttggccg gggttccctc ccttccccag
      241 ctgcccagtc atgggggctg ctgtgttttt cggatgcacc ttcgtcgcgt tcggcccagc
      301 cttctccctt ttcctgatca ctgtagctgg agacccactt cgggttatca tcctggtggc
      361 gggagccttt ttctggctgg tctccctgct cttggcttct gtggtctggt tcatcttggt
      421 ccatgtgaca gaccgatcag atgcacggct ccagtatggc ctcctgattt ttggtgctgc
      481 tgtctctgtc cttctacagg aagtgttccg ttttgcttac tacaagctcc ttaagaaggc
      541 agatgagggc ttagcatcac tgagtgagga cggaagatca cccatctcca tccgacagat
      601 ggcctatgtt tctggtctgt ccttcggtat catcagtggt gtcttctctg ttatcaatat
      661 tttggctgat gcacttgggc caggtgtggt tgggatccat ggagactcac cctattactt
      721 cctgacttca gcctttctga cagcagccat tatcctgctc cacacctttt ggggagttgt
      781 gttctttgat gcctgtgaga ggagacggta ctgggctttg ggcctggtag ttgggagtca
      841 ccttctgaca tcgggactga cattcctgaa cccctggtat gaggctagcc tgctgcccat
      901 ctatgcagtc accgtttcca tggggctctg ggcgttcatc acagccggag gctccctccg
      961 aagtatccag cgcagccttt cgtgtaagga ctgactacct ggactgatcg cccgacagat
     1021 cccatctgcc tatccactgc ccatgactga acccagcccc agcccgggtc cattgccctc
     1081 atcctccgtc tcctcgctga tgtgccccgc ttccttccgg gtttggcgtt gtccatttgt
     1141 gacctgtagt ctctaagctt tctcaggagc agcctgggtg cagccagtca gggactggtg
     1201 ggtttgaatc tgcatctctc cccaccacct ggggaccccc ttgttgtcca ggtctcccca
     1261 tgtgtcagtg ctccaccctc accctgccca tgactcaccc cgcttcccct ctgcaggccg
     1321 ccggcaggag gacagtcggg tgatggtgta ctctgccctg cgcatcccac ccgaggactg
     1381 agggaacatg ggggggcccc tgggcctggg gtgccctccc gatctcctcg tcccgtattt
     1441 ctccatctcc agttctggac agtgcaggtt gccaagaaaa gggacctagc ttagccatgg
     1501 ccctggagat gaagttactg aggctgaggg tagatgggtt cagttcagtg tctcctgccc
     1561 agactggaca tcttggtctt tttctcaggt ctgaaaggaa ccattttttg gtatgataaa
     1621 gaccccaaaa tgcctttttt ttaaagtggg gagagggagg aggtacgccg ggagcctctt
     1681 taacctccat aggctgtgtt tgctcccaaa tctgctgatg gtggctcatt tctatcctgt
     1741 tttccctttg gtcccaggcc ctgggggaaa ggaaggaagt gcatgcttgg ggactggtcc
     1801 cactggatct ctatcctaac gtccatggcc gtcagcaccc ctcctttccc caaggtgaaa
     1861 tggagggtgc tgtgggggcc tgcccactcc atggcagtgc cctgaaggag tcagactacc
     1921 atggcatcgc aggcccagag ggcagacatt ttttctagtt tttaattggg gtgtgggagg
     1981 gtttggggag gttttctatc actgtgttgt ttttctgctg agggtggaat attctgtcct
     2041 tttaatcaag gtgattgtga ttttgactaa taaaaaggac tttataattg tggggggact
     2101 tggctttaag aggggtaatg gattgagatt tctagctccg ggtggctccg gtccatcctc
     2161 cctagccaag tgcctgtgat gttcaccatt ggtgtgatga gagaagcatc attagtggtg
     2221 taacttgtgg aagttaactt cctagaagta ggtctccctt gtccaggaac aggatacaag
     2281 gagttaatta atcatacccc tgccccttct ctttctctat gtctatctct gccactcaac
     2341 agacagagga actctcccac tcttgaaagc cacaaaaaaa cattcaagaa ttaagatcaa
     2401 aaacttttaa tttccaaaca tatattgagc aaaaaataat taaaatccca gcagcagccc
     2461 ttttttccta gaggaaaaaa aaaaactaca acgtatatct aagggagaga acatggcggt
     2521 gtgaggtgaa agatggcagt ttatcctcag cttcttccaa ccaagcatga ggacagggaa
     2581 tctcctcatc cacagctttg aaggccaaag gctcagccct tcctgaagag ctggggtccc
     2641 tggtgtatag agagggttac ctagcaggac acgtgcctgc ctacaactgg tcgtccagtg
     2701 cctgcagccc tcagagaggc tccctggcag gaggagaggg aggcatctgc agcatcttga
     2761 gacagagttc acgcctctgt ggtagcccga gcagaggtga aaaccacact tttcctgttt
     2821 cccagccgct tcttcctgga aaggggagca atggttcatg ggagtgacta gcctcctaag
     2881 tgagagtaga catagaatag gaaatacatt taaaaaaaaa aaaaaaactc aataagtata
     2941 tagtcatgac cttaaatgtt ctctttcccc cacctcctga gtacaagtat gtgccagcag
     3001 gccaggttta atgtggtgct agggatcaaa cccagggctt gggcacacct ggcaagcact
     3061 ccgccaactg agctacagcc tcagagaatt tcgttggagt tgggggtggg ggagactggg
     3121 ttatctcact atggagacca ggctggcctt gaacacacag agatcatcct gcttccagct
     3181 cccaagcgtt gggattaaag ttatgcacta ccatg
//
