LOCUS       NM_031301               4138 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens aph-1 homolog B, gamma-secretase subunit (APH1B),
            transcript variant 1, mRNA.
ACCESSION   NM_031301
VERSION     NM_031301.4
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 4138)
  AUTHORS   Park,Y.H., Pyun,J.M., Hodges,A., Jang,J.W., Bice,P.J., Kim,S.,
            Saykin,A.J. and Nho,K.
  CONSRTM   AddNeuroMed consortium and the Alzheimer's Disease Neuroimaging
            Initiative
  TITLE     Dysregulated expression levels of APH1B in peripheral blood are
            associated with brain atrophy and amyloid-beta deposition in
            Alzheimer's disease
  JOURNAL   Alzheimers Res Ther 13 (1), 183 (2021)
   PUBMED   34732252
  REMARK    GeneRIF: Dysregulated expression levels of APH1B in peripheral
            blood are associated with brain atrophy and amyloid-beta deposition
            in Alzheimer's disease.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4138)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   3  (bases 1 to 4138)
  AUTHORS   Zhang,X., Zhang,C., Prokopenko,D., Liang,Y., Han,W., Tanzi,R.E. and
            Sisodia,S.S.
  TITLE     Negative evidence for a role of APH1B T27I variant in Alzheimer's
            disease
  JOURNAL   Hum Mol Genet 29 (6), 955-966 (2020)
   PUBMED   31995180
  REMARK    GeneRIF: Negative evidence for a role of APH1B T27I variant in
            Alzheimer's disease.
REFERENCE   4  (bases 1 to 4138)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 4138)
  AUTHORS   Yonemura,Y., Futai,E., Yagishita,S., Kaether,C. and Ishiura,S.
  TITLE     Specific combinations of presenilins and Aph1s affect the substrate
            specificity and activity of gamma-secretase
  JOURNAL   Biochem Biophys Res Commun 478 (4), 1751-1757 (2016)
   PUBMED   27608597
  REMARK    GeneRIF: Data show that presenilin 1
            (PS1)/anterior-pharynx-defective protein 1 (Aph1b), presenilin 2
            (PS2)/Aph1aL, PS2/Aph1aS and PS2/anterior pharynx defective 1
            homolog B (Aph1b) gamma-secretase produced amyloid beta peptide
            (Abeta) with a higher Abeta42+Abeta43-to-Abeta40
            (Abeta42(43)/Abeta40) ratio than the other gamma-secretases.
REFERENCE   6  (bases 1 to 4138)
  AUTHORS   Gu,Y., Chen,F., Sanjo,N., Kawarai,T., Hasegawa,H., Duthie,M.,
            Li,W., Ruan,X., Luthra,A., Mount,H.T., Tandon,A., Fraser,P.E. and
            St George-Hyslop,P.
  TITLE     APH-1 interacts with mature and immature forms of presenilins and
            nicastrin and may play a role in maturation of presenilin.nicastrin
            complexes
  JOURNAL   J Biol Chem 278 (9), 7374-7380 (2003)
   PUBMED   12471034
REFERENCE   7  (bases 1 to 4138)
  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   8  (bases 1 to 4138)
  AUTHORS   Francis,R., McGrath,G., Zhang,J., Ruddy,D.A., Sym,M., Apfeld,J.,
            Nicoll,M., Maxwell,M., Hai,B., Ellis,M.C., Parks,A.L., Xu,W.,
            Li,J., Gurney,M., Myers,R.L., Himes,C.S., Hiebsch,R., Ruble,C.,
            Nye,J.S. and Curtis,D.
  TITLE     aph-1 and pen-2 are required for Notch pathway signaling,
            gamma-secretase cleavage of betaAPP, and presenilin protein
            accumulation
  JOURNAL   Dev Cell 3 (1), 85-97 (2002)
   PUBMED   12110170
REFERENCE   9  (bases 1 to 4138)
  AUTHORS   Simpson,J.C., Wellenreuther,R., Poustka,A., Pepperkok,R. and
            Wiemann,S.
  TITLE     Systematic subcellular localization of novel proteins identified by
            large-scale cDNA sequencing
  JOURNAL   EMBO Rep 1 (3), 287-292 (2000)
   PUBMED   11256614
REFERENCE   10 (bases 1 to 4138)
  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     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA397427.1, AK291204.1, AC016207.9 and AI693802.1.
            
            On Nov 22, 2018 this sequence version replaced NM_031301.3.
            
            Summary: This gene encodes a multi-pass transmembrane protein that
            is a functional component of the gamma-secretase complex, which
            also contains presenilin and nicastrin. This protein represents a
            stabilizing cofactor for the presenilin holoprotein in the complex.
            The gamma-secretase complex catalyzes the cleavage of integral
            proteins such as notch receptors and beta-amyloid precursor
            protein. [provided by RefSeq, Sep 2011].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: SRR1660805.158726.1,
                                           SRR1660809.186662.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000261879.10/ ENSP00000261879.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 DA397427.1         56-58
            4-1567              AK291204.1         1-1564
            1568-3710           AC016207.9         13933-16075         c
            3711-4138           AI693802.1         13-440              c
FEATURES             Location/Qualifiers
     source          1..4138
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q22.2"
     gene            1..4138
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="aph-1 homolog B, gamma-secretase subunit"
                     /db_xref="GeneID:83464"
                     /db_xref="HGNC:HGNC:24080"
                     /db_xref="MIM:607630"
     exon            1..132
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     CDS             20..793
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="isoform 1 is encoded by transcript variant 1;
                     gamma-secretase subunit APH-1B; anterior pharynx defective
                     1 homolog B; APH1B gamma secretase subunit"
                     /codon_start=1
                     /product="gamma-secretase subunit APH-1B isoform 1"
                     /protein_id="NP_112591.2"
                     /db_xref="CCDS:CCDS10184.1"
                     /db_xref="GeneID:83464"
                     /db_xref="HGNC:HGNC:24080"
                     /db_xref="MIM:607630"
                     /translation="MTAAVFFGCAFIAFGPALALYVFTIATEPLRIIFLIAGAFFWLV
                     SLLISSLVWFMARVIIDNKDGPTQKYLLIFGAFVSVYIQEMFRFAYYKLLKKASEGLK
                     SINPGETAPSMRLLAYVSGLGFGIMSGVFSFVNTLSDSLGPGTVGIHGDSPQFFLYSA
                     FMTLVIILLHVFWGIVFFDGCEKKKWGILLIVLLTHLLVSAQTFISSYYGINLASAFI
                     ILVLMGTWAFLAAGGSCRSLKLCLLCQDKNFLLYNQRSR"
     exon            133..303
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     exon            304..374
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     exon            375..497
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     exon            498..625
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     exon            626..4138
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /inference="alignment:Splign:2.1.0"
     regulatory      896..901
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="hexamer: AATAAA"
     polyA_site      926
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="major polyA site"
     regulatory      4112..4117
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="hexamer: AATAAA"
     polyA_site      4138
                     /gene="APH1B"
                     /gene_synonym="APH-1B; aph-1beta; PRO1328; PSFL; TAAV688"
                     /note="major polyA site"
ORIGIN      
        1 gtcggtttcc gcggtggcca tgactgcggc cgtgttcttc ggctgcgcct tcattgcctt
       61 cgggcctgcg ctcgcccttt atgtcttcac catcgccacc gagccgttgc gtatcatctt
      121 cctcatcgcc ggagctttct tctggttggt gtctctactg atttcgtccc ttgtttggtt
      181 catggcaaga gtcattattg acaacaaaga tggaccaaca cagaaatatc tgctgatctt
      241 tggagcgttt gtctctgtct atatccaaga aatgttccga tttgcatatt ataaactctt
      301 aaaaaaagcc agtgaaggtt tgaagagtat aaacccaggt gagacagcac cctctatgcg
      361 actgctggcc tatgtttctg gcttgggctt tggaatcatg agtggagtat tttcctttgt
      421 gaatacccta tctgactcct tggggccagg cacagtgggc attcatggag attctcctca
      481 attcttcctt tattcagctt tcatgacgct ggtcattatc ttgctgcatg tattctgggg
      541 cattgtattt tttgatggct gtgagaagaa aaagtggggc atcctcctta tcgttctcct
      601 gacccacctg ctggtgtcag cccagacctt cataagttct tattatggaa taaacctggc
      661 gtcagcattt ataatcctgg tgctcatggg cacctgggca ttcttagctg cgggaggcag
      721 ctgccgaagc ctgaaactct gcctgctctg ccaagacaag aactttcttc tttacaacca
      781 gcgctccaga taacctcagg gaaccagcac ttcccaaacc gcagactaca tctttagagg
      841 aagcacaact gtgccttttt ctgaaaatcc ctttttctgg tggaattgag aaagaaataa
      901 aactatgcag atatgcgttc cattcacttg gctttcacac aactgctctc cgaaaggggt
      961 gctcagtggt gtgcgtcctg gctgcacgag aatcacctgg gacagtgtaa agccgactga
     1021 ttctgggctc caccttccag agctaattgg cctgggcacg tggtgagttt taaaagcttc
     1081 ccaggtgatt ctgatgtgca gccatgttga gacccactgg tttggtatcc aaataggagc
     1141 ttcctgagaa caccttaagt ggatgagaat ctggtcttta gctgtctcct aactcaactc
     1201 gtgctgagca agtaagtatc tgaatgtcaa atcctggtta tcttttatct tcctaagttc
     1261 tgaagtcaca aaaggctaaa gggctatcac ccctgctcac tgtttgcgtg tacttcacca
     1321 tcttaggaga acacggtagg ttgggcttct aaatgcaata ataaattacg ctgactgtgg
     1381 taacttagcc aaagtaagat actgattaag ccgtattttt ctgaagtgct tccattccag
     1441 gttttgcttt ctgaggcatt acattgtttt tgagtataga ttacatttta ttaactaaaa
     1501 atgattgttt tgtgacttcc ttgggaaggt attttaaaat caggaatttt tatgcaatgt
     1561 ctataagcct gtttaaagct ttccatgggc tctgccccaa ggccgttggc tgcagcgttc
     1621 accatctgag tgccagttgc tggactagtt gaggtgaagt gcattgtttt ctctctgagc
     1681 agctgtgcgg ggagctgagt gatgtgccct gggacaggct tcactggagc tggtggaagt
     1741 ataaccagaa gcacaaggaa atgagccaaa agggtgtcat tgacactttt catttgctcc
     1801 tgtgatacta acaacacttt cacccaaatg gcttaatgta atattggaaa tagatcttaa
     1861 actgccaaat ctcacactat tgcataatcc atatgctctt tagatctagt cagtgtctct
     1921 gggttttggt agcagataca gcgttccctt tacaggaata cccaaggtgt tctttcagct
     1981 tccagacagg tcctttgatt tcctttataa agggaaaatt ctggcaaatc gtgcctttac
     2041 tattagaaat tgttcccagt tgatgtcttt tggggagctg gtggcatgaa atgcaaatga
     2101 cctatacatt aaagtgatgt ctcagtgaat accatacatg cagtagaaca ttcagaagag
     2161 aggagcagca atcctgaggg gctgggggag tgacagtggc aggacggatg ggcgggtttg
     2221 acagattgtg gtgggaagaa gaatgatcat gtttaaagct aacatagcca gtgttttggg
     2281 ctagccacac atcattccag agaccaaaac cttactcatg aactagacct ttatcgatat
     2341 cagtgaaccc ccatgtttaa aatattagaa tgtttagaga taaaatagag ataatagaga
     2401 taaaagaaga ggagggcttc tatcaatgct gtaaacagtc tgataagcga ctgtggttat
     2461 tcccctaaag tttacttcag cactaacact agtgcttccg ctggagtttg cagttttcca
     2521 gctttataca ggattttcct ttgactggaa gagtcaagga tatagagact caacagtgac
     2581 atttattgta caacatcaag gggaatagga tactcatcaa actgggatta ttcttatcaa
     2641 aacatggtct tctttgaata agaaaaatac atagttggtt attatggact taaaactgtg
     2701 ttaaatggat attctgataa aatatttgct gctctgtaga gtgtggaaag tctgagaata
     2761 ttagctttac tcatcttgag ctttgaggat gttctctgta cgccgatggt ttcatattaa
     2821 ctaaaaaagc tgggtattgt aaaatctcat ttataaaaac tcagatgaga agaaaatttt
     2881 ctttgatggt gagactgttg tcttagttca ggaaattatt taataatcct ttgttacctg
     2941 tgaatgaagg aactttgtaa ttctgattta tcgtaaaaca tgagcctttc cagagtcagc
     3001 ttagacactg ttgtcgcaaa tagccatgct ttgccttatg ccaaggaggc ccagagggag
     3061 ggcctagtct tcctctgttg ctgtacatat attgaaatgc tttttttttt ttattttgca
     3121 tttgttatct ataatgagct ttctgagccc tgatattatg tgagacaaac aggagttatt
     3181 gatgttatac actcccttcc attcaggatt ttctgcttgg agggaaatat gttgacctta
     3241 gagaattgtg aatattgttg caattcttga atatattacc atgtgaataa tagagactgt
     3301 gttgctctct agtataagct atatttattt ttgattcatt tgaattacta gttataactg
     3361 gagaaatttt gttacctcta tcctggcttg cctgactggc tgtataatag cagcagcctc
     3421 ttttagagca tcttaatgaa aacatggatg aaaggaatta atgatgatat ctgcagactg
     3481 cgtagaaaat ggcttttgtt cccagcgtta acattttctt ctcaatcaca tttcaatgtt
     3541 tgtggagagt ggcagattca caccagaaac actaggtgtt catatccata gcatggatgc
     3601 agaataagca gttgggagag aagcttcttc ctacctggta ctcctcccat tcacctcagc
     3661 ccagccccag acaggcgtta gcattcagtg tgggccctca ggcagccctg aagcctggct
     3721 gggtcatcag atgggggcag cctgtgacgg gcaccagcgg cctgattcca gggaagagtt
     3781 cctggagggt gttggctgtt tttgttagct cagttttttt ctgggctcca ccattcctaa
     3841 ctccaggtag acaagataga tgtcacacac aacaatttta aagtattttg cttagtgcat
     3901 tttgtttatg attgcagtgt ttgtttctta tttaataggc tttttacttc attctattaa
     3961 attttagtgt ttagaagagg cgggtactgt cactgtgtaa aatatgtaat attttatatg
     4021 ttataccatg tcatatatac ttgcaatatc agaccttgca ttcaatatac aatgcaattg
     4081 actctttgca gacctgcatt tttcagtgaa caataaaaag attgtctggc actcctca
//
