LOCUS       NM_172341               1124 bp    mRNA    linear   PRI 08-JUN-2024
DEFINITION  Homo sapiens presenilin enhancer, gamma-secretase subunit (PSENEN),
            transcript variant 1, mRNA.
ACCESSION   NM_172341
VERSION     NM_172341.4
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 1124)
  AUTHORS   Klein,M., Kaleem,A., Oetjen,S., Wunkhaus,D., Binkle,L.,
            Schilling,S., Gjorgjieva,M., Scholz,R., Gruber-Schoffnegger,D.,
            Storch,S., Kins,S., Drewes,G., Hoffmeister-Ullerich,S., Kuhl,D. and
            Hermey,G.
  TITLE     Converging roles of PSENEN/PEN2 and CLN3 in the autophagy-lysosome
            system
  JOURNAL   Autophagy 18 (9), 2068-2085 (2022)
   PUBMED   34964690
  REMARK    GeneRIF: Converging roles of PSENEN/PEN2 and CLN3 in the
            autophagy-lysosome system.
REFERENCE   2  (bases 1 to 1124)
  AUTHORS   Crite,M. and DiMaio,D.
  TITLE     Human Papillomavirus L2 Capsid Protein Stabilizes gamma-Secretase
            during Viral Infection
  JOURNAL   Viruses 14 (4), 804 (2022)
   PUBMED   35458534
  REMARK    GeneRIF: Human Papillomavirus L2 Capsid Protein Stabilizes
            gamma-Secretase during Viral Infection.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1124)
  AUTHORS   Zhou,P., Liu,J., Xu,T., Guo,Y., Han,Y., He,Y., Lin,L. and Xiao,X.
  TITLE     Mutations in gamma-secretase subunit-encoding PSENEN gene alone may
            not be sufficient for the development of acne inversa
  JOURNAL   J Dermatol Sci 103 (2), 73-81 (2021)
   PUBMED   34330582
  REMARK    GeneRIF: Mutations in gamma-secretase subunit-encoding PSENEN gene
            alone may not be sufficient for the development of acne inversa.
REFERENCE   4  (bases 1 to 1124)
  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   5  (bases 1 to 1124)
  AUTHORS   Escamilla-Ayala,A.A., Sannerud,R., Mondin,M., Poersch,K.,
            Vermeire,W., Paparelli,L., Berlage,C., Koenig,M.,
            Chavez-Gutierrez,L., Ulbrich,M.H., Munck,S., Mizuno,H. and
            Annaert,W.
  TITLE     Super-resolution microscopy reveals majorly mono- and dimeric
            presenilin1/gamma-secretase at the cell surface
  JOURNAL   Elife 9, e56679 (2020)
   PUBMED   32631487
  REMARK    GeneRIF: Super-resolution microscopy reveals majorly mono- and
            dimeric presenilin1/gamma-secretase at the cell surface.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1124)
  AUTHORS   Crystal,A.S., Morais,V.A., Pierson,T.C., Pijak,D.S., Carlin,D.,
            Lee,V.M. and Doms,R.W.
  TITLE     Membrane topology of gamma-secretase component PEN-2
  JOURNAL   J Biol Chem 278 (22), 20117-20123 (2003)
   PUBMED   12639958
  REMARK    GeneRIF: examination of membrane topology
REFERENCE   7  (bases 1 to 1124)
  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
  REMARK    GeneRIF: role in regulating proteolytic processing of presenilin 1
            in conjunction with APH-1
REFERENCE   8  (bases 1 to 1124)
  AUTHORS   Steiner,H., Winkler,E., Edbauer,D., Prokop,S., Basset,G.,
            Yamasaki,A., Kostka,M. and Haass,C.
  TITLE     PEN-2 is an integral component of the gamma-secretase complex
            required for coordinated expression of presenilin and nicastrin
  JOURNAL   J Biol Chem 277 (42), 39062-39065 (2002)
   PUBMED   12198112
  REMARK    GeneRIF: a component of the gamma-secretase complex
REFERENCE   9  (bases 1 to 1124)
  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   10 (bases 1 to 1124)
  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 AF220053.1, BE563017.1,
            AA252937.1 and AI215167.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_172341.3.
            
            Summary: Presenilins, which are components of the gamma-secretase
            protein complex, are required for intramembranous processing of
            some type I transmembrane proteins, such as the Notch proteins and
            the beta-amyloid precursor protein. Signaling by Notch receptors
            mediates a wide range of developmental cell fates. Processing of
            the beta-amyloid precursor protein generates neurotoxic amyloid
            beta peptides, the major component of senile plaques associated
            with Alzheimer's disease. This gene encodes a protein that is
            required for Notch pathway signaling, and for the activity and
            accumulation of gamma-secretase. Mutations resulting in
            haploinsufficiency for this gene cause familial acne inversa-2
            (ACNINV2). Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Jul 2013].
            
            Transcript Variant: This variant (1) represents the longer
            transcript. Variants 1 and 2 encode the same protein.
            
            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 :: DB291008.1, SRR1163658.469143.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000587708.7/ ENSP00000468411.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-607               AF220053.1         53-659
            608-760             BE563017.1         487-639
            761-1017            AA252937.1         198-454
            1018-1124           AI215167.1         11-117              c
FEATURES             Location/Qualifiers
     source          1..1124
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.12"
     gene            1..1124
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /note="presenilin enhancer, gamma-secretase subunit"
                     /db_xref="GeneID:55851"
                     /db_xref="HGNC:HGNC:30100"
                     /db_xref="MIM:607632"
     exon            1..50
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /inference="alignment:Splign:2.1.0"
     exon            51..207
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /inference="alignment:Splign:2.1.0"
     CDS             147..452
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /note="hematopoietic stem/progenitor cells protein MDS033;
                     presenilin enhancer 2 homolog"
                     /codon_start=1
                     /product="gamma-secretase subunit PEN-2"
                     /protein_id="NP_758844.1"
                     /db_xref="CCDS:CCDS12474.1"
                     /db_xref="GeneID:55851"
                     /db_xref="HGNC:HGNC:30100"
                     /db_xref="MIM:607632"
                     /translation="MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLV
                     PAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP"
     exon            208..312
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /inference="alignment:Splign:2.1.0"
     exon            313..1124
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      588..593
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /note="hexamer: AATAAA"
     polyA_site      607
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /note="major polyA site"
     regulatory      1094..1099
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
                     /note="hexamer: AATAAA"
     polyA_site      1124
                     /gene="PSENEN"
                     /gene_synonym="ACNINV2; MDS033; MSTP064; PEN-2; PEN2"
ORIGIN      
        1 ataactgaaa gtagctaagg caccccagcc ggaggaagtg agctctcctg gggcgtggtt
       61 gttcgtgatc cttgcatctg ttacttaggg tcaaggcttg ggtcttgccc cgcagaccct
      121 tgggacgacc cggccccagc gcagctatga acctggagcg agtgtccaat gaggagaaat
      181 tgaacctgtg ccggaagtac tacctggggg ggtttgcttt cctgcctttt ctctggttgg
      241 tcaacatctt ctggttcttc cgagaggcct tccttgtccc agcctacaca gaacagagcc
      301 aaatcaaagg ctatgtctgg cgctcagctg tgggcttcct cttctgggtg atagtgctca
      361 cctcctggat caccatcttc cagatctacc ggccccgctg gggtgccctt ggggactacc
      421 tctccttcac catacccctg ggcaccccct gacaacttct gcacatactg gggccctgct
      481 tattctccca ggacaggctc cttaaagcag aggagcctgt cctgggagcc ccttctcaaa
      541 ctcctaagac ttgttttcat gtcccacgtt ctctgctgac atcccccaat aaaggaccct
      601 aactttcgat actgacttcc tgggatcttt tagaggttga ggcataaatg attattaata
      661 tttaaaaaca tctgttgaga gctttgtacg aggcttagta tttagacatg atgtacattt
      721 tttacagtgc atactactca taatcttctg aactaggaac tttcctgctc aggaaactat
      781 tagatgagaa actaagaaag gaatagtgct tccatttctt tttctttttt cttttttttt
      841 tttttttttg agacagagtc ttgctctgtc agccaggctg gagtgcagtg gtaggatcgg
      901 cctagtgctt ccatttctag gggctgttat cctgtactgg tagtcgtgaa ttcaaaaata
      961 taactttcct actgtgggct gcagtattct catcagaagt gtagatcacg atgctacttc
     1021 ctgggattta tctggaccaa gacgtgtgac aaatggaagt ttcccgtttt ctgaaggaag
     1081 tgttgtctgc aaaaataaaa atagtcaaga gctttctcag agaa
//
