ID PEN2_DROME Reviewed; 101 AA.
AC Q86BE9; A8E6Z8; Q8MUT4;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 3.
DT 24-JAN-2024, entry version 141.
DE RecName: Full=Gamma-secretase subunit pen-2;
DE AltName: Full=Presenilin enhancer protein 2;
GN Name=pen-2; ORFNames=CG33198;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=12110170; DOI=10.1016/s1534-5807(02)00189-2;
RA Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J., Nicoll M.,
RA Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J., Gurney M.,
RA Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S., Curtis D.;
RT "aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase
RT cleavage of betaAPP, and presenilin protein accumulation.";
RL Dev. Cell 3:85-97(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX, AND INTERACTION WITH APH-1; PSN
RP AND NCT.
RX PubMed=12660785; DOI=10.1038/nature01506;
RA Takasugi N., Tomita T., Hayashi I., Tsuruoka M., Niimura M., Takahashi Y.,
RA Thinakaran G., Iwatsubo T.;
RT "The role of presenilin cofactors in the gamma-secretase complex.";
RL Nature 422:438-441(2003).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch. It probably represents the
CC last step of maturation of gamma-secretase, facilitating
CC endoproteolysis of presenilin and conferring gamma-secretase activity.
CC {ECO:0000269|PubMed:12110170, ECO:0000269|PubMed:12660785}.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex composed
CC of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the PEN-2 family. {ECO:0000305}.
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DR EMBL; AF512426; AAM88323.1; -; mRNA.
DR EMBL; AE013599; AAO41356.2; -; Genomic_DNA.
DR EMBL; BT030940; ABV82322.1; -; mRNA.
DR EMBL; BT030980; ABV82362.1; -; mRNA.
DR RefSeq; NP_001286566.1; NM_001299637.1.
DR RefSeq; NP_788401.2; NM_176221.4.
DR AlphaFoldDB; Q86BE9; -.
DR SMR; Q86BE9; -.
DR BioGRID; 75540; 7.
DR ComplexPortal; CPX-2673; Gamma-secretase complex.
DR STRING; 7227.FBpp0309291; -.
DR PaxDb; 7227-FBpp0088783; -.
DR DNASU; 251430; -.
DR EnsemblMetazoa; FBtr0089842; FBpp0088783; FBgn0053198.
DR EnsemblMetazoa; FBtr0340331; FBpp0309291; FBgn0053198.
DR GeneID; 251430; -.
DR KEGG; dme:Dmel_CG33198; -.
DR AGR; FB:FBgn0053198; -.
DR CTD; 251430; -.
DR FlyBase; FBgn0053198; pen-2.
DR VEuPathDB; VectorBase:FBgn0053198; -.
DR eggNOG; KOG3402; Eukaryota.
DR GeneTree; ENSGT00390000016319; -.
DR HOGENOM; CLU_124142_2_0_1; -.
DR InParanoid; Q86BE9; -.
DR OMA; WFFQEAF; -.
DR OrthoDB; 4233at2759; -.
DR PhylomeDB; Q86BE9; -.
DR Reactome; R-DME-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-DME-3928665; EPH-ephrin mediated repulsion of cells.
DR SignaLink; Q86BE9; -.
DR BioGRID-ORCS; 251430; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Pen; fly.
DR GenomeRNAi; 251430; -.
DR PRO; PR:Q86BE9; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0053198; Expressed in saliva-secreting gland and 24 other cell types or tissues.
DR ExpressionAtlas; Q86BE9; baseline and differential.
DR Genevisible; Q86BE9; DM.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0055037; C:recycling endosome; IDA:FlyBase.
DR GO; GO:0034205; P:amyloid-beta formation; IDA:FlyBase.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:FlyBase.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0035333; P:Notch receptor processing, ligand-dependent; IGI:FlyBase.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:FlyBase.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IGI:UniProtKB.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR PANTHER; PTHR16318; GAMMA-SECRETASE SUBUNIT PEN-2; 1.
DR PANTHER; PTHR16318:SF0; GAMMA-SECRETASE SUBUNIT PEN-2; 1.
DR Pfam; PF10251; PEN-2; 1.
PE 1: Evidence at protein level;
KW Membrane; Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..101
FT /note="Gamma-secretase subunit pen-2"
FT /id="PRO_0000190904"
FT TOPO_DOM 1..17
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..101
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT CONFLICT 2
FT /note="D -> N (in Ref. 1; AAM88323)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 101 AA; 11725 MW; AE7A84CC4899ECE8 CRC64;
MDISKAPNPR KLELCRKYFF AGFAFLPFVW AINVCWFFTE AFHKPPFSEQ SQIKRYVIYS
AVGTLFWLIV LTAWIIIFQT NRTAWGATAD YMSFIIPLGS A
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