APH1_DROME
ID APH1_DROME Reviewed; 238 AA.
AC Q9VQG2;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Gamma-secretase subunit Aph-1;
DE AltName: Full=Presenilin-stabilization factor;
GN Name=aph-1; Synonyms=PSF; ORFNames=CG2855;
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].
RA Lee H.-J., Kim T.-W.;
RT "PSF is essential for gamma-secretase activity and stabilization of
RT presenilin and nicastrin.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
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; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP 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 [6]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX, AND INTERACTION WITH PEN-2; 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 a
CC stabilizing cofactor for the presenilin homodimer that promotes the
CC formation of a stable complex. {ECO:0000269|PubMed:12110170,
CC 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 APH-1 family. {ECO:0000305}.
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DR EMBL; AF508786; AAN63815.1; -; mRNA.
DR EMBL; AE014134; AAF51212.1; -; Genomic_DNA.
DR EMBL; AY051658; AAK93082.1; -; mRNA.
DR RefSeq; NP_001259963.1; NM_001273034.1.
DR RefSeq; NP_608710.1; NM_134866.3.
DR AlphaFoldDB; Q9VQG2; -.
DR SMR; Q9VQG2; -.
DR BioGRID; 59690; 10.
DR IntAct; Q9VQG2; 10.
DR STRING; 7227.FBpp0077400; -.
DR PaxDb; Q9VQG2; -.
DR PRIDE; Q9VQG2; -.
DR DNASU; 33467; -.
DR EnsemblMetazoa; FBtr0077716; FBpp0077400; FBgn0031458.
DR EnsemblMetazoa; FBtr0335127; FBpp0307126; FBgn0031458.
DR GeneID; 33467; -.
DR KEGG; dme:Dmel_CG2855; -.
DR CTD; 33467; -.
DR FlyBase; FBgn0031458; aph-1.
DR VEuPathDB; VectorBase:FBgn0031458; -.
DR eggNOG; KOG3972; Eukaryota.
DR GeneTree; ENSGT00390000002049; -.
DR HOGENOM; CLU_086389_0_0_1; -.
DR InParanoid; Q9VQG2; -.
DR OMA; FFNAFDT; -.
DR OrthoDB; 1085102at2759; -.
DR PhylomeDB; Q9VQG2; -.
DR Reactome; R-DME-1251985; Nuclear signaling by ERBB4.
DR SignaLink; Q9VQG2; -.
DR BioGRID-ORCS; 33467; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Alp1; fly.
DR GenomeRNAi; 33467; -.
DR PRO; PR:Q9VQG2; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031458; Expressed in saliva-secreting gland and 25 other tissues.
DR ExpressionAtlas; Q9VQG2; baseline and differential.
DR Genevisible; Q9VQG2; DM.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0055037; C:recycling endosome; IDA:FlyBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
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:UniProtKB.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IEA:InterPro.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR InterPro; IPR009294; Aph-1.
DR PANTHER; PTHR12889; PTHR12889; 1.
DR Pfam; PF06105; Aph-1; 1.
PE 1: Evidence at protein level;
KW Membrane; Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..238
FT /note="Gamma-secretase subunit Aph-1"
FT /id="PRO_0000221058"
FT TRANSMEM 6..26
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
SQ SEQUENCE 238 AA; 26437 MW; C61A24518DCA150F CRC64;
MTLPEFFGCT FIAFGPPFAL FVFTIANDPV RIIILIAAAF FWLLSLLISS LWYALIPLKE
FLAFGVVFSV CFQEAFRYII YRILRSTEQG LHAVAEDTRV TDNKHILAYV SGLGFGIISG
MFALVNVLAD MSGPGTMGLK GGTELFFVTS AAQALSIILL HTFWSVIFFN AFDTNNYIHI
GYVVFSHLFV SLITLLNANE LYTTTLLINY LVTILTGVLA FRVAGGTSRS FRKFITCQ
