ID A4_DROME Reviewed; 887 AA.
AC P14599; Q9TVV0; Q9U4H3; Q9W5F1;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 24-JAN-2024, entry version 188.
DE RecName: Full=Amyloid-beta-like protein;
DE Flags: Precursor;
GN Name=Appl; ORFNames=CG7727;
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 [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=2494667; DOI=10.1073/pnas.86.7.2478;
RA Rosen D.R., Martin-Morris L., Luo L., White K.;
RT "A Drosophila gene encoding a protein resembling the human beta-amyloid
RT protein precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2478-2482(1989).
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 GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-83, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=2127912; DOI=10.1242/dev.110.1.185;
RA Martin-Morris L.E., White K.;
RT "The Drosophila transcript encoded by the beta-amyloid protein precursor-
RT like gene is restricted to the nervous system.";
RL Development 110:185-195(1990).
RN [7]
RP FUNCTION, INTERACTION WITH APP-BP1, AND DISRUPTION PHENOTYPE.
RX PubMed=16628230; DOI=10.1038/sj.cdd.4401935;
RA Kim H.J., Kim S.H., Shim S.O., Park E., Kim C., Kim K., Tanouye M.A.,
RA Yim J.;
RT "Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with
RT APPL during Drosophila development.";
RL Cell Death Differ. 14:103-115(2007).
CC -!- FUNCTION: During development, plays a role in the regulation of the
CC neddylation pathway. Appl and APP-BP1 interact antagonistically during
CC development. {ECO:0000269|PubMed:16628230}.
CC -!- SUBUNIT: Interacts (via the intracellular domain, ICD) with APP-BP1.
CC {ECO:0000269|PubMed:16628230}.
CC -!- INTERACTION:
CC P14599; Q9W0K0: Aplip1; NbExp=6; IntAct=EBI-74135, EBI-74120;
CC P14599; P34082: Fas2; NbExp=3; IntAct=EBI-74135, EBI-868243;
CC P14599; Q9GQQ6: X11L; NbExp=3; IntAct=EBI-74135, EBI-2027617;
CC P14599; Q9VX41: X11L; NbExp=3; IntAct=EBI-74135, EBI-74153;
CC P14599; Q9ERE9: Mapk8ip2; Xeno; NbExp=2; IntAct=EBI-74135, EBI-74576;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in postmitotic neurons in the central and
CC peripheral nervous systems. Within the nervous system, transcripts are
CC not observed in neuroblasts, newly generated neurons and at least one
CC class of presumed glial cells. {ECO:0000269|PubMed:2127912,
CC ECO:0000269|PubMed:2494667}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all developmental stages.
CC {ECO:0000269|PubMed:2127912, ECO:0000269|PubMed:2494667}.
CC -!- DOMAIN: The NPTY motif mediates the interaction with clathrin (By
CC similarity). The clathrin-binding site is essential for its association
CC with X11-alpha, -beta, and -gamma. The sequence specific recognition
CC extends to peptide residues that are C-terminal to the NPXY motif. This
CC interaction appears to be independent of phosphorylation (By
CC similarity). {ECO:0000250, ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Overexpression inhibits the Nedd8 conjugation
CC pathway, disrupts the normal bristle pattern in the fly thorax, and
CC induces apoptosis in wing imaginal disks.
CC {ECO:0000269|PubMed:16628230}.
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC ProRule:PRU01217}.
CC -!- CAUTION: Was originally (PubMed:2494667) thought to be vnd but further
CC analysis (PubMed:2127912) has clearly shown that it corresponds to
CC Appl. {ECO:0000305|PubMed:2127912, ECO:0000305|PubMed:2494667}.
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DR EMBL; J04516; AAA28874.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF45520.2; -; Genomic_DNA.
DR EMBL; AL031883; CAA21409.1; -; Genomic_DNA.
DR EMBL; AL022139; CAA21409.1; JOINED; Genomic_DNA.
DR EMBL; AL022139; CAA18093.1; -; Genomic_DNA.
DR EMBL; AL031883; CAA18093.1; JOINED; Genomic_DNA.
DR EMBL; AF181628; AAD55414.1; -; mRNA.
DR EMBL; X55774; CAA39294.1; -; Genomic_DNA.
DR EMBL; X55775; CAA39294.1; JOINED; Genomic_DNA.
DR PIR; A32758; A32758.
DR RefSeq; NP_476626.2; NM_057278.5.
DR AlphaFoldDB; P14599; -.
DR SMR; P14599; -.
DR BioGRID; 57571; 22.
DR IntAct; P14599; 8.
DR STRING; 7227.FBpp0298292; -.
DR GlyCosmos; P14599; 5 sites, No reported glycans.
DR GlyGen; P14599; 5 sites.
DR PaxDb; 7227-FBpp0298292; -.
DR EnsemblMetazoa; FBtr0070109; FBpp0070104; FBgn0000108.
DR GeneID; 31002; -.
DR KEGG; dme:Dmel_CG7727; -.
DR AGR; FB:FBgn0000108; -.
DR CTD; 31002; -.
DR FlyBase; FBgn0000108; Appl.
DR VEuPathDB; VectorBase:FBgn0000108; -.
DR eggNOG; KOG3540; Eukaryota.
DR GeneTree; ENSGT00530000063252; -.
DR InParanoid; P14599; -.
DR PhylomeDB; P14599; -.
DR Reactome; R-DME-114608; Platelet degranulation.
DR Reactome; R-DME-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DME-8957275; Post-translational protein phosphorylation.
DR Reactome; R-DME-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR SignaLink; P14599; -.
DR BioGRID-ORCS; 31002; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Appl; fly.
DR GenomeRNAi; 31002; -.
DR PRO; PR:P14599; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0000108; Expressed in eye disc (Drosophila) and 13 other cell types or tissues.
DR ExpressionAtlas; P14599; baseline and differential.
DR Genevisible; P14599; DM.
DR GO; GO:0030424; C:axon; IDA:FlyBase.
DR GO; GO:0005576; C:extracellular region; IDA:FlyBase.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0008201; F:heparin binding; IEA:InterPro.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0007611; P:learning or memory; IMP:FlyBase.
DR GO; GO:0007616; P:long-term memory; IDA:FlyBase.
DR GO; GO:0016319; P:mushroom body development; IMP:FlyBase.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:FlyBase.
DR GO; GO:0007422; P:peripheral nervous system development; IMP:FlyBase.
DR GO; GO:0048678; P:response to axon injury; IMP:FlyBase.
DR GO; GO:0051602; P:response to electrical stimulus; IMP:FlyBase.
DR GO; GO:0007614; P:short-term memory; IMP:FlyBase.
DR GO; GO:0050808; P:synapse organization; IMP:FlyBase.
DR Gene3D; 1.20.120.770; Amyloid precursor protein, E2 domain; 1.
DR Gene3D; 3.30.1490.140; Amyloidogenic glycoprotein, copper-binding domain; 1.
DR Gene3D; 3.90.570.10; Amyloidogenic glycoprotein, heparin-binding domain; 1.
DR InterPro; IPR036669; Amyloid_Cu-bd_sf.
DR InterPro; IPR008155; Amyloid_glyco.
DR InterPro; IPR011178; Amyloid_glyco_Cu-bd.
DR InterPro; IPR024329; Amyloid_glyco_E2_domain.
DR InterPro; IPR008154; Amyloid_glyco_extra.
DR InterPro; IPR015849; Amyloid_glyco_heparin-bd.
DR InterPro; IPR036454; Amyloid_glyco_heparin-bd_sf.
DR InterPro; IPR019745; Amyloid_glyco_intracell_CS.
DR InterPro; IPR019543; APP_amyloid_C.
DR InterPro; IPR019744; APP_CUBD_CS.
DR InterPro; IPR036176; E2_sf.
DR PANTHER; PTHR23103; ALZHEIMER'S DISEASE BETA-AMYLOID RELATED; 1.
DR PANTHER; PTHR23103:SF15; AMYLOID-BETA-LIKE PROTEIN; 1.
DR Pfam; PF10515; APP_amyloid; 1.
DR Pfam; PF12924; APP_Cu_bd; 1.
DR Pfam; PF12925; APP_E2; 1.
DR Pfam; PF02177; APP_N; 1.
DR SMART; SM00006; A4_EXTRA; 1.
DR SUPFAM; SSF56491; A heparin-binding domain; 1.
DR SUPFAM; SSF89811; Amyloid beta a4 protein copper binding domain (domain 2); 1.
DR SUPFAM; SSF109843; CAPPD, an extracellular domain of amyloid beta A4 protein; 1.
DR PROSITE; PS00319; APP_CUBD; 1.
DR PROSITE; PS51869; APP_E1; 1.
DR PROSITE; PS51870; APP_E2; 1.
DR PROSITE; PS00320; APP_INTRA; 1.
PE 1: Evidence at protein level;
KW Amyloid; Developmental protein; Differentiation; Disulfide bond;
KW Glycoprotein; Membrane; Neurogenesis; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..887
FT /note="Amyloid-beta-like protein"
FT /id="PRO_0000000202"
FT TOPO_DOM 28..813
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 814..834
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 835..887
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..199
FT /note="E1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DOMAIN 395..597
FT /note="E2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01218"
FT REGION 30..133
FT /note="GFLD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 141..199
FT /note="CuBD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 225..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 875..880
FT /note="YENPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P05067"
FT COMPBIAS 245..268
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..315
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..703
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 574
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..70
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 81..128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 106..116
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 143..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 154..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DISULFID 168..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT CONFLICT 177
FT /note="S -> T (in Ref. 1; AAA28874)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="Missing (in Ref. 1; AAA28874)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="V -> M (in Ref. 4; CAA21409/CAA18093)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="S -> T (in Ref. 1; AAA28874)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 887 AA; 98333 MW; F0F0855AD65A5275 CRC64;
MCAALRRNLL LRSLWVVLAI GTAQVQAASP RWEPQIAVLC EAGQIYQPQY LSEEGRWVTD
LSKKTTGPTC LRDKMDLLDY CKKAYPNRDI TNIVESSHYQ KIGGWCRQGA LNAAKCKGSH
RWIKPFRCLG PFQSDALLVP EGCLFDHIHN ASRCWPFVRW NQTGAAACQE RGMQMRSFAM
LLPCGISVFS GVEFVCCPKH FKTDEIHVKK TDLPVMPAAQ INSANDELVM NDEDDSNDSN
YSKDANEDDL DDEDDLMGDD EEDDMVADEA ATAGGSPNTG SSGDSNSGSL DDINAEYDSG
EEGDNYEEDG AGSESEAEVE ASWDQSGGAK VVSLKSDSSS PSSAPVAPAP EKAPVKSESV
TSTPQLSASA AAFVAANSGN SGTGAGAPPS TAQPTSDPYF THFDPHYEHQ SYKVSQKRLE
ESHREKVTRV MKDWSDLEEK YQDMRLADPK AAQSFKQRMT ARFQTSVQAL EEEGNAEKHQ
LAAMHQQRVL AHINQRKREA MTCYTQALTE QPPNAHHVEK CLQKLLRALH KDRAHALAHY
RHLLNSGGPG GLEAAASERP RTLERLIDID RAVNQSMTML KRYPELSAKI AQLMNDYILA
LRSKDDIPGS SLGMSEEAEA GILDKYRVEI ERKVAEKERL RLAEKQRKEQ RAAEREKLRE
EKLRLEAKKV DDMLKSQVAE QQSQPTQSST QSQAQQQQQE KSLPGKELGP DAALVTAANP
NLETTKSEKD LSDTEYGEAT VSSTKVQTVL PTVDDDAVQR AVEDVAAAVA HQEAEPQVQH
FMTHDLGHRE SSFSLRREFA QHAHAAKEGR NVYFTLSFAG IALMAAVFVG VAVAKWRTSR
SPHAQGFIEV DQNVTTHHPI VREEKIVPNM QINGYENPTY KYFEVKE
//
