APP_DROME
ID APP_DROME Reviewed; 693 AA.
AC A2VEY9; B7Z0A6; M9NDQ1; M9NF95;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Palmitoyltransferase app {ECO:0000303|PubMed:18804377};
DE EC=2.3.1.225 {ECO:0000255|RuleBase:RU079119, ECO:0000269|PubMed:27692068};
DE AltName: Full=Protein approximated {ECO:0000303|PubMed:18804377};
GN Name=app {ECO:0000303|PubMed:18804377, ECO:0000312|FlyBase:FBgn0260941};
GN ORFNames=CG42318 {ECO:0000312|FlyBase:FBgn0260941};
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 {ECO:0000312|EMBL:ABN49447.1};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [3] {ECO:0000312|EMBL:ABN49447.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ABN49447.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:ABN49447.1};
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18804377; DOI=10.1016/j.cub.2008.07.067;
RA Matakatsu H., Blair S.S.;
RT "The DHHC palmitoyltransferase approximated regulates Fat signaling and
RT Dachs localization and activity.";
RL Curr. Biol. 18:1390-1395(2008).
RN [5] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18719403; DOI=10.4161/fly.6621;
RA Bannan B.A., Van Etten J., Kohler J.A., Tsoi Y., Hansen N.M., Sigmon S.,
RA Fowler E., Buff H., Williams T.S., Ault J.G., Glaser R.L., Korey C.A.;
RT "The Drosophila protein palmitoylome: characterizing palmitoyl-
RT thioesterases and DHHC palmitoyl-transferases.";
RL Fly 2:198-214(2008).
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH DLISH AND FT.
RX PubMed=27692068; DOI=10.7554/elife.16624;
RA Zhang Y., Wang X., Matakatsu H., Fehon R., Blair S.S.;
RT "The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in
RT Drosophila by binding and regulating Dachs.";
RL Elife 5:E16624-E16624(2016).
RN [7]
RP ERRATUM OF PUBMED:27692068.
RX PubMed=27824307; DOI=10.7554/elife.22672;
RA Zhang Y., Wang X., Matakatsu H., Fehon R., Blair S.S.;
RL Elife 5:E22672-E22672(2016).
CC -!- FUNCTION: Palmitoylates Dlish which is required for the apical cell
CC cortex localization, total cellular level and full activity of dachs.
CC {ECO:0000269|PubMed:18804377, ECO:0000269|PubMed:27692068}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-
CC hexadecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:36683, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:74151;
CC EC=2.3.1.225; Evidence={ECO:0000255|RuleBase:RU079119,
CC ECO:0000269|PubMed:27692068};
CC -!- SUBUNIT: Interacts with Dlish (via N-terminus including SH3 domain 1);
CC this leads to palmitoylation of Dlish by app. Interacts with ft; this
CC is likely to interfere with the interaction between app and Dlish,
CC reducing the ability of app to palmitoylate Dlish and tether it to the
CC apical cell cortex. {ECO:0000269|PubMed:27692068}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18719403}; Multi-pass membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:18804377};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=L {ECO:0000312|FlyBase:FBgn0260941}; Synonyms=M
CC {ECO:0000312|FlyBase:FBgn0260941}, R {ECO:0000312|FlyBase:FBgn0260941},
CC T {ECO:0000312|FlyBase:FBgn0260941};
CC IsoId=A2VEY9-1; Sequence=Displayed;
CC Name=S {ECO:0000312|FlyBase:FBgn0260941};
CC IsoId=A2VEY9-2; Sequence=VSP_058747;
CC Name=H {ECO:0000312|FlyBase:FBgn0260941}; Synonyms=I
CC {ECO:0000312|FlyBase:FBgn0260941};
CC IsoId=A2VEY9-3; Sequence=VSP_058748, VSP_058751;
CC Name=O {ECO:0000312|FlyBase:FBgn0260941};
CC IsoId=A2VEY9-4; Sequence=VSP_058749, VSP_058750;
CC -!- TISSUE SPECIFICITY: Detected in embryo, imaginal disks and pupal wings
CC (at protein level) (PubMed:18804377). Enriched in the somatic
CC musculature and gut throughout embryonic development (PubMed:18719403).
CC {ECO:0000269|PubMed:18719403}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000255|RuleBase:RU079119}.
CC -!- DISRUPTION PHENOTYPE: Semi-lethal in homozygotes and heterozygotes with
CC adult escapers showing abdominal planar cell polarity defects and also
CC extensive wing planar cell polarity defects, both proximally and in a
CC distal region between the third and fourth longitudinal veins. Greatly
CC reduced accumulation of dachs at the apical cell cortex.
CC {ECO:0000269|PubMed:18804377}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC ERF2/ZDHHC9 subfamily. {ECO:0000305}.
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DR EMBL; AE014296; ACL83291.1; -; Genomic_DNA.
DR EMBL; AE014296; ACL83292.1; -; Genomic_DNA.
DR EMBL; AE014296; ACL83293.2; -; Genomic_DNA.
DR EMBL; AE014296; ACL83294.2; -; Genomic_DNA.
DR EMBL; AE014296; AFH04402.2; -; Genomic_DNA.
DR EMBL; AE014296; AFH04403.1; -; Genomic_DNA.
DR EMBL; AE014296; AFH04404.2; -; Genomic_DNA.
DR EMBL; AE014296; AHN58068.1; -; Genomic_DNA.
DR EMBL; BT030308; ABN49447.1; -; mRNA.
DR RefSeq; NP_001137936.1; NM_001144464.2. [A2VEY9-1]
DR RefSeq; NP_001137937.1; NM_001144465.2. [A2VEY9-1]
DR RefSeq; NP_001137938.2; NM_001144466.3. [A2VEY9-3]
DR RefSeq; NP_001137939.2; NM_001144467.3. [A2VEY9-3]
DR RefSeq; NP_001246731.2; NM_001259802.2. [A2VEY9-1]
DR RefSeq; NP_001246732.1; NM_001259803.2. [A2VEY9-4]
DR RefSeq; NP_001246733.2; NM_001259804.2. [A2VEY9-2]
DR RefSeq; NP_001287043.1; NM_001300114.1. [A2VEY9-1]
DR AlphaFoldDB; A2VEY9; -.
DR SMR; A2VEY9; -.
DR IntAct; A2VEY9; 3.
DR STRING; 7227.FBpp0290276; -.
DR PRIDE; A2VEY9; -.
DR DNASU; 39399; -.
DR EnsemblMetazoa; FBtr0301052; FBpp0290274; FBgn0260941. [A2VEY9-3]
DR EnsemblMetazoa; FBtr0301053; FBpp0290275; FBgn0260941. [A2VEY9-3]
DR EnsemblMetazoa; FBtr0301056; FBpp0290278; FBgn0260941. [A2VEY9-1]
DR EnsemblMetazoa; FBtr0301057; FBpp0290279; FBgn0260941. [A2VEY9-1]
DR EnsemblMetazoa; FBtr0304661; FBpp0293203; FBgn0260941. [A2VEY9-4]
DR EnsemblMetazoa; FBtr0334102; FBpp0306224; FBgn0260941. [A2VEY9-1]
DR EnsemblMetazoa; FBtr0334103; FBpp0306225; FBgn0260941. [A2VEY9-2]
DR EnsemblMetazoa; FBtr0339925; FBpp0308957; FBgn0260941. [A2VEY9-1]
DR GeneID; 39399; -.
DR KEGG; dme:Dmel_CG42318; -.
DR CTD; 351; -.
DR FlyBase; FBgn0260941; app.
DR VEuPathDB; VectorBase:FBgn0260941; -.
DR eggNOG; KOG1311; Eukaryota.
DR GeneTree; ENSGT00940000156483; -.
DR HOGENOM; CLU_018741_6_0_1; -.
DR OMA; ISVRIKY; -.
DR BioGRID-ORCS; 39399; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 39399; -.
DR PRO; PR:A2VEY9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0260941; Expressed in crop (Drosophila) and 30 other tissues.
DR ExpressionAtlas; A2VEY9; baseline and differential.
DR GO; GO:0045179; C:apical cortex; IDA:FlyBase.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:FlyBase.
DR GO; GO:0048104; P:establishment of body hair or bristle planar orientation; IMP:FlyBase.
DR GO; GO:0001737; P:establishment of imaginal disc-derived wing hair orientation; IMP:FlyBase.
DR GO; GO:0007389; P:pattern specification process; IMP:FlyBase.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IBA:GO_Central.
DR GO; GO:0018345; P:protein palmitoylation; ISS:FlyBase.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR Pfam; PF01529; DHHC; 1.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Cell membrane;
KW Endoplasmic reticulum; Lipoprotein; Membrane; Palmitate;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..693
FT /note="Palmitoyltransferase app"
FT /id="PRO_0000438852"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 147..197
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT REGION 377..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT VAR_SEQ 1..217
FT /note="Missing (in isoform S)"
FT /evidence="ECO:0000305"
FT /id="VSP_058747"
FT VAR_SEQ 378..398
FT /note="SNPSSSTLEGNGGAINGHGNG -> VSGQSSGHIESIQEHPFTTEI (in
FT isoform H)"
FT /evidence="ECO:0000305"
FT /id="VSP_058748"
FT VAR_SEQ 378..382
FT /note="SNPSS -> VIPIV (in isoform O)"
FT /evidence="ECO:0000305"
FT /id="VSP_058749"
FT VAR_SEQ 383..693
FT /note="Missing (in isoform O)"
FT /evidence="ECO:0000305"
FT /id="VSP_058750"
FT VAR_SEQ 399..693
FT /note="Missing (in isoform H)"
FT /evidence="ECO:0000305"
FT /id="VSP_058751"
SQ SEQUENCE 693 AA; 75008 MW; 9D9CA4161D0ABF0E CRC64;
MNLLCCCCCS NMAPNQRVTR KWELFAGRNK FYCDGLLMSA PHTGVFYLTC ILITGTSALF
FAFDCPFLAD SINPAIPIVG AVLYFFTMSS LLRTTFTDPG VIPRASNDEA AYIEKQIEVP
NSLNSPTYRP PPRTKEVLVK GQTVKLKYCF TCKIFRPPRA SHCSLCDNCV DRFDHHCPWV
GNCVGKRNYR FFYLFLVSLA FLAVFIFSCS VTHLVLLMKK EHEVFNVIKA APFTVIVVFI
CFFSIWSVIG LAGFHTYLTT SDQTTNEDLK GSFSSKGGPR TQNPYSRGNI CLNCCHILCG
PMTPSLIDRR GIATDEFIQQ MQHQSSPRHA LSDVLSASHM VTTSQPMMGG LGGGGIGGAG
GGISIGGAEL KPRFYDESNP SSSTLEGNGG AINGHGNGHG NGFDHPPPSY DLVQNGNSNS
LAQLVDNEIP LVQMDIPAYT HQTATQARQY RHRHHKQRQI CNGGTVSYEN QLANASSEDE
LDDPDVVVVG SPEVVAAVAA IASNKAREMR NRSGSYSNLF DADFEAALVN SSLADNHVRG
EGASSSGKPS AGAALLAAAI SGKTENMYSN VLPVDNDTDP ADSTLHVYSN IIDERKQQEQ
ANNVLSSTLL CDDLDLDDPV SASCHVKRKS LGDGAEQVKS AERLRMLHDN TMIDTALDLD
SLDGSSMGNN SQSCLVKSGK PNATSVTTNV AIV
