CED6_DROME
ID CED6_DROME Reviewed; 517 AA.
AC Q7JUY7;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=PTB domain-containing adapter protein ced-6;
DE AltName: Full=Cell death protein 6 homolog;
GN Name=ced-6; ORFNames=CG11804;
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].
RX PubMed=10574763; DOI=10.1016/s0960-9822(00)80062-7;
RA Smits E., Van Criekinge W., Plaetinck G., Bogaert T.;
RT "The human homologue of Caenorhabditis elegans CED-6 specifically promotes
RT phagocytosis of apoptotic cells.";
RL Curr. Biol. 9:1351-1354(1999).
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, INTERACTION WITH DRPR, AND DEVELOPMENTAL STAGE.
RX PubMed=16772168; DOI=10.1016/j.neuron.2006.04.027;
RA Awasaki T., Tatsumi R., Takahashi K., Arai K., Nakanishi Y., Ueda R.,
RA Ito K.;
RT "Essential role of the apoptotic cell engulfment genes draper and ced-6 in
RT programmed axon pruning during Drosophila metamorphosis.";
RL Neuron 50:855-867(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-338; SER-469 AND THR-480, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-338; SER-374; SER-376 AND
RP SER-378, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19927123; DOI=10.1038/emboj.2009.343;
RA Kuraishi T., Nakagawa Y., Nagaosa K., Hashimoto Y., Ishimoto T., Moki T.,
RA Fujita Y., Nakayama H., Dohmae N., Shiratsuchi A., Yamamoto N., Ueda K.,
RA Yamaguchi M., Awasaki T., Nakanishi Y.;
RT "Pretaporter, a Drosophila protein serving as a ligand for Draper in the
RT phagocytosis of apoptotic cells.";
RL EMBO J. 28:3868-3878(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19890048; DOI=10.4049/jimmunol.0901032;
RA Hashimoto Y., Tabuchi Y., Sakurai K., Kutsuna M., Kurokawa K., Awasaki T.,
RA Sekimizu K., Nakanishi Y., Shiratsuchi A.;
RT "Identification of lipoteichoic acid as a ligand for draper in the
RT phagocytosis of Staphylococcus aureus by Drosophila hemocytes.";
RL J. Immunol. 183:7451-7460(2009).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19707574; DOI=10.1371/journal.pbio.1000184;
RA Fuentes-Medel Y., Logan M.A., Ashley J., Ataman B., Budnik V.,
RA Freeman M.R.;
RT "Glia and muscle sculpt neuromuscular arbors by engulfing destabilized
RT synaptic boutons and shed presynaptic debris.";
RL PLoS Biol. 7:E1000184-E1000184(2009).
CC -!- FUNCTION: Plays a role in axon pruning in larval mushroom body neurons
CC during metamorphosis (PubMed:16772168). Plays a role in the
CC infiltration of glial cell processes into mushroom body lobes and the
CC subsequent engulfment of degenerating axon branches (PubMed:16772168).
CC Involved in Drpr-mediated phagocytosis of apoptotic cells
CC (PubMed:19927123). Required for bacterial phagocytosis
CC (PubMed:19890048). During neuromuscular junction development, required
CC for the clearance of pruned ghost boutons and presynaptic debris and
CC for normal synaptic growth (PubMed:19707574).
CC {ECO:0000269|PubMed:16772168, ECO:0000269|PubMed:19707574,
CC ECO:0000269|PubMed:19890048, ECO:0000269|PubMed:19927123}.
CC -!- SUBUNIT: May interact with Drpr. {ECO:0000269|PubMed:16772168}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DEVELOPMENTAL STAGE: Detected in brain cells adjacent to the mushroom
CC body. Expression is low in wandering larvae, elevated 6 hours after
CC puparium formation and back to low levels 12 hours after puparium
CC formation. Detected in infiltrating processes of a subset of glial
CC cells adjacent to mushroom body dorsal lobes.
CC {ECO:0000269|PubMed:16772168}.
CC -!- DISRUPTION PHENOTYPE: Embryonic hemocytes display a reduced level of
CC apoptotic cell phagocytosis (PubMed:19927123). Larval hemocytes display
CC reduced bacterial phagocytosis (PubMed:19890048). RNAi-mediated
CC knockdown in muscle leads to an increase in the number of ghost
CC synaptic boutons but does not affect the deposition of presynaptic
CC debris while RNAi-mediated knockdown in glia leads to a significant
CC increase in presynaptic debris deposition but does not affect the
CC number of ghost boutons (PubMed:19707574).
CC {ECO:0000269|PubMed:19707574, ECO:0000269|PubMed:19890048,
CC ECO:0000269|PubMed:19927123}.
CC -!- SIMILARITY: Belongs to the ced-6 family. {ECO:0000305}.
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DR EMBL; AF204777; AAF22653.1; -; mRNA.
DR EMBL; AE013599; AAG22292.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM71067.1; -; Genomic_DNA.
DR EMBL; AY119596; AAM50250.1; -; mRNA.
DR RefSeq; NP_610488.1; NM_136644.3.
DR RefSeq; NP_724789.1; NM_165675.3.
DR RefSeq; NP_724790.1; NM_165676.2.
DR AlphaFoldDB; Q7JUY7; -.
DR SMR; Q7JUY7; -.
DR BioGRID; 61802; 4.
DR IntAct; Q7JUY7; 1.
DR STRING; 7227.FBpp0297720; -.
DR iPTMnet; Q7JUY7; -.
DR PaxDb; Q7JUY7; -.
DR DNASU; 35971; -.
DR EnsemblMetazoa; FBtr0088548; FBpp0087631; FBgn0029092.
DR EnsemblMetazoa; FBtr0088549; FBpp0087632; FBgn0029092.
DR EnsemblMetazoa; FBtr0088550; FBpp0087633; FBgn0029092.
DR GeneID; 35971; -.
DR KEGG; dme:Dmel_CG11804; -.
DR UCSC; CG11804-RA; d. melanogaster.
DR CTD; 35971; -.
DR FlyBase; FBgn0029092; ced-6.
DR VEuPathDB; VectorBase:FBgn0029092; -.
DR eggNOG; KOG3536; Eukaryota.
DR GeneTree; ENSGT00940000156186; -.
DR InParanoid; Q7JUY7; -.
DR OrthoDB; 878397at2759; -.
DR PhylomeDB; Q7JUY7; -.
DR SignaLink; Q7JUY7; -.
DR BioGRID-ORCS; 35971; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 35971; -.
DR PRO; PR:Q7JUY7; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0029092; Expressed in cleaving embryo and 29 other tissues.
DR ExpressionAtlas; Q7JUY7; baseline and differential.
DR Genevisible; Q7JUY7; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:FlyBase.
DR GO; GO:0016319; P:mushroom body development; IMP:UniProtKB.
DR GO; GO:0016322; P:neuron remodeling; IMP:FlyBase.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF00640; PID; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Phagocytosis; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..517
FT /note="PTB domain-containing adapter protein ced-6"
FT /id="PRO_0000296684"
FT DOMAIN 83..265
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..388
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 338
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656,
FT ECO:0000269|PubMed:18327897"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 480
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17372656"
SQ SEQUENCE 517 AA; 56140 MW; C9A75B4B791F5DC4 CRC64;
MPYQPANSGG TSGGSKAAAK MAQLKFWNKQ NSSKQQQQDK DKDAADGGNN TSGGGTGSNS
NGDAKSEAKN GKRNWLHTPE QLISGHAVYL VKFFGNLSVD QPKGIEVVKE AIRKLQFAQQ
MKKAETGTQE KFKKLEITIS IKGVAIQEPR THKILHQFPL YNISYCADEK GVKKFFSFIA
KTVKTQDGSD PTSNGHANGN GDGSAKVEES HECFVFISNK LASDITLTIG QAFDLAYRKY
MDSTEKTNLS KAQQQINHLQ QTVNVYKERL REVSAKLPKA ELDALLFNLG IKDILEAPTT
EPQNGIEVAS EALSNGKLDD DKLLIDTNST TASTHSASPS SFLPIVPPRN NLSSQISIGG
KSNSQKMDEL LLNSDSDSDF DPRADETQEI GGTGRSAISN MFGFEPANSF GQHLFSNNND
HKLQNNNSSL LITSNNNSIN SSGFSSELNI TPPLLAPPPK IAAPRRLNSV TTGNGLNGNT
DLFGSDPFEL NNGPNIFKQN QLNLDDFSLE SLDPLRK
