DIE_DROME
ID DIE_DROME Reviewed; 115 AA.
AC Q9VAK8;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein Diedel {ECO:0000303|PubMed:22442689};
DE Flags: Precursor;
GN Name=Diedel {ECO:0000312|FlyBase:FBgn0039666};
GN Synonyms=die {ECO:0000303|PubMed:26739560};
GN ORFNames=CG11501 {ECO:0000312|FlyBase:FBgn0039666};
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|Proteomes:UP000000803};
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:AAL48174.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48174.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL48174.1};
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 [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY VIRAL
RP INFECTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26739560; DOI=10.1073/pnas.1516122113;
RA Lamiable O., Kellenberger C., Kemp C., Troxler L., Pelte N., Boutros M.,
RA Marques J.T., Daeffler L., Hoffmann J.A., Roussel A., Imler J.L.;
RT "Cytokine Diedel and a viral homologue suppress the IMD pathway in
RT Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:698-703(2016).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=30036358; DOI=10.1371/journal.pbio.2005796;
RA Mlih M., Khericha M., Birdwell C., West A.P., Karpac J.;
RT "A virus-acquired host cytokine controls systemic aging by antagonizing
RT apoptosis.";
RL PLoS Biol. 16:E2005796-E2005796(2018).
RN [6] {ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR}
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 25-115, SUBCELLULAR LOCATION,
RP DOMAIN, AND DISULFIDE BONDS.
RX PubMed=22442689; DOI=10.1371/journal.pone.0033416;
RA Coste F., Kemp C., Bobezeau V., Hetru C., Kellenberger C., Imler J.L.,
RA Roussel A.;
RT "Crystal structure of Diedel, a marker of the immune response of Drosophila
RT melanogaster.";
RL PLoS ONE 7:E33416-E33416(2012).
CC -!- FUNCTION: Cytokine which promotes survival following infection by
CC Sindbis virus by suppressing the immune deficiency pathway
CC (PubMed:26739560). Following infection by the enteropathogenic bacteria
CC E.carotovora limits intestinal stem cells proliferation
CC (PubMed:30036358). When secreted from muscle or adipose tissue, can
CC attenuate age-related intestinal tissue degeneration by inhibiting
CC apoptosis (PubMed:30036358). {ECO:0000269|PubMed:26739560,
CC ECO:0000269|PubMed:30036358}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22442689,
CC ECO:0000269|PubMed:26739560, ECO:0000269|PubMed:30036358}.
CC Note=Secreted into the hemolymph. {ECO:0000269|PubMed:26739560}.
CC -!- TISSUE SPECIFICITY: Detected in hemolymph (at protein level). Also
CC expressed in the fat body and is probably synthesized in the fat body
CC and secreted into the hemolymph. {ECO:0000269|PubMed:26739560}.
CC -!- DEVELOPMENTAL STAGE: Expressed in muscle and fat body with levels
CC increasing in the adult stage. {ECO:0000269|PubMed:30036358}.
CC -!- INDUCTION: By viral infection with Drosophila C virus (DCV), feline
CC herpesvirus (FHV), Sindbis virus (SINV) and vesicular stomatitis virus
CC (VSV). Strongest induction occurs with SINV and VSV. Highest levels of
CC induction occur 6-24 hours after infection with levels declining
CC steadily until 96 hours after infection. Induction requires the dorsal-
CC related immunity factor Dif but does not require the myeloid
CC differentiation primary response protein MyD88 (PubMed:26739560). By
CC muscle tissue stress (PubMed:30036358). {ECO:0000269|PubMed:26739560,
CC ECO:0000269|PubMed:30036358}.
CC -!- DOMAIN: Contains two subdomains, SD1 and SD2. SD1 is composed of an
CC antiparallel beta-sheet covered by an alpha-helix and displays a
CC ferredoxin-like fold. SD2 displays a new protein fold made of loops
CC connected by four disulfide bridges. {ECO:0000269|PubMed:22442689}.
CC -!- DISRUPTION PHENOTYPE: Mutants have a shortened lifespan and succumb
CC more rapidly than controls to SINV infection (PubMed:26739560). RNAi-
CC mediated knockdown in fat body leads to accelerated aging of the
CC intestine with intestinal stem cell hyperproliferation, epithelial
CC dysplasia and accelerated induction of apoptosis in the aging midgut
CC (PubMed:30036358). RNAi-mediated knockdown in muscle had no impact on
CC systemic intestinal tissue aging (PubMed:30036358).
CC {ECO:0000269|PubMed:26739560, ECO:0000269|PubMed:30036358}.
CC -!- MISCELLANEOUS: The name 'Diedel' is the German translation of Tweedle
CC and is based on the fictional Lewis Carroll characters Tweedledum and
CC Tweedledee due to the presence of two subdomains within the protein.
CC {ECO:0000303|PubMed:22442689}.
CC -!- SIMILARITY: Belongs to the Diedel family. {ECO:0000305}.
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DR EMBL; AE014297; AAF56898.1; -; Genomic_DNA.
DR EMBL; AY070703; AAL48174.1; -; mRNA.
DR RefSeq; NP_651695.1; NM_143438.3.
DR PDB; 3ZZO; X-ray; 1.15 A; A=25-115.
DR PDB; 3ZZR; X-ray; 1.45 A; A=25-115.
DR PDBsum; 3ZZO; -.
DR PDBsum; 3ZZR; -.
DR AlphaFoldDB; Q9VAK8; -.
DR SMR; Q9VAK8; -.
DR STRING; 7227.FBpp0084794; -.
DR PaxDb; Q9VAK8; -.
DR DNASU; 43474; -.
DR EnsemblMetazoa; FBtr0085426; FBpp0084794; FBgn0039666.
DR GeneID; 43474; -.
DR KEGG; dme:Dmel_CG11501; -.
DR UCSC; CG11501-RA; d. melanogaster.
DR CTD; 43474; -.
DR FlyBase; FBgn0039666; Diedel.
DR VEuPathDB; VectorBase:FBgn0039666; -.
DR eggNOG; ENOG502T9YA; Eukaryota.
DR GeneTree; ENSGT00540000073736; -.
DR HOGENOM; CLU_152773_0_0_1; -.
DR InParanoid; Q9VAK8; -.
DR OMA; CCTSREL; -.
DR OrthoDB; 1541849at2759; -.
DR PhylomeDB; Q9VAK8; -.
DR BioGRID-ORCS; 43474; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43474; -.
DR PRO; PR:Q9VAK8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039666; Expressed in head capsule and 6 other tissues.
DR ExpressionAtlas; Q9VAK8; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0009617; P:response to bacterium; IMP:UniProtKB.
DR InterPro; IPR025061; Diedel.
DR Pfam; PF13164; Diedel; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytokine; Disulfide bond; Immunity; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..115
FT /note="Protein Diedel"
FT /id="PRO_5006752568"
FT DISULFID 26..81
FT /evidence="ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR"
FT DISULFID 27..87
FT /evidence="ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR"
FT DISULFID 42..55
FT /evidence="ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR"
FT DISULFID 60..71
FT /evidence="ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR"
FT DISULFID 76..83
FT /evidence="ECO:0007744|PDB:3ZZO, ECO:0007744|PDB:3ZZR"
FT STRAND 30..40
FT /evidence="ECO:0007829|PDB:3ZZO"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:3ZZO"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:3ZZO"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:3ZZO"
FT STRAND 105..114
FT /evidence="ECO:0007829|PDB:3ZZO"
SQ SEQUENCE 115 AA; 12448 MW; 0C1995F347A5CD03 CRC64;
MASPVVSLLL VGICALAFVH VARSECCTSR ELVEFKMDRG DCEAVRAIEN YPNGCEVTIC
ADGVAQLGAY CGQGSCNIFG CNCDGGCLSG DWSQEFVRRN QQYGIQIIKV TRLPF
