DIF_DROME
ID DIF_DROME Reviewed; 667 AA.
AC P98149; Q1LYZ5; Q8MT54; Q9VJE2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Dorsal-related immunity factor Dif;
GN Name=Dif {ECO:0000312|FlyBase:FBgn0011274};
GN ORFNames=CG6794 {ECO:0000312|FlyBase:FBgn0011274};
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], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Imaginal disk;
RX PubMed=8242747; DOI=10.1016/0092-8674(93)90495-c;
RA Ip Y.T., Reach M., Engstrom Y., Kadalayil L., Cai H., Gonzalez-Crespo S.,
RA Tatei K., Levine M.A.;
RT "Dif, a dorsal-related gene that mediates an immune response in
RT Drosophila.";
RL Cell 75:753-763(1993).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND MUTAGENESIS OF GLY-181.
RX PubMed=12456640; DOI=10.1093/emboj/cdf661;
RA Ligoxygakis P., Pelte N., Ji C., Leclerc V., Duvic B., Belvin M., Jiang H.,
RA Hoffmann J.A., Reichhart J.M.;
RT "A serpin mutant links Toll activation to melanization in the host defence
RT of Drosophila.";
RL EMBO J. 21:6330-6337(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17032737; DOI=10.1242/jcs.03201;
RA Xylourgidis N., Roth P., Sabri N., Tsarouhas V., Samakovlis C.;
RT "The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates
RT NFkappaB activation in Drosophila.";
RL J. Cell Sci. 119:4409-4419(2006).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF GLY-181.
RX PubMed=18000549; DOI=10.1371/journal.pone.0001178;
RA Ayyar S., Pistillo D., Calleja M., Brookfield A., Gittins K., Goldstone C.,
RA Simpson P.;
RT "NF-kappaB/Rel-mediated regulation of the neural fate in Drosophila.";
RL PLoS ONE 2:E1178-E1178(2007).
RN [9]
RP MUTAGENESIS OF GLY-181.
RX PubMed=21576362; DOI=10.1128/mcb.01397-10;
RA Fullaondo A., Garcia-Sanchez S., Sanz-Parra A., Recio E., Lee S.Y.,
RA Gubb D.;
RT "Spn1 regulates the GNBP3-dependent Toll signaling pathway in Drosophila
RT melanogaster.";
RL Mol. Cell. Biol. 31:2960-2972(2011).
RN [10]
RP FUNCTION.
RX PubMed=25477468; DOI=10.1126/science.1258236;
RA Meyer S.N., Amoyel M., Bergantinos C., de la Cova C., Schertel C.,
RA Basler K., Johnston L.A.;
RT "An ancient defense system eliminates unfit cells from developing tissues
RT during cell competition.";
RL Science 346:1258236-1258236(2014).
CC -!- FUNCTION: Mediates an immune response in larvae (PubMed:8242747). DIF
CC binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the
CC enhancer region of the immunity gene CECA1 (PubMed:8242747). Involved
CC in the melanization immune response to bacterial challenge, possibly by
CC acting in a Toll signaling pathway that down-regulates Spn27A in
CC response to infection (PubMed:12456640). Part of a signaling pathway
CC involving NF-kappa-B (rel) and Toll-related receptors, that functions
CC in the apoptosis of unfit cells during cell competition
CC (PubMed:25477468). May be part of a NF-kappa-B and Tollo signaling
CC cascade that regulates development of the peripheral nervous system
CC (PubMed:18000549). {ECO:0000269|PubMed:12456640,
CC ECO:0000269|PubMed:18000549, ECO:0000269|PubMed:25477468,
CC ECO:0000269|PubMed:8242747}.
CC -!- INTERACTION:
CC P98149; P15330: dl; NbExp=2; IntAct=EBI-188843, EBI-198375;
CC P98149; Q94527: Rel; NbExp=3; IntAct=EBI-188843, EBI-869024;
CC P98149; Q94527-1: Rel; NbExp=2; IntAct=EBI-188843, EBI-15786027;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17032737,
CC ECO:0000269|PubMed:8242747}. Nucleus {ECO:0000269|PubMed:17032737,
CC ECO:0000269|PubMed:8242747}. Note=Accumulates in the nucleus upon
CC bacterial infection or injury. {ECO:0000269|PubMed:17032737,
CC ECO:0000269|PubMed:8242747}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM48404.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L29015; AAA28465.1; -; mRNA.
DR EMBL; AE014134; AAF53608.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10989.1; -; Genomic_DNA.
DR EMBL; AY118375; AAM48404.1; ALT_FRAME; mRNA.
DR EMBL; BT025231; ABF17922.1; -; mRNA.
DR PIR; A49435; A49435.
DR RefSeq; NP_001162999.1; NM_001169528.1.
DR RefSeq; NP_523589.2; NM_078865.4.
DR RefSeq; NP_724050.1; NM_165216.3.
DR AlphaFoldDB; P98149; -.
DR SMR; P98149; -.
DR BioGRID; 61041; 13.
DR DIP; DIP-34965N; -.
DR IntAct; P98149; 95.
DR STRING; 7227.FBpp0290792; -.
DR PaxDb; P98149; -.
DR PRIDE; P98149; -.
DR DNASU; 35045; -.
DR EnsemblMetazoa; FBtr0081008; FBpp0080561; FBgn0011274.
DR EnsemblMetazoa; FBtr0081009; FBpp0080562; FBgn0011274.
DR EnsemblMetazoa; FBtr0301578; FBpp0290793; FBgn0011274.
DR GeneID; 35045; -.
DR KEGG; dme:Dmel_CG6794; -.
DR CTD; 35045; -.
DR FlyBase; FBgn0011274; Dif.
DR VEuPathDB; VectorBase:FBgn0011274; -.
DR eggNOG; ENOG502QQS6; Eukaryota.
DR GeneTree; ENSGT00940000171058; -.
DR HOGENOM; CLU_452907_0_0_1; -.
DR InParanoid; P98149; -.
DR PhylomeDB; P98149; -.
DR Reactome; R-DME-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-DME-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-DME-202424; Downstream TCR signaling.
DR Reactome; R-DME-209400; Transcriptional activtion by phosphorylated DL/DIF dimer.
DR Reactome; R-DME-209406; Degradation of NF-kappa-B inhibitor, CACT.
DR Reactome; R-DME-209560; NF-kB is activated and signals survival.
DR Reactome; R-DME-214842; DL and DIF homodimers bind to TUB and phosphorylated PLL in the TL receptor 'signalling complex'.
DR Reactome; R-DME-214844; DL and DIF homodimers complexed with CACT are all phosphorylated in the TL receptor 'signalling complex'.
DR Reactome; R-DME-214869; Phosphorylated CACT, DL and DIF homodimers dissociate from the TL receptor 'signalling complex'.
DR Reactome; R-DME-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-DME-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
DR Reactome; R-DME-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-DME-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-DME-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-DME-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-DME-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-9020702; Interleukin-1 signaling.
DR Reactome; R-DME-933542; TRAF6 mediated NF-kB activation.
DR BioGRID-ORCS; 35045; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35045; -.
DR PRO; PR:P98149; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0011274; Expressed in saliva-secreting gland and 13 other tissues.
DR ExpressionAtlas; P98149; baseline and differential.
DR Genevisible; P98149; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:FlyBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:FlyBase.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:FlyBase.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0048935; P:peripheral nervous system neuron development; IMP:FlyBase.
DR GO; GO:0002804; P:positive regulation of antifungal peptide production; IMP:FlyBase.
DR GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IMP:FlyBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0035206; P:regulation of hemocyte proliferation; IDA:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0035070; P:salivary gland histolysis; IMP:FlyBase.
DR GO; GO:0008063; P:Toll signaling pathway; IMP:FlyBase.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR InterPro; IPR011363; Dif.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR000451; NFkB/Dor.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR030492; RHD_CS.
DR InterPro; IPR032397; RHD_dimer.
DR InterPro; IPR011539; RHD_DNA_bind_dom.
DR InterPro; IPR037059; RHD_DNA_bind_dom_sf.
DR PANTHER; PTHR24169; PTHR24169; 1.
DR Pfam; PF16179; RHD_dimer; 1.
DR Pfam; PF00554; RHD_DNA_bind; 1.
DR PIRSF; PIRSF001716; Dorsal; 1.
DR PRINTS; PR00057; NFKBTNSCPFCT.
DR SMART; SM00429; IPT; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS01204; REL_1; 1.
DR PROSITE; PS50254; REL_2; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..667
FT /note="Dorsal-related immunity factor Dif"
FT /id="PRO_0000205163"
FT DOMAIN 78..372
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT REGION 445..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 364..368
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 343
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MUTAGEN 181
FT /note="G->D: In Dif1; immune response defective. Reduced
FT survival following infection with fungi, and reduced levels
FT of Drs following immune challenge with fungi or bacteria.
FT No down-regulation of the serpin Spn27A in response to
FT bacterial infection. Ectopic bristles form on the
FT dorsocentral, scutellar and lateral regions of the notum."
FT /evidence="ECO:0000269|PubMed:12456640,
FT ECO:0000269|PubMed:18000549, ECO:0000269|PubMed:21576362"
FT CONFLICT 403
FT /note="K -> T (in Ref. 1; AAA28465)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 667 AA; 73935 MW; DB548B2AE35AC86C CRC64;
MFEEAFGDIQ EIINASMELN GGATGGGSVA GAVGGGGAAH HILSQSTSLP VMPSHIPLHL
QNQNMNQNLP EPSARSGPHL RIVEEPTSNI IRFRYKCEGR TAGSIPGMNS SSETGKTFPT
IEVCNYDGPV IIVVSCVTSD EPFRQHPHWL VSKEEADACK SGIYQKKLPP EERRLVLQKV
GIQCAKKLEM RDSLVERERR NIDPFNAKFD HKDQIDKINR YELRLCYQAF ITVGNSKVPL
DPIVSSPIYG KSSELTITRL CSCAATANGG DEIIMLCEKI AKDDIEVRFY ETDKDGRETW
FANAEFQPTD VFKQMAIAFK TPRYRNTEIT QSVNVELKLV RPSDGATSAP LPFEYYPNPE
LLTKHNRRVA QKTVESLKRS LMSTNLHPSK QVKTSSQYTI FSKPQIATTT PQTQVSPGMP
LMFPGGSPNF VQDIKMENGF MDVDSQSSQC PSVERNFASP RSNCSTVDSI PPMQMGQNQT
HLYLPDATNF TFNGNFASPS SNCSTVDSIP PFQIGQRNNH MYLPENSNFP VNGCSPTHFS
GGSMTPINNN NNVLINNNNN DFLSQKMSAI SIPPQGNFGI KQVYQQTQQF LPQLQPESIP
YLAQSHPEQS QYQQQQQPQE QQPPADEPTQ SFSDLISSSI GMAPIDTSEL IQDIEAELNS
LGIQPFK
