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Dorsal-related immunity factor Dif

 DIF_DROME               Reviewed;         667 AA.
P98149; Q1LYZ5; Q8MT54; Q9VJE2;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-JUN-2001, sequence version 2.
18-JUL-2018, entry version 169.
RecName: Full=Dorsal-related immunity factor Dif;
Name=Dif {ECO:0000312|FlyBase:FBgn0011274};
ORFNames=CG6794 {ECO:0000312|FlyBase:FBgn0011274};
Drosophila melanogaster (Fruit fly).
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta;
Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha;
Ephydroidea; Drosophilidae; Drosophila; Sophophora.
NCBI_TaxID=7227;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
TISSUE=Imaginal disk;
PubMed=8242747; DOI=10.1016/0092-8674(93)90495-C;
Ip Y.T., Reach M., Engstrom Y., Kadalayil L., Cai H.,
Gonzalez-Crespo S., Tatei K., Levine M.A.;
"Dif, a dorsal-related gene that mediates an immune response in
Drosophila.";
Cell 75:753-763(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Berkeley;
PubMed=10731132; DOI=10.1126/science.287.5461.2185;
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X.,
Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D.,
Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G.,
Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D.,
Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M.,
Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S.,
Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P.,
Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I.,
Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P.,
de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M.,
Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P.,
Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W.,
Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K.,
Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J.,
Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C.,
Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A.,
Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z.,
Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X.,
Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D.,
Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A.,
Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L.,
Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M.,
Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G.,
Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H.,
Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
Spier E., Spradling A.C., Stapleton M., Strong R., Sun E.,
Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X.,
Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J.,
Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A.,
Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L.,
Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X.,
Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
"The genome sequence of Drosophila melanogaster.";
Science 287:2185-2195(2000).
[3]
GENOME REANNOTATION.
STRAIN=Berkeley;
PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q.,
Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M.,
Lewis S.E.;
"Annotation of the Drosophila melanogaster euchromatic genome: a
systematic review.";
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Berkeley; TISSUE=Embryo;
PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M.,
George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H.,
Rubin G.M., Celniker S.E.;
"A Drosophila full-length cDNA resource.";
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Berkeley;
Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H.,
Yu C., Celniker S.E.;
Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
[6]
FUNCTION, AND MUTAGENESIS OF GLY-181.
PubMed=12456640; DOI=10.1093/emboj/cdf661;
Ligoxygakis P., Pelte N., Ji C., Leclerc V., Duvic B., Belvin M.,
Jiang H., Hoffmann J.A., Reichhart J.M.;
"A serpin mutant links Toll activation to melanization in the host
defence of Drosophila.";
EMBO J. 21:6330-6337(2002).
[7]
FUNCTION, AND MUTAGENESIS OF GLY-181.
PubMed=18000549; DOI=10.1371/journal.pone.0001178;
Ayyar S., Pistillo D., Calleja M., Brookfield A., Gittins K.,
Goldstone C., Simpson P.;
"NF-kappaB/Rel-mediated regulation of the neural fate in Drosophila.";
PLoS ONE 2:E1178-E1178(2007).
[8]
MUTAGENESIS OF GLY-181.
PubMed=21576362; DOI=10.1128/MCB.01397-10;
Fullaondo A., Garcia-Sanchez S., Sanz-Parra A., Recio E., Lee S.Y.,
Gubb D.;
"Spn1 regulates the GNBP3-dependent Toll signaling pathway in
Drosophila melanogaster.";
Mol. Cell. Biol. 31:2960-2972(2011).
[9]
FUNCTION.
PubMed=25477468; DOI=10.1126/science.1258236;
Meyer S.N., Amoyel M., Bergantinos C., de la Cova C., Schertel C.,
Basler K., Johnston L.A.;
"An ancient defense system eliminates unfit cells from developing
tissues during cell competition.";
Science 346:1258236-1258236(2014).
-!- FUNCTION: Mediates an immune response in larvae (PubMed:8242747).
DIF binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3',
located in the enhancer region of the immunity gene CECA1
(PubMed:8242747). Involved in the melanization immune response to
bacterial challenge, possibly by acting in a Toll signaling
pathway that downregulates Spn27A in response to infection
(PubMed:12456640). Part of a signaling pathway involving NF-kappa-
B (rel) and Toll-related receptors, that functions in the
apoptosis of unfit cells during cell competition
(PubMed:25477468). May be part of a NF-kappa-B and Tollo signaling
cascade that regulates development of the peripheral nervous
system (PubMed:18000549). {ECO:0000269|PubMed:12456640,
ECO:0000269|PubMed:18000549, ECO:0000269|PubMed:25477468,
ECO:0000269|PubMed:8242747}.
-!- INTERACTION:
P15330:dl; NbExp=2; IntAct=EBI-188843, EBI-198375;
Q94527:Rel; NbExp=4; IntAct=EBI-188843, EBI-869024;
Q94527-1:Rel; NbExp=2; IntAct=EBI-188843, EBI-15786027;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8242747}.
Nucleus {ECO:0000269|PubMed:8242747}. Note=Accumulates in the
nucleus upon bacterial infection of injury.
-!- SEQUENCE CAUTION:
Sequence=AAM48404.1; Type=Frameshift; Positions=495; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; L29015; AAA28465.1; -; mRNA.
EMBL; AE014134; AAF53608.1; -; Genomic_DNA.
EMBL; AE014134; AAN10989.1; -; Genomic_DNA.
EMBL; AY118375; AAM48404.1; ALT_FRAME; mRNA.
EMBL; BT025231; ABF17922.1; -; mRNA.
PIR; A49435; A49435.
RefSeq; NP_001162999.1; NM_001169528.1.
RefSeq; NP_523589.2; NM_078865.4.
RefSeq; NP_724050.1; NM_165216.3.
UniGene; Dm.19845; -.
ProteinModelPortal; P98149; -.
SMR; P98149; -.
BioGrid; 61041; 10.
DIP; DIP-34965N; -.
IntAct; P98149; 5.
STRING; 7227.FBpp0290792; -.
PaxDb; P98149; -.
PRIDE; P98149; -.
EnsemblMetazoa; FBtr0081008; FBpp0080561; FBgn0011274.
EnsemblMetazoa; FBtr0081009; FBpp0080562; FBgn0011274.
EnsemblMetazoa; FBtr0301578; FBpp0290793; FBgn0011274.
GeneID; 35045; -.
KEGG; dme:Dmel_CG6794; -.
CTD; 35045; -.
FlyBase; FBgn0011274; Dif.
eggNOG; ENOG410KBSN; Eukaryota.
eggNOG; ENOG4110MZ9; LUCA.
GeneTree; ENSGT00500000044765; -.
InParanoid; P98149; -.
KO; K09254; -.
OrthoDB; EOG091G07RW; -.
PhylomeDB; P98149; -.
Reactome; R-DME-1169091; Activation of NF-kappaB in B cells.
Reactome; R-DME-1810476; RIP-mediated NFkB activation via ZBP1.
Reactome; R-DME-202424; Downstream TCR signaling.
Reactome; R-DME-209400; Transcriptional activtion by phosphorylated DL/DIF dimer.
Reactome; R-DME-209406; Degradation of NF-kappa-B inhibitor, CACT.
Reactome; R-DME-209560; NF-kB is activated and signals survival.
Reactome; R-DME-214842; DL and DIF homodimers bind to TUB and phosphorylated PLL in the TL receptor 'signalling complex'.
Reactome; R-DME-214844; DL and DIF homodimers complexed with CACT are all phosphorylated in the TL receptor 'signalling complex'.
Reactome; R-DME-214869; Phosphorylated CACT, DL and DIF homodimers dissociate from the TL receptor 'signalling complex'.
Reactome; R-DME-2871837; FCERI mediated NF-kB activation.
Reactome; R-DME-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
Reactome; R-DME-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
Reactome; R-DME-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
Reactome; R-DME-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-DME-5621575; CD209 (DC-SIGN) signaling.
Reactome; R-DME-5676590; NIK-->noncanonical NF-kB signaling.
Reactome; R-DME-9020702; Interleukin-1 signaling.
Reactome; R-DME-933542; TRAF6 mediated NF-kB activation.
GenomeRNAi; 35045; -.
PRO; PR:P98149; -.
Proteomes; UP000000803; Chromosome 2L.
Bgee; FBgn0011274; -.
ExpressionAtlas; P98149; baseline and differential.
Genevisible; P98149; DM.
GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
GO; GO:0005829; C:cytosol; IBA:GO_Central.
GO; GO:0033256; C:I-kappaB/NF-kappaB complex; IBA:GO_Central.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:FlyBase.
GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
GO; GO:0003677; F:DNA binding; IDA:FlyBase.
GO; GO:0003700; F:DNA binding transcription factor activity; IDA:FlyBase.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IBA:GO_Central.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:FlyBase.
GO; GO:0002781; P:antifungal peptide production; IMP:FlyBase.
GO; GO:0006952; P:defense response; TAS:FlyBase.
GO; GO:0050832; P:defense response to fungus; IMP:FlyBase.
GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:FlyBase.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
GO; GO:0006955; P:immune response; IMP:FlyBase.
GO; GO:0045087; P:innate immune response; TAS:FlyBase.
GO; GO:0035171; P:lamellocyte differentiation; IMP:FlyBase.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
GO; GO:0038061; P:NIK/NF-kappaB signaling; IBA:GO_Central.
GO; GO:0048935; P:peripheral nervous system neuron development; IMP:FlyBase.
GO; GO:0042387; P:plasmatocyte differentiation; IMP:FlyBase.
GO; GO:0006967; P:positive regulation of antifungal peptide biosynthetic process; TAS:FlyBase.
GO; GO:0006964; P:positive regulation of biosynthetic process of antibacterial peptides active against Gram-negative bacteria; IMP:FlyBase.
GO; GO:0010628; P:positive regulation of gene expression; IGI:FlyBase.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
GO; GO:0035206; P:regulation of hemocyte proliferation; IDA:FlyBase.
GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
GO; GO:0009620; P:response to fungus; TAS:FlyBase.
GO; GO:0035070; P:salivary gland histolysis; IMP:FlyBase.
GO; GO:0008063; P:Toll signaling pathway; TAS:FlyBase.
Gene3D; 2.60.40.10; -; 1.
Gene3D; 2.60.40.340; -; 1.
InterPro; IPR011363; Dif.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR014756; Ig_E-set.
InterPro; IPR002909; IPT_dom.
InterPro; IPR000451; NFkB/Dor.
InterPro; IPR008967; p53-like_TF_DNA-bd.
InterPro; IPR030492; RHD_CS.
InterPro; IPR032397; RHD_dimer.
InterPro; IPR011539; RHD_DNA_bind_dom.
InterPro; IPR037059; RHD_DNA_bind_dom_sf.
PANTHER; PTHR24169; PTHR24169; 1.
Pfam; PF16179; RHD_dimer; 1.
Pfam; PF00554; RHD_DNA_bind; 1.
PIRSF; PIRSF001716; Dorsal; 1.
PRINTS; PR00057; NFKBTNSCPFCT.
SMART; SM00429; IPT; 1.
SUPFAM; SSF49417; SSF49417; 1.
SUPFAM; SSF81296; SSF81296; 1.
PROSITE; PS01204; REL_1; 1.
PROSITE; PS50254; REL_2; 1.
1: Evidence at protein level;
Activator; Complete proteome; Cytoplasm; DNA-binding; Nucleus;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 667 Dorsal-related immunity factor Dif.
/FTId=PRO_0000205163.
DOMAIN 78 372 RHD. {ECO:0000255|PROSITE-
ProRule:PRU00265}.
MOTIF 364 368 Nuclear localization signal.
{ECO:0000255}.
COMPBIAS 548 560 Asn-rich.
COMPBIAS 582 622 Gln-rich.
MOD_RES 343 343 Phosphoserine; by PKA. {ECO:0000255}.
MUTAGEN 181 181 G->D: In Dif1; immune response defective.
Reduced survival following infection with
fungi, and reduced levels of Drs
following immune challenge with fungi or
bacteria. No down-regulation of the
serpin Spn27A in response to bacterial
infection. Ectopic bristles form on the
dorsocentral, scutellar and lateral
regions of the notum.
{ECO:0000269|PubMed:12456640,
ECO:0000269|PubMed:18000549,
ECO:0000269|PubMed:21576362}.
CONFLICT 403 403 K -> T (in Ref. 1; AAA28465).
{ECO:0000305}.
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


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