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AKIRN_DROME
ID   AKIRN_DROME             Reviewed;         201 AA.
AC   Q9VS59;
DT   25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 144.
DE   RecName: Full=Akirin {ECO:0000303|PubMed:18066067};
DE   AltName: Full=Protein bhringi {ECO:0000303|PubMed:22396663};
GN   Name=akirin {ECO:0000303|PubMed:18066067, ECO:0000312|FlyBase:FBgn0082598};
GN   Synonyms=bhr {ECO:0000303|PubMed:22396663};
GN   ORFNames=CG8580 {ECO:0000312|FlyBase:FBgn0082598};
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] {ECO:0000312|EMBL:AAF50569.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAF50569.1};
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|EMBL:AAF50569.1}
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAF50569.1};
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:AAM12282.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAM12282.1};
RC   TISSUE=Embryo {ECO:0000269|PubMed:12537569};
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; SER-41; SER-67; SER-123
RP   AND SER-129, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Embryo {ECO:0000269|PubMed:18327897};
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   [5] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18066067; DOI=10.1038/ni1543;
RA   Goto A., Matsushita K., Gesellchen V., El Chamy L., Kuttenkeuler D.,
RA   Takeuchi O., Hoffmann J.A., Akira S., Boutros M., Reichhart J.-M.;
RT   "Akirins are highly conserved nuclear proteins required for NF-kappaB-
RT   dependent gene expression in Drosophila and mice.";
RL   Nat. Immunol. 9:97-104(2008).
RN   [6]
RP   ERRATUM OF PUBMED:18066067.
RA   Goto A., Matsushita K., Gesellchen V., El Chamy L., Kuttenkeuler D.,
RA   Takeuchi O., Hoffmann J.A., Akira S., Boutros M., Reichhart J.-M.;
RL   Nat. Immunol. 9:216-216(2008).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP   TWI.
RX   PubMed=22396663; DOI=10.1371/journal.pgen.1002547;
RA   Nowak S.J., Aihara H., Gonzalez K., Nibu Y., Baylies M.K.;
RT   "Akirin links twist-regulated transcription with the Brahma chromatin
RT   remodeling complex during embryogenesis.";
RL   PLoS Genet. 8:e1002547-e1002547(2012).
RN   [8]
RP   INTERACTION WITH BAP60; BAP55 AND REL, TISSUE SPECIFICITY, SUBCELLULAR
RP   LOCATION, AND FUNCTION.
RX   PubMed=25180232; DOI=10.15252/embj.201488456;
RA   Bonnay F., Nguyen X.H., Cohen-Berros E., Troxler L., Batsche E.,
RA   Camonis J., Takeuchi O., Reichhart J.M., Matt N.;
RT   "Akirin specifies NF-kappaB selectivity of Drosophila innate immune
RT   response via chromatin remodeling.";
RL   EMBO J. 33:2349-2362(2014).
RN   [9]
RP   INTERACTION WITH DMAP1.
RX   PubMed=24947515; DOI=10.1074/jbc.c114.553719;
RA   Goto A., Fukuyama H., Imler J.L., Hoffmann J.A.;
RT   "The chromatin regulator DMAP1 modulates activity of the nuclear factor B
RT   (NF-B) transcription factor Relish in the Drosophila innate immune
RT   response.";
RL   J. Biol. Chem. 289:20470-20476(2014).
RN   [10]
RP   UBIQUITINATION BY HYD, FUNCTION, AND INTERACTION WITH REL.
RX   PubMed=32339205; DOI=10.1371/journal.ppat.1008458;
RA   Cammarata-Mouchtouris A., Nguyen X.H., Acker A., Bonnay F., Goto A.,
RA   Orian A., Fauvarque M.O., Boutros M., Reichhart J.M., Matt N.;
RT   "Hyd ubiquitinates the NF-kappaB co-factor Akirin to operate an effective
RT   immune response in Drosophila.";
RL   PLoS Pathog. 16:e1008458-e1008458(2020).
RN   [11]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=32950464; DOI=10.1016/j.ydbio.2020.09.001;
RA   Howard A.M., Milner H., Hupp M., Willett C., Palermino K., Nowak S.J.;
RT   "Akirin is critical for early tinman induction and subsequent formation of
RT   the heart in Drosophila melanogaster.";
RL   Dev. Biol. 469:1-11(2021).
CC   -!- FUNCTION: Molecular adapter that acts as a bridge between a variety of
CC       multiprotein complexes, and which is required for embryonic development
CC       and for normal innate immune response (PubMed:18066067,
CC       PubMed:22396663, PubMed:25180232, PubMed:32950464). Acts as a regulator
CC       of embryonic myogenesis by bridging Twist (twi) with the SWI/SNF-like
CC       Brahma complex, promoting expression of twi-regulated genes during
CC       myogenesis (PubMed:22396663). Effector of immune deficiency pathway
CC       (Imd) by acting either downstream of, or at the level of, the NF-kappa-
CC       B factor Relish (Rel) (PubMed:18066067, PubMed:25180232,
CC       PubMed:32950464). Acts by bridging the NF-kappa-B factor Rel and the
CC       Brahma complex through bap60 interaction, leading to activation a
CC       subset of NF-kappa-B factor Relish (Rel) effector genes
CC       (PubMed:25180232). Not part of the Toll pathway (PubMed:18066067).
CC       Required for the formation of the heart by promoting expression ot
CC       tinman (tin) (PubMed:32950464). {ECO:0000269|PubMed:18066067,
CC       ECO:0000269|PubMed:22396663, ECO:0000269|PubMed:25180232,
CC       ECO:0000269|PubMed:32950464}.
CC   -!- SUBUNIT: Interacts with dmap1 (PubMed:24947515). Interacts with bap60
CC       and rel; interaction is immune stimulation-dependent; activates
CC       selected rel target gene promoters (PubMed:25180232, PubMed:32950464).
CC       Interacts with bap55; interaction is immune stimulation-dependent
CC       (PubMed:25180232). Interacts with twi (PubMed:22396663).
CC       {ECO:0000269|PubMed:22396663, ECO:0000269|PubMed:24947515,
CC       ECO:0000269|PubMed:25180232, ECO:0000269|PubMed:32950464}.
CC   -!- INTERACTION:
CC       Q9VS59; Q9VYG2: Bap60; NbExp=4; IntAct=EBI-96644, EBI-75169;
CC       Q9VS59; Q94527: Rel; NbExp=4; IntAct=EBI-96644, EBI-869024;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18066067,
CC       ECO:0000269|PubMed:22396663, ECO:0000269|PubMed:25180232}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:25180232}.
CC   -!- PTM: Polyubiquitinated via 'Lys-63'-linked ubiquitin by Hyd, promoting
CC       interaction with rel. {ECO:0000269|PubMed:32950464}.
CC   -!- DISRUPTION PHENOTYPE: Homozygous embryonic lethal; early to mid
CC       embryonic stages (PubMed:18066067). Embryos display a range of somatic
CC       body wall muscle defects (PubMed:22396663). Embryos show morphological
CC       defects in the heart, such as abnormal spacing between rows of aortic
CC       cells and abnormal patterning of the aortic outflow tract
CC       (PubMed:32950464). {ECO:0000269|PubMed:18066067,
CC       ECO:0000269|PubMed:22396663, ECO:0000269|PubMed:32950464}.
CC   -!- MISCELLANEOUS: 'Akiraka ni suru' means 'making things clear' in
CC       Japanese. The name is given based on the presence of the clear nuclear
CC       localization signal.
CC   -!- SIMILARITY: Belongs to the akirin family.
CC       {ECO:0000305|PubMed:18066067}.
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DR   EMBL; AE014296; AAF50569.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12062.1; -; Genomic_DNA.
DR   EMBL; AY095189; AAM12282.1; -; mRNA.
DR   RefSeq; NP_001189058.1; NM_001202129.2.
DR   RefSeq; NP_001189059.1; NM_001202130.2.
DR   RefSeq; NP_001189060.1; NM_001202131.2.
DR   RefSeq; NP_001261511.1; NM_001274582.1.
DR   RefSeq; NP_648113.1; NM_139856.4.
DR   RefSeq; NP_729249.1; NM_168211.3.
DR   AlphaFoldDB; Q9VS59; -.
DR   SMR; Q9VS59; -.
DR   BioGRID; 64261; 31.
DR   IntAct; Q9VS59; 32.
DR   MINT; Q9VS59; -.
DR   STRING; 7227.FBpp0076560; -.
DR   iPTMnet; Q9VS59; -.
DR   PaxDb; Q9VS59; -.
DR   DNASU; 38821; -.
DR   EnsemblMetazoa; FBtr0076848; FBpp0076559; FBgn0082598.
DR   EnsemblMetazoa; FBtr0076849; FBpp0076560; FBgn0082598.
DR   EnsemblMetazoa; FBtr0302543; FBpp0291699; FBgn0082598.
DR   EnsemblMetazoa; FBtr0302544; FBpp0291700; FBgn0082598.
DR   EnsemblMetazoa; FBtr0302545; FBpp0291701; FBgn0082598.
DR   EnsemblMetazoa; FBtr0332730; FBpp0304976; FBgn0082598.
DR   GeneID; 38821; -.
DR   KEGG; dme:Dmel_CG8580; -.
DR   UCSC; CG8580-RA; d. melanogaster.
DR   CTD; 38821; -.
DR   FlyBase; FBgn0082598; akirin.
DR   VEuPathDB; VectorBase:FBgn0082598; -.
DR   eggNOG; KOG4330; Eukaryota.
DR   GeneTree; ENSGT00940000174557; -.
DR   HOGENOM; CLU_119227_0_0_1; -.
DR   InParanoid; Q9VS59; -.
DR   OMA; RRCAPIM; -.
DR   OrthoDB; 1420469at2759; -.
DR   PhylomeDB; Q9VS59; -.
DR   SignaLink; Q9VS59; -.
DR   BioGRID-ORCS; 38821; 1 hit in 3 CRISPR screens.
DR   ChiTaRS; akirin; fly.
DR   GenomeRNAi; 38821; -.
DR   PRO; PR:Q9VS59; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0082598; Expressed in eye disc (Drosophila) and 23 other tissues.
DR   ExpressionAtlas; Q9VS59; baseline and differential.
DR   Genevisible; Q9VS59; DM.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0000791; C:euchromatin; IDA:FlyBase.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0005700; C:polytene chromosome; IDA:FlyBase.
DR   GO; GO:0003712; F:transcription coregulator activity; IGI:FlyBase.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:FlyBase.
DR   GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0007526; P:larval somatic muscle development; IMP:FlyBase.
DR   GO; GO:0045089; P:positive regulation of innate immune response; IMP:FlyBase.
DR   GO; GO:0061059; P:positive regulation of peptidoglycan recognition protein signaling pathway; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0045088; P:regulation of innate immune response; IMP:FlyBase.
DR   InterPro; IPR024132; Akirin.
DR   PANTHER; PTHR13293; PTHR13293; 1.
PE   1: Evidence at protein level;
KW   Developmental protein; Immunity; Innate immunity; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   CHAIN           1..201
FT                   /note="Akirin"
FT                   /id="PRO_0000355123"
FT   REGION          1..133
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           20..25
FT                   /note="Nuclear localization signal"
FT   COMPBIAS        32..74
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        103..119
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         39
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         41
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         67
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         123
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         129
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
SQ   SEQUENCE   201 AA;  22705 MW;  442BB98BCBD81529 CRC64;
     MACATLKRAL DWESMNQRPP KRRRCNPFGQ AGSNAGPASP SRDGPSTSAG LPHTPSNRFA
     KDSTEPSPFS ESSLAKMSPD KMAESLCNEI KRLHKRKQLP ITSSALERMQ DSESSGSEMG
     PESPRRPDSP QNLMRHGEKA LFTFKQVQLI CESMIKEREN QLRERYESVL TTKLAEQYDA
     FVKFTYDQIQ RRYEAAPSYL S
 
 
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