ID   ELP3_DROME              Reviewed;         552 AA.
AC   Q9VQZ6;
DT   17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 163.
DE   RecName: Full=Elongator complex protein 3 {ECO:0000305};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:D5VRB9};
DE   AltName: Full=tRNA uridine(34) acetyltransferase {ECO:0000305};
GN   Name=Elp3; ORFNames=CG15433;
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 [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   [2]
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   [3]
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   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20626565; DOI=10.1111/j.1471-4159.2010.06892.x;
RA   Singh N., Lorbeck M.T., Zervos A., Zimmerman J., Elefant F.;
RT   "The histone acetyltransferase Elp3 plays in active role in the control of
RT   synaptic bouton expansion and sleep in Drosophila.";
RL   J. Neurochem. 115:493-504(2010).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-531.
RX   PubMed=21288872; DOI=10.1534/genetics.110.123893;
RA   Walker J., Kwon S.Y., Badenhorst P., East P., McNeill H., Svejstrup J.Q.;
RT   "Role of elongator subunit Elp3 in Drosophila melanogaster larval
RT   development and immunity.";
RL   Genetics 187:1067-1075(2011).
CC   -!- FUNCTION: Catalytic tRNA acetyltransferase subunit of the elongator
CC       complex which is required for multiple tRNA modifications, including
CC       mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-
CC       methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl
CC       uridine) (By similarity). In the elongator complex, acts as a tRNA
CC       uridine(34) acetyltransferase by mediating formation of
CC       carboxymethyluridine in the wobble base at position 34 in tRNAs (By
CC       similarity). Plays a role in the control of synaptic bouton expansion
CC       (PubMed:20626565). Required for larval development (PubMed:21288872).
CC       {ECO:0000250|UniProtKB:D5VRB9, ECO:0000250|UniProtKB:Q9H9T3,
CC       ECO:0000269|PubMed:20626565, ECO:0000269|PubMed:21288872}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + H2O + S-adenosyl-L-methionine + uridine(34) in
CC         tRNA = 5'-deoxyadenosine + 5-(carboxymethyl)uridine(34) in tRNA + CoA
CC         + 2 H(+) + L-methionine; Xref=Rhea:RHEA:61020, Rhea:RHEA-COMP:10407,
CC         Rhea:RHEA-COMP:11727, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17319, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:57844, ChEBI:CHEBI:59789, ChEBI:CHEBI:65315,
CC         ChEBI:CHEBI:74882; Evidence={ECO:0000250|UniProtKB:D5VRB9};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61021;
CC         Evidence={ECO:0000250|UniProtKB:D5VRB9};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250|UniProtKB:Q02908};
CC       Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC       cysteines and an exchangeable S-adenosyl-L-methionine.
CC       {ECO:0000250|UniProtKB:Q02908};
CC   -!- PATHWAY: tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA
CC       biosynthesis. {ECO:0000250|UniProtKB:Q9H9T3}.
CC   -!- SUBUNIT: Component of the elongator complex.
CC       {ECO:0000250|UniProtKB:Q9H9T3}.
CC   -!- DISRUPTION PHENOTYPE: Pronounced larval developmental delay and death
CC       at the pupal stage with delayed and reduced ecdysone-induced
CC       transcription, developmental of melanotic nodules and up-regulation of
CC       stress-induced genes (PubMed:21288872). RNAi-mediated knockdown results
CC       in lethality at the late pupal stage (PubMed:20626565). RNAi-mediated
CC       knockdown in the central nervous system results in a hyperactive
CC       phenotype, sleep loss in adult females, a significant expansion in
CC       synaptic bouton number in the larval neuromuscular junction (NMJ),
CC       increased larval NMJ axonal length and branching, and misregulation of
CC       genes known to be involved in these processes with a marked increase in
CC       Hsc70-3 and Syb mRNA levels and a marked decrease in qvr/sss mRNA
CC       levels (PubMed:20626565). RNAi-mediated knockdown in hemocytes results
CC       in reduced hemocyte numbers and hemocyte aggregation (PubMed:21288872).
CC       {ECO:0000269|PubMed:20626565, ECO:0000269|PubMed:21288872}.
CC   -!- SIMILARITY: Belongs to the ELP3 family. {ECO:0000305}.
CC   -!- CAUTION: The elongator complex was originally thought to play a role in
CC       transcription elongation. However, it is no longer thought to play a
CC       direct role in this process and its primary function is thought to be
CC       in tRNA modification. {ECO:0000250|UniProtKB:Q9H9T3}.
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DR   EMBL; AE014134; AAF51012.1; -; Genomic_DNA.
DR   EMBL; AY089621; AAL90359.1; -; mRNA.
DR   RefSeq; NP_608834.1; NM_134990.3.
DR   AlphaFoldDB; Q9VQZ6; -.
DR   SMR; Q9VQZ6; -.
DR   BioGRID; 59843; 6.
DR   IntAct; Q9VQZ6; 1.
DR   STRING; 7227.FBpp0077129; -.
DR   PaxDb; 7227-FBpp0077129; -.
DR   DNASU; 33649; -.
DR   EnsemblMetazoa; FBtr0077439; FBpp0077129; FBgn0031604.
DR   GeneID; 33649; -.
DR   KEGG; dme:Dmel_CG15433; -.
DR   UCSC; CG15433-RA; d. melanogaster.
DR   AGR; FB:FBgn0031604; -.
DR   CTD; 55140; -.
DR   FlyBase; FBgn0031604; Elp3.
DR   VEuPathDB; VectorBase:FBgn0031604; -.
DR   eggNOG; KOG2535; Eukaryota.
DR   GeneTree; ENSGT00390000013141; -.
DR   HOGENOM; CLU_025983_2_1_1; -.
DR   InParanoid; Q9VQZ6; -.
DR   OMA; TFETRPD; -.
DR   OrthoDB; 46095at2759; -.
DR   PhylomeDB; Q9VQZ6; -.
DR   BRENDA; 2.3.1.48; 1994.
DR   SignaLink; Q9VQZ6; -.
DR   UniPathway; UPA00988; -.
DR   BioGRID-ORCS; 33649; 1 hit in 1 CRISPR screen.
DR   GenomeRNAi; 33649; -.
DR   PRO; PR:Q9VQZ6; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0031604; Expressed in egg chamber and 46 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR   GO; GO:0033588; C:elongator holoenzyme complex; IDA:FlyBase.
DR   GO; GO:0005634; C:nucleus; ISS:FlyBase.
DR   GO; GO:0045202; C:synapse; IDA:FlyBase.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0016407; F:acetyltransferase activity; IDA:FlyBase.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008607; F:phosphorylase kinase regulator activity; ISS:UniProtKB.
DR   GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0051392; F:tRNA N-acetyltransferase activity; IDA:FlyBase.
DR   GO; GO:0106261; F:tRNA uridine(34) acetyltransferase activity; IEA:RHEA.
DR   GO; GO:0048789; P:cytoskeletal matrix organization at active zone; IMP:FlyBase.
DR   GO; GO:0061867; P:establishment of mitotic spindle asymmetry; IDA:FlyBase.
DR   GO; GO:0030097; P:hemopoiesis; IMP:FlyBase.
DR   GO; GO:0002168; P:instar larval development; IMP:FlyBase.
DR   GO; GO:0007626; P:locomotory behavior; IMP:FlyBase.
DR   GO; GO:0018394; P:peptidyl-lysine acetylation; IDA:FlyBase.
DR   GO; GO:2000289; P:regulation of photoreceptor cell axon guidance; IMP:FlyBase.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0030431; P:sleep; IMP:FlyBase.
DR   GO; GO:0050808; P:synapse organization; IMP:FlyBase.
DR   GO; GO:0051124; P:synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR   GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; IBA:GO_Central.
DR   CDD; cd01335; Radical_SAM; 1.
DR   Gene3D; 3.40.630.30; -; 1.
DR   InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR   InterPro; IPR039661; ELP3.
DR   InterPro; IPR034687; ELP3-like.
DR   InterPro; IPR006638; Elp3/MiaA/NifB-like_rSAM.
DR   InterPro; IPR000182; GNAT_dom.
DR   InterPro; IPR032432; Radical_SAM_C.
DR   InterPro; IPR007197; rSAM.
DR   NCBIfam; TIGR01211; ELP3; 1.
DR   PANTHER; PTHR11135:SF0; ELONGATOR COMPLEX PROTEIN 3; 1.
DR   PANTHER; PTHR11135; HISTONE ACETYLTRANSFERASE-RELATED; 1.
DR   Pfam; PF04055; Radical_SAM; 1.
DR   Pfam; PF16199; Radical_SAM_C; 1.
DR   PIRSF; PIRSF005669; Hist_AcTrfase_ELP3; 1.
DR   SFLD; SFLDG01086; elongater_protein-like; 1.
DR   SFLD; SFLDF00344; ELP3-like; 1.
DR   SMART; SM00729; Elp3; 1.
DR   SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1.
DR   SUPFAM; SSF102114; Radical SAM enzymes; 1.
DR   PROSITE; PS51186; GNAT; 1.
DR   PROSITE; PS51918; RADICAL_SAM; 1.
DR   Genevisible; Q9VQZ6; DM.
PE   1: Evidence at protein level;
KW   4Fe-4S; Acyltransferase; Iron; Iron-sulfur; Metal-binding;
KW   Reference proteome; RNA-binding; S-adenosyl-L-methionine; Transferase;
KW   tRNA processing; tRNA-binding.
FT   CHAIN           1..552
FT                   /note="Elongator complex protein 3"
FT                   /id="PRO_0000283992"
FT   DOMAIN          84..374
FT                   /note="Radical SAM core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT   DOMAIN          398..552
FT                   /note="N-acetyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT   BINDING         101
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_note="4Fe-4S-S-AdoMet"
FT                   /evidence="ECO:0000250|UniProtKB:Q02908"
FT   BINDING         111
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_note="4Fe-4S-S-AdoMet"
FT                   /evidence="ECO:0000250|UniProtKB:Q02908"
FT   BINDING         114
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_note="4Fe-4S-S-AdoMet"
FT                   /evidence="ECO:0000250|UniProtKB:Q02908"
FT   BINDING         166
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         476..479
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         499..501
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         532
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   MUTAGEN         531
FT                   /note="Y->F: Embryonic lethality."
FT                   /evidence="ECO:0000269|PubMed:21288872"
SQ   SEQUENCE   552 AA;  62821 MW;  3CE7D4D46EEE0C1F CRC64;
     MKAKKKLGVG LSRQERQVLV IGEIIQELLK AHEAKKDVNL NRMKSLVASK YGLDSSPRLV
     DIIAAVPQDA KKILLPKLRA KPIRTASGIA VVAVMCKPHR CPHINMTGNI CVYCPGGPDS
     DFEYSTQSYT GYEPTSMRAI RSRYDPFLQT RHRVEQLKQL GHSVDKVEFI VMGGTFMCLP
     EEYRDYFIRN LHDALSGHSS ANVAEAVRYS EKSRTKCIGI TIETRPDYCL KRHISDMLSY
     GCTRLEIGVQ SVYEDVARDT NRGHTVRAVC ESFQLGKDAG YKIVTHMMPD LPNVDFERDI
     EQFIEYFENP AFRSDGLKIY PTLVIRGTGL YELWKTGRYK SYPPSMLVDL VAKILALVPP
     WTRVYRVQRD IPMPLVSSGV EHGNLRELAL ARMKDLGTTC RDVRTREVGI QEIHNKVRPY
     EIELIRRDYV ANGGWETFLS YEDPEQDILV GLLRLRKCSP DTFRPELKGE CSIVRELHVY
     GSVVPVNARD PTKFQHQGFG MLLMEEAERI AREEHGSTKL AVISGVGTRN YYRKMGYQLD
     GPYMSKSIEE NN
//