ID   ELP3_DANRE              Reviewed;         548 AA.
AC   Q5RIC0; Q4V9M7; Q58ER7;
DT   17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   12-JUN-2007, sequence version 3.
DT   27-MAR-2024, entry version 129.
DE   RecName: Full=Elongator complex protein 3 {ECO:0000250|UniProtKB:Q9H9T3};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:D5VRB9};
DE   AltName: Full=tRNA uridine(34) acetyltransferase {ECO:0000305};
GN   Name=elp3 {ECO:0000250|UniProtKB:Q9H9T3};
GN   ORFNames=si:ch211-63o20.8, zgc:113140;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Embryo;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18996918; DOI=10.1093/hmg/ddn375;
RA   Simpson C.L., Lemmens R., Miskiewicz K., Broom W.J., Hansen V.K.,
RA   van Vught P.W., Landers J.E., Sapp P., Van Den Bosch L., Knight J.,
RA   Neale B.M., Turner M.R., Veldink J.H., Ophoff R.A., Tripathi V.B.,
RA   Beleza A., Shah M.N., Proitsi P., Van Hoecke A., Carmeliet P.,
RA   Horvitz H.R., Leigh P.N., Shaw C.E., van den Berg L.H., Sham P.C.,
RA   Powell J.F., Verstreken P., Brown R.H. Jr., Robberecht W., Al-Chalabi A.;
RT   "Variants of the elongator protein 3 (ELP3) gene are associated with motor
RT   neuron degeneration.";
RL   Hum. Mol. Genet. 18:472-481(2009).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=32023806; DOI=10.3390/ijms21030925;
RA   Rojas-Benitez D., Allende M.L.;
RT   "Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development.";
RL   Int. J. Mol. Sci. 21:0-0(2020).
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). Involved in neurogenesis (PubMed:18996918). Involved in
CC       somite development (PubMed:32023806). {ECO:0000250|UniProtKB:D5VRB9,
CC       ECO:0000250|UniProtKB:Q9H9T3, ECO:0000269|PubMed:18996918,
CC       ECO:0000269|PubMed:32023806}.
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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H9T3}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9H9T3}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q5RIC0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5RIC0-2; Sequence=VSP_026084;
CC       Name=3;
CC         IsoId=Q5RIC0-3; Sequence=VSP_026085;
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown in embryos results in
CC       reduced tRNA modification with decreased levels of mcm5s2U (5-
CC       methoxycarbonylmethyl-2-thiouridine) (PubMed:32023806). Morphant larvae
CC       display a ventrally curved body where somites present a distortion of
CC       their typical chevron shape, being rounded with a different angle
CC       compared to controls (PubMed:32023806). Morphants also show disruption
CC       of the horizontal myoseptum, diminished somite area, disorganised
CC       muscle fibers, a small neural tube and reduced Shh signaling activity
CC       (PubMed:32023806). One study has shown that morpholino knockdown in
CC       embryos at 27 hpf results in abnormal motor neuron axonal branching and
CC       length (PubMed:18996918). However, another study observed shortening in
CC       only 5% of motor neurons at 27 hpf and normal length by 48 hpf
CC       (PubMed:32023806). {ECO:0000269|PubMed:18996918,
CC       ECO:0000269|PubMed:32023806}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAI12039.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; BX279523; CAI12039.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC091787; AAH91787.1; -; mRNA.
DR   EMBL; BC096810; AAH96810.1; -; mRNA.
DR   RefSeq; NP_001014344.2; NM_001014322.2. [Q5RIC0-1]
DR   AlphaFoldDB; Q5RIC0; -.
DR   SMR; Q5RIC0; -.
DR   STRING; 7955.ENSDARP00000113240; -.
DR   PaxDb; 7955-ENSDARP00000113240; -.
DR   GeneID; 541509; -.
DR   KEGG; dre:541509; -.
DR   AGR; ZFIN:ZDB-GENE-050327-35; -.
DR   CTD; 55140; -.
DR   ZFIN; ZDB-GENE-050327-35; elp3.
DR   eggNOG; KOG2535; Eukaryota.
DR   HOGENOM; CLU_025983_2_1_1; -.
DR   InParanoid; Q5RIC0; -.
DR   OMA; TFETRPD; -.
DR   OrthoDB; 46095at2759; -.
DR   PhylomeDB; Q5RIC0; -.
DR   TreeFam; TF105752; -.
DR   UniPathway; UPA00988; -.
DR   PRO; PR:Q5RIC0; -.
DR   Proteomes; UP000000437; Chromosome 20.
DR   Bgee; ENSDARG00000042005; Expressed in mature ovarian follicle and 20 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0033588; C:elongator holoenzyme complex; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
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:0106261; F:tRNA uridine(34) acetyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0007409; P:axonogenesis; IMP:ZFIN.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0061053; P:somite development; IMP:ZFIN.
DR   GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; IBA:GO_Central.
DR   GO; GO:0002098; P:tRNA wobble uridine modification; ISS:UniProtKB.
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.
PE   2: Evidence at transcript level;
KW   4Fe-4S; Acyltransferase; Alternative splicing; Cytoplasm; Iron;
KW   Iron-sulfur; Metal-binding; Neurogenesis; Nucleus; Reference proteome;
KW   RNA-binding; S-adenosyl-L-methionine; Transferase; tRNA processing;
KW   tRNA-binding.
FT   CHAIN           1..548
FT                   /note="Elongator complex protein 3"
FT                   /id="PRO_0000283989"
FT   DOMAIN          83..373
FT                   /note="Radical SAM core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT   DOMAIN          397..548
FT                   /note="N-acetyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT   BINDING         100
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         110
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         113
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         165
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         475..478
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         498..500
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   BINDING         531
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT   VAR_SEQ         1..93
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_026085"
FT   VAR_SEQ         1..15
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_026084"
FT   CONFLICT        263
FT                   /note="H -> Y (in Ref. 2; AAH91787)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   548 AA;  62259 MW;  8761FBFC0FE684DE CRC64;
     MGKPKKKSDL SRAELMMMTI ADVIKQLVEA HEEGKDINLN KVKTKTSAKY GLSAQPRLVD
     IIAAVPPHYR RALVPKLKAK PIRTASGIAV VAVMCKPHRC PHISFTGNIC VYCPGGPDSD
     FEYSTQSYTG YEPTSMRAIR ARYDPYLQTR HRVEQLKQLG HSVDKVEFIV MGGTFMALPE
     EYRDYFIRNL HDALSGHTSN NVTEAVRYSE RSNTKCVGIT IETRPDYCLK RHLSDMLGYG
     CTRLEIGVQS VYEDVARDTN RGHTVRAVCE SFHLAKDAGF KVVAHMMPDL PNVGMERDVE
     QFIEFFENPA FRPDGLKLYP TLVIRGTGLY ELWKTGRYKS YSPSALVDLV ARILALVPPW
     TRVYRVQRDI PMPLVSSGVE HGNLRELALA RMKDMGTECR DVRTREVGIQ EIHHKVRPYQ
     VELIRRDYVA NGGWETFLSY EDPEQDILIG LLRLRRCSPQ SFRPELKGGV SIVRELHVYG
     SVVPVSSRDP SKFQHQGFGM MLMEEAERIA RDEHGSSKLA VISGVGTRNY YRKMGYELEG
     PYMVKNLY
//