ELP3_DANRE
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 03-AUG-2022, entry version 121.
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 + carboxymethyluridine(34) in tRNA + CoA + 2
CC 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; Q5RIC0; -.
DR Ensembl; ENSDART00000138226; ENSDARP00000113240; ENSDARG00000042005. [Q5RIC0-2]
DR Ensembl; ENSDART00000152836; ENSDARP00000127220; ENSDARG00000042005. [Q5RIC0-3]
DR GeneID; 541509; -.
DR KEGG; dre:541509; -.
DR CTD; 55140; -.
DR ZFIN; ZDB-GENE-050327-35; elp3.
DR eggNOG; KOG2535; Eukaryota.
DR GeneTree; ENSGT00390000013141; -.
DR HOGENOM; CLU_025983_2_1_1; -.
DR InParanoid; Q5RIC0; -.
DR OMA; TFETRPD; -.
DR PhylomeDB; Q5RIC0; -.
DR TreeFam; TF105752; -.
DR UniPathway; UPA00988; -.
DR PRO; PR:Q5RIC0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000042005; Expressed in mature ovarian follicle and 20 other 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:0008080; F:N-acetyltransferase activity; IEA:InterPro.
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 InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR039661; ELP3.
DR InterPro; IPR034687; ELP3-like.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR032432; Radical_SAM_C.
DR InterPro; IPR007197; rSAM.
DR PANTHER; PTHR11135; PTHR11135; 1.
DR PANTHER; PTHR11135:SF0; PTHR11135:SF0; 1.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR Pfam; PF16199; Radical_SAM_C; 1.
DR PIRSF; PIRSF005669; Hist_AcTrfase_ELP3; 1.
DR SFLD; SFLDF00344; ELP3-like; 1.
DR SMART; SM00729; Elp3; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR TIGRFAMs; TIGR01211; ELP3; 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
