ELP3_MOUSE
ID ELP3_MOUSE Reviewed; 547 AA.
AC Q9CZX0; Q8C2K2; Q8R369;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Elongator complex protein 3 {ECO:0000303|PubMed:19185337};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:D5VRB9};
DE AltName: Full=tRNA uridine(34) acetyltransferase {ECO:0000305};
GN Name=Elp3 {ECO:0000303|PubMed:19185337, ECO:0000312|MGI:MGI:1921445};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION IN NEUROGENESIS, AND SUBCELLULAR LOCATION.
RX PubMed=19185337; DOI=10.1016/j.cell.2008.11.043;
RA Creppe C., Malinouskaya L., Volvert M.L., Gillard M., Close P., Malaise O.,
RA Laguesse S., Cornez I., Rahmouni S., Ormenese S., Belachew S.,
RA Malgrange B., Chapelle J.P., Siebenlist U., Moonen G., Chariot A.,
RA Nguyen L.;
RT "Elongator controls the migration and differentiation of cortical neurons
RT through acetylation of alpha-tubulin.";
RL Cell 136:551-564(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=22854966; DOI=10.1074/jbc.m112.402727;
RA Close P., Gillard M., Ladang A., Jiang Z., Papuga J., Hawkes N., Nguyen L.,
RA Chapelle J.P., Bouillenne F., Svejstrup J., Fillet M., Chariot A.;
RT "DERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of
RT melanoma cells as subunits of Elongator.";
RL J. Biol. Chem. 287:32535-32545(2012).
RN [6]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=27476491; DOI=10.1016/j.bbrc.2016.07.120;
RA Yoo H., Son D., Jang Y.J., Hong K.;
RT "Indispensable role for mouse ELP3 in embryonic stem cell maintenance and
RT early development.";
RL Biochem. Biophys. Res. Commun. 478:631-636(2016).
RN [7]
RP FUNCTION.
RX PubMed=28507509; DOI=10.3389/fncel.2017.00122;
RA Laguesse S., Close P., Van Hees L., Chariot A., Malgrange B., Nguyen L.;
RT "Loss of Elp3 impairs the acetylation and distribution of connexin-43 in
RT the developing cerebral cortex.";
RL Front. Cell. Neurosci. 11:122-122(2017).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=29415125; DOI=10.1093/hmg/ddy043;
RA Bento-Abreu A., Jager G., Swinnen B., Rue L., Hendrickx S., Jones A.,
RA Staats K.A., Taes I., Eykens C., Nonneman A., Nuyts R., Timmers M.,
RA Silva L., Chariot A., Nguyen L., Ravits J., Lemmens R., Cabooter D.,
RA Van Den Bosch L., Van Damme P., Al-Chalabi A., Bystrom A., Robberecht W.;
RT "Elongator subunit 3 (ELP3) modifies ALS through tRNA modification.";
RL Hum. Mol. Genet. 27:1276-1289(2018).
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). May also act as a protein lysine acetyltransferase by
CC mediating acetylation of target proteins; such activity is however
CC unclear in vivo and recent evidences suggest that ELP3 primarily acts
CC as a tRNA acetyltransferase (By similarity). Involved in neurogenesis:
CC regulates the migration and branching of projection neurons in the
CC developing cerebral cortex, through a process depending on alpha-
CC tubulin acetylation (PubMed:19185337). Required for acetylation of GJA1
CC in the developing cerebral cortex (PubMed:28507509).
CC {ECO:0000250|UniProtKB:D5VRB9, ECO:0000250|UniProtKB:Q9H9T3,
CC ECO:0000269|PubMed:19185337, ECO:0000269|PubMed:22854966,
CC ECO:0000269|PubMed:28507509}.
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 which consists of ELP1,
CC ELP2, ELP3, ELP4, ELP5 and ELP6. ELP1, ELP2 and ELP3 form the elongator
CC core complex. Interacts with alpha-tubulin.
CC {ECO:0000250|UniProtKB:Q9H9T3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19185337}. Nucleus
CC {ECO:0000250|UniProtKB:Q9H9T3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CZX0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CZX0-2; Sequence=VSP_024408;
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in blastocysts and 10.5 dpc
CC embryos (PubMed:27476491). Expression increases during embryonic stem
CC cell maintenance differentiation (PubMed:27476491).
CC {ECO:0000269|PubMed:27476491}.
CC -!- PTM: Tyrosine-phosphorylated. Also serine/threonine-phosphorylated.
CC {ECO:0000250|UniProtKB:Q9H9T3}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality by 12.5 dpc caused by severe
CC growth retardation (PubMed:27476491, PubMed:29415125). Conditional
CC deletion in adults is also lethal (PubMed:29415125).
CC {ECO:0000269|PubMed:27476491, ECO:0000269|PubMed:29415125}.
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 -!- CAUTION: The relevance of the protein lysine acetyltransferase activity
CC is unclear (By similarity). The publication reporting acetylation of
CC GJA1 does not provide direct evidence of lysine acetyltransferase
CC activity of ELP3 (PubMed:28507509). {ECO:0000250|UniProtKB:Q9H9T3,
CC ECO:0000269|PubMed:28507509}.
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DR EMBL; AK012072; BAB28009.1; -; mRNA.
DR EMBL; AK088457; BAC40364.1; -; mRNA.
DR EMBL; BC026461; AAH26461.1; -; mRNA.
DR EMBL; BC057453; AAH57453.1; -; mRNA.
DR CCDS; CCDS56965.1; -. [Q9CZX0-2]
DR CCDS; CCDS88691.1; -. [Q9CZX0-1]
DR RefSeq; NP_001240741.1; NM_001253812.1. [Q9CZX0-2]
DR RefSeq; NP_083087.1; NM_028811.3. [Q9CZX0-1]
DR AlphaFoldDB; Q9CZX0; -.
DR SMR; Q9CZX0; -.
DR BioGRID; 216566; 24.
DR IntAct; Q9CZX0; 2.
DR STRING; 10090.ENSMUSP00000022609; -.
DR iPTMnet; Q9CZX0; -.
DR PhosphoSitePlus; Q9CZX0; -.
DR SwissPalm; Q9CZX0; -.
DR EPD; Q9CZX0; -.
DR MaxQB; Q9CZX0; -.
DR PaxDb; Q9CZX0; -.
DR PeptideAtlas; Q9CZX0; -.
DR PRIDE; Q9CZX0; -.
DR ProteomicsDB; 275746; -. [Q9CZX0-1]
DR ProteomicsDB; 275747; -. [Q9CZX0-2]
DR Antibodypedia; 23089; 229 antibodies from 31 providers.
DR DNASU; 74195; -.
DR Ensembl; ENSMUST00000022609; ENSMUSP00000022609; ENSMUSG00000022031. [Q9CZX0-2]
DR Ensembl; ENSMUST00000225355; ENSMUSP00000153462; ENSMUSG00000022031. [Q9CZX0-1]
DR GeneID; 74195; -.
DR KEGG; mmu:74195; -.
DR UCSC; uc007ujk.2; mouse. [Q9CZX0-1]
DR UCSC; uc007ujl.2; mouse. [Q9CZX0-2]
DR CTD; 55140; -.
DR MGI; MGI:1921445; Elp3.
DR VEuPathDB; HostDB:ENSMUSG00000022031; -.
DR eggNOG; KOG2535; Eukaryota.
DR GeneTree; ENSGT00390000013141; -.
DR HOGENOM; CLU_025983_2_1_1; -.
DR InParanoid; Q9CZX0; -.
DR OMA; TFETRPD; -.
DR OrthoDB; 320059at2759; -.
DR PhylomeDB; Q9CZX0; -.
DR TreeFam; TF105752; -.
DR UniPathway; UPA00988; -.
DR BioGRID-ORCS; 74195; 18 hits in 78 CRISPR screens.
DR ChiTaRS; Elp3; mouse.
DR PRO; PR:Q9CZX0; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9CZX0; protein.
DR Bgee; ENSMUSG00000022031; Expressed in cortical plate and 264 other tissues.
DR ExpressionAtlas; Q9CZX0; baseline and differential.
DR Genevisible; Q9CZX0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0033588; C:elongator holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
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:0016407; F:acetyltransferase activity; ISO:MGI.
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:0007417; P:central nervous system development; IMP:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
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 1: Evidence at protein level;
KW 4Fe-4S; Acyltransferase; Alternative splicing; Cytoplasm; Iron;
KW Iron-sulfur; Metal-binding; Methylation; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; S-adenosyl-L-methionine;
KW Transferase; tRNA processing; tRNA-binding.
FT CHAIN 1..547
FT /note="Elongator complex protein 3"
FT /id="PRO_0000283987"
FT DOMAIN 82..372
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT DOMAIN 396..547
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 99
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 109
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 112
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 164
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT BINDING 474..477
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT BINDING 497..499
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT BINDING 530
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:A0A1C7D1B7"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H9T3"
FT MOD_RES 251
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9H9T3"
FT VAR_SEQ 7
FT /note="G -> GAKYVGQGRKGGSGFSEITG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_024408"
SQ SEQUENCE 547 AA; 62385 MW; 9234BB4DDD145FF4 CRC64;
MRQKRKGDLS PAELMMLTIG DVIKQLVEAH EQGKDVDLNK MKTKTAAKYG LASQPRLVDI
IAAVPPHYRK ILIPKLKAKP VRTASGIAVV AVMCKPHRCP HISFTGNICI YCPGGPDSDF
EYSTQSYTGY EPTSMRAIRA RYDPFLQTRH RIEQLKQLGH SVDKVEFIVM GGTFMALPEE
YRDYFIRSLH DALSGHTSNN IHEAIKYSER SFTKCVGITI ETRPDYCMKR HLSDMLTYGC
TRLEIGVQSV YEDVARDTNR GHTVKAACES FHLAKDSGFK VVTHMMPDLP NVGLERDIEQ
FIEFFENPAF RPDGLKLYPT LVIRGTGLYE LWKSGRYRSY SPSDLIELVA RILALVPPWT
RVYRVQRDIP MPLVSSGVEH GNLRELAFAR MKDLGIQCRD VRTREVGIQE IHHRVRPYQV
ELVRRDYVAN GGWETFLSYE DPDQDILIGL LRLRKCSEET FRFELGGGVS IVRELHVYGS
VVPVSSRDPT KFQHQGFGML LMEEAERIAR EEHGSGKMAV ISGVGTRNYY RKIGYRLQGP
YMVKMLK
