ELP3_HUMAN
ID ELP3_HUMAN Reviewed; 547 AA.
AC Q9H9T3; B4DE19; B4DIG1; E2QRI5; Q53G84; Q6AWB0; Q9BVF7; Q9NVZ1;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Elongator complex protein 3 {ECO:0000303|PubMed:11714725};
DE Short=hELP3 {ECO:0000303|PubMed:11714725};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:D5VRB9};
DE AltName: Full=tRNA uridine(34) acetyltransferase {ECO:0000305};
GN Name=ELP3 {ECO:0000303|PubMed:15902492, ECO:0000312|HGNC:HGNC:20696};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Amygdala, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Amygdala, and Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-547 (ISOFORM 1).
RC TISSUE=Thyroid;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP IDENTIFICATION IN THE ELONGATOR COMPLEX, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11714725; DOI=10.1074/jbc.m110445200;
RA Hawkes N.A., Otero G., Winkler G.S., Marshall N., Dahmus M.E.,
RA Krappmann D., Scheidereit C., Thomas C.L., Schiavo G.,
RA Erdjument-Bromage H., Tempst P., Svejstrup J.Q.;
RT "Purification and characterization of the human elongator complex.";
RL J. Biol. Chem. 277:3047-3052(2002).
RN [7]
RP IDENTIFICATION IN THE ELONGATOR CORE COMPLEX, INTERACTION WITH ELP1,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11818576; DOI=10.1073/pnas.251672198;
RA Kim J.H., Lane W.S., Reinberg D.;
RT "Human Elongator facilitates RNA polymerase II transcription through
RT chromatin.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1241-1246(2002).
RN [8]
RP DISPUTED FUNCTION IN HISTONE ACETYLATION.
RX PubMed=15902492; DOI=10.1007/s00438-005-1120-2;
RA Li F., Lu J., Han Q., Zhang G., Huang B.;
RT "The Elp3 subunit of human Elongator complex is functionally similar to its
RT counterpart in yeast.";
RL Mol. Genet. Genomics 273:264-272(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-202, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP DISPUTED FUNCTION IN HISTONE ACETYLATION.
RX PubMed=16713582; DOI=10.1016/j.molcel.2006.04.017;
RA Close P., Hawkes N., Cornez I., Creppe C., Lambert C.A., Rogister B.,
RA Siebenlist U., Merville M.P., Slaugenhaupt S.A., Bours V., Svejstrup J.Q.,
RA Chariot A.;
RT "Transcription impairment and cell migration defects in elongator-depleted
RT cells: implication for familial dysautonomia.";
RL Mol. Cell 22:521-531(2006).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ELP1 AND
RP ALPHA-TUBULIN.
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 [12]
RP TISSUE SPECIFICITY, AND INVOLVEMENT IN ALS.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP IDENTIFICATION IN THE ELONGATOR COMPLEX, AND SUBCELLULAR LOCATION.
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 [16]
RP SUBCELLULAR LOCATION.
RX PubMed=22002106; DOI=10.1074/mcp.m111.013680;
RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.;
RT "Systematic analysis of protein pools, isoforms, and modifications
RT affecting turnover and subcellular localization.";
RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012).
RN [17]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-229, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [18]
RP INTERACTION WITH ELP1 AND ELP2.
RX PubMed=25960406; DOI=10.1016/j.str.2015.03.018;
RA Dong C., Lin Z., Diao W., Li D., Chu X., Wang Z., Zhou H., Xie Z., Shen Y.,
RA Long J.;
RT "The Elp2 subunit is essential for elongator complex assembly and
RT functional regulation.";
RL Structure 23:1078-1086(2015).
RN [19]
RP REVIEW.
RX PubMed=29332244; DOI=10.1007/s00018-018-2747-6;
RA Dalwadi U., Yip C.K.;
RT "Structural insights into the function of Elongator.";
RL Cell. Mol. Life Sci. 75:1613-1622(2018).
RN [20]
RP PHOSPHORYLATION AT TYR-202 AND TYR-251, AND MUTAGENESIS OF TYR-202;
RP TYR-207; TYR-251; TYR-318; TYR-329 AND TYR-427.
RX PubMed=31341009; DOI=10.1042/bcj20190106;
RA Li M.T., Liang J.Y., Sun Y.P., Jin J., Xiong Y., Guan K.L., Yuan H.X.;
RT "ELP3 Acetyltransferase is phosphorylated and regulated by the oncogenic
RT anaplastic lymphoma kinase (ALK).";
RL Biochem. J. 476:2239-2254(2019).
RN [21]
RP INVOLVEMENT IN ALS, FUNCTION, AND PATHWAY.
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) (PubMed:29415125). 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 (PubMed:29415125). Involved in
CC neurogenesis: regulates the migration and branching of projection
CC neurons in the developing cerebral cortex, through a process depending
CC on alpha-tubulin acetylation (PubMed:19185337). Required for
CC acetylation of GJA1 in the developing cerebral cortex (By similarity).
CC {ECO:0000250|UniProtKB:D5VRB9, ECO:0000250|UniProtKB:Q9CZX0,
CC ECO:0000269|PubMed:19185337, ECO:0000269|PubMed:29415125}.
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:0000269|PubMed:29415125}.
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 (PubMed:11714725, PubMed:11818576, PubMed:19185337,
CC PubMed:22854966, PubMed:25960406). Interacts with alpha-tubulin
CC (PubMed:19185337). {ECO:0000269|PubMed:11714725,
CC ECO:0000269|PubMed:11818576, ECO:0000269|PubMed:19185337,
CC ECO:0000269|PubMed:22854966, ECO:0000269|PubMed:25960406}.
CC -!- INTERACTION:
CC Q9H9T3; O95163: ELP1; NbExp=8; IntAct=EBI-355217, EBI-347559;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11818576,
CC ECO:0000269|PubMed:19185337, ECO:0000269|PubMed:22854966}. Nucleus
CC {ECO:0000269|PubMed:11714725, ECO:0000269|PubMed:11818576,
CC ECO:0000269|PubMed:22854966}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:22002106}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:22002106}. Nucleus {ECO:0000269|PubMed:22002106}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9H9T3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H9T3-2; Sequence=VSP_024406;
CC Name=3;
CC IsoId=Q9H9T3-4; Sequence=VSP_055285, VSP_055286;
CC Name=4;
CC IsoId=Q9H9T3-5; Sequence=VSP_055284;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum and spinal motor
CC neurons. {ECO:0000269|PubMed:18996918}.
CC -!- PTM: Tyrosine-phosphorylated; phosphorylation on Tyr-202 does not
CC affect elongator complex integrity or ELP3 protein stability
CC (PubMed:31341009). Also serine/threonine-phosphorylated
CC (PubMed:31341009). {ECO:0000269|PubMed:31341009}.
CC -!- DISEASE: Amyotrophic lateral sclerosis (ALS) [MIM:105400]: A
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:18996918, ECO:0000305|PubMed:29415125}. Note=The
CC gene represented in this entry may act as a disease modifier.
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:0000305|PubMed:11714725,
CC ECO:0000305|PubMed:11818576, ECO:0000305|PubMed:15902492,
CC ECO:0000305|PubMed:16713582, ECO:0000305|PubMed:29332244}.
CC -!- CAUTION: The relevance of the protein lysine acetyltransferase activity
CC is unclear (PubMed:29415125). The publication reporting acetylation of
CC GJA1 does not provide direct evidence of lysine acetyltransferase
CC activity of ELP3 (By similarity). {ECO:0000250|UniProtKB:Q9CZX0,
CC ECO:0000269|PubMed:29415125}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91600.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=CAH10573.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK001284; BAA91600.1; ALT_SEQ; mRNA.
DR EMBL; AK022626; BAB14138.1; -; mRNA.
DR EMBL; AK293424; BAG56930.1; -; mRNA.
DR EMBL; AK295574; BAG58473.1; -; mRNA.
DR EMBL; AK315985; BAH14356.1; -; mRNA.
DR EMBL; AL834273; CAD38948.1; -; mRNA.
DR EMBL; BX648011; CAH10573.1; ALT_FRAME; mRNA.
DR EMBL; AC019031; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001240; AAH01240.1; -; mRNA.
DR EMBL; AK223047; BAD96767.1; -; mRNA.
DR CCDS; CCDS6065.1; -. [Q9H9T3-1]
DR CCDS; CCDS64860.1; -. [Q9H9T3-5]
DR CCDS; CCDS64861.1; -. [Q9H9T3-4]
DR CCDS; CCDS75717.1; -. [Q9H9T3-2]
DR RefSeq; NP_001271151.1; NM_001284222.1. [Q9H9T3-2]
DR RefSeq; NP_001271153.1; NM_001284224.1. [Q9H9T3-4]
DR RefSeq; NP_001271154.1; NM_001284225.1. [Q9H9T3-4]
DR RefSeq; NP_001271155.1; NM_001284226.1. [Q9H9T3-5]
DR RefSeq; NP_060561.3; NM_018091.5. [Q9H9T3-1]
DR RefSeq; XP_006716417.1; XM_006716354.2. [Q9H9T3-4]
DR AlphaFoldDB; Q9H9T3; -.
DR SMR; Q9H9T3; -.
DR BioGRID; 120444; 123.
DR ComplexPortal; CPX-1949; Elongator holoenzyme complex.
DR CORUM; Q9H9T3; -.
DR DIP; DIP-53227N; -.
DR IntAct; Q9H9T3; 34.
DR MINT; Q9H9T3; -.
DR STRING; 9606.ENSP00000256398; -.
DR CarbonylDB; Q9H9T3; -.
DR GlyGen; Q9H9T3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H9T3; -.
DR PhosphoSitePlus; Q9H9T3; -.
DR BioMuta; ELP3; -.
DR DMDM; 145558902; -.
DR EPD; Q9H9T3; -.
DR jPOST; Q9H9T3; -.
DR MassIVE; Q9H9T3; -.
DR MaxQB; Q9H9T3; -.
DR PaxDb; Q9H9T3; -.
DR PeptideAtlas; Q9H9T3; -.
DR PRIDE; Q9H9T3; -.
DR ProteomicsDB; 3914; -.
DR ProteomicsDB; 4303; -.
DR ProteomicsDB; 81361; -. [Q9H9T3-1]
DR ProteomicsDB; 81362; -. [Q9H9T3-2]
DR Antibodypedia; 23089; 229 antibodies from 31 providers.
DR DNASU; 55140; -.
DR Ensembl; ENST00000256398.13; ENSP00000256398.8; ENSG00000134014.17. [Q9H9T3-1]
DR Ensembl; ENST00000380353.8; ENSP00000369711.4; ENSG00000134014.17. [Q9H9T3-5]
DR Ensembl; ENST00000521015.5; ENSP00000428449.1; ENSG00000134014.17. [Q9H9T3-2]
DR Ensembl; ENST00000537665.2; ENSP00000445558.1; ENSG00000134014.17. [Q9H9T3-4]
DR GeneID; 55140; -.
DR KEGG; hsa:55140; -.
DR MANE-Select; ENST00000256398.13; ENSP00000256398.8; NM_018091.6; NP_060561.3.
DR UCSC; uc003xgn.6; human. [Q9H9T3-1]
DR CTD; 55140; -.
DR DisGeNET; 55140; -.
DR GeneCards; ELP3; -.
DR HGNC; HGNC:20696; ELP3.
DR HPA; ENSG00000134014; Low tissue specificity.
DR MIM; 105400; phenotype.
DR MIM; 612722; gene.
DR neXtProt; NX_Q9H9T3; -.
DR OpenTargets; ENSG00000134014; -.
DR PharmGKB; PA134992603; -.
DR VEuPathDB; HostDB:ENSG00000134014; -.
DR eggNOG; KOG2535; Eukaryota.
DR GeneTree; ENSGT00390000013141; -.
DR InParanoid; Q9H9T3; -.
DR OMA; TFETRPD; -.
DR OrthoDB; 320059at2759; -.
DR PhylomeDB; Q9H9T3; -.
DR TreeFam; TF105752; -.
DR BRENDA; 2.3.1.48; 2681.
DR PathwayCommons; Q9H9T3; -.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR SignaLink; Q9H9T3; -.
DR UniPathway; UPA00988; -.
DR BioGRID-ORCS; 55140; 693 hits in 1082 CRISPR screens.
DR ChiTaRS; ELP3; human.
DR GeneWiki; ELP3; -.
DR GenomeRNAi; 55140; -.
DR Pharos; Q9H9T3; Tbio.
DR PRO; PR:Q9H9T3; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H9T3; protein.
DR Bgee; ENSG00000134014; Expressed in endothelial cell and 200 other tissues.
DR ExpressionAtlas; Q9H9T3; baseline and differential.
DR Genevisible; Q9H9T3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0033588; C:elongator holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HGNC-UCL.
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; IDA:BHF-UCL.
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; IDA: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; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IC:ComplexPortal.
DR GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; IBA:GO_Central.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IDA: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 SFLD; SFLDS00029; Radical_SAM; 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;
KW Amyotrophic lateral sclerosis; Cytoplasm; Iron; Iron-sulfur; Metal-binding;
KW Methylation; Neurodegeneration; Neurogenesis; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; S-adenosyl-L-methionine; Transferase;
KW tRNA processing; tRNA-binding.
FT CHAIN 1..547
FT /note="Elongator complex protein 3"
FT /id="PRO_0000283986"
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:0000250|UniProtKB:Q9CZX0"
FT MOD_RES 202
FT /note="Phosphotyrosine; by ALK"
FT /evidence="ECO:0000269|PubMed:31341009,
FT ECO:0007744|PubMed:15592455"
FT MOD_RES 229
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 251
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:31341009"
FT VAR_SEQ 1..92
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055284"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_024406"
FT VAR_SEQ 1..12
FT /note="MRQKRKGDLSPA -> MSTHQFYRKYMC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055285"
FT VAR_SEQ 13..131
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055286"
FT MUTAGEN 202
FT /note="Y->E,F: Substantial reduction in tyrosine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT MUTAGEN 207
FT /note="Y->F: No effect on tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT MUTAGEN 251
FT /note="Y->F: Small reduction in tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT MUTAGEN 318
FT /note="Y->F: No effect on tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT MUTAGEN 329
FT /note="Y->F: No effect on tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT MUTAGEN 427
FT /note="Y->F: No effect on tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:31341009"
FT CONFLICT 10
FT /note="S -> G (in Ref. 1; BAA91600)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="H -> Y (in Ref. 5; BAD96767)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="E -> K (in Ref. 2; CAH10573)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="K -> M (in Ref. 1; BAB14138)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 547 AA; 62259 MW; 60898ADD3DBAD035 CRC64;
MRQKRKGDLS PAELMMLTIG DVIKQLIEAH EQGKDIDLNK VKTKTAAKYG LSAQPRLVDI
IAAVPPQYRK VLMPKLKAKP IRTASGIAVV AVMCKPHRCP HISFTGNICV YCPGGPDSDF
EYSTQSYTGY EPTSMRAIRA RYDPFLQTRH RIEQLKQLGH SVDKVEFIVM GGTFMALPEE
YRDYFIRNLH DALSGHTSNN IYEAVKYSER SLTKCIGITI ETRPDYCMKR HLSDMLTYGC
TRLEIGVQSV YEDVARDTNR GHTVKAVCES FHLAKDSGFK VVAHMMPDLP NVGLERDIEQ
FTEFFENPAF RPDGLKLYPT LVIRGTGLYE LWKSGRYKSY SPSDLVELVA RILALVPPWT
RVYRVQRDIP MPLVSSGVEH GNLRELALAR MKDLGIQCRD VRTREVGIQE IHHKVRPYQV
ELVRRDYVAN GGWETFLSYE DPDQDILIGL LRLRKCSEET FRFELGGGVS IVRELHVYGS
VVPVSSRDPT KFQHQGFGML LMEEAERIAR EEHGSGKIAV ISGVGTRNYY RKIGYRLQGP
YMVKMLK
