ELP4_HUMAN
ID ELP4_HUMAN Reviewed; 424 AA.
AC Q96EB1; B4E3W0; E7EPZ6; Q9H4E8; Q9NX11;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Elongator complex protein 4;
DE Short=hELP4;
DE AltName: Full=PAX6 neighbor gene protein;
GN Name=ELP4; Synonyms=C11orf19, PAXNEB;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [GENOMIC DNA] OF 1-74, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11889558; DOI=10.1007/s00335-001-3058-y;
RA Kleinjan D.A., Seawright A., Elgar G., van Heyningen V.;
RT "Characterization of a novel gene adjacent to PAX6, revealing synteny
RT conservation with functional significance.";
RL Mamm. Genome 13:102-107(2002).
RN [6]
RP IDENTIFICATION IN THE ELONGATOR COMPLEX, AND IDENTIFICATION BY MASS
RP 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 SUBCELLULAR LOCATION.
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=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 [9]
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 [10]
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 [11]
RP INVOLVEMENT IN AN2.
RX PubMed=24290376; DOI=10.1016/j.ajhg.2013.10.028;
RA Bhatia S., Bengani H., Fish M., Brown A., Divizia M.T., de Marco R.,
RA Damante G., Grainger R., van Heyningen V., Kleinjan D.A.;
RT "Disruption of autoregulatory feedback by a mutation in a remote,
RT ultraconserved PAX6 enhancer causes aniridia.";
RL Am. J. Hum. Genet. 93:1126-1134(2013).
RN [12]
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).
CC -!- FUNCTION: Component of the elongator complex which is required for
CC multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl
CC uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U
CC (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex
CC catalyzes the formation of carboxymethyluridine in the wobble base at
CC position 34 in tRNAs (PubMed:29332244). {ECO:0000303|PubMed:29332244}.
CC -!- PATHWAY: tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA
CC biosynthesis. {ECO:0000303|PubMed:29332244}.
CC -!- SUBUNIT: Component of the elongator complex which consists of ELP1,
CC ELP2, ELP3, ELP4, ELP5 and ELP6 (PubMed:11714725, PubMed:22854966).
CC {ECO:0000269|PubMed:11714725, ECO:0000269|PubMed:22854966}.
CC -!- INTERACTION:
CC Q96EB1; Q8TE02: ELP5; NbExp=4; IntAct=EBI-3951755, EBI-946189;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11818576,
CC ECO:0000269|PubMed:11889558, ECO:0000269|PubMed:22854966}. Nucleus
CC {ECO:0000269|PubMed:11889558}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96EB1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96EB1-2; Sequence=VSP_024409;
CC Name=3;
CC IsoId=Q96EB1-3; Sequence=VSP_054128, VSP_054129;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11889558}.
CC -!- DISEASE: Aniridia 2 (AN2) [MIM:617141]: A form of aniridia, a
CC congenital, bilateral, panocular disorder characterized by complete
CC absence of the iris or extreme iris hypoplasia. Aniridia is not just an
CC isolated defect in iris development but it is associated with macular
CC and optic nerve hypoplasia, cataract, corneal changes, nystagmus.
CC Visual acuity is generally low but is unrelated to the degree of iris
CC hypoplasia. Glaucoma is a secondary problem causing additional visual
CC loss over time. {ECO:0000269|PubMed:24290376}. Note=The disease is
CC caused by variants affecting the gene represented in this entry. A
CC disease-causing mutation is located in intron 9 of ELP4. The mutation
CC does not alter normal ELP4 expression and function, but disrupts a
CC long-range cis-regulatory element of PAX6 expression, known as SIMO.
CC SIMO is contained within ELP4 intron 9 and located 150 kb downstream of
CC PAX6. {ECO:0000269|PubMed:24290376}.
CC -!- SIMILARITY: Belongs to the ELP4 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:16713582,
CC ECO:0000305|PubMed:29332244}.
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DR EMBL; AL136677; CAB66612.1; -; mRNA.
DR EMBL; AK000505; BAA91212.1; -; mRNA.
DR EMBL; AK304885; BAG65622.1; -; mRNA.
DR EMBL; AC108456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC131571; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83306; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012514; AAH12514.1; -; mRNA.
DR EMBL; AJ276005; CAC08200.1; -; Genomic_DNA.
DR CCDS; CCDS73271.1; -. [Q96EB1-3]
DR CCDS; CCDS73272.1; -. [Q96EB1-2]
DR CCDS; CCDS7875.2; -. [Q96EB1-1]
DR RefSeq; NP_001275654.1; NM_001288725.1. [Q96EB1-3]
DR RefSeq; NP_001275655.1; NM_001288726.1.
DR RefSeq; NP_061913.3; NM_019040.4. [Q96EB1-1]
DR AlphaFoldDB; Q96EB1; -.
DR SMR; Q96EB1; -.
DR BioGRID; 117764; 49.
DR ComplexPortal; CPX-1949; Elongator holoenzyme complex.
DR CORUM; Q96EB1; -.
DR IntAct; Q96EB1; 11.
DR MINT; Q96EB1; -.
DR STRING; 9606.ENSP00000379267; -.
DR iPTMnet; Q96EB1; -.
DR PhosphoSitePlus; Q96EB1; -.
DR BioMuta; ELP4; -.
DR DMDM; 145558903; -.
DR EPD; Q96EB1; -.
DR jPOST; Q96EB1; -.
DR MassIVE; Q96EB1; -.
DR MaxQB; Q96EB1; -.
DR PaxDb; Q96EB1; -.
DR PeptideAtlas; Q96EB1; -.
DR PRIDE; Q96EB1; -.
DR ProteomicsDB; 5926; -.
DR ProteomicsDB; 76391; -. [Q96EB1-1]
DR ProteomicsDB; 76392; -. [Q96EB1-2]
DR Antibodypedia; 25549; 155 antibodies from 26 providers.
DR DNASU; 26610; -.
DR Ensembl; ENST00000379163.10; ENSP00000368461.5; ENSG00000109911.19. [Q96EB1-3]
DR Ensembl; ENST00000640961.2; ENSP00000492152.1; ENSG00000109911.19. [Q96EB1-1]
DR GeneID; 26610; -.
DR KEGG; hsa:26610; -.
DR MANE-Select; ENST00000640961.2; ENSP00000492152.1; NM_019040.5; NP_061913.3.
DR UCSC; uc001mtb.5; human. [Q96EB1-1]
DR CTD; 26610; -.
DR DisGeNET; 26610; -.
DR GeneCards; ELP4; -.
DR HGNC; HGNC:1171; ELP4.
DR HPA; ENSG00000109911; Tissue enhanced (brain).
DR MalaCards; ELP4; -.
DR MIM; 606985; gene.
DR MIM; 617141; phenotype.
DR neXtProt; NX_Q96EB1; -.
DR OpenTargets; ENSG00000109911; -.
DR PharmGKB; PA27764; -.
DR VEuPathDB; HostDB:ENSG00000109911; -.
DR eggNOG; KOG3949; Eukaryota.
DR GeneTree; ENSGT00390000001443; -.
DR HOGENOM; CLU_031345_3_1_1; -.
DR InParanoid; Q96EB1; -.
DR OrthoDB; 450922at2759; -.
DR PhylomeDB; Q96EB1; -.
DR TreeFam; TF320797; -.
DR PathwayCommons; Q96EB1; -.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR SignaLink; Q96EB1; -.
DR UniPathway; UPA00988; -.
DR BioGRID-ORCS; 26610; 456 hits in 1095 CRISPR screens.
DR ChiTaRS; ELP4; human.
DR GeneWiki; ELP4; -.
DR GenomeRNAi; 26610; -.
DR Pharos; Q96EB1; Tbio.
DR PRO; PR:Q96EB1; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96EB1; protein.
DR Bgee; ENSG00000109911; Expressed in ventricular zone and 168 other tissues.
DR ExpressionAtlas; Q96EB1; baseline and differential.
DR Genevisible; Q96EB1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0033588; C:elongator holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0008607; F:phosphorylase kinase regulator activity; IDA: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:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:BHF-UCL.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR008728; Elongator_complex_protein_4.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR12896; PTHR12896; 1.
DR Pfam; PF05625; PAXNEB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Reference proteome;
KW tRNA processing.
FT CHAIN 1..424
FT /note="Elongator complex protein 4"
FT /id="PRO_0000284004"
FT VAR_SEQ 171
FT /note="E -> EQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054128"
FT VAR_SEQ 382..424
FT /note="RLHLPPDLSDTVSRSSKMDLAESAKRLGPGCGMMAGGKKHLDF -> AGVQW
FT HDLGSRRPRLLGSGGSPASASLVAGITGAHHHAQLIFVFLVEMGFHHVGQAGLELLTSG
FT DSSASASQSAGIAGMSYRARPRALYFKENKSKVGARQLLETREEHLSSRLLILTQAERL
FT CMGRRFFTAFHIFNELPCKGDCICLQTCQTQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024409"
FT VAR_SEQ 382..424
FT /note="RLHLPPDLSDTVSRSSKMDLAESAKRLGPGCGMMAGGKKHLDF -> WVQDN
FT YLRQERNIYPPGFSYLLKQKDSAWGEGSLQHSTFLMSFLAKATAFASRLVRHSEPLKQN
FT GSGRIRQAAGPRLWHDGRRQEAPGLLGIPP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054129"
FT VARIANT 300
FT /note="I -> L (in dbSNP:rs34804357)"
FT /id="VAR_053881"
SQ SEQUENCE 424 AA; 46588 MW; A044C964F7C91E73 CRC64;
MAAVATCGSV AASTGSAVAT ASKSNVTSFQ RRGPRASVTN DSGPRLVSIA GTRPSVRNGQ
LLVSTGLPAL DQLLGGGLAV GTVLLIEEDK YNIYSPLLFK YFLAEGIVNG HTLLVASAKE
DPANILQELP APLLDDKCKK EFDEDVYNHK TPESNIKMKI AWRYQLLPKM EIGPVSSSRF
GHYYDASKRM PQELIEASNW HGFFLPEKIS STLKVEPCSL TPGYTKLLQF IQNIIYEEGF
DGSNPQKKQR NILRIGIQNL GSPLWGDDIC CAENGGNSHS LTKFLYVLRG LLRTSLSACI
ITMPTHLIQN KAIIARVTTL SDVVVGLESF IGSERETNPL YKDYHGLIHI RQIPRLNNLI
CDESDVKDLA FKLKRKLFTI ERLHLPPDLS DTVSRSSKMD LAESAKRLGP GCGMMAGGKK
HLDF
