ELAV4_HUMAN
ID ELAV4_HUMAN Reviewed; 385 AA.
AC P26378; B1APY6; B1APY7; B1APY8; B7Z4G7; Q8IYD4; Q96J74; Q96J75; Q9UD24;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 3.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=ELAV-like protein 4;
DE AltName: Full=Hu-antigen D;
DE Short=HuD;
DE AltName: Full=Paraneoplastic encephalomyelitis antigen HuD;
GN Name=ELAVL4; Synonyms=HUD, PNEM;
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 [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP VARIANT SER-275.
RC TISSUE=Brain;
RX PubMed=1655278; DOI=10.1016/0092-8674(91)90184-z;
RA Szabo A., Dalmau J., Manley G., Rosenfeld M., Wong E., Henson J.,
RA Posner J.B., Furneaux H.M.;
RT "HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding
RT domains and is homologous to Elav and Sex-lethal.";
RL Cell 67:325-333(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), AND VARIANT SER-275.
RC TISSUE=Neuroblastoma;
RX PubMed=12209604; DOI=10.1002/ijc.10550;
RA Behrends U., Jandl T., Golbeck A., Lechner B., Mueller-Weihrich S.,
RA Schmid I., Till H., Berthold F., Voltz R., Mautner J.M.;
RT "Novel products of the HuD, HuC, NNP-1 and alpha-internexin genes
RT identified by autologous antibody screening of a pediatric neuroblastoma
RT library.";
RL Int. J. Cancer 100:669-677(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS GLY-171
RP AND THR-361.
RC TISSUE=Hypothalamus;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 245-284 (ISOFORM 1), FUNCTION, ALTERNATIVE
RP SPLICING, AND VARIANT SER-275.
RX PubMed=7898713; DOI=10.1212/wnl.45.3.544;
RA Liu J., Dalmau J., Szabo A., Rosenfeld M., Huber J., Furneaux H.;
RT "Paraneoplastic encephalomyelitis antigens bind to the AU-rich elements of
RT mRNA.";
RL Neurology 45:544-550(1995).
RN [8]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=10710437; DOI=10.1093/nar/28.7.e20;
RA King P.H.;
RT "RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-
RT untranslated regions using a novel ELISA-based assay.";
RL Nucleic Acids Res. 28:E20-E20(2000).
RN [9]
RP FUNCTION.
RX PubMed=12034726; DOI=10.1074/jbc.m201982200;
RA Beckel-Mitchener A.C., Miera A., Keller R., Perrone-Bizzozero N.I.;
RT "Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-
RT binding protein HuD.";
RL J. Biol. Chem. 277:27996-28002(2002).
RN [10]
RP FUNCTION.
RX PubMed=12468554; DOI=10.1074/jbc.m209383200;
RA Deschenes-Furry J., Belanger G., Perrone-Bizzozero N., Jasmin B.J.;
RT "Post-transcriptional regulation of acetylcholinesterase mRNAs in nerve
RT growth factor-treated PC12 cells by the RNA-binding protein HuD.";
RL J. Biol. Chem. 278:5710-5717(2003).
RN [11]
RP FUNCTION.
RX PubMed=17035636; DOI=10.1091/mbc.e06-02-0099;
RA Zhu H., Hasman R.A., Barron V.A., Luo G., Lou H.;
RT "A nuclear function of Hu proteins as neuron-specific alternative RNA
RT processing regulators.";
RL Mol. Biol. Cell 17:5105-5114(2006).
RN [12]
RP METHYLATION AT ARG-248.
RX PubMed=16508003; DOI=10.1128/mcb.26.6.2273-2285.2006;
RA Fujiwara T., Mori Y., Chu D.L., Koyama Y., Miyata S., Tanaka H., Yachi K.,
RA Kubo T., Yoshikawa H., Tohyama M.;
RT "CARM1 regulates proliferation of PC12 cells by methylating HuD.";
RL Mol. Cell. Biol. 26:2273-2285(2006).
RN [13]
RP FUNCTION.
RX PubMed=17234598; DOI=10.1523/jneurosci.4626-06.2007;
RA Deschenes-Furry J., Mousavi K., Bolognani F., Neve R.L., Parks R.J.,
RA Perrone-Bizzozero N.I., Jasmin B.J.;
RT "The RNA-binding protein HuD binds acetylcholinesterase mRNA in neurons and
RT regulates its expression after axotomy.";
RL J. Neurosci. 27:665-675(2007).
RN [14]
RP FUNCTION.
RX PubMed=18218628; DOI=10.1074/jbc.m706082200;
RA Ratti A., Fallini C., Colombrita C., Pascale A., Laforenza U.,
RA Quattrone A., Silani V.;
RT "Post-transcriptional regulation of neuro-oncological ventral antigen 1 by
RT the neuronal RNA-binding proteins ELAV.";
RL J. Biol. Chem. 283:7531-7541(2008).
RN [15]
RP INTERACTION WITH SMN, SUBCELLULAR LOCATION, AND METHYLATION.
RX PubMed=21088113; DOI=10.1093/hmg/ddq500;
RA Hubers L., Valderrama-Carvajal H., Laframboise J., Timbers J., Sanchez G.,
RA Cote J.;
RT "HuD interacts with survival motor neuron protein and can rescue spinal
RT muscular atrophy-like neuronal defects.";
RL Hum. Mol. Genet. 20:553-579(2011).
RN [16]
RP INTERACTION WITH SMN.
RX PubMed=21389246; DOI=10.1523/jneurosci.3631-10.2011;
RA Fallini C., Zhang H., Su Y., Silani V., Singer R.H., Rossoll W.,
RA Bassell G.J.;
RT "The survival of motor neuron (SMN) protein interacts with the mRNA-binding
RT protein HuD and regulates localization of poly(A) mRNA in primary motor
RT neuron axons.";
RL J. Neurosci. 31:3914-3925(2011).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=22387028; DOI=10.1016/j.molcel.2012.01.016;
RA Lee E.K., Kim W., Tominaga K., Martindale J.L., Yang X., Subaran S.S.,
RA Carlson O.D., Mercken E.M., Kulkarni R.N., Akamatsu W., Okano H.,
RA Perrone-Bizzozero N.I., de Cabo R., Egan J.M., Gorospe M.;
RT "RNA-binding protein HuD controls insulin translation.";
RL Mol. Cell 45:826-835(2012).
RN [18]
RP FUNCTION.
RX PubMed=24857657; DOI=10.1016/j.celrep.2014.04.050;
RA Kang M.J., Abdelmohsen K., Hutchison E.R., Mitchell S.J., Grammatikakis I.,
RA Guo R., Noh J.H., Martindale J.L., Yang X., Lee E.K., Faghihi M.A.,
RA Wahlestedt C., Troncoso J.C., Pletnikova O., Perrone-Bizzozero N.,
RA Resnick S.M., de Cabo R., Mattson M.P., Gorospe M.;
RT "HuD regulates coding and noncoding RNA to induce APP[?]Abeta processing.";
RL Cell Rep. 7:1401-1409(2014).
RN [19]
RP INTERACTION WITH SMN.
RX PubMed=29061699; DOI=10.1523/jneurosci.1528-17.2017;
RA Hao le T., Duy P.Q., An M., Talbot J., Iyer C.C., Wolman M., Beattie C.E.;
RT "HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are
RT Essential for Motoneuron Development, Function, and mRNA Regulation.";
RL J. Neurosci. 37:11559-11571(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 49-215 IN COMPLEX WITH RNA.
RX PubMed=11175903; DOI=10.1038/84131;
RA Wang X., Tanaka Hall T.M.;
RT "Structural basis for recognition of AU-rich element RNA by the HuD
RT protein.";
RL Nat. Struct. Biol. 8:141-145(2001).
CC -!- FUNCTION: RNA-binding protein that is involved in the post-
CC transcriptional regulation of mRNAs (PubMed:7898713, PubMed:10710437,
CC PubMed:12034726, PubMed:12468554, PubMed:17035636, PubMed:17234598).
CC Plays a role in the regulation of mRNA stability, alternative splicing
CC and translation (PubMed:7898713, PubMed:10710437, PubMed:12034726,
CC PubMed:12468554, PubMed:17035636, PubMed:17234598). Binds to AU-rich
CC element (ARE) sequences in the 3' untranslated region (UTR) of target
CC mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA
CC (PubMed:7898713, PubMed:10710437, PubMed:12034726, PubMed:12468554).
CC Many of the target mRNAs are coding for RNA-binding proteins,
CC transcription factors and proteins involved in RNA processing and/or
CC neuronal development and function (By similarity). By binding to the
CC mRNA 3'UTR, decreases mRNA deadenylation and thereby contributes to the
CC stabilization of mRNA molecules and their protection from decay
CC (PubMed:12034726). Also binds to the polyadenylated (poly(A)) tail in
CC the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding
CC (PubMed:12034726). Mainly plays a role in neuron-specific RNA
CC processing by stabilization of mRNAs such as GAP43, ACHE and mRNAs of
CC other neuronal proteins, thereby contributing to the differentiation of
CC neural progenitor cells, nervous system development, learning and
CC memory mechanisms (PubMed:12034726, PubMed:12468554, PubMed:17234598,
CC PubMed:18218628). Involved in the negative regulation of the
CC proliferative activity of neuronal stem cells and in the positive
CC regulation of neuronal differentiation of neural progenitor cells (By
CC similarity). Promotes neuronal differentiation of neural
CC stem/progenitor cells in the adult subventricular zone of the
CC hippocampus by binding to and stabilizing SATB1 mRNA (By similarity).
CC Binds and stabilizes MSI1 mRNA in neural stem cells (By similarity).
CC Exhibits increased binding to ACHE mRNA during neuronal
CC differentiation, thereby stabilizing ACHE mRNA and enhancing its
CC expression (PubMed:12468554, PubMed:17234598). Protects CDKN1A mRNA
CC from decay by binding to its 3'-UTR (By similarity). May bind to APP
CC and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization
CC (PubMed:24857657). Plays a role in neurite outgrowth and in the
CC establishment and maturation of dendritic arbors, thereby contributing
CC to neocortical and hippocampal circuitry function (By similarity).
CC Stabilizes GAP43 mRNA and protects it from decay during postembryonic
CC development in the brain (PubMed:12034726). By promoting the
CC stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite
CC outgrowth (By similarity). Binds to BDNF long 3'UTR mRNA, thereby
CC leading to its stabilization and increased dendritic translation after
CC activation of PKC (By similarity). By increasing translation of BDNF
CC after nerve injury, may contribute to nerve regeneration (By
CC similarity). Acts as a stabilizing factor by binding to the 3'UTR of
CC NOVA1 mRNA, thereby increasing its translation and enhancing its
CC functional activity in neuron-specific splicing (PubMed:18218628).
CC Stimulates translation of mRNA in a poly(A)- and cap-dependent manner,
CC possibly by associating with the EIF4F cap-binding complex (By
CC similarity). May also negatively regulate translation by binding to the
CC 5'UTR of Ins2 mRNA, thereby repressing its translation (By similarity).
CC Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and
CC translational inhibition is abolished (By similarity). Also plays a
CC role in the regulation of alternative splicing (PubMed:17035636). May
CC regulate alternative splicing of CALCA pre-mRNA into Calcitonin and
CC Calcitonin gene-related peptide 1 (CGRP) by competing with splicing
CC regulator TIAR for binding to U-rich intronic sequences of CALCA pre-
CC mRNA (PubMed:17035636). {ECO:0000250|UniProtKB:O09032,
CC ECO:0000250|UniProtKB:Q61701, ECO:0000269|PubMed:10710437,
CC ECO:0000269|PubMed:12034726, ECO:0000269|PubMed:12468554,
CC ECO:0000269|PubMed:17035636, ECO:0000269|PubMed:17234598,
CC ECO:0000269|PubMed:18218628, ECO:0000269|PubMed:24857657,
CC ECO:0000269|PubMed:7898713}.
CC -!- SUBUNIT: Component of a TAU mRNP complex, at least composed of IGF2BP1,
CC ELAVL4 and G3BP (By similarity). Associates with the EIF4F cap-binding
CC complex, composed of EIF4G, EIF4A, EIF4E and PABP (By similarity).
CC Within the EIF4F cap-binding complex, interacts with EIF4A (By
CC similarity). Interacts with SMN (via Tudor domain) in an RNA-
CC independent manner; the interaction is required for localization of
CC ELAVL4 to RNA granules (PubMed:21088113, PubMed:21389246,
CC PubMed:29061699). Interacts with MAP1 light chain LC1 (via C-terminus);
CC the interaction contributes to the association of ELAVL4 with
CC microtubules (By similarity). Interacts with MAP1 light chain LC2 (By
CC similarity). {ECO:0000250|UniProtKB:Q61701,
CC ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:21389246,
CC ECO:0000269|PubMed:29061699}.
CC -!- INTERACTION:
CC P26378-2; Q00994: BEX3; NbExp=3; IntAct=EBI-21603100, EBI-741753;
CC P26378-2; Q5H9J7: BEX5; NbExp=3; IntAct=EBI-21603100, EBI-10243741;
CC P26378-2; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-21603100, EBI-350590;
CC P26378-2; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-21603100, EBI-3508943;
CC P26378-2; Q9Y6C2-2: EMILIN1; NbExp=3; IntAct=EBI-21603100, EBI-11748557;
CC P26378-2; Q99504: EYA3; NbExp=3; IntAct=EBI-21603100, EBI-9089567;
CC P26378-2; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-21603100, EBI-6425864;
CC P26378-2; O60341: KDM1A; NbExp=3; IntAct=EBI-21603100, EBI-710124;
CC P26378-2; Q9HAF1: MEAF6; NbExp=3; IntAct=EBI-21603100, EBI-399266;
CC P26378-2; Q9H204: MED28; NbExp=3; IntAct=EBI-21603100, EBI-514199;
CC P26378-2; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-21603100, EBI-1390168;
CC P26378-2; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-21603100, EBI-21250407;
CC P26378-2; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-21603100, EBI-9092052;
CC P26378-2; Q8NC67-2: NETO2; NbExp=3; IntAct=EBI-21603100, EBI-25852289;
CC P26378-2; Q96MF7: NSMCE2; NbExp=3; IntAct=EBI-21603100, EBI-2557388;
CC P26378-2; Q9NP74: PALMD; NbExp=3; IntAct=EBI-21603100, EBI-2811699;
CC P26378-2; O75925: PIAS1; NbExp=3; IntAct=EBI-21603100, EBI-629434;
CC P26378-2; P17612: PRKACA; NbExp=3; IntAct=EBI-21603100, EBI-476586;
CC P26378-2; P54725: RAD23A; NbExp=3; IntAct=EBI-21603100, EBI-746453;
CC P26378-2; Q5TAB7: RIPPLY2; NbExp=3; IntAct=EBI-21603100, EBI-10246897;
CC P26378-2; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-21603100, EBI-21535400;
CC P26378-2; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-21603100, EBI-25829984;
CC P26378-2; Q8N488: RYBP; NbExp=3; IntAct=EBI-21603100, EBI-752324;
CC P26378-2; O75446: SAP30; NbExp=3; IntAct=EBI-21603100, EBI-632609;
CC P26378-2; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-21603100, EBI-2510414;
CC P26378-2; Q15554-4: TERF2; NbExp=3; IntAct=EBI-21603100, EBI-25840535;
CC P26378-2; P37173: TGFBR2; NbExp=3; IntAct=EBI-21603100, EBI-296151;
CC P26378-2; Q9BZW5-2: TM6SF1; NbExp=3; IntAct=EBI-21603100, EBI-25852210;
CC P26378-2; Q6PID6: TTC33; NbExp=3; IntAct=EBI-21603100, EBI-2555404;
CC P26378-2; P55072: VCP; NbExp=3; IntAct=EBI-21603100, EBI-355164;
CC P26378-2; P58304: VSX2; NbExp=3; IntAct=EBI-21603100, EBI-6427899;
CC P26378-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-21603100, EBI-358545;
CC P26378-2; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-21603100, EBI-2602314;
CC P26378-2; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-21603100, EBI-749023;
CC P26378-2; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-21603100, EBI-8489702;
CC P26378-2; Q9UID6: ZNF639; NbExp=3; IntAct=EBI-21603100, EBI-947476;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21088113}.
CC Perikaryon {ECO:0000250|UniProtKB:O09032}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:O09032}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q61701}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q61701}. Note=Co-localizes with ribosomal RNA in
CC polysomes. {ECO:0000250|UniProtKB:O09032}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=6; Synonyms=Long {ECO:0000305};
CC IsoId=P26378-6; Sequence=Displayed;
CC Name=1; Synonyms=HUD1PRO;
CC IsoId=P26378-1; Sequence=VSP_060281;
CC Name=2; Synonyms=HUD1;
CC IsoId=P26378-2; Sequence=VSP_060281, VSP_060283;
CC Name=3; Synonyms=HUD4;
CC IsoId=P26378-3; Sequence=VSP_060282, VSP_060283;
CC Name=4; Synonyms=HUD3;
CC IsoId=P26378-4; Sequence=VSP_060279, VSP_060283;
CC Name=5;
CC IsoId=P26378-5; Sequence=VSP_060280, VSP_060283;
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic beta cells (at protein
CC level) (PubMed:22387028). Expressed in the brain (PubMed:1655278,
CC PubMed:14702039). {ECO:0000269|PubMed:14702039,
CC ECO:0000269|PubMed:1655278, ECO:0000269|PubMed:22387028}.
CC -!- DOMAIN: The RRM 3 domain is required for binding to poly(A) RNA, for
CC the association with polysomes and with the EIF4F cap-binding complex
CC and for the stimulation of translation (By similarity). The RRM 1 and
CC RRM 2 domains may contribute to polysome association and stimulation of
CC translation (By similarity). {ECO:0000250|UniProtKB:Q61701}.
CC -!- PTM: Methylated by CARM1, which leads to reduced RNA-binding activity
CC and enhanced interaction with SMN (PubMed:21088113). Methylation at
CC Arg-248 by CARM1 weakens protective binding to the 3'UTR of CDKN1A mRNA
CC and down-regulates CDKN1A protein expression, thereby maintaining cells
CC in a proliferative state (By similarity). Methylation is inhibited by
CC NGF, which facilitates neurite outgrowth (By similarity).
CC {ECO:0000250|UniProtKB:O09032, ECO:0000269|PubMed:21088113}.
CC -!- SIMILARITY: Belongs to the RRM elav family. {ECO:0000305}.
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DR EMBL; M62843; AAA58396.1; -; mRNA.
DR EMBL; AY033995; AAK57538.1; -; mRNA.
DR EMBL; AY033996; AAK57539.1; -; mRNA.
DR EMBL; AY033997; AAK57540.1; -; mRNA.
DR EMBL; AY033998; AAK57541.1; -; mRNA.
DR EMBL; AK297338; BAH12553.1; -; mRNA.
DR EMBL; AL583843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06845.1; -; Genomic_DNA.
DR EMBL; BC036071; AAH36071.1; -; mRNA.
DR CCDS; CCDS44138.1; -. [P26378-4]
DR CCDS; CCDS44140.1; -. [P26378-2]
DR CCDS; CCDS53315.1; -. [P26378-5]
DR CCDS; CCDS553.1; -. [P26378-1]
DR CCDS; CCDS81321.1; -. [P26378-6]
DR PIR; A40348; A40348.
DR RefSeq; NP_001138246.1; NM_001144774.2. [P26378-2]
DR RefSeq; NP_001138247.2; NM_001144775.2.
DR RefSeq; NP_001138248.1; NM_001144776.2. [P26378-4]
DR RefSeq; NP_001138249.1; NM_001144777.2. [P26378-5]
DR RefSeq; NP_001281277.1; NM_001294348.1.
DR RefSeq; NP_001311142.1; NM_001324213.1. [P26378-6]
DR RefSeq; NP_068771.2; NM_021952.4. [P26378-1]
DR PDB; 1FXL; X-ray; 1.80 A; A=49-215.
DR PDB; 1G2E; X-ray; 2.30 A; A=49-215.
DR PDBsum; 1FXL; -.
DR PDBsum; 1G2E; -.
DR AlphaFoldDB; P26378; -.
DR SMR; P26378; -.
DR BioGRID; 108311; 58.
DR IntAct; P26378; 43.
DR STRING; 9606.ENSP00000349594; -.
DR iPTMnet; P26378; -.
DR PhosphoSitePlus; P26378; -.
DR BioMuta; ELAVL4; -.
DR DMDM; 223590202; -.
DR jPOST; P26378; -.
DR MassIVE; P26378; -.
DR MaxQB; P26378; -.
DR PaxDb; P26378; -.
DR PeptideAtlas; P26378; -.
DR PRIDE; P26378; -.
DR ProteomicsDB; 3315; -.
DR ProteomicsDB; 54330; -. [P26378-1]
DR ProteomicsDB; 54331; -. [P26378-2]
DR ProteomicsDB; 54332; -. [P26378-3]
DR ProteomicsDB; 54333; -. [P26378-4]
DR ProteomicsDB; 54334; -. [P26378-5]
DR Antibodypedia; 3839; 254 antibodies from 29 providers.
DR DNASU; 1996; -.
DR Ensembl; ENST00000371821.6; ENSP00000360886.1; ENSG00000162374.18. [P26378-6]
DR Ensembl; ENST00000371823.8; ENSP00000360888.4; ENSG00000162374.18. [P26378-1]
DR Ensembl; ENST00000371824.7; ENSP00000360889.2; ENSG00000162374.18. [P26378-2]
DR Ensembl; ENST00000371827.5; ENSP00000360892.1; ENSG00000162374.18. [P26378-4]
DR Ensembl; ENST00000448907.7; ENSP00000399939.2; ENSG00000162374.18. [P26378-5]
DR GeneID; 1996; -.
DR KEGG; hsa:1996; -.
DR MANE-Select; ENST00000371824.7; ENSP00000360889.2; NM_001144774.3; NP_001138246.1. [P26378-2]
DR UCSC; uc001cry.3; human. [P26378-6]
DR CTD; 1996; -.
DR DisGeNET; 1996; -.
DR GeneCards; ELAVL4; -.
DR HGNC; HGNC:3315; ELAVL4.
DR HPA; ENSG00000162374; Tissue enriched (brain).
DR MIM; 168360; gene.
DR neXtProt; NX_P26378; -.
DR OpenTargets; ENSG00000162374; -.
DR PharmGKB; PA27743; -.
DR VEuPathDB; HostDB:ENSG00000162374; -.
DR eggNOG; KOG0145; Eukaryota.
DR GeneTree; ENSGT00940000157399; -.
DR HOGENOM; CLU_026186_2_2_1; -.
DR InParanoid; P26378; -.
DR OMA; GSEWCIF; -.
DR OrthoDB; 614259at2759; -.
DR PhylomeDB; P26378; -.
DR TreeFam; TF313377; -.
DR PathwayCommons; P26378; -.
DR SignaLink; P26378; -.
DR SIGNOR; P26378; -.
DR BioGRID-ORCS; 1996; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; ELAVL4; human.
DR EvolutionaryTrace; P26378; -.
DR GeneWiki; HuD_(protein); -.
DR GenomeRNAi; 1996; -.
DR Pharos; P26378; Tbio.
DR PRO; PR:P26378; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P26378; protein.
DR Bgee; ENSG00000162374; Expressed in endothelial cell and 135 other tissues.
DR ExpressionAtlas; P26378; baseline and differential.
DR Genevisible; P26378; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0042788; C:polysomal ribosome; IEA:Ensembl.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0008143; F:poly(A) binding; IDA:UniProtKB.
DR GO; GO:0097158; F:pre-mRNA intronic pyrimidine-rich binding; IDA:UniProtKB.
DR GO; GO:0045182; F:translation regulator activity; IEA:Ensembl.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IEA:Ensembl.
DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc.
DR GO; GO:1905870; P:positive regulation of 3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; IEA:Ensembl.
DR GO; GO:0031099; P:regeneration; IEA:Ensembl.
DR GO; GO:0099547; P:regulation of translation at synapse, modulating synaptic transmission; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0006396; P:RNA processing; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd12650; RRM1_Hu; 1.
DR CDD; cd12656; RRM3_HuD; 1.
DR Gene3D; 3.30.70.330; -; 3.
DR InterPro; IPR006548; ELAD_HU_SF.
DR InterPro; IPR034775; ELAV/Hu_RRM1.
DR InterPro; IPR034918; HuD_RRM3.
DR InterPro; IPR002343; Hud_Sxl_RNA.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 3.
DR PRINTS; PR00961; HUDSXLRNA.
DR SMART; SM00360; RRM; 3.
DR SUPFAM; SSF54928; SSF54928; 2.
DR TIGRFAMs; TIGR01661; ELAV_HUD_SF; 1.
DR PROSITE; PS50102; RRM; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Cytoplasm;
KW Methylation; mRNA processing; mRNA splicing; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..385
FT /note="ELAV-like protein 4"
FT /id="PRO_0000081583"
FT DOMAIN 51..129
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 137..217
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 302..380
FT /note="RRM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 12..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61701"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61701"
FT MOD_RES 248
FT /note="Asymmetric dimethylarginine; by CARM1; alternate"
FT /evidence="ECO:0000269|PubMed:16508003"
FT MOD_RES 248
FT /note="Omega-N-methylarginine; by CARM1; alternate"
FT /evidence="ECO:0000269|PubMed:16508003"
FT VAR_SEQ 1..8
FT /note="MEWNGLKM -> MEQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12209604"
FT /id="VSP_060279"
FT VAR_SEQ 1..8
FT /note="MEWNGLKM -> MRLKNQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_060280"
FT VAR_SEQ 1..7
FT /note="MEWNGLK -> MV (in isoform 1 and isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060281"
FT VAR_SEQ 1..7
FT /note="MEWNGLK -> MRLLLLREIVINESRNCSF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12209604"
FT /id="VSP_060282"
FT VAR_SEQ 264..277
FT /note="Missing (in isoform 2, isoform 3, isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:12209604,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1655278"
FT /id="VSP_060283"
FT VARIANT 171
FT /note="D -> G (in dbSNP:rs17853533)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_058091"
FT VARIANT 275
FT /note="P -> S (in dbSNP:rs2494876)"
FT /evidence="ECO:0000269|PubMed:12209604,
FT ECO:0000269|PubMed:1655278, ECO:0000269|PubMed:7898713"
FT /id="VAR_052204"
FT VARIANT 361
FT /note="A -> T (in dbSNP:rs17853531)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_058092"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:1FXL"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 150..157
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:1FXL"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 177..187
FT /evidence="ECO:0007829|PDB:1FXL"
FT HELIX 188..198
FT /evidence="ECO:0007829|PDB:1FXL"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:1FXL"
SQ SEQUENCE 385 AA; 42398 MW; A253E05DE653F4EE CRC64;
MEWNGLKMII STMEPQVSNG PTSNTSNGPS SNNRNCPSPM QTGATTDDSK TNLIVNYLPQ
NMTQEEFRSL FGSIGEIESC KLVRDKITGQ SLGYGFVNYI DPKDAEKAIN TLNGLRLQTK
TIKVSYARPS SASIRDANLY VSGLPKTMTQ KELEQLFSQY GRIITSRILV DQVTGVSRGV
GFIRFDKRIE AEEAIKGLNG QKPSGATEPI TVKFANNPSQ KSSQALLSQL YQSPNRRYPG
PLHHQAQRFR LDNLLNMAYG VKRLMSGPVP PSACPPRFSP ITIDGMTSLV GMNIPGHTGT
GWCIFVYNLS PDSDESVLWQ LFGPFGAVNN VKVIRDFNTN KCKGFGFVTM TNYDEAAMAI
ASLNGYRLGD RVLQVSFKTN KAHKS
