EMAL4_HUMAN
ID EMAL4_HUMAN Reviewed; 981 AA.
AC Q9HC35; A6H8Y6; A6P4T4; A6P4V4; B2RBK3; B2RTW7; B5MCW9; Q3SWW0; Q53R29;
AC Q53TW8; Q6PJ45; Q9NV40;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Echinoderm microtubule-associated protein-like 4;
DE Short=EMAP-4;
DE AltName: Full=Restrictedly overexpressed proliferation-associated protein;
DE AltName: Full=Ropp 120;
GN Name=EML4; Synonyms=C2orf2, EMAPL4;
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] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP VARIANTS GLU-283 AND VAL-382.
RX PubMed=10995578; DOI=10.1006/geno.2000.6301;
RA Heidebrecht H.J., Buck F., Pollmann M., Siebert R., Parwaresch R.;
RT "Cloning and localization of C2orf2(ropp120), a previously unknown WD
RT repeat protein.";
RL Genomics 68:348-350(2000).
RN [2]
RP SEQUENCE REVISION TO 121 AND 398.
RA Heidebrecht H.J.;
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLU-283; VAL-382 AND
RP ARG-398.
RC TISSUE=Hippocampus, and Ovarian carcinoma;
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP GLU-283; VAL-382 AND ARG-398.
RC TISSUE=Brain, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-747, VARIANTS GLU-283 AND VAL-382, AND
RP CHROMOSOMAL TRANSLOCATION WITH ALK.
RX PubMed=17625570; DOI=10.1038/nature05945;
RA Soda M., Choi Y.L., Enomoto M., Takada S., Yamashita Y., Ishikawa S.,
RA Fujiwara S., Watanabe H., Kurashina K., Hatanaka H., Bando M., Ohno S.,
RA Ishikawa Y., Aburatani H., Niki T., Sohara Y., Sugiyama Y., Mano H.;
RT "Identification of the transforming EML4-ALK fusion gene in non-small-cell
RT lung cancer.";
RL Nature 448:561-566(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226, 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 [8]
RP FUNCTION, MICROTUBULE-BINDING, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=16890222; DOI=10.1016/j.yexcr.2006.06.035;
RA Pollmann M., Parwaresch R., Adam-Klages S., Kruse M.L., Buck F.,
RA Heidebrecht H.J.;
RT "Human EML4, a novel member of the EMAP family, is essential for
RT microtubule formation.";
RL Exp. Cell Res. 312:3241-3251(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144; SER-146; SER-895;
RP THR-897; THR-899 AND SER-903, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-897 AND THR-899, AND
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-7; SER-13; SER-16; SER-61; SER-144; THR-899 AND SER-978,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144; SER-146 AND SER-978, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; SER-144; SER-146;
RP SER-171; SER-200; THR-201; THR-897 AND THR-899, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-96; THR-237; SER-891 AND
RP THR-899, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NUDC.
RX PubMed=25789526; DOI=10.1080/15384101.2015.1026514;
RA Chen D., Ito S., Yuan H., Hyodo T., Kadomatsu K., Hamaguchi M., Senga T.;
RT "EML4 promotes the loading of NUDC to the spindle for mitotic
RT progression.";
RL Cell Cycle 14:1529-1539(2015).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, TUBULIN-BINDING, PHOSPHORYLATION AT
RP SER-134; SER-144; SER-146; THR-490; THR-609 AND SER-981, AND MUTAGENESIS OF
RP SER-144 AND SER-146.
RX PubMed=31409757; DOI=10.1126/scisignal.aaw2939;
RA Adib R., Montgomery J.M., Atherton J., O'Regan L., Richards M.W.,
RA Straatman K.R., Roth D., Straube A., Bayliss R., Moores C.A., Fry A.M.;
RT "Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity
RT of EML4 to promote chromosome congression.";
RL Sci. Signal. 12:0-0(2019).
RN [20] {ECO:0007744|PDB:4CGC}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 6-64 OF MUTANT MET-38, SUBUNIT,
RP AND COILED COIL.
RX PubMed=25740311; DOI=10.1042/bj20150039;
RA Richards M.W., O'Regan L., Roth D., Montgomery J.M., Straube A., Fry A.M.,
RA Bayliss R.;
RT "Microtubule association of EML proteins and the EML4-ALK variant 3
RT oncoprotein require an N-terminal trimerization domain.";
RL Biochem. J. 467:529-536(2015).
CC -!- FUNCTION: Essential for the formation and stability of microtubules
CC (MTs) (PubMed:16890222, PubMed:31409757). Required for the organization
CC of the mitotic spindle and for the proper attachment of kinetochores to
CC MTs (PubMed:25789526). Promotes the recruitment of NUDC to the mitotic
CC spindle for mitotic progression (PubMed:25789526).
CC {ECO:0000269|PubMed:16890222, ECO:0000269|PubMed:25789526,
CC ECO:0000269|PubMed:31409757}.
CC -!- SUBUNIT: Homotrimer; self-association is mediated by the N-terminal
CC coiled coil (PubMed:25740311). Interacts (via WD repeats) with NUDC
CC (PubMed:25789526). Interacts with alpha- and beta-tubulin during
CC mitosis (PubMed:31409757). {ECO:0000269|PubMed:25740311,
CC ECO:0000269|PubMed:25789526, ECO:0000269|PubMed:31409757}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:16890222, ECO:0000269|PubMed:31409757,
CC ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:16890222}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:16890222,
CC ECO:0000269|PubMed:25789526}. Cytoplasm, cytoskeleton, microtubule
CC organizing center {ECO:0000269|PubMed:16890222,
CC ECO:0000269|PubMed:25789526}. Midbody {ECO:0000269|PubMed:25789526}.
CC Note=Localizes to microtubules (MTs) during interphase with a
CC significantly reduced affinity for MTs during mitosis.
CC {ECO:0000269|PubMed:31409757}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HC35-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HC35-2; Sequence=VSP_047192;
CC -!- PTM: Phosphorylated during mitosis (PubMed:16890222). Phosphorylation
CC at Ser-144 and Ser-146 promotes its dissociation from microtubules
CC during mitosis which is required for efficient chromosome congression
CC (PubMed:31409757). {ECO:0000269|PubMed:16890222,
CC ECO:0000269|PubMed:31409757}.
CC -!- DISEASE: Note=A chromosomal aberration involving EML4 has been
CC identified in a subset of patients with non-small-cell lung carcinoma.
CC This aberration leads to the production of a fusion protein between the
CC N-terminus of EML4 and the C-terminus of ALK. It is unclear whether the
CC fusion protein is caused by a simple inversion within 2p
CC (inv(2)(p21p23)) or whether the chromosome translocation involving 2p
CC is more complex. When tested in a heterologous system, the fusion
CC protein EML4-ALK possesses transforming activity that is dependent on
CC ALK catalytic activity, possibly due to spontaneous dimerization
CC mediated by the EML4 moiety, leading to ALK kinase activation.
CC {ECO:0000269|PubMed:17625570}.
CC -!- SIMILARITY: Belongs to the WD repeat EMAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI04648.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAA91919.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/EML4ID44353ch2p21.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF177377; AAG09279.2; -; mRNA.
DR EMBL; AK001804; BAA91919.1; ALT_INIT; mRNA.
DR EMBL; AK314702; BAG37250.1; -; mRNA.
DR EMBL; AC006038; AAY15086.1; -; Genomic_DNA.
DR EMBL; AC083949; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096668; AAY14895.1; -; Genomic_DNA.
DR EMBL; BC023522; AAH23522.1; -; mRNA.
DR EMBL; BC104647; AAI04648.1; ALT_SEQ; mRNA.
DR EMBL; BC140845; AAI40846.1; -; mRNA.
DR EMBL; BC146799; AAI46800.1; -; mRNA.
DR EMBL; AB274722; BAF73611.1; -; mRNA.
DR EMBL; AB275889; BAF73612.1; -; mRNA.
DR CCDS; CCDS1807.1; -. [Q9HC35-1]
DR CCDS; CCDS46266.1; -. [Q9HC35-2]
DR RefSeq; NP_001138548.1; NM_001145076.2. [Q9HC35-2]
DR RefSeq; NP_061936.2; NM_019063.4. [Q9HC35-1]
DR PDB; 4CGC; X-ray; 2.90 A; A/B/C=6-64.
DR PDBsum; 4CGC; -.
DR AlphaFoldDB; Q9HC35; -.
DR SMR; Q9HC35; -.
DR BioGRID; 118169; 72.
DR IntAct; Q9HC35; 24.
DR MINT; Q9HC35; -.
DR STRING; 9606.ENSP00000320663; -.
DR BindingDB; Q9HC35; -.
DR GlyGen; Q9HC35; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HC35; -.
DR PhosphoSitePlus; Q9HC35; -.
DR BioMuta; EML4; -.
DR DMDM; 296439364; -.
DR EPD; Q9HC35; -.
DR jPOST; Q9HC35; -.
DR MassIVE; Q9HC35; -.
DR MaxQB; Q9HC35; -.
DR PaxDb; Q9HC35; -.
DR PeptideAtlas; Q9HC35; -.
DR PRIDE; Q9HC35; -.
DR ProteomicsDB; 6116; -.
DR ProteomicsDB; 81631; -. [Q9HC35-1]
DR Antibodypedia; 29721; 150 antibodies from 26 providers.
DR DNASU; 27436; -.
DR Ensembl; ENST00000318522.10; ENSP00000320663.5; ENSG00000143924.19. [Q9HC35-1]
DR Ensembl; ENST00000402711.6; ENSP00000385059.2; ENSG00000143924.19. [Q9HC35-2]
DR GeneID; 27436; -.
DR KEGG; hsa:27436; -.
DR MANE-Select; ENST00000318522.10; ENSP00000320663.5; NM_019063.5; NP_061936.3.
DR UCSC; uc002rsi.3; human. [Q9HC35-1]
DR CTD; 27436; -.
DR DisGeNET; 27436; -.
DR GeneCards; EML4; -.
DR HGNC; HGNC:1316; EML4.
DR HPA; ENSG00000143924; Low tissue specificity.
DR MIM; 607442; gene.
DR neXtProt; NX_Q9HC35; -.
DR OpenTargets; ENSG00000143924; -.
DR Orphanet; 357191; Selection of therapeutic option in non-small cell lung carcinoma.
DR PharmGKB; PA27769; -.
DR VEuPathDB; HostDB:ENSG00000143924; -.
DR eggNOG; KOG2106; Eukaryota.
DR GeneTree; ENSGT00940000158434; -.
DR HOGENOM; CLU_011754_0_1_1; -.
DR InParanoid; Q9HC35; -.
DR OMA; LSSAAKX; -.
DR PhylomeDB; Q9HC35; -.
DR TreeFam; TF317832; -.
DR PathwayCommons; Q9HC35; -.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR Reactome; R-HSA-9700645; ALK mutants bind TKIs.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer.
DR SignaLink; Q9HC35; -.
DR BioGRID-ORCS; 27436; 22 hits in 1088 CRISPR screens.
DR ChiTaRS; EML4; human.
DR GeneWiki; EML4; -.
DR GenomeRNAi; 27436; -.
DR Pharos; Q9HC35; Tbio.
DR PRO; PR:Q9HC35; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HC35; protein.
DR Bgee; ENSG00000143924; Expressed in tibia and 181 other tissues.
DR ExpressionAtlas; Q9HC35; baseline and differential.
DR Genevisible; Q9HC35; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005815; C:microtubule organizing center; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0008608; P:attachment of spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007017; P:microtubule-based process; NAS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; NAS:UniProtKB.
DR GO; GO:0007080; P:mitotic metaphase plate congression; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR005108; HELP.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF03451; HELP; 1.
DR Pfam; PF00400; WD40; 5.
DR SMART; SM00320; WD40; 9.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 4.
DR PROSITE; PS50294; WD_REPEATS_REGION; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Chromosomal rearrangement; Coiled coil; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Microtubule; Mitosis; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..981
FT /note="Echinoderm microtubule-associated protein-like 4"
FT /id="PRO_0000050963"
FT REPEAT 259..297
FT /note="WD 1"
FT REPEAT 301..348
FT /note="WD 2"
FT REPEAT 356..396
FT /note="WD 3"
FT REPEAT 403..438
FT /note="WD 4"
FT REPEAT 445..484
FT /note="WD 5"
FT REPEAT 500..538
FT /note="WD 6"
FT REPEAT 543..579
FT /note="WD 7"
FT REPEAT 582..621
FT /note="WD 8"
FT REPEAT 625..662
FT /note="WD 9"
FT REPEAT 668..704
FT /note="WD 10"
FT REPEAT 711..750
FT /note="WD 11"
FT REPEAT 760..818
FT /note="WD 12"
FT REPEAT 825..864
FT /note="WD 13"
FT REGION 1..249
FT /note="Microtubule-binding"
FT /evidence="ECO:0000269|PubMed:16890222,
FT ECO:0000269|PubMed:31409757"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 881..981
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 14..63
FT /evidence="ECO:0000269|PubMed:25740311"
FT COMPBIAS 64..110
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..136
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 137..174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 881..897
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 906..929
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 934..950
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 496..497
FT /note="Breakpoint for translocation to form the EML4-ALK
FT fusion protein (variant 1)"
FT /evidence="ECO:0000269|PubMed:17625570"
FT SITE 747..748
FT /note="Breakpoint for translocation to form the EML4-ALK
FT fusion protein (variant 2)"
FT /evidence="ECO:0000269|PubMed:17625570"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 96
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 134
FT /note="Phosphoserine; by NEK7"
FT /evidence="ECO:0000269|PubMed:31409757"
FT MOD_RES 144
FT /note="Phosphoserine; by NEK6"
FT /evidence="ECO:0000269|PubMed:31409757,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 146
FT /note="Phosphoserine; by NEK7"
FT /evidence="ECO:0000269|PubMed:31409757,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 201
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 226
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 237
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 490
FT /note="Phosphothreonine; by NEK6"
FT /evidence="ECO:0000269|PubMed:31409757"
FT MOD_RES 609
FT /note="Phosphothreonine; by NEK6 and NEK7"
FT /evidence="ECO:0000269|PubMed:31409757"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 895
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 897
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 899
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 981
FT /note="Phosphoserine; by NEK6 and NEK7"
FT /evidence="ECO:0000269|PubMed:31409757"
FT VAR_SEQ 112..169
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047192"
FT VARIANT 283
FT /note="K -> E (in dbSNP:rs6736913)"
FT /evidence="ECO:0000269|PubMed:10995578,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17625570"
FT /id="VAR_031726"
FT VARIANT 382
FT /note="I -> V (in dbSNP:rs10202624)"
FT /evidence="ECO:0000269|PubMed:10995578,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17625570"
FT /id="VAR_031727"
FT VARIANT 398
FT /note="K -> R (in dbSNP:rs28651764)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_031728"
FT VARIANT 978
FT /note="S -> L (in dbSNP:rs28364731)"
FT /id="VAR_031729"
FT MUTAGEN 144
FT /note="S->A: Phosphorylation-deficient mutant which shows
FT increased localization to microtubules during mitosis,
FT increased microtubule stability and impaired chromosome
FT congression; when associated with A-146."
FT /evidence="ECO:0000269|PubMed:31409757"
FT MUTAGEN 144
FT /note="S->D: Phosphomimetic mutant which shows reduced
FT localization to microtubules during interphase; when
FT associated with D-146."
FT /evidence="ECO:0000269|PubMed:31409757"
FT MUTAGEN 146
FT /note="S->A: Phosphorylation-deficient mutant which shows
FT increased localization to microtubules during mitosis,
FT increased microtubule stability and impaired chromosome
FT congression; when associated with A-144."
FT /evidence="ECO:0000269|PubMed:31409757"
FT MUTAGEN 146
FT /note="S->D: Phosphomimetic mutant which shows reduced
FT localization to microtubules during interphase; when
FT associated with D-144."
FT /evidence="ECO:0000269|PubMed:31409757"
FT CONFLICT 768..773
FT /note="WTTYTC -> SSRPCW (in Ref. 4; AAY15086)"
FT /evidence="ECO:0000305"
FT HELIX 18..43
FT /evidence="ECO:0007829|PDB:4CGC"
SQ SEQUENCE 981 AA; 108916 MW; 7E8F2585747736B9 CRC64;
MDGFAGSLDD SISAASTSDV QDRLSALESR VQQQEDEITV LKAALADVLR RLAISEDHVA
SVKKSVSSKG QPSPRAVIPM SCITNGSGAN RKPSHTSAVS IAGKETLSSA AKSGTEKKKE
KPQGQREKKE ESHSNDQSPQ IRASPSPQPS SQPLQIHRQT PESKNATPTK SIKRPSPAEK
SHNSWENSDD SRNKLSKIPS TPKLIPKVTK TADKHKDVII NQEGEYIKMF MRGRPITMFI
PSDVDNYDDI RTELPPEKLK LEWAYGYRGK DCRANVYLLP TGKIVYFIAS VVVLFNYEER
TQRHYLGHTD CVKCLAIHPD KIRIATGQIA GVDKDGRPLQ PHVRVWDSVT LSTLQIIGLG
TFERGVGCLD FSKADSGVHL CIIDDSNEHM LTVWDWQKKA KGAEIKTTNE VVLAVEFHPT
DANTIITCGK SHIFFWTWSG NSLTRKQGIF GKYEKPKFVQ CLAFLGNGDV LTGDSGGVML
IWSKTTVEPT PGKGPKGVYQ ISKQIKAHDG SVFTLCQMRN GMLLTGGGKD RKIILWDHDL
NPEREIEVPD QYGTIRAVAE GKADQFLVGT SRNFILRGTF NDGFQIEVQG HTDELWGLAT
HPFKDLLLTC AQDRQVCLWN SMEHRLEWTR LVDEPGHCAD FHPSGTVVAI GTHSGRWFVL
DAETRDLVSI HTDGNEQLSV MRYSIDGTFL AVGSHDNFIY LYVVSENGRK YSRYGRCTGH
SSYITHLDWS PDNKYIMSNS GDYEILYWDI PNGCKLIRNR SDCKDIDWTT YTCVLGFQVF
GVWPEGSDGT DINALVRSHN RKVIAVADDF CKVHLFQYPC SKAKAPSHKY SAHSSHVTNV
SFTHNDSHLI STGGKDMSII QWKLVEKLSL PQNETVADTT LTKAPVSSTE SVIQSNTPTP
PPSQPLNETA EEESRISSSP TLLENSLEQT VEPSEDHSEE ESEEGSGDLG EPLYEEPCNE
ISKEQAKATL LEDQQDPSPS S
