DCTN1_HUMAN
ID DCTN1_HUMAN Reviewed; 1278 AA.
AC Q14203; A8MY36; B4DM45; E9PFS5; E9PGE1; G5E9H4; O95296; Q6IQ37; Q9BRM9;
AC Q9UIU1; Q9UIU2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Dynactin subunit 1;
DE AltName: Full=150 kDa dynein-associated polypeptide;
DE AltName: Full=DAP-150;
DE Short=DP-150;
DE AltName: Full=p135;
DE AltName: Full=p150-glued;
GN Name=DCTN1;
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 [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9799602; DOI=10.1006/geno.1998.5542;
RA Collin G.B., Nishina P.M., Marshall J.D., Naggert J.K.;
RT "Human DCTN1: genomic structure and evaluation as a candidate for Alstrom
RT syndrome.";
RL Genomics 53:359-364(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Brain, and Trachea;
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=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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Brain;
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 [GENOMIC DNA] OF 9-1278.
RC TISSUE=Brain;
RX PubMed=8838327; DOI=10.1006/geno.1996.0068;
RA Holzbaur E.L.F., Tokito M.K.;
RT "Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13
RT by fluorescence in situ hybridization.";
RL Genomics 31:398-399(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-1278 (ISOFORM 6), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=8856662; DOI=10.1091/mbc.7.8.1167;
RA Tokito M.K., Howland D.S., Lee V.M.-Y., Holzbaur E.L.F.;
RT "Functionally distinct isoforms of dynactin are expressed in human
RT neurons.";
RL Mol. Biol. Cell 7:1167-1180(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 18-1278.
RX PubMed=9805007; DOI=10.1016/s0167-4781(98)00195-x;
RA Tokito M.K., Holzbaur E.L.F.;
RT "The genomic structure of DCTN1, a candidate gene for limb-girdle muscular
RT dystrophy.";
RL Biochim. Biophys. Acta 1442:432-436(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1081-1278.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP INTERACTION WITH MAPRE1; MAPRE2 AND MAPRE3.
RX PubMed=14514668; DOI=10.1074/jbc.m306194200;
RA Bu W., Su L.-K.;
RT "Characterization of functional domains of human EB1 family proteins.";
RL J. Biol. Chem. 278:49721-49731(2003).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=17532294; DOI=10.1016/j.bbrc.2007.05.068;
RA Zhang N., Liu J., Ding X., Aikhionbare F., Jin C., Yao X.;
RT "FBXL5 interacts with p150Glued and regulates its ubiquitination.";
RL Biochem. Biophys. Res. Commun. 359:34-39(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [15]
RP INTERACTION WITH SNX6.
RX PubMed=19935774; DOI=10.1038/cr.2009.130;
RA Hong Z., Yang Y., Zhang C., Niu Y., Li K., Zhao X., Liu J.J.;
RT "The retromer component SNX6 interacts with dynactin p150(Glued) and
RT mediates endosome-to-TGN transport.";
RL Cell Res. 19:1334-1349(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-108, AND IDENTIFICATION BY
RP 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 [17]
RP INTERACTION WITH ECPAS.
RX PubMed=20682791; DOI=10.1074/jbc.m110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S., Hughes R.E.,
RA Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [18]
RP INTERACTION WITH PARD6A, AND SUBCELLULAR LOCATION.
RX PubMed=20719959; DOI=10.1091/mbc.e10-05-0430;
RA Kodani A., Tonthat V., Wu B., Suetterlin C.;
RT "Par6 alpha interacts with the dynactin subunit p150 Glued and is a
RT critical regulator of centrosomal protein recruitment.";
RL Mol. Biol. Cell 21:3376-3385(2010).
RN [19]
RP INTERACTION WITH DYNAP.
RX PubMed=20978158; DOI=10.1158/1535-7163.mct-10-0730;
RA Kunoh T., Noda T., Koseki K., Sekigawa M., Takagi M., Shin-ya K.,
RA Goshima N., Iemura S., Natsume T., Wada S., Mukai Y., Ohta S., Sasaki R.,
RA Mizukami T.;
RT "A novel human dynactin-associated protein, dynAP, promotes activation of
RT Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of
RT human cancer cells.";
RL Mol. Cancer Ther. 9:2934-2942(2010).
RN [20]
RP PHOSPHORYLATION AT SER-179 AND SER-212, MUTAGENESIS OF SER-179 AND SER-212,
RP INTERACTION WITH PLK1 AND CLIP1, AND SUBCELLULAR LOCATION.
RX PubMed=20679239; DOI=10.1073/pnas.1006615107;
RA Li H., Liu X.S., Yang X., Song B., Wang Y., Liu X.;
RT "Polo-like kinase 1 phosphorylation of p150Glued facilitates nuclear
RT envelope breakdown during prophase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:14633-14638(2010).
RN [21]
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 [22]
RP INTERACTION WITH DCDC1.
RX PubMed=22159412; DOI=10.1242/jcs.085407;
RA Kaplan A., Reiner O.;
RT "Linking cytoplasmic dynein and transport of Rab8 vesicles to the midbody
RT during cytokinesis by the doublecortin domain-containing 5 protein.";
RL J. Cell Sci. 124:3989-4000(2011).
RN [23]
RP INTERACTION WITH CLN3.
RX PubMed=22261744; DOI=10.1007/s00018-011-0913-1;
RA Uusi-Rauva K., Kyttala A., van der Kant R., Vesa J., Tanhuanpaa K.,
RA Neefjes J., Olkkonen V.M., Jalanko A.;
RT "Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins
RT and modifies location of late endosomal compartments.";
RL Cell. Mol. Life Sci. 69:2075-2089(2012).
RN [24]
RP INTERACTION WITH CEP131.
RX PubMed=22797915; DOI=10.1242/jcs.104059;
RA Staples C.J., Myers K.N., Beveridge R.D., Patil A.A., Lee A.J., Swanton C.,
RA Howell M., Boulton S.J., Collis S.J.;
RT "The centriolar satellite protein Cep131 is important for genome
RT stability.";
RL J. Cell Sci. 125:4770-4779(2012).
RN [25]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22327364; DOI=10.1038/ncb2440;
RA Kiyomitsu T., Cheeseman I.M.;
RT "Chromosome- and spindle-pole-derived signals generate an intrinsic code
RT for spindle position and orientation.";
RL Nat. Cell Biol. 14:311-317(2012).
RN [26]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23386061; DOI=10.1038/emboj.2013.3;
RA Kodani A., Salome Sirerol-Piquer M., Seol A., Garcia-Verdugo J.M.,
RA Reiter J.F.;
RT "Kif3a interacts with Dynactin subunit p150 Glued to organize centriole
RT subdistal appendages.";
RL EMBO J. 32:597-607(2013).
RN [27]
RP INTERACTION WITH MISP.
RX PubMed=23509069; DOI=10.1083/jcb.201207050;
RA Zhu M., Settele F., Kotak S., Sanchez-Pulido L., Ehret L., Ponting C.P.,
RA Goenczy P., Hoffmann I.;
RT "MISP is a novel Plk1 substrate required for proper spindle orientation and
RT mitotic progression.";
RL J. Cell Biol. 200:773-787(2013).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [29]
RP PHOSPHORYLATION AT THR-145; THR-146 AND THR-147, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF THR-145; THR-146 AND THR-147.
RX PubMed=23985322; DOI=10.1091/mbc.e13-03-0137;
RA Zhapparova O.N., Fokin A.I., Vorobyeva N.E., Bryantseva S.A.,
RA Nadezhdina E.S.;
RT "Ste20-like protein kinase SLK (LOSK) regulates microtubule organization by
RT targeting dynactin to the centrosome.";
RL Mol. Biol. Cell 24:3205-3214(2013).
RN [30]
RP INTERACTION WITH CEP126.
RX PubMed=24867236; DOI=10.1111/boc.201300087;
RA Bonavita R., Walas D., Brown A.K., Luini A., Stephens D.J., Colanzi A.;
RT "Cep126 is required for pericentriolar satellite localisation to the
RT centrosome and for primary cilium formation.";
RL Biol. Cell 106:254-267(2014).
RN [31]
RP INTERACTION WITH HPS6.
RX PubMed=25189619; DOI=10.1242/jcs.141978;
RA Li K., Yang L., Zhang C., Niu Y., Li W., Liu J.J.;
RT "HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking
RT and maturation of lysosomes.";
RL J. Cell Sci. 127:4574-4588(2014).
RN [32]
RP 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 [33]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25774020; DOI=10.1002/jcb.25160;
RA Chen T.Y., Syu J.S., Han T.Y., Cheng H.L., Lu F.I., Wang C.Y.;
RT "Cell cycle-dependent localization of dynactin subunit p150 glued at
RT centrosome.";
RL J. Cell. Biochem. 116:2049-2060(2015).
RN [34]
RP ASSOCIATION WITH MICROTUBULES, AND DOMAIN CAP-GLY.
RX PubMed=26968983; DOI=10.15252/embj.201593071;
RA McKenney R.J., Huynh W., Vale R.D., Sirajuddin M.;
RT "Tyrosination of alpha-tubulin controls the initiation of processive
RT dynein-dynactin motility.";
RL EMBO J. 35:1175-1185(2016).
RN [35]
RP INTERACTION WITH BCCIP.
RX PubMed=28394342; DOI=10.1038/onc.2017.92;
RA Huhn S.C., Liu J., Ye C., Lu H., Jiang X., Feng X., Ganesan S., White E.,
RA Shen Z.;
RT "Regulation of spindle integrity and mitotic fidelity by BCCIP.";
RL Oncogene 36:4750-4766(2017).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 15-107 IN COMPLEX WITH MAPRE1,
RP AND INTERACTION WITH MAPRE1.
RX PubMed=16109370; DOI=10.1016/j.molcel.2005.06.034;
RA Hayashi I., Wilde A., Mal T.K., Ikura M.;
RT "Structural basis for the activation of microtubule assembly by the EB1 and
RT p150Glued complex.";
RL Mol. Cell 19:449-460(2005).
RN [37]
RP STRUCTURE BY NMR OF 1-99.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CAP-Gly domain in human dynactin 1.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 18-111 IN COMPLEX WITH MAPRE1,
RP AND INTERACTION WITH MAPRE1.
RX PubMed=16949363; DOI=10.1016/j.molcel.2006.07.013;
RA Honnappa S., Okhrimenko O., Jaussi R., Jawhari H., Jelesarov I.,
RA Winkler F.K., Steinmetz M.O.;
RT "Key interaction modes of dynamic +TIP networks.";
RL Mol. Cell 23:663-671(2006).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 15-111 IN COMPLEX WITH CLIP1,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CLIP1.
RX PubMed=17828277; DOI=10.1038/nsmb1291;
RA Weisbrich A., Honnappa S., Jaussi R., Okhrimenko O., Frey D., Jelesarov I.,
RA Akhmanova A., Steinmetz M.O.;
RT "Structure-function relationship of CAP-Gly domains.";
RL Nat. Struct. Mol. Biol. 14:959-967(2007).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 15-107 IN COMPLEX WITH CLIP1,
RP INTERACTION WITH CLIP1, AND MUTAGENESIS OF LYS-68 AND ARG-90.
RX PubMed=17828275; DOI=10.1038/nsmb1299;
RA Hayashi I., Plevin M.J., Ikura M.;
RT "CLIP170 autoinhibition mimics intermolecular interactions with p150Glued
RT or EB1.";
RL Nat. Struct. Mol. Biol. 14:980-981(2007).
RN [41]
RP VARIANT HMN7B SER-59.
RX PubMed=12627231; DOI=10.1038/ng1123;
RA Puls I., Jonnakuty C., LaMonte B.H., Holzbaur E.L., Tokito M., Mann E.,
RA Floeter M.K., Bidus K., Drayna D., Oh S.J., Brown R.H. Jr., Ludlow C.L.,
RA Fischbeck K.H.;
RT "Mutant dynactin in motor neuron disease.";
RL Nat. Genet. 33:455-456(2003).
RN [42]
RP INVOLVEMENT IN ALS, AND VARIANTS ALS THR-571; TRP-785 AND ILE-1249.
RX PubMed=15326253; DOI=10.1212/01.wnl.0000134608.83927.b1;
RA Muench C., Sedlmeier R., Meyer T., Homberg V., Sperfeld A.D., Kurt A.,
RA Prudlo J., Peraus G., Hanemann C.O., Stumm G., Ludolph A.C.;
RT "Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS.";
RL Neurology 63:724-726(2004).
RN [43]
RP VARIANT ALS LYS-1101.
RX PubMed=16240349; DOI=10.1002/ana.20631;
RA Muench C., Rosenbohm A., Sperfeld A.-D., Uttner I., Reske S., Krause B.J.,
RA Sedlmeier R., Meyer T., Hanemann C.O., Stumm G., Ludolph A.C.;
RT "Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and
RT FTD.";
RL Ann. Neurol. 58:777-780(2005).
RN [44]
RP CHARACTERIZATION OF VARIANT HMN7B SER-59, AND INTERACTION WITH MAPRE1.
RX PubMed=16505168; DOI=10.1083/jcb.200511068;
RA Levy J.R., Sumner C.J., Caviston J.P., Tokito M.K., Ranganathan S.,
RA Ligon L.A., Wallace K.E., LaMonte B.H., Harmison G.G., Puls I.,
RA Fischbeck K.H., Holzbaur E.L.F.;
RT "A motor neuron disease-associated mutation in p150Glued perturbs dynactin
RT function and induces protein aggregation.";
RL J. Cell Biol. 172:733-745(2006).
RN [45]
RP VARIANTS VAL-196; GLN-495 AND ILE-1249.
RX PubMed=17824900; DOI=10.1111/j.1600-0404.2007.00884.x;
RA Muench C., Meyer R., Linke P., Meyer T., Ludolph A.C., Haas J., Hemmer B.;
RT "The p150 subunit of dynactin (DCTN1) gene in multiple sclerosis.";
RL Acta Neurol. Scand. 116:231-234(2007).
RN [46]
RP VARIANTS PERRYS ARG-71; GLU-71; ALA-71; PRO-72 AND PRO-74, CHARACTERIZATION
RP OF VARIANTS PERRYS ARG-71 AND PRO-74, AND CHARACTERIZATION OF VARIANT HMN7B
RP SER-59.
RX PubMed=19136952; DOI=10.1038/ng.293;
RA Farrer M.J., Hulihan M.M., Kachergus J.M., Daechsel J.C., Stoessl A.J.,
RA Grantier L.L., Calne S., Calne D.B., Lechevalier B., Chapon F., Tsuboi Y.,
RA Yamada T., Gutmann L., Elibol B., Bhatia K.P., Wider C.,
RA Vilarino-Gueell C., Ross O.A., Brown L.A., Castanedes-Casey M.,
RA Dickson D.W., Wszolek Z.K.;
RT "DCTN1 mutations in Perry syndrome.";
RL Nat. Genet. 41:163-165(2009).
RN [47]
RP VARIANT ILE-1249.
RX PubMed=19506225; DOI=10.1212/wnl.0b013e3181a92c4c;
RA Vilarino-Gueell C., Wider C., Soto-Ortolaza A.I., Cobb S.A.,
RA Kachergus J.M., Keeling B.H., Dachsel J.C., Hulihan M.M., Dickson D.W.,
RA Wszolek Z.K., Uitti R.J., Graff-Radford N.R., Boeve B.F., Josephs K.A.,
RA Miller B., Boylan K.B., Gwinn K., Adler C.H., Aasly J.O., Hentati F.,
RA Destee A., Krygowska-Wajs A., Chartier-Harlin M.-C., Ross O.A.,
RA Rademakers R., Farrer M.J.;
RT "Characterization of DCTN1 genetic variability in neurodegeneration.";
RL Neurology 72:2024-2028(2009).
RN [48]
RP CHARACTERIZATION OF VARIANT HMN7B SER-59.
RX PubMed=19279216; DOI=10.1073/pnas.0810828106;
RA Moore J.K., Sept D., Cooper J.A.;
RT "Neurodegeneration mutations in dynactin impair dynein-dependent nuclear
RT migration.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5147-5152(2009).
RN [49]
RP CHARACTERIZATION OF VARIANT HMN7B SER-59, CHARACTERIZATION OF VARIANT
RP 196-ILE, INTERACTION WITH TBCB, AND SUBCELLULAR LOCATION.
RX PubMed=22777741; DOI=10.1007/s00441-012-1463-z;
RA Kuh G.F., Stockmann M., Meyer-Ohlendorf M., Linta L., Proepper C.,
RA Ludolph A.C., Bockmann J., Boeckers T.M., Liebau S.;
RT "Tubulin-binding cofactor B is a direct interaction partner of the dynactin
RT subunit p150(Glued).";
RL Cell Tissue Res. 350:13-26(2012).
RN [50]
RP CHARACTERIZATION OF VARIANT PERRYS PRO-74, FUNCTION, SUBUNIT, AND
RP INTERACTION WITH MAPRE1.
RX PubMed=23874158; DOI=10.1371/journal.pbio.1001611;
RA Lazarus J.E., Moughamian A.J., Tokito M.K., Holzbaur E.L.;
RT "Dynactin subunit p150(Glued) is a neuron-specific anti-catastrophe
RT factor.";
RL PLoS Biol. 11:E1001611-E1001611(2013).
RN [51]
RP VARIANT PHE-670.
RX PubMed=24627108; DOI=10.1007/s00415-014-7289-8;
RA Schabhuettl M., Wieland T., Senderek J., Baets J., Timmerman V.,
RA De Jonghe P., Reilly M.M., Stieglbauer K., Laich E., Windhager R., Erwa W.,
RA Trajanoski S., Strom T.M., Auer-Grumbach M.;
RT "Whole-exome sequencing in patients with inherited neuropathies: outcome
RT and challenges.";
RL J. Neurol. 261:970-982(2014).
RN [52]
RP VARIANT PERRYS LEU-52.
RX PubMed=24676999; DOI=10.1002/mds.25833;
RA Araki E., Tsuboi Y., Daechsel J., Milnerwood A., Vilarino-Guell C.,
RA Fujii N., Mishima T., Oka T., Hara H., Fukae J., Farrer M.J.;
RT "A Novel DCTN1 mutation with late-onset parkinsonism and frontotemporal
RT atrophy.";
RL Mov. Disord. 29:1201-1204(2014).
RN [53]
RP CHARACTERIZATION OF VARIANTS PERRYS ARG-71 AND PRO-74, FUNCTION,
RP INTERACTION WITH DYNEIN INTERMEDIATE CHAIN AND DYNEIN HEAVY CHAIN, AND
RP DOMAIN CAP-GLY.
RX PubMed=25185702; DOI=10.1038/ncomms5807;
RA Ayloo S., Lazarus J.E., Dodda A., Tokito M., Ostap E.M., Holzbaur E.L.;
RT "Dynactin functions as both a dynamic tether and brake during dynein-driven
RT motility.";
RL Nat. Commun. 5:4807-4807(2014).
RN [54]
RP VARIANTS PERRYS ARG-71 AND CYS-78, AND CHARACTERIZATION OF VARIANTS PERRYS
RP ARG-71 AND CYS-78.
RX PubMed=24881494; DOI=10.1016/j.parkreldis.2014.05.004;
RA Tacik P., Fiesel F.C., Fujioka S., Ross O.A., Pretelt F.,
RA Castaneda Cardona C., Kidd A., Hlavac M., Raizis A., Okun M.S., Traynor S.,
RA Strongosky A.J., Springer W., Wszolek Z.K.;
RT "Three families with Perry syndrome from distinct parts of the world.";
RL Parkinsonism Relat. Disord. 20:884-888(2014).
RN [55]
RP CHARACTERIZATION OF VARIANT PERRYS ARG-71, SUBCELLULAR LOCATION, DOMAIN
RP CAP-GLY, INTERACTION WITH CLIP1, AND ASSOCIATION WITH MICROTUBULES.
RX PubMed=26972003; DOI=10.1016/j.celrep.2016.02.046;
RA Nirschl J.J., Magiera M.M., Lazarus J.E., Janke C., Holzbaur E.L.;
RT "Alpha-tubulin tyrosination and CLIP-170 phosphorylation regulate the
RT initiation of dynein-driven transport in neurons.";
RL Cell Rep. 14:2637-2652(2016).
CC -!- FUNCTION: Plays a key role in dynein-mediated retrograde transport of
CC vesicles and organelles along microtubules by recruiting and tethering
CC dynein to microtubules. Binds to both dynein and microtubules providing
CC a link between specific cargos, microtubules and dynein. Essential for
CC targeting dynein to microtubule plus ends, recruiting dynein to
CC membranous cargos and enhancing dynein processivity (the ability to
CC move along a microtubule for a long distance without falling off the
CC track). Can also act as a brake to slow the dynein motor during
CC motility along the microtubule (PubMed:25185702). Can regulate
CC microtubule stability by promoting microtubule formation, nucleation
CC and polymerization and by inhibiting microtubule catastrophe in
CC neurons. Inhibits microtubule catastrophe by binding both to
CC microtubules and to tubulin, leading to enhanced microtubule stability
CC along the axon (PubMed:23874158). Plays a role in metaphase spindle
CC orientation (PubMed:22327364). Plays a role in centriole cohesion and
CC subdistal appendage organization and function. Its recruitment to the
CC centriole in a KIF3A-dependent manner is essential for the maintenance
CC of centriole cohesion and the formation of subdistal appendage. Also
CC required for microtubule anchoring at the mother centriole
CC (PubMed:23386061). Plays a role in primary cilia formation
CC (PubMed:25774020). {ECO:0000269|PubMed:22327364,
CC ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158,
CC ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:23874158). Dynactin is a large
CC macromolecular complex of at least 10 components; p150(glued) binds
CC directly to microtubules and to cytoplasmic dynein. Interacts with the
CC C-terminus of MAPRE1, MAPRE2 and MAPRE3. Interacts (via C-terminus)
CC with SNX6. Interacts with CLN3, DYNAP, ECPAS and FBXL5. Interacts with
CC MISP; this interaction regulates its distribution at the cell cortex.
CC Interacts with CEP131. Interacts with CEP126 (PubMed:24867236).
CC Interacts with CLIP1 (PubMed:17828275, PubMed:17828277,
CC PubMed:26972003, PubMed:20679239). Interacts with dynein intermediate
CC chain and dynein heavy chain (PubMed:25185702). Interacts with PLK1
CC (via POLO-box domain) (PubMed:20679239). Interacts with TBCB
CC (PubMed:22777741). Binds preferentially to tyrosinated microtubules
CC than to detyrosinated microtubules (PubMed:26972003, PubMed:26968983).
CC Interacts with PARD6A (PubMed:20719959). Interacts with HPS6
CC (PubMed:25189619). Interacts with KIF3A. Interacts with BICD2 (By
CC similarity). Interacts with DST (isoform 9) (By similarity). Interacts
CC with DST (isoform 1) (By similarity). Identified in a complex with MREG
CC and RILP (By similarity). Interacts with BCCIP (isoform 2/alpha)
CC (PubMed:28394342). Interacts with DCDC1 (PubMed:22159412). Interacts
CC with AKNA (By similarity). Interacts with DYNC1I2 (By similarity).
CC {ECO:0000250|UniProtKB:O08788, ECO:0000269|PubMed:14514668,
CC ECO:0000269|PubMed:16109370, ECO:0000269|PubMed:16505168,
CC ECO:0000269|PubMed:16949363, ECO:0000269|PubMed:17532294,
CC ECO:0000269|PubMed:17828275, ECO:0000269|PubMed:17828277,
CC ECO:0000269|PubMed:19935774, ECO:0000269|PubMed:20679239,
CC ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:20719959,
CC ECO:0000269|PubMed:20978158, ECO:0000269|PubMed:22159412,
CC ECO:0000269|PubMed:22261744, ECO:0000269|PubMed:22777741,
CC ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:23509069,
CC ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:24867236,
CC ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25189619,
CC ECO:0000269|PubMed:26968983, ECO:0000269|PubMed:26972003,
CC ECO:0000269|PubMed:28394342}.
CC -!- INTERACTION:
CC Q14203; P42025: ACTR1B; NbExp=3; IntAct=EBI-724352, EBI-367493;
CC Q14203; Q96RK4: BBS4; NbExp=3; IntAct=EBI-724352, EBI-1805814;
CC Q14203; P30622-1: CLIP1; NbExp=7; IntAct=EBI-724352, EBI-9640673;
CC Q14203; Q15691: MAPRE1; NbExp=7; IntAct=EBI-724352, EBI-1004115;
CC Q14203; P10636-8: MAPT; NbExp=9; IntAct=EBI-724352, EBI-366233;
CC Q14203; Q9UNH7: SNX6; NbExp=2; IntAct=EBI-724352, EBI-949294;
CC Q14203; P54256: Hap1; Xeno; NbExp=4; IntAct=EBI-724352, EBI-994539;
CC Q14203-5; Q6ZTN6-2: ANKRD13D; NbExp=3; IntAct=EBI-25840379, EBI-25840993;
CC Q14203-5; P63010-2: AP2B1; NbExp=3; IntAct=EBI-25840379, EBI-11529439;
CC Q14203-5; P05067: APP; NbExp=5; IntAct=EBI-25840379, EBI-77613;
CC Q14203-5; O95671: ASMTL; NbExp=3; IntAct=EBI-25840379, EBI-743231;
CC Q14203-5; P18847: ATF3; NbExp=3; IntAct=EBI-25840379, EBI-712767;
CC Q14203-5; P46379-2: BAG6; NbExp=3; IntAct=EBI-25840379, EBI-10988864;
CC Q14203-5; Q8NFJ9: BBS1; NbExp=3; IntAct=EBI-25840379, EBI-1805484;
CC Q14203-5; O15392: BIRC5; NbExp=3; IntAct=EBI-25840379, EBI-518823;
CC Q14203-5; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-25840379, EBI-2837444;
CC Q14203-5; P42574: CASP3; NbExp=3; IntAct=EBI-25840379, EBI-524064;
CC Q14203-5; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-25840379, EBI-350590;
CC Q14203-5; O75935-2: DCTN3; NbExp=3; IntAct=EBI-25840379, EBI-12091947;
CC Q14203-5; O60479: DLX3; NbExp=3; IntAct=EBI-25840379, EBI-3908248;
CC Q14203-5; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-25840379, EBI-25840445;
CC Q14203-5; Q8TC29: ENKUR; NbExp=3; IntAct=EBI-25840379, EBI-9246952;
CC Q14203-5; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-25840379, EBI-10213520;
CC Q14203-5; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-25840379, EBI-396453;
CC Q14203-5; Q9UBN7: HDAC6; NbExp=6; IntAct=EBI-25840379, EBI-301697;
CC Q14203-5; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-25840379, EBI-9091197;
CC Q14203-5; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-25840379, EBI-21911304;
CC Q14203-5; Q96EK5: KIFBP; NbExp=3; IntAct=EBI-25840379, EBI-744150;
CC Q14203-5; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-25840379, EBI-714379;
CC Q14203-5; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-25840379, EBI-11985629;
CC Q14203-5; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-25840379, EBI-1108377;
CC Q14203-5; O95777: LSM8; NbExp=3; IntAct=EBI-25840379, EBI-347779;
CC Q14203-5; P43360: MAGEA6; NbExp=3; IntAct=EBI-25840379, EBI-1045155;
CC Q14203-5; P10636-6: MAPT; NbExp=3; IntAct=EBI-25840379, EBI-7796455;
CC Q14203-5; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-25840379, EBI-21250407;
CC Q14203-5; Q8N594: MPND; NbExp=3; IntAct=EBI-25840379, EBI-2512452;
CC Q14203-5; O15381-5: NVL; NbExp=3; IntAct=EBI-25840379, EBI-18577082;
CC Q14203-5; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-25840379, EBI-1058491;
CC Q14203-5; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-25840379, EBI-25830200;
CC Q14203-5; Q9BR81: PCDHGC3; NbExp=3; IntAct=EBI-25840379, EBI-22012354;
CC Q14203-5; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-25840379, EBI-6309018;
CC Q14203-5; P17980: PSMC3; NbExp=3; IntAct=EBI-25840379, EBI-359720;
CC Q14203-5; Q9UJ41-4: RABGEF1; NbExp=3; IntAct=EBI-25840379, EBI-14093916;
CC Q14203-5; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-25840379, EBI-25829984;
CC Q14203-5; Q8IYW5: RNF168; NbExp=3; IntAct=EBI-25840379, EBI-914207;
CC Q14203-5; Q96D59: RNF183; NbExp=3; IntAct=EBI-25840379, EBI-743938;
CC Q14203-5; Q92834-6: RPGR; NbExp=3; IntAct=EBI-25840379, EBI-16431517;
CC Q14203-5; Q8N488: RYBP; NbExp=3; IntAct=EBI-25840379, EBI-752324;
CC Q14203-5; Q15436: SEC23A; NbExp=3; IntAct=EBI-25840379, EBI-81088;
CC Q14203-5; Q9HCE7-2: SMURF1; NbExp=3; IntAct=EBI-25840379, EBI-9845742;
CC Q14203-5; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-25840379, EBI-11959123;
CC Q14203-5; O75886: STAM2; NbExp=3; IntAct=EBI-25840379, EBI-373258;
CC Q14203-5; Q15554-4: TERF2; NbExp=3; IntAct=EBI-25840379, EBI-25840535;
CC Q14203-5; Q71RG4-4: TMUB2; NbExp=3; IntAct=EBI-25840379, EBI-25831574;
CC Q14203-5; Q9H0E2: TOLLIP; NbExp=3; IntAct=EBI-25840379, EBI-74615;
CC Q14203-5; P19474: TRIM21; NbExp=3; IntAct=EBI-25840379, EBI-81290;
CC Q14203-5; Q8WVJ9: TWIST2; NbExp=3; IntAct=EBI-25840379, EBI-1797313;
CC Q14203-5; P62987: UBA52; NbExp=3; IntAct=EBI-25840379, EBI-357304;
CC Q14203-5; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-25840379, EBI-749370;
CC Q14203-5; Q8NBM4-4: UBAC2; NbExp=3; IntAct=EBI-25840379, EBI-25840976;
CC Q14203-5; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-25840379, EBI-7353612;
CC Q14203-5; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-25840379, EBI-11530712;
CC Q14203-5; Q96RL1-2: UIMC1; NbExp=3; IntAct=EBI-25840379, EBI-17761788;
CC Q14203-5; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-25840379, EBI-358545;
CC Q14203-5; O00308: WWP2; NbExp=3; IntAct=EBI-25840379, EBI-743923;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17828277}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:17828277,
CC ECO:0000269|PubMed:22777741, ECO:0000269|PubMed:25774020,
CC ECO:0000269|PubMed:26972003}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:14654843,
CC ECO:0000269|PubMed:20719959, ECO:0000269|PubMed:23985322,
CC ECO:0000269|PubMed:25774020}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole {ECO:0000269|PubMed:23386061,
CC ECO:0000269|PubMed:25774020}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:25774020}. Nucleus envelope
CC {ECO:0000269|PubMed:20679239}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:22327364}. Note=Localizes to microtubule plus ends
CC (PubMed:17828277, PubMed:22777741, PubMed:25774020). Localizes
CC preferentially to the ends of tyrosinated microtubules
CC (PubMed:26972003). Localization at centrosome is regulated by SLK-
CC dependent phosphorylation (PubMed:23985322). Localizes to centrosome in
CC a PARKDA-dependent manner (PubMed:20719959). Localizes to the subdistal
CC appendage region of the centriole in a KIF3A-dependent manner
CC (PubMed:23386061). PLK1-mediated phosphorylation at Ser-179 is
CC essential for its localization in the nuclear envelope
CC (PubMed:20679239). {ECO:0000269|PubMed:17828277,
CC ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:20719959,
CC ECO:0000269|PubMed:22777741, ECO:0000269|PubMed:23386061,
CC ECO:0000269|PubMed:23985322, ECO:0000269|PubMed:25774020,
CC ECO:0000269|PubMed:26972003}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=p150;
CC IsoId=Q14203-1; Sequence=Displayed;
CC Name=p135;
CC IsoId=Q14203-2; Sequence=VSP_000760;
CC Name=3;
CC IsoId=Q14203-3; Sequence=VSP_045392, VSP_045393, VSP_045394;
CC Name=4;
CC IsoId=Q14203-4; Sequence=VSP_045393, VSP_045394;
CC Name=5;
CC IsoId=Q14203-5; Sequence=VSP_000760, VSP_045394;
CC Name=6;
CC IsoId=Q14203-6; Sequence=VSP_047174;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The CAP-Gly domain is essential for interactions with
CC microtubules and its binding partners and for its motion along the
CC microtubules. Essential for its preferential binding to tyrosinated
CC microtubules and for promoting the sustained interaction of the dynein
CC motor with microtubules. {ECO:0000269|PubMed:25185702,
CC ECO:0000269|PubMed:26968983, ECO:0000269|PubMed:26972003}.
CC -!- PTM: Ubiquitinated by a SCF complex containing FBXL5, leading to its
CC degradation by the proteasome. {ECO:0000269|PubMed:17532294}.
CC -!- PTM: Phosphorylation by SLK at Thr-145, Thr-146 and Thr-147 targets
CC DCTN1 to the centrosome. It is uncertain if SLK phosphorylates all
CC three threonines or one or two of them. PLK1-mediated phosphorylation
CC at Ser-179 is essential for its localization in the nuclear envelope,
CC promotes its dissociation from microtubules during early mitosis and
CC positively regulates nuclear envelope breakdown during prophase.
CC {ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:23985322}.
CC -!- DISEASE: Neuronopathy, distal hereditary motor, 7B (HMN7B)
CC [MIM:607641]: A neuromuscular disorder. Distal hereditary motor
CC neuronopathies constitute a heterogeneous group of neuromuscular
CC disorders caused by selective degeneration of motor neurons in the
CC anterior horn of the spinal cord, without sensory deficit in the
CC posterior horn. The overall clinical picture consists of a classical
CC distal muscular atrophy syndrome in the legs without clinical sensory
CC loss. The disease starts with weakness and wasting of distal muscles of
CC the anterior tibial and peroneal compartments of the legs. Later on,
CC weakness and atrophy may expand to the proximal muscles of the lower
CC limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12627231,
CC ECO:0000269|PubMed:16505168, ECO:0000269|PubMed:19136952,
CC ECO:0000269|PubMed:19279216, ECO:0000269|PubMed:22777741}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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:15326253, ECO:0000269|PubMed:16240349}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Perry syndrome (PERRYS) [MIM:168605]: A neuropsychiatric
CC disorder characterized by mental depression not responsive to
CC antidepressant drugs or electroconvulsive therapy, sleep disturbances,
CC exhaustion and marked weight loss. Parkinsonism develops later and
CC respiratory failure occurred terminally. {ECO:0000269|PubMed:19136952,
CC ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:24676999,
CC ECO:0000269|PubMed:24881494, ECO:0000269|PubMed:25185702,
CC ECO:0000269|PubMed:26972003}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the dynactin 150 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AF064205; AAD55811.1; -; Genomic_DNA.
DR EMBL; AF064203; AAD55811.1; JOINED; Genomic_DNA.
DR EMBL; AF064204; AAD55811.1; JOINED; Genomic_DNA.
DR EMBL; AF064205; AAD55812.1; -; Genomic_DNA.
DR EMBL; AF064204; AAD55812.1; JOINED; Genomic_DNA.
DR EMBL; AK297286; BAG59757.1; -; mRNA.
DR EMBL; AK314352; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC005041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99684.1; -; Genomic_DNA.
DR EMBL; BC071583; AAH71583.1; -; mRNA.
DR EMBL; X98801; CAA67333.1; -; mRNA.
DR EMBL; AF086947; AAD03694.1; -; Genomic_DNA.
DR EMBL; AF086927; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086928; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086929; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086930; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086931; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086932; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086933; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086934; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086935; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086936; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086937; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086938; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086939; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086940; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086941; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086942; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086943; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086944; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086945; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; AF086946; AAD03694.1; JOINED; Genomic_DNA.
DR EMBL; BT006758; AAP35404.1; -; mRNA.
DR CCDS; CCDS1939.1; -. [Q14203-1]
DR CCDS; CCDS46341.1; -. [Q14203-4]
DR CCDS; CCDS46342.1; -. [Q14203-5]
DR CCDS; CCDS46343.1; -. [Q14203-2]
DR CCDS; CCDS54368.1; -. [Q14203-3]
DR CCDS; CCDS54369.1; -. [Q14203-6]
DR RefSeq; NP_001128512.1; NM_001135040.2. [Q14203-4]
DR RefSeq; NP_001128513.1; NM_001135041.2. [Q14203-5]
DR RefSeq; NP_001177765.1; NM_001190836.1. [Q14203-3]
DR RefSeq; NP_001177766.1; NM_001190837.1. [Q14203-6]
DR RefSeq; NP_004073.2; NM_004082.4. [Q14203-1]
DR RefSeq; NP_075408.1; NM_023019.3. [Q14203-2]
DR PDB; 1TXQ; X-ray; 1.80 A; A=15-107.
DR PDB; 2COY; NMR; -; A=1-99.
DR PDB; 2HKN; X-ray; 1.87 A; A/B=18-111.
DR PDB; 2HKQ; X-ray; 1.86 A; B=18-111.
DR PDB; 2HL3; X-ray; 2.03 A; A/B=18-111.
DR PDB; 2HL5; X-ray; 1.93 A; C/D=18-111.
DR PDB; 2HQH; X-ray; 1.80 A; A/B/C/D=15-107.
DR PDB; 3E2U; X-ray; 2.60 A; A/B/C/D=18-111.
DR PDB; 3TQ7; X-ray; 2.30 A; P/Q=27-97.
DR PDBsum; 1TXQ; -.
DR PDBsum; 2COY; -.
DR PDBsum; 2HKN; -.
DR PDBsum; 2HKQ; -.
DR PDBsum; 2HL3; -.
DR PDBsum; 2HL5; -.
DR PDBsum; 2HQH; -.
DR PDBsum; 3E2U; -.
DR PDBsum; 3TQ7; -.
DR AlphaFoldDB; Q14203; -.
DR BMRB; Q14203; -.
DR SMR; Q14203; -.
DR BioGRID; 108007; 374.
DR CORUM; Q14203; -.
DR DIP; DIP-31365N; -.
DR IntAct; Q14203; 281.
DR MINT; Q14203; -.
DR STRING; 9606.ENSP00000354791; -.
DR CarbonylDB; Q14203; -.
DR GlyGen; Q14203; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14203; -.
DR MetOSite; Q14203; -.
DR PhosphoSitePlus; Q14203; -.
DR SwissPalm; Q14203; -.
DR BioMuta; DCTN1; -.
DR DMDM; 17375490; -.
DR OGP; Q14203; -.
DR EPD; Q14203; -.
DR jPOST; Q14203; -.
DR MassIVE; Q14203; -.
DR MaxQB; Q14203; -.
DR PaxDb; Q14203; -.
DR PeptideAtlas; Q14203; -.
DR PRIDE; Q14203; -.
DR ProteomicsDB; 20166; -.
DR ProteomicsDB; 20302; -.
DR ProteomicsDB; 2371; -.
DR ProteomicsDB; 33940; -.
DR ProteomicsDB; 59925; -. [Q14203-1]
DR ProteomicsDB; 59926; -. [Q14203-2]
DR ABCD; Q14203; 1 sequenced antibody.
DR Antibodypedia; 3966; 329 antibodies from 42 providers.
DR DNASU; 1639; -.
DR Ensembl; ENST00000394003.7; ENSP00000377571.3; ENSG00000204843.13. [Q14203-6]
DR Ensembl; ENST00000409240.5; ENSP00000386406.1; ENSG00000204843.13. [Q14203-3]
DR Ensembl; ENST00000409438.5; ENSP00000387270.1; ENSG00000204843.13. [Q14203-5]
DR Ensembl; ENST00000409567.7; ENSP00000386843.3; ENSG00000204843.13. [Q14203-4]
DR Ensembl; ENST00000628224.3; ENSP00000487279.2; ENSG00000204843.13. [Q14203-1]
DR Ensembl; ENST00000633691.1; ENSP00000487724.1; ENSG00000204843.13. [Q14203-2]
DR GeneID; 1639; -.
DR KEGG; hsa:1639; -.
DR MANE-Select; ENST00000628224.3; ENSP00000487279.2; NM_004082.5; NP_004073.2.
DR UCSC; uc002sku.4; human. [Q14203-1]
DR CTD; 1639; -.
DR DisGeNET; 1639; -.
DR GeneCards; DCTN1; -.
DR GeneReviews; DCTN1; -.
DR HGNC; HGNC:2711; DCTN1.
DR HPA; ENSG00000204843; Low tissue specificity.
DR MalaCards; DCTN1; -.
DR MIM; 105400; phenotype.
DR MIM; 168605; phenotype.
DR MIM; 601143; gene.
DR MIM; 607641; phenotype.
DR neXtProt; NX_Q14203; -.
DR OpenTargets; ENSG00000204843; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 139589; Distal hereditary motor neuropathy type 7.
DR Orphanet; 178509; Perry syndrome.
DR PharmGKB; PA27180; -.
DR VEuPathDB; HostDB:ENSG00000204843; -.
DR eggNOG; KOG0971; Eukaryota.
DR GeneTree; ENSGT00940000155378; -.
DR HOGENOM; CLU_002523_0_0_1; -.
DR InParanoid; Q14203; -.
DR OMA; ADKNMRY; -.
DR PhylomeDB; Q14203; -.
DR TreeFam; TF105246; -.
DR PathwayCommons; Q14203; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. [Q14203-2]
DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes. [Q14203-2]
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes. [Q14203-2]
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome. [Q14203-2]
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes. [Q14203-2]
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. [Q14203-2]
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2. [Q14203-2]
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR SignaLink; Q14203; -.
DR SIGNOR; Q14203; -.
DR BioGRID-ORCS; 1639; 253 hits in 1080 CRISPR screens.
DR ChiTaRS; DCTN1; human.
DR EvolutionaryTrace; Q14203; -.
DR GeneWiki; DCTN1; -.
DR GenomeRNAi; 1639; -.
DR Pharos; Q14203; Tbio.
DR PRO; PR:Q14203; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14203; protein.
DR Bgee; ENSG00000204843; Expressed in right frontal lobe and 190 other tissues.
DR ExpressionAtlas; Q14203; baseline and differential.
DR Genevisible; Q14203; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0099738; C:cell cortex region; IDA:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0120103; C:centriolar subdistal appendage; IDA:GO_Central.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030286; C:dynein complex; IEA:UniProtKB-KW.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; IMP:ARUK-UCL.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0035371; C:microtubule plus-end; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0051010; F:microtubule plus-end binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0010457; P:centriole-centriole cohesion; IMP:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IBA:GO_Central.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0099558; P:maintenance of synapse structure; TAS:ARUK-UCL.
DR GO; GO:0032402; P:melanosome transport; IEA:Ensembl.
DR GO; GO:0034454; P:microtubule anchoring at centrosome; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; NAS:ProtInc.
DR GO; GO:0061744; P:motor behavior; IMP:ARUK-UCL.
DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:ARUK-UCL.
DR GO; GO:0050905; P:neuromuscular process; IMP:ARUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:ARUK-UCL.
DR GO; GO:1990535; P:neuron projection maintenance; IMP:ARUK-UCL.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:UniProtKB.
DR GO; GO:0051081; P:nuclear membrane disassembly; IMP:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; IDA:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IDA:UniProtKB.
DR GO; GO:1904398; P:positive regulation of neuromuscular junction development; IMP:ARUK-UCL.
DR GO; GO:0060236; P:regulation of mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR GO; GO:0021517; P:ventral spinal cord development; IMP:ARUK-UCL.
DR Gene3D; 2.30.30.190; -; 1.
DR InterPro; IPR036859; CAP-Gly_dom_sf.
DR InterPro; IPR000938; CAP-Gly_domain.
DR InterPro; IPR022157; Dynactin.
DR Pfam; PF01302; CAP_GLY; 1.
DR Pfam; PF12455; Dynactin; 1.
DR SMART; SM01052; CAP_GLY; 1.
DR SUPFAM; SSF74924; SSF74924; 1.
DR PROSITE; PS00845; CAP_GLY_1; 1.
DR PROSITE; PS50245; CAP_GLY_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis;
KW Cell cycle; Cell division; Coiled coil; Cytoplasm; Cytoskeleton; Dynein;
KW Microtubule; Mitosis; Neurodegeneration; Neuropathy; Nucleus; Parkinsonism;
KW Phosphoprotein; Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1..1278
FT /note="Dynactin subunit 1"
FT /id="PRO_0000083518"
FT DOMAIN 48..90
FT /note="CAP-Gly"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 911..1278
FT /note="Interaction with HPS6"
FT /evidence="ECO:0000269|PubMed:25189619"
FT COILED 213..547
FT /evidence="ECO:0000255"
FT COILED 943..1049
FT /evidence="ECO:0000255"
FT COILED 1182..1211
FT /evidence="ECO:0000255"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..150
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 145
FT /note="Phosphothreonine; by SLK"
FT /evidence="ECO:0000269|PubMed:23985322"
FT MOD_RES 146
FT /note="Phosphothreonine; by SLK"
FT /evidence="ECO:0000269|PubMed:23985322"
FT MOD_RES 147
FT /note="Phosphothreonine; by SLK"
FT /evidence="ECO:0000269|PubMed:23985322"
FT MOD_RES 179
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000269|PubMed:20679239"
FT MOD_RES 212
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:20679239"
FT VAR_SEQ 1..138
FT /note="MAQSKRHVYSRTPSGSRMSAEASARPLRVGSRVEVIGKGHRGTVAYVGATLF
FT ATGKWVGVILDEAKGKNDGTVQGRKYFTCDEGHGIFVRQSQIQVFEDGADTTSPETPDS
FT SASKVLKREGTDTTAKTSKLRGLKPKK -> MMRQ (in isoform p135 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000760"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045392"
FT VAR_SEQ 132..151
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045393"
FT VAR_SEQ 132..138
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:8856662"
FT /id="VSP_047174"
FT VAR_SEQ 1066..1070
FT /note="Missing (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_045394"
FT VARIANT 52
FT /note="F -> L (in PERRYS; mutation carriers either do not
FT develop depression or they do develop it late in the
FT disease course; dbSNP:rs886039227)"
FT /evidence="ECO:0000269|PubMed:24676999"
FT /id="VAR_071452"
FT VARIANT 59
FT /note="G -> S (in HMN7B; reduced affinity for microtubules
FT which has been suggested to impair axonal transport; the
FT effect is identical to that of complete loss of the CAP-Gly
FT domain; decreased interaction with MAPRE1; no effect on its
FT interaction with TBCB; dbSNP:rs121909342)"
FT /evidence="ECO:0000269|PubMed:12627231,
FT ECO:0000269|PubMed:16505168, ECO:0000269|PubMed:19136952,
FT ECO:0000269|PubMed:19279216, ECO:0000269|PubMed:22777741"
FT /id="VAR_015850"
FT VARIANT 71
FT /note="G -> A (in PERRYS; dbSNP:rs67586389)"
FT /evidence="ECO:0000269|PubMed:19136952"
FT /id="VAR_063867"
FT VARIANT 71
FT /note="G -> E (in PERRYS; dbSNP:rs67586389)"
FT /evidence="ECO:0000269|PubMed:19136952"
FT /id="VAR_063868"
FT VARIANT 71
FT /note="G -> R (in PERRYS; reduced microtubule binding;
FT results in the accumulation of intracytoplasmic inclusions;
FT loss of interaction with CLIP1; significant decrease in
FT motility of dynein-dynactin complex along microtubules;
FT dbSNP:rs72466485)"
FT /evidence="ECO:0000269|PubMed:19136952,
FT ECO:0000269|PubMed:24881494, ECO:0000269|PubMed:25185702,
FT ECO:0000269|PubMed:26972003"
FT /id="VAR_063869"
FT VARIANT 72
FT /note="T -> P (in PERRYS; dbSNP:rs72466486)"
FT /evidence="ECO:0000269|PubMed:19136952"
FT /id="VAR_063870"
FT VARIANT 74
FT /note="Q -> P (in PERRYS; diminishes microtubule binding
FT and lead to intracytoplasmic inclusions; significant
FT decrease in motility of dynein-dynactin complex along
FT microtubules; defective in inhibiting microtubule
FT catastrophe in neurons; dbSNP:rs72466487)"
FT /evidence="ECO:0000269|PubMed:19136952,
FT ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702"
FT /id="VAR_063871"
FT VARIANT 78
FT /note="Y -> C (in PERRYS; significantly reduced microtubule
FT binding; dbSNP:rs886039229)"
FT /evidence="ECO:0000269|PubMed:24881494"
FT /id="VAR_071453"
FT VARIANT 163
FT /note="A -> P"
FT /id="VAR_001373"
FT VARIANT 196
FT /note="I -> V (no effect of its interaction with TBCB; no
FT loss of localization to microtubules; dbSNP:rs55862001)"
FT /evidence="ECO:0000269|PubMed:17824900,
FT ECO:0000269|PubMed:22777741"
FT /id="VAR_076920"
FT VARIANT 287
FT /note="L -> M (in dbSNP:rs13420401)"
FT /id="VAR_048677"
FT VARIANT 495
FT /note="R -> Q (in dbSNP:rs17721059)"
FT /evidence="ECO:0000269|PubMed:17824900"
FT /id="VAR_048678"
FT VARIANT 571
FT /note="M -> T (in ALS; associated with disease
FT susceptibility; dbSNP:rs121909343)"
FT /evidence="ECO:0000269|PubMed:15326253"
FT /id="VAR_063872"
FT VARIANT 670
FT /note="Y -> F (found in a patient with hereditary motor and
FT sensory neuropathy; unknown pathological significance;
FT dbSNP:rs765819985)"
FT /evidence="ECO:0000269|PubMed:24627108"
FT /id="VAR_073287"
FT VARIANT 785
FT /note="R -> W (in ALS; associated with disease
FT susceptibility; dbSNP:rs121909344)"
FT /evidence="ECO:0000269|PubMed:15326253"
FT /id="VAR_063873"
FT VARIANT 1101
FT /note="R -> K (in ALS; associated with disease
FT susceptibility; dbSNP:rs121909345)"
FT /evidence="ECO:0000269|PubMed:16240349"
FT /id="VAR_063874"
FT VARIANT 1249
FT /note="T -> I (in ALS; unknown pathological significance;
FT dbSNP:rs72466496)"
FT /evidence="ECO:0000269|PubMed:15326253,
FT ECO:0000269|PubMed:17824900, ECO:0000269|PubMed:19506225"
FT /id="VAR_063875"
FT MUTAGEN 68
FT /note="K->A: Abolishes interaction with CLIP1."
FT /evidence="ECO:0000269|PubMed:17828275"
FT MUTAGEN 90
FT /note="R->E: Abolishes interaction with CLIP1."
FT /evidence="ECO:0000269|PubMed:17828275"
FT MUTAGEN 145
FT /note="T->A: Affects centrosomal localization; when
FT associated with A-146 and A-147."
FT /evidence="ECO:0000269|PubMed:23985322"
FT MUTAGEN 146
FT /note="T->A: Affects centrosomal localization; when
FT associated with A-145 and A-147."
FT /evidence="ECO:0000269|PubMed:23985322"
FT MUTAGEN 147
FT /note="T->A: Affects centrosomal localization; when
FT associated with A-145 and A-146."
FT /evidence="ECO:0000269|PubMed:23985322"
FT MUTAGEN 179
FT /note="S->A: Non-phosphorylatable by PLK1. Decreased
FT nuclear envelope localization. No loss of microtubule-
FT binding. No effect on its interaction with CLIP1."
FT /evidence="ECO:0000269|PubMed:20679239"
FT MUTAGEN 179
FT /note="S->D: No loss of localization to nuclear envelope.
FT Decrease in microtubule-binding. No effect on its
FT interaction with CLIP1."
FT /evidence="ECO:0000269|PubMed:20679239"
FT MUTAGEN 212
FT /note="S->A: No effect on its interaction with CLIP1 and
FT PLK1."
FT /evidence="ECO:0000269|PubMed:20679239"
FT CONFLICT 10
FT /note="S -> N (in Ref. 7; CAA67333)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="Q -> R (in Ref. 2; BAG59757)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="K -> R (in Ref. 2; AK314352)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="A -> V (in Ref. 2; AK314352)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="H -> N (in Ref. 5; AAH71583)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="K -> R (in Ref. 5; AAH71583)"
FT /evidence="ECO:0000305"
FT CONFLICT 712
FT /note="D -> V (in Ref. 7; CAA67333)"
FT /evidence="ECO:0000305"
FT CONFLICT 1081
FT /note="V -> M (in Ref. 9; AAP35404)"
FT /evidence="ECO:0000305"
FT CONFLICT 1261
FT /note="R -> Q (in Ref. 2; BAG59757)"
FT /evidence="ECO:0000305"
FT CONFLICT 1274
FT /note="S -> I (in Ref. 5; AAH71583)"
FT /evidence="ECO:0000305"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:2COY"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:1TXQ"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 57..65
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:1TXQ"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:2HQH"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:1TXQ"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1TXQ"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:1TXQ"
SQ SEQUENCE 1278 AA; 141695 MW; 6DCEA5E67856E4BC CRC64;
MAQSKRHVYS RTPSGSRMSA EASARPLRVG SRVEVIGKGH RGTVAYVGAT LFATGKWVGV
ILDEAKGKND GTVQGRKYFT CDEGHGIFVR QSQIQVFEDG ADTTSPETPD SSASKVLKRE
GTDTTAKTSK LRGLKPKKAP TARKTTTRRP KPTRPASTGV AGASSSLGPS GSASAGELSS
SEPSTPAQTP LAAPIIPTPV LTSPGAVPPL PSPSKEEEGL RAQVRDLEEK LETLRLKRAE
DKAKLKELEK HKIQLEQVQE WKSKMQEQQA DLQRRLKEAR KEAKEALEAK ERYMEEMADT
ADAIEMATLD KEMAEERAES LQQEVEALKE RVDELTTDLE ILKAEIEEKG SDGAASSYQL
KQLEEQNARL KDALVRMRDL SSSEKQEHVK LQKLMEKKNQ ELEVVRQQRE RLQEELSQAE
STIDELKEQV DAALGAEEMV EMLTDRNLNL EEKVRELRET VGDLEAMNEM NDELQENARE
TELELREQLD MAGARVREAQ KRVEAAQETV ADYQQTIKKY RQLTAHLQDV NRELTNQQEA
SVERQQQPPP ETFDFKIKFA ETKAHAKAIE MELRQMEVAQ ANRHMSLLTA FMPDSFLRPG
GDHDCVLVLL LMPRLICKAE LIRKQAQEKF ELSENCSERP GLRGAAGEQL SFAAGLVYSL
SLLQATLHRY EHALSQCSVD VYKKVGSLYP EMSAHERSLD FLIELLHKDQ LDETVNVEPL
TKAIKYYQHL YSIHLAEQPE DCTMQLADHI KFTQSALDCM SVEVGRLRAF LQGGQEATDI
ALLLRDLETS CSDIRQFCKK IRRRMPGTDA PGIPAALAFG PQVSDTLLDC RKHLTWVVAV
LQEVAAAAAQ LIAPLAENEG LLVAALEELA FKASEQIYGT PSSSPYECLR QSCNILISTM
NKLATAMQEG EYDAERPPSK PPPVELRAAA LRAEITDAEG LGLKLEDRET VIKELKKSLK
IKGEELSEAN VRLSLLEKKL DSAAKDADER IEKVQTRLEE TQALLRKKEK EFEETMDALQ
ADIDQLEAEK AELKQRLNSQ SKRTIEGLRG PPPSGIATLV SGIAGEEQQR GAIPGQAPGS
VPGPGLVKDS PLLLQQISAM RLHISQLQHE NSILKGAQMK ASLASLPPLH VAKLSHEGPG
SELPAGALYR KTSQLLETLN QLSTHTHVVD ITRTSPAAKS PSAQLMEQVA QLKSLSDTVE
KLKDEVLKET VSQRPGATVP TDFATFPSSA FLRAKEEQQD DTVYMGKVTF SCAAGFGQRH
RLVLTQEQLH QLHSRLIS
