DYHC1_HUMAN
ID DYHC1_HUMAN Reviewed; 4646 AA.
AC Q14204; B0I1R0; Q6DKQ7; Q8WU28; Q92814; Q9Y4G5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 5.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Cytoplasmic dynein 1 heavy chain 1;
DE AltName: Full=Cytoplasmic dynein heavy chain 1;
DE AltName: Full=Dynein heavy chain, cytosolic;
GN Name=DYNC1H1; Synonyms=DHC1, DNCH1, DNCL, DNECL, DYHC, KIAA0325;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-4029.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Yamakawa H., Nomura N.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yamakawa H., Kikuno R.F., Nagase T., Ohara O.;
RT "Multiplex amplification and cloning of 5'-ends of cDNA by ligase-free
RT recombination: preparation of full-length cDNA clones encoding motor
RT proteins.";
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-3902 AND GLN-4029.
RG NIEHS SNPs program;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1130-2026.
RX PubMed=8666668; DOI=10.1083/jcb.133.4.831;
RA Vaisberg E.A., Grissom P.M., McIntosh J.R.;
RT "Mammalian cells express three distinct dynein heavy chains that are
RT localized to different cytoplasmic organelles.";
RL J. Cell Biol. 133:831-842(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1884-2024.
RX PubMed=8227145; DOI=10.1083/jcb.123.4.849;
RA Vaisberg E.A., Koonce M.P., McIntosh J.R.;
RT "Cytoplasmic dynein plays a role in mammalian mitotic spindle formation.";
RL J. Cell Biol. 123:849-858(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3658-4646.
RC TISSUE=Placenta;
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4368, AND IDENTIFICATION BY
RP 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 [11]
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 LYS-1125; LYS-3480 AND LYS-4283, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-4162; THR-4366 AND
RP SER-4368, AND IDENTIFICATION BY MASS 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 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [19]
RP FUNCTION.
RX PubMed=27462074; DOI=10.1074/jbc.m116.724831;
RA Chu X., Chen X., Wan Q., Zheng Z., Du Q.;
RT "Nuclear mitotic apparatus (NuMA) interacts with and regulates astrin at
RT the mitotic spindle.";
RL J. Biol. Chem. 291:20055-20067(2016).
RN [20]
RP INTERACTION WITH CRACR2A.
RX PubMed=31092558; DOI=10.1083/jcb.201810118;
RA Miteva K.T., Pedicini L., Wilson L.A., Jayasinghe I., Slip R.G.,
RA Marszalek K., Gaunt H.J., Bartoli F., Deivasigamani S., Sobradillo D.,
RA Beech D.J., McKeown L.;
RT "Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo
RT release from Weibel-Palade bodies.";
RL J. Cell Biol. 218:2232-2246(2019).
RN [21]
RP VARIANT MRD13 PRO-3822.
RX PubMed=21076407; DOI=10.1038/ng.712;
RA Vissers L.E., de Ligt J., Gilissen C., Janssen I., Steehouwer M.,
RA de Vries P., van Lier B., Arts P., Wieskamp N., del Rosario M.,
RA van Bon B.W., Hoischen A., de Vries B.B., Brunner H.G., Veltman J.A.;
RT "A de novo paradigm for mental retardation.";
RL Nat. Genet. 42:1109-1112(2010).
RN [22]
RP VARIANT CMT2O ARG-306.
RX PubMed=21820100; DOI=10.1016/j.ajhg.2011.07.002;
RA Weedon M.N., Hastings R., Caswell R., Xie W., Paszkiewicz K., Antoniadi T.,
RA Williams M., King C., Greenhalgh L., Newbury-Ecob R., Ellard S.;
RT "Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with
RT dominant axonal Charcot-Marie-Tooth disease.";
RL Am. J. Hum. Genet. 89:308-312(2011).
RN [23]
RP VARIANT MRD13 LYS-1518.
RX PubMed=22368300; DOI=10.1136/jmedgenet-2011-100542;
RA Willemsen M.H., Vissers L.E., Willemsen M.A., van Bon B.W., Kroes T.,
RA de Ligt J., de Vries B.B., Schoots J., Lugtenberg D., Hamel B.C.,
RA van Bokhoven H., Brunner H.G., Veltman J.A., Kleefstra T.;
RT "Mutations in DYNC1H1 cause severe intellectual disability with neuronal
RT migration defects.";
RL J. Med. Genet. 49:179-183(2012).
RN [24]
RP VARIANT SMALED1 ARG-306.
RX PubMed=22847149; DOI=10.1007/s10048-012-0337-6;
RA Tsurusaki Y., Saitoh S., Tomizawa K., Sudo A., Asahina N., Shiraishi H.,
RA Ito J.I., Tanaka H., Doi H., Saitsu H., Miyake N., Matsumoto N.;
RT "A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower
RT extremity predominance.";
RL Neurogenetics 13:327-332(2012).
RN [25]
RP VARIANTS SMALED1 LEU-584; GLU-671 AND CYS-970, AND CHARACTERIZATION OF
RP VARIANT SMALED1 LEU-584.
RX PubMed=22459677; DOI=10.1212/wnl.0b013e3182556c05;
RA Harms M.B., Ori-McKenney K.M., Scoto M., Tuck E.P., Bell S., Ma D.,
RA Masi S., Allred P., Al-Lozi M., Reilly M.M., Miller L.J., Jani-Acsadi A.,
RA Pestronk A., Shy M.E., Muntoni F., Vallee R.B., Baloh R.H.;
RT "Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular
RT atrophy.";
RL Neurology 78:1714-1720(2012).
RN [26]
RP VARIANT MRD13 LYS-1518, AND VARIANTS ALA-142; LEU-1250; MET-2247; CYS-4143;
RP SER-4285; THR-4421; SER-4507 AND GLY-4603.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [27]
RP VARIANTS MRD13 ILE-129; 659-THR--MET-662 DEL; GLN-1567; CYS-1962; THR-3241;
RP ASN-3336; GLN-3344 AND GLN-3384, AND CHARACTERIZATION OF VARIANTS MRD13
RP ASN-3336 AND GLN-3384.
RX PubMed=23603762; DOI=10.1038/ng.2613;
RA Poirier K., Lebrun N., Broix L., Tian G., Saillour Y., Boscheron C.,
RA Parrini E., Valence S., Pierre B.S., Oger M., Lacombe D., Genevieve D.,
RA Fontana E., Darra F., Cances C., Barth M., Bonneau D., Bernadina B.D.,
RA N'guyen S., Gitiaux C., Parent P., des Portes V., Pedespan J.M., Legrez V.,
RA Castelnau-Ptakine L., Nitschke P., Hieu T., Masson C., Zelenika D.,
RA Andrieux A., Francis F., Guerrini R., Cowan N.J., Bahi-Buisson N.,
RA Chelly J.;
RT "Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of
RT cortical development and microcephaly.";
RL Nat. Genet. 45:639-647(2013).
RN [28]
RP VARIANT LYS-94, VARIANT SMALED1 LEU-264, VARIANT CMT2O CYS-598,
RP CHARACTERIZATION OF VARIANT SMALED1 LEU-264, CHARACTERIZATION OF VARIANT
RP CMT2O CYS-598, AND INTERACTION WITH BICD2.
RX PubMed=25512093; DOI=10.1002/humu.22744;
RA Peeters K., Bervoets S., Chamova T., Litvinenko I., De Vriendt E.,
RA Bichev S., Kancheva D., Mitev V., Kennerson M., Timmerman V., De Jonghe P.,
RA Tournev I., MacMillan J., Jordanova A.;
RT "Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical
RT spectrum of dyneinopathies.";
RL Hum. Mutat. 36:287-291(2015).
RN [29]
RP VARIANTS CMT2O ARG-1194 AND LYS-3048, AND CHARACTERIZATION OF VARIANTS
RP CMT2O ARG-1194 AND LYS-3048.
RX PubMed=24307404; DOI=10.1002/humu.22491;
RA Fiorillo C., Moro F., Yi J., Weil S., Brisca G., Astrea G., Severino M.,
RA Romano A., Battini R., Rossi A., Minetti C., Bruno C., Santorelli F.M.,
RA Vallee R.;
RT "Novel dynein DYNC1H1 neck and motor domain mutations link distal spinal
RT muscular atrophy and abnormal cortical development.";
RL Hum. Mutat. 35:298-302(2014).
RN [30]
RP VARIANT SMALED1 CYS-598.
RX PubMed=25484024; DOI=10.1016/j.pediatrneurol.2014.09.003;
RA Punetha J., Monges S., Franchi M.E., Hoffman E.P., Cirak S., Tesi-Rocha C.;
RT "Exome Sequencing Identifies DYNC1H1 Variant Associated With Vertebral
RT Abnormality and Spinal Muscular Atrophy With Lower Extremity
RT Predominance.";
RL Pediatr. Neurol. 52:239-244(2015).
RN [31]
RP VARIANT SMALED1 LEU-776.
RX PubMed=26846447; DOI=10.1038/srep20423;
RA Ding D., Chen Z., Li K., Long Z., Ye W., Tang Z., Xia K., Qiu R., Tang B.,
RA Jiang H.;
RT "Identification of a de novo DYNC1H1 mutation via WES according to
RT published guidelines.";
RL Sci. Rep. 6:20423-20423(2016).
RN [32]
RP VARIANT SMALED1 GLU-1132, AND VARIANT MRD13 GLN-3384.
RX PubMed=28193117; DOI=10.1177/0883073816683083;
RA Chen Y., Xu Y., Li G., Li N., Yu T., Yao R.E., Wang X., Shen Y., Wang J.;
RT "Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With
RT Distal Spinal Muscular Atrophy and Malformations of Cortical Development.";
RL J. Child Neurol. 32:379-386(2017).
CC -!- FUNCTION: Cytoplasmic dynein 1 acts as a motor for the intracellular
CC retrograde motility of vesicles and organelles along microtubules.
CC Dynein has ATPase activity; the force-producing power stroke is thought
CC to occur on release of ADP. Plays a role in mitotic spindle assembly
CC and metaphase plate congression (PubMed:27462074).
CC {ECO:0000269|PubMed:27462074}.
CC -!- SUBUNIT: Homodimer. The cytoplasmic dynein 1 complex consists of two
CC catalytic heavy chains (HCs) and a number of non-catalytic subunits
CC presented by intermediate chains (ICs), light intermediate chains
CC (LICs) and light chains (LCs); the composition seems to vary in respect
CC to the IC, LIC and LC composition. The heavy chain homodimer serves as
CC a scaffold for the probable homodimeric assembly of the respective non-
CC catalytic subunits. The ICs and LICs bind directly to the HC dimer and
CC dynein LCs assemble on the IC dimer. Interacts with DYNC1LI1; DYNC1LI1
CC and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with
CC DYNC1LI2; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1.
CC Interacts with DYNC1I2 (By similarity). Interacts with BICD2
CC (PubMed:25512093). Interacts with isoform 2 of CRACR2A
CC (PubMed:31092558). Interacts with DNALI1 (By similarity).
CC {ECO:0000250|UniProtKB:P38650, ECO:0000250|UniProtKB:Q9JHU4,
CC ECO:0000269|PubMed:25512093, ECO:0000269|PubMed:31092558}.
CC -!- INTERACTION:
CC Q14204; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-356015, EBI-2875816;
CC Q14204; Q12797-6: ASPH; NbExp=3; IntAct=EBI-356015, EBI-12092171;
CC Q14204; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-356015, EBI-12811889;
CC Q14204; O95817: BAG3; NbExp=3; IntAct=EBI-356015, EBI-747185;
CC Q14204; Q9BXY8: BEX2; NbExp=3; IntAct=EBI-356015, EBI-745073;
CC Q14204; Q7L1Q6-2: BZW1; NbExp=3; IntAct=EBI-356015, EBI-21557060;
CC Q14204; P49336-2: CDK8; NbExp=3; IntAct=EBI-356015, EBI-11039720;
CC Q14204; Q9Y281: CFL2; NbExp=3; IntAct=EBI-356015, EBI-351218;
CC Q14204; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-356015, EBI-10260134;
CC Q14204; P26998: CRYBB3; NbExp=3; IntAct=EBI-356015, EBI-1965681;
CC Q14204; P09668: CTSH; NbExp=3; IntAct=EBI-356015, EBI-6189940;
CC Q14204; Q9BTE7: DCUN1D5; NbExp=3; IntAct=EBI-356015, EBI-3924013;
CC Q14204; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-356015, EBI-529989;
CC Q14204; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-356015, EBI-3443946;
CC Q14204; Q13144: EIF2B5; NbExp=3; IntAct=EBI-356015, EBI-4401110;
CC Q14204; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-356015, EBI-11337888;
CC Q14204; P24522: GADD45A; NbExp=3; IntAct=EBI-356015, EBI-448167;
CC Q14204; B2RAF7: hCG_1818547; NbExp=3; IntAct=EBI-356015, EBI-25844370;
CC Q14204; P42858: HTT; NbExp=8; IntAct=EBI-356015, EBI-466029;
CC Q14204; Q14005-2: IL16; NbExp=3; IntAct=EBI-356015, EBI-17178971;
CC Q14204; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-356015, EBI-9088829;
CC Q14204; Q99683: MAP3K5; NbExp=3; IntAct=EBI-356015, EBI-476263;
CC Q14204; Q15759: MAPK11; NbExp=3; IntAct=EBI-356015, EBI-298304;
CC Q14204; Q92886: NEUROG1; NbExp=3; IntAct=EBI-356015, EBI-10279647;
CC Q14204; P20783-2: NTF3; NbExp=3; IntAct=EBI-356015, EBI-25844111;
CC Q14204; P32243-2: OTX2; NbExp=3; IntAct=EBI-356015, EBI-9087860;
CC Q14204; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-356015, EBI-9091052;
CC Q14204; O75381: PEX14; NbExp=4; IntAct=EBI-356015, EBI-594898;
CC Q14204; P19388: POLR2E; NbExp=3; IntAct=EBI-356015, EBI-395189;
CC Q14204; O60237-2: PPP1R12B; NbExp=3; IntAct=EBI-356015, EBI-10700351;
CC Q14204; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-356015, EBI-2860740;
CC Q14204; P49810: PSEN2; NbExp=3; IntAct=EBI-356015, EBI-2010251;
CC Q14204; Q96DX8: RTP4; NbExp=3; IntAct=EBI-356015, EBI-12275482;
CC Q14204; P48443: RXRG; NbExp=3; IntAct=EBI-356015, EBI-712405;
CC Q14204; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-356015, EBI-25837959;
CC Q14204; Q5T0L3: SPATA46; NbExp=3; IntAct=EBI-356015, EBI-750105;
CC Q14204; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-356015, EBI-11123832;
CC Q14204; O15273: TCAP; NbExp=3; IntAct=EBI-356015, EBI-954089;
CC Q14204; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-356015, EBI-12090309;
CC Q14204; O60830: TIMM17B; NbExp=3; IntAct=EBI-356015, EBI-2372529;
CC Q14204; Q8IU80-2: TMPRSS6; NbExp=3; IntAct=EBI-356015, EBI-25839648;
CC Q14204; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-356015, EBI-9089156;
CC Q14204; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-356015, EBI-10316321;
CC Q14204; P61964: WDR5; NbExp=3; IntAct=EBI-356015, EBI-540834;
CC Q14204; O00308: WWP2; NbExp=3; IntAct=EBI-356015, EBI-743923;
CC Q14204; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-356015, EBI-25830993;
CC Q14204; Q96EJ4; NbExp=3; IntAct=EBI-356015, EBI-750454;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- DOMAIN: Dynein heavy chains probably consist of an N-terminal stem
CC (which binds cargo and interacts with other dynein components), and the
CC head or motor domain. The motor contains six tandemly-linked AAA
CC domains in the head, which form a ring. A stalk-like structure (formed
CC by two of the coiled coil domains) protrudes between AAA 4 and AAA 5
CC and terminates in a microtubule-binding site. A seventh domain may also
CC contribute to this ring; it is not clear whether the N-terminus or the
CC C-terminus forms this extra domain. There are four well-conserved and
CC two non-conserved ATPase sites, one per AAA domain. Probably only one
CC of these (within AAA 1) actually hydrolyzes ATP, the others may serve a
CC regulatory function.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2O (CMT2O) [MIM:614228]: An axonal
CC form of Charcot-Marie-Tooth disease, a disorder of the peripheral
CC nervous system, characterized by progressive weakness and atrophy,
CC initially of the peroneal muscles and later of the distal muscles of
CC the arms. Charcot-Marie-Tooth disease is classified in two main groups
CC on the basis of electrophysiologic properties and histopathology:
CC primary peripheral demyelinating neuropathies (designated CMT1 when
CC they are dominantly inherited) and primary peripheral axonal
CC neuropathies (CMT2). Neuropathies of the CMT2 group are characterized
CC by signs of axonal degeneration in the absence of obvious myelin
CC alterations, normal or slightly reduced nerve conduction velocities,
CC and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:21820100, ECO:0000269|PubMed:24307404,
CC ECO:0000269|PubMed:25512093}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 13
CC (MRD13) [MIM:614563]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRD13
CC is associated with variable neuronal migration defects and mild
CC dysmorphic features. Some patients may also show signs of peripheral
CC neuropathy, such as abnormal gait and hyporeflexia.
CC {ECO:0000269|PubMed:21076407, ECO:0000269|PubMed:22368300,
CC ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23603762,
CC ECO:0000269|PubMed:28193117}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spinal muscular atrophy, lower extremity-predominant 1,
CC autosomal dominant (SMALED1) [MIM:158600]: A form of spinal muscular
CC atrophy, a neuromuscular disorder characterized by degeneration of the
CC anterior horn cells of the spinal cord, leading to symmetrical muscle
CC weakness and atrophy. SMALED1 is characterized by muscle weakness
CC predominantly affecting the proximal lower extremities.
CC {ECO:0000269|PubMed:22459677, ECO:0000269|PubMed:22847149,
CC ECO:0000269|PubMed:25484024, ECO:0000269|PubMed:25512093,
CC ECO:0000269|PubMed:26846447, ECO:0000269|PubMed:28193117}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the dynein heavy chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20783.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dnch1/";
CC ---------------------------------------------------------------------------
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DR EMBL; AB002323; BAA20783.3; ALT_INIT; mRNA.
DR EMBL; AB290157; BAG06711.1; -; mRNA.
DR EMBL; AY682080; AAT74625.1; -; Genomic_DNA.
DR EMBL; U53530; AAB09727.1; -; mRNA.
DR EMBL; L23958; AAA16065.1; -; mRNA.
DR EMBL; BC021297; AAH21297.2; -; mRNA.
DR CCDS; CCDS9966.1; -.
DR PIR; A49019; A49019.
DR PIR; G02529; G02529.
DR RefSeq; NP_001367.2; NM_001376.4.
DR PDB; 5NUG; EM; 3.80 A; A/B=1-4646.
DR PDB; 5OWO; X-ray; 1.79 A; A/B/C/D=1-201.
DR PDB; 6F1T; EM; 3.50 A; e/f/m/n=1-1053.
DR PDB; 6F1U; EM; 3.40 A; f/m/n=1-1186.
DR PDB; 6F1V; EM; 3.40 A; f/m=1-1186.
DR PDB; 6F1Y; EM; 3.40 A; f=780-927.
DR PDB; 6F38; EM; 6.70 A; e/f/m/n=1-1455.
DR PDB; 6F3A; EM; 8.20 A; e/f=1-1455.
DR PDBsum; 5NUG; -.
DR PDBsum; 5OWO; -.
DR PDBsum; 6F1T; -.
DR PDBsum; 6F1U; -.
DR PDBsum; 6F1V; -.
DR PDBsum; 6F1Y; -.
DR PDBsum; 6F38; -.
DR PDBsum; 6F3A; -.
DR BMRB; Q14204; -.
DR SMR; Q14204; -.
DR BioGRID; 108117; 285.
DR ComplexPortal; CPX-5025; Cytoplasmic dynein complex, variant 1.
DR CORUM; Q14204; -.
DR DIP; DIP-37544N; -.
DR IntAct; Q14204; 176.
DR MINT; Q14204; -.
DR STRING; 9606.ENSP00000348965; -.
DR CarbonylDB; Q14204; -.
DR GlyGen; Q14204; 5 sites, 2 O-linked glycans (5 sites).
DR iPTMnet; Q14204; -.
DR MetOSite; Q14204; -.
DR PhosphoSitePlus; Q14204; -.
DR SwissPalm; Q14204; -.
DR BioMuta; DYNC1H1; -.
DR DMDM; 57015308; -.
DR EPD; Q14204; -.
DR jPOST; Q14204; -.
DR MassIVE; Q14204; -.
DR MaxQB; Q14204; -.
DR PaxDb; Q14204; -.
DR PeptideAtlas; Q14204; -.
DR PRIDE; Q14204; -.
DR ProteomicsDB; 59927; -.
DR Antibodypedia; 122; 151 antibodies from 27 providers.
DR DNASU; 1778; -.
DR Ensembl; ENST00000360184.10; ENSP00000348965.4; ENSG00000197102.14.
DR GeneID; 1778; -.
DR KEGG; hsa:1778; -.
DR MANE-Select; ENST00000360184.10; ENSP00000348965.4; NM_001376.5; NP_001367.2.
DR UCSC; uc001yks.3; human.
DR CTD; 1778; -.
DR DisGeNET; 1778; -.
DR GeneCards; DYNC1H1; -.
DR GeneReviews; DYNC1H1; -.
DR HGNC; HGNC:2961; DYNC1H1.
DR HPA; ENSG00000197102; Low tissue specificity.
DR MalaCards; DYNC1H1; -.
DR MIM; 158600; phenotype.
DR MIM; 600112; gene.
DR MIM; 614228; phenotype.
DR MIM; 614563; phenotype.
DR neXtProt; NX_Q14204; -.
DR OpenTargets; ENSG00000197102; -.
DR Orphanet; 284232; Autosomal dominant Charcot-Marie-Tooth disease type 2O.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 209341; DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy.
DR PharmGKB; PA27432; -.
DR VEuPathDB; HostDB:ENSG00000197102; -.
DR eggNOG; KOG3595; Eukaryota.
DR GeneTree; ENSGT00940000156103; -.
DR HOGENOM; CLU_000038_7_0_1; -.
DR InParanoid; Q14204; -.
DR OMA; FIMDEAN; -.
DR OrthoDB; 26380at2759; -.
DR PhylomeDB; Q14204; -.
DR TreeFam; TF101165; -.
DR PathwayCommons; Q14204; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
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.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
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-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9646399; Aggrephagy.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q14204; -.
DR SIGNOR; Q14204; -.
DR BioGRID-ORCS; 1778; 790 hits in 1091 CRISPR screens.
DR ChiTaRS; DYNC1H1; human.
DR GeneWiki; DYNC1H1; -.
DR GenomeRNAi; 1778; -.
DR Pharos; Q14204; Tbio.
DR PRO; PR:Q14204; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q14204; protein.
DR Bgee; ENSG00000197102; Expressed in cortical plate and 201 other tissues.
DR ExpressionAtlas; Q14204; baseline and differential.
DR Genevisible; Q14204; HS.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005868; C:cytoplasmic dynein complex; IDA:GO_Central.
DR GO; GO:0005881; C:cytoplasmic microtubule; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030286; C:dynein complex; IPI:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045505; F:dynein intermediate chain binding; IBA:GO_Central.
DR GO; GO:0051959; F:dynein light intermediate chain binding; IPI:FlyBase.
DR GO; GO:0008569; F:minus-end-directed microtubule motor activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IBA:GO_Central.
DR GO; GO:0051293; P:establishment of spindle localization; IMP:CACAO.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0072382; P:minus-end-directed vesicle transport along microtubule; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007052; P:mitotic spindle organization; NAS:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0033962; P:P-body assembly; ISS:BHF-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0032388; P:positive regulation of intracellular transport; IMP:UniProtKB.
DR GO; GO:1905832; P:positive regulation of spindle assembly; IMP:UniProtKB.
DR GO; GO:0090235; P:regulation of metaphase plate congression; IMP:UniProtKB.
DR GO; GO:0060236; P:regulation of mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0008090; P:retrograde axonal transport; IBA:GO_Central.
DR GO; GO:0034063; P:stress granule assembly; ISS:BHF-UCL.
DR Gene3D; 1.10.8.710; -; 1.
DR Gene3D; 1.10.8.720; -; 1.
DR Gene3D; 1.20.140.100; -; 1.
DR Gene3D; 3.10.490.20; -; 1.
DR Gene3D; 3.20.180.20; -; 1.
DR Gene3D; 3.40.50.300; -; 5.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR035699; AAA_6.
DR InterPro; IPR035706; AAA_9.
DR InterPro; IPR041658; AAA_lid_11.
DR InterPro; IPR042219; AAA_lid_11_sf.
DR InterPro; IPR042222; Dynein_2_N.
DR InterPro; IPR043157; Dynein_AAA1S.
DR InterPro; IPR041466; Dynein_AAA5_ext.
DR InterPro; IPR041228; Dynein_C.
DR InterPro; IPR043160; Dynein_C_barrel.
DR InterPro; IPR024743; Dynein_HC_stalk.
DR InterPro; IPR024317; Dynein_heavy_chain_D4_dom.
DR InterPro; IPR004273; Dynein_heavy_D6_P-loop.
DR InterPro; IPR013602; Dynein_heavy_linker.
DR InterPro; IPR013594; Dynein_heavy_tail.
DR InterPro; IPR042228; Dynein_linker_3.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF12774; AAA_6; 1.
DR Pfam; PF12780; AAA_8; 1.
DR Pfam; PF12781; AAA_9; 1.
DR Pfam; PF18198; AAA_lid_11; 1.
DR Pfam; PF08385; DHC_N1; 1.
DR Pfam; PF08393; DHC_N2; 1.
DR Pfam; PF17852; Dynein_AAA_lid; 1.
DR Pfam; PF18199; Dynein_C; 1.
DR Pfam; PF03028; Dynein_heavy; 1.
DR Pfam; PF12777; MT; 1.
DR SMART; SM00382; AAA; 4.
DR SUPFAM; SSF52540; SSF52540; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Charcot-Marie-Tooth disease; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Dynein; Intellectual disability; Microtubule; Mitosis;
KW Motor protein; Neurodegeneration; Neuropathy; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..4646
FT /note="Cytoplasmic dynein 1 heavy chain 1"
FT /id="PRO_0000114627"
FT REGION 53..1867
FT /note="Stem"
FT /evidence="ECO:0000250"
FT REGION 448..703
FT /note="Interaction with DYNC1I2"
FT /evidence="ECO:0000250"
FT REGION 651..802
FT /note="Interaction with DYNC1LI2"
FT /evidence="ECO:0000250"
FT REGION 1868..2099
FT /note="AAA 1"
FT /evidence="ECO:0000250"
FT REGION 2180..2452
FT /note="AAA 2"
FT /evidence="ECO:0000250"
FT REGION 2390..2411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2556..2805
FT /note="AAA 3"
FT /evidence="ECO:0000250"
FT REGION 2899..3168
FT /note="AAA 4"
FT /evidence="ECO:0000250"
FT REGION 3189..3500
FT /note="Stalk"
FT /evidence="ECO:0000250"
FT REGION 3553..3782
FT /note="AAA 5"
FT /evidence="ECO:0000250"
FT REGION 4005..4221
FT /note="AAA 6"
FT /evidence="ECO:0000250"
FT COILED 181..202
FT /evidence="ECO:0000255"
FT COILED 455..478
FT /evidence="ECO:0000255"
FT COILED 543..566
FT /evidence="ECO:0000255"
FT COILED 1171..1252
FT /evidence="ECO:0000255"
FT COILED 1357..1373
FT /evidence="ECO:0000255"
FT COILED 3189..3275
FT /evidence="ECO:0000255"
FT COILED 3396..3500
FT /evidence="ECO:0000255"
FT COILED 3737..3800
FT /evidence="ECO:0000255"
FT COMPBIAS 2390..2408
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1906..1913
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 2224..2231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 2595..2602
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 2937..2944
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1125
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1230
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHU4"
FT MOD_RES 3480
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 4162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 4283
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 4366
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 4368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 94
FT /note="E -> K (found in a patient with spinal muscular
FT atrophy; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25512093"
FT /id="VAR_073155"
FT VARIANT 129
FT /note="K -> I (in MRD13; dbSNP:rs1555407885)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070580"
FT VARIANT 142
FT /note="E -> A"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069437"
FT VARIANT 264
FT /note="R -> L (in SMALED1; slight increased BICD2-binding;
FT dbSNP:rs713993043)"
FT /evidence="ECO:0000269|PubMed:25512093"
FT /id="VAR_073156"
FT VARIANT 306
FT /note="H -> R (in CMT2O and SMALED1; dbSNP:rs387906738)"
FT /evidence="ECO:0000269|PubMed:21820100,
FT ECO:0000269|PubMed:22847149"
FT /id="VAR_066651"
FT VARIANT 584
FT /note="I -> L (in SMALED1; disrupts dynein complex
FT stability and function; dbSNP:rs387906741)"
FT /evidence="ECO:0000269|PubMed:22459677"
FT /id="VAR_067820"
FT VARIANT 598
FT /note="R -> C (in CMT2O and SMALED1; slight increased
FT BICD2-binding; dbSNP:rs587780564)"
FT /evidence="ECO:0000269|PubMed:25484024,
FT ECO:0000269|PubMed:25512093"
FT /id="VAR_073157"
FT VARIANT 659..662
FT /note="Missing (in MRD13)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070581"
FT VARIANT 671
FT /note="K -> E (in SMALED1; dbSNP:rs387906742)"
FT /evidence="ECO:0000269|PubMed:22459677"
FT /id="VAR_067821"
FT VARIANT 776
FT /note="P -> L (in SMALED1; dbSNP:rs1057518083)"
FT /evidence="ECO:0000269|PubMed:26846447"
FT /id="VAR_078241"
FT VARIANT 970
FT /note="Y -> C (in SMALED1; dbSNP:rs387906743)"
FT /evidence="ECO:0000269|PubMed:22459677"
FT /id="VAR_067822"
FT VARIANT 1132
FT /note="G -> E (in SMALED1)"
FT /evidence="ECO:0000269|PubMed:28193117"
FT /id="VAR_078242"
FT VARIANT 1194
FT /note="Q -> R (in CMT2O; impairs function;
FT dbSNP:rs1555408964)"
FT /evidence="ECO:0000269|PubMed:24307404"
FT /id="VAR_072092"
FT VARIANT 1250
FT /note="V -> L (in dbSNP:rs369914512)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069438"
FT VARIANT 1518
FT /note="E -> K (in MRD13; dbSNP:rs387906740)"
FT /evidence="ECO:0000269|PubMed:22368300,
FT ECO:0000269|PubMed:23033978"
FT /id="VAR_067823"
FT VARIANT 1567
FT /note="R -> Q (in MRD13; dbSNP:rs797044901)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070582"
FT VARIANT 1962
FT /note="R -> C (in MRD13; dbSNP:rs879253881)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070583"
FT VARIANT 2247
FT /note="V -> M (in dbSNP:rs1064796963)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069439"
FT VARIANT 3048
FT /note="E -> K (in CMT2O; impairs function;
FT dbSNP:rs1555410941)"
FT /evidence="ECO:0000269|PubMed:24307404"
FT /id="VAR_072093"
FT VARIANT 3241
FT /note="K -> T (in MRD13; dbSNP:rs1555411145)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070584"
FT VARIANT 3336
FT /note="K -> N (in MRD13; shows a substantial reduction in
FT the microtubule binding affinity compared to the wild-type
FT control protein; dbSNP:rs397509410)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070585"
FT VARIANT 3344
FT /note="R -> Q (in MRD13; dbSNP:rs397509412)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070586"
FT VARIANT 3384
FT /note="R -> Q (in MRD13; patients manifest malformations of
FT cortical development; shows a substantial reduction in the
FT microtubule binding affinity compared to the wild-type
FT control protein; dbSNP:rs397509411)"
FT /evidence="ECO:0000269|PubMed:23603762,
FT ECO:0000269|PubMed:28193117"
FT /id="VAR_070587"
FT VARIANT 3822
FT /note="H -> P (in MRD13; de novo mutation;
FT dbSNP:rs387906739)"
FT /evidence="ECO:0000269|PubMed:21076407"
FT /id="VAR_065085"
FT VARIANT 3902
FT /note="D -> N (in dbSNP:rs17512818)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020889"
FT VARIANT 4029
FT /note="H -> Q (in dbSNP:rs10129889)"
FT /evidence="ECO:0000269|PubMed:9205841, ECO:0000269|Ref.4"
FT /id="VAR_020890"
FT VARIANT 4143
FT /note="R -> C (in dbSNP:rs1316357429)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069440"
FT VARIANT 4285
FT /note="A -> S (in dbSNP:rs749486351)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069441"
FT VARIANT 4421
FT /note="A -> T (in dbSNP:rs376492799)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069442"
FT VARIANT 4507
FT /note="I -> S"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069443"
FT VARIANT 4603
FT /note="S -> G"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069444"
FT CONFLICT 1778..1779
FT /note="LH -> SD (in Ref. 5; AAB09727)"
FT /evidence="ECO:0000305"
FT CONFLICT 1941
FT /note="M -> R (in Ref. 5; AAB09727)"
FT /evidence="ECO:0000305"
FT CONFLICT 2025
FT /note="R -> N (in Ref. 5; AAB09727)"
FT /evidence="ECO:0000305"
FT HELIX 27..41
FT /evidence="ECO:0007829|PDB:5OWO"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:5OWO"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:6F1T"
FT STRAND 76..85
FT /evidence="ECO:0007829|PDB:5OWO"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:5OWO"
FT STRAND 113..124
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:5OWO"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 178..199
FT /evidence="ECO:0007829|PDB:5OWO"
FT HELIX 211..222
FT /evidence="ECO:0007829|PDB:6F1U"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 239..260
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 271..293
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 295..306
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 322..332
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 350..363
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:6F1T"
FT TURN 368..370
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 374..397
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 401..403
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 406..440
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 442..444
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 455..482
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 519..533
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 534..537
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 539..541
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 542..574
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 578..587
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 590..593
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 597..603
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 605..624
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 627..629
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 631..638
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 643..669
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 670..675
FT /evidence="ECO:0007829|PDB:6F1U"
FT STRAND 676..678
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 679..692
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 696..706
FT /evidence="ECO:0007829|PDB:6F1U"
FT TURN 707..717
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 729..731
FT /evidence="ECO:0007829|PDB:6F1T"
FT HELIX 742..755
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 762..772
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 775..796
FT /evidence="ECO:0007829|PDB:6F1U"
FT HELIX 801..821
FT /evidence="ECO:0007829|PDB:6F1U"
FT STRAND 826..828
FT /evidence="ECO:0007829|PDB:6F1V"
FT HELIX 830..862
FT /evidence="ECO:0007829|PDB:6F1V"
FT TURN 863..866
FT /evidence="ECO:0007829|PDB:6F1V"
FT HELIX 871..890
FT /evidence="ECO:0007829|PDB:6F1V"
FT HELIX 896..925
FT /evidence="ECO:0007829|PDB:6F1V"
FT HELIX 989..992
FT /evidence="ECO:0007829|PDB:6F1T"
FT HELIX 994..997
FT /evidence="ECO:0007829|PDB:6F1T"
FT HELIX 999..1002
FT /evidence="ECO:0007829|PDB:6F1T"
FT TURN 1009..1011
FT /evidence="ECO:0007829|PDB:6F1T"
FT STRAND 1021..1023
FT /evidence="ECO:0007829|PDB:6F1T"
FT TURN 1024..1027
FT /evidence="ECO:0007829|PDB:6F1T"
FT HELIX 1033..1050
FT /evidence="ECO:0007829|PDB:6F1T"
SQ SEQUENCE 4646 AA; 532408 MW; D4D4E15DFBDE4797 CRC64;
MSEPGGGGGE DGSAGLEVSA VQNVADVSVL QKHLRKLVPL LLEDGGEAPA ALEAALEEKS
ALEQMRKFLS DPQVHTVLVE RSTLKEDVGD EGEEEKEFIS YNINIDIHYG VKSNSLAFIK
RTPVIDADKP VSSQLRVLTL SEDSPYETLH SFISNAVAPF FKSYIRESGK ADRDGDKMAP
SVEKKIAELE MGLLHLQQNI EIPEISLPIH PMITNVAKQC YERGEKPKVT DFGDKVEDPT
FLNQLQSGVN RWIREIQKVT KLDRDPASGT ALQEISFWLN LERALYRIQE KRESPEVLLT
LDILKHGKRF HATVSFDTDT GLKQALETVN DYNPLMKDFP LNDLLSATEL DKIRQALVAI
FTHLRKIRNT KYPIQRALRL VEAISRDLSS QLLKVLGTRK LMHVAYEEFE KVMVACFEVF
QTWDDEYEKL QVLLRDIVKR KREENLKMVW RINPAHRKLQ ARLDQMRKFR RQHEQLRAVI
VRVLRPQVTA VAQQNQGEVP EPQDMKVAEV LFDAADANAI EEVNLAYENV KEVDGLDVSK
EGTEAWEAAM KRYDERIDRV ETRITARLRD QLGTAKNANE MFRIFSRFNA LFVRPHIRGA
IREYQTQLIQ RVKDDIESLH DKFKVQYPQS QACKMSHVRD LPPVSGSIIW AKQIDRQLTA
YMKRVEDVLG KGWENHVEGQ KLKQDGDSFR MKLNTQEIFD DWARKVQQRN LGVSGRIFTI
ESTRVRGRTG NVLKLKVNFL PEIITLSKEV RNLKWLGFRV PLAIVNKAHQ ANQLYPFAIS
LIESVRTYER TCEKVEERNT ISLLVAGLKK EVQALIAEGI ALVWESYKLD PYVQRLAETV
FNFQEKVDDL LIIEEKIDLE VRSLETCMYD HKTFSEILNR VQKAVDDLNL HSYSNLPIWV
NKLDMEIERI LGVRLQAGLR AWTQVLLGQA EDKAEVDMDT DAPQVSHKPG GEPKIKNVVH
ELRITNQVIY LNPPIEECRY KLYQEMFAWK MVVLSLPRIQ SQRYQVGVHY ELTEEEKFYR
NALTRMPDGP VALEESYSAV MGIVSEVEQY VKVWLQYQCL WDMQAENIYN RLGEDLNKWQ
ALLVQIRKAR GTFDNAETKK EFGPVVIDYG KVQSKVNLKY DSWHKEVLSK FGQMLGSNMT
EFHSQISKSR QELEQHSVDT ASTSDAVTFI TYVQSLKRKI KQFEKQVELY RNGQRLLEKQ
RFQFPPSWLY IDNIEGEWGA FNDIMRRKDS AIQQQVANLQ MKIVQEDRAV ESRTTDLLTD
WEKTKPVTGN LRPEEALQAL TIYEGKFGRL KDDREKCAKA KEALELTDTG LLSGSEERVQ
VALEELQDLK GVWSELSKVW EQIDQMKEQP WVSVQPRKLR QNLDALLNQL KSFPARLRQY
ASYEFVQRLL KGYMKINMLV IELKSEALKD RHWKQLMKRL HVNWVVSELT LGQIWDVDLQ
KNEAIVKDVL LVAQGEMALE EFLKQIREVW NTYELDLVNY QNKCRLIRGW DDLFNKVKEH
INSVSAMKLS PYYKVFEEDA LSWEDKLNRI MALFDVWIDV QRRWVYLEGI FTGSADIKHL
LPVETQRFQS ISTEFLALMK KVSKSPLVMD VLNIQGVQRS LERLADLLGK IQKALGEYLE
RERSSFPRFY FVGDEDLLEI IGNSKNVAKL QKHFKKMFAG VSSIILNEDN SVVLGISSRE
GEEVMFKTPV SITEHPKINE WLTLVEKEMR VTLAKLLAES VTEVEIFGKA TSIDPNTYIT
WIDKYQAQLV VLSAQIAWSE NVETALSSMG GGGDAAPLHS VLSNVEVTLN VLADSVLMEQ
PPLRRRKLEH LITELVHQRD VTRSLIKSKI DNAKSFEWLS QMRFYFDPKQ TDVLQQLSIQ
MANAKFNYGF EYLGVQDKLV QTPLTDRCYL TMTQALEARL GGSPFGPAGT GKTESVKALG
HQLGRFVLVF NCDETFDFQA MGRIFVGLCQ VGAWGCFDEF NRLEERMLSA VSQQVQCIQE
ALREHSNPNY DKTSAPITCE LLNKQVKVSP DMAIFITMNP GYAGRSNLPD NLKKLFRSLA
MTKPDRQLIA QVMLYSQGFR TAEVLANKIV PFFKLCDEQL SSQSHYDFGL RALKSVLVSA
GNVKRERIQK IKREKEERGE AVDEGEIAEN LPEQEILIQS VCETMVPKLV AEDIPLLFSL
LSDVFPGVQY HRGEMTALRE ELKKVCQEMY LTYGDGEEVG GMWVEKVLQL YQITQINHGL
MMVGPSGSGK SMAWRVLLKA LERLEGVEGV AHIIDPKAIS KDHLYGTLDP NTREWTDGLF
THVLRKIIDS VRGELQKRQW IVFDGDVDPE WVENLNSVLD DNKLLTLPNG ERLSLPPNVR
IMFEVQDLKY ATLATVSRCG MVWFSEDVLS TDMIFNNFLA RLRSIPLDEG EDEAQRRRKG
KEDEGEEAAS PMLQIQRDAA TIMQPYFTSN GLVTKALEHA FQLEHIMDLT RLRCLGSLFS
MLHQACRNVA QYNANHPDFP MQIEQLERYI QRYLVYAILW SLSGDSRLKM RAELGEYIRR
ITTVPLPTAP NIPIIDYEVS ISGEWSPWQA KVPQIEVETH KVAAPDVVVP TLDTVRHEAL
LYTWLAEHKP LVLCGPPGSG KTMTLFSALR ALPDMEVVGL NFSSATTPEL LLKTFDHYCE
YRRTPNGVVL APVQLGKWLV LFCDEINLPD MDKYGTQRVI SFIRQMVEHG GFYRTSDQTW
VKLERIQFVG ACNPPTDPGR KPLSHRFLRH VPVVYVDYPG PASLTQIYGT FNRAMLRLIP
SLRTYAEPLT AAMVEFYTMS QERFTQDTQP HYIYSPREMT RWVRGIFEAL RPLETLPVEG
LIRIWAHEAL RLFQDRLVED EERRWTDENI DTVALKHFPN IDREKAMSRP ILYSNWLSKD
YIPVDQEELR DYVKARLKVF YEEELDVPLV LFNEVLDHVL RIDRIFRQPQ GHLLLIGVSG
AGKTTLSRFV AWMNGLSVYQ IKVHRKYTGE DFDEDLRTVL RRSGCKNEKI AFIMDESNVL
DSGFLERMNT LLANGEVPGL FEGDEYATLM TQCKEGAQKE GLMLDSHEEL YKWFTSQVIR
NLHVVFTMNP SSEGLKDRAA TSPALFNRCV LNWFGDWSTE ALYQVGKEFT SKMDLEKPNY
IVPDYMPVVY DKLPQPPSHR EAIVNSCVFV HQTLHQANAR LAKRGGRTMA ITPRHYLDFI
NHYANLFHEK RSELEEQQMH LNVGLRKIKE TVDQVEELRR DLRIKSQELE VKNAAANDKL
KKMVKDQQEA EKKKVMSQEI QEQLHKQQEV IADKQMSVKE DLDKVEPAVI EAQNAVKSIK
KQHLVEVRSM ANPPAAVKLA LESICLLLGE STTDWKQIRS IIMRENFIPT IVNFSAEEIS
DAIREKMKKN YMSNPSYNYE IVNRASLACG PMVKWAIAQL NYADMLKRVE PLRNELQKLE
DDAKDNQQKA NEVEQMIRDL EASIARYKEE YAVLISEAQA IKADLAAVEA KVNRSTALLK
SLSAERERWE KTSETFKNQM STIAGDCLLS AAFIAYAGYF DQQMRQNLFT TWSHHLQQAN
IQFRTDIART EYLSNADERL RWQASSLPAD DLCTENAIML KRFNRYPLII DPSGQATEFI
MNEYKDRKIT RTSFLDDAFR KNLESALRFG NPLLVQDVES YDPVLNPVLN REVRRTGGRV
LITLGDQDID LSPSFVIFLS TRDPTVEFPP DLCSRVTFVN FTVTRSSLQS QCLNEVLKAE
RPDVDEKRSD LLKLQGEFQL RLRQLEKSLL QALNEVKGRI LDDDTIITTL ENLKREAAEV
TRKVEETDIV MQEVETVSQQ YLPLSTACSS IYFTMESLKQ IHFLYQYSLQ FFLDIYHNVL
YENPNLKGVT DHTQRLSIIT KDLFQVAFNR VARGMLHQDH ITFAMLLARI KLKGTVGEPT
YDAEFQHFLR GNEIVLSAGS TPRIQGLTVE QAEAVVRLSC LPAFKDLIAK VQADEQFGIW
LDSSSPEQTV PYLWSEETPA TPIGQAIHRL LLIQAFRPDR LLAMAHMFVS TNLGESFMSI
MEQPLDLTHI VGTEVKPNTP VLMCSVPGYD ASGHVEDLAA EQNTQITSIA IGSAEGFNQA
DKAINTAVKS GRWVMLKNVH LAPGWLMQLE KKLHSLQPHA CFRLFLTMEI NPKVPVNLLR
AGRIFVFEPP PGVKANMLRT FSSIPVSRIC KSPNERARLY FLLAWFHAII QERLRYAPLG
WSKKYEFGES DLRSACDTVD TWLDDTAKGR QNISPDKIPW SALKTLMAQS IYGGRVDNEF
DQRLLNTFLE RLFTTRSFDS EFKLACKVDG HKDIQMPDGI RREEFVQWVE LLPDTQTPSW
LGLPNNAERV LLTTQGVDMI SKMLKMQMLE DEDDLAYAET EKKTRTDSTS DGRPAWMRTL
HTTASNWLHL IPQTLSHLKR TVENIKDPLF RFFEREVKMG AKLLQDVRQD LADVVQVCEG
KKKQTNYLRT LINELVKGIL PRSWSHYTVP AGMTVIQWVS DFSERIKQLQ NISLAAASGG
AKELKNIHVC LGGLFVPEAY ITATRQYVAQ ANSWSLEELC LEVNVTTSQG ATLDACSFGV
TGLKLQGATC NNNKLSLSNA ISTALPLTQL RWVKQTNTEK KASVVTLPVY LNFTRADLIF
TVDFEIATKE DPRSFYERGV AVLCTE
