DCTN1_RAT
ID DCTN1_RAT Reviewed; 1280 AA.
AC P28023;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 166.
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=p150-glued;
GN Name=Dctn1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=1828535; DOI=10.1038/351579a0;
RA Holzbaur E.L.F., Hammarback J.A., Paschal B.M., Kravit N.G., Pfister K.K.,
RA Vallee R.B.;
RT "Homology of a 150K cytoplasmic dynein-associated polypeptide with the
RT Drosophila gene Glued.";
RL Nature 351:579-583(1991).
RN [2]
RP SEQUENCE REVISION.
RA Holzbaur E.L.F., Hammarback J.A., Paschal B.M., Kravit N.G., Pfister K.K.,
RA Vallee R.B.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [5]
RP STRUCTURE BY NMR OF 19-107, INTERACTION WITH MAPRE1, AND SUBUNIT.
RX PubMed=23648839; DOI=10.1016/j.jmb.2013.04.027;
RA Yan S., Hou G., Schwieters C.D., Ahmed S., Williams J.C., Polenova T.;
RT "Three-dimensional structure of CAP-Gly domain of mammalian dynactin
RT determined by magic angle spinning NMR spectroscopy: conformational
RT plasticity and interactions with end-binding protein EB1.";
RL J. Mol. Biol. 425:4249-4266(2013).
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. Can regulate microtubule stability by
CC promoting microtubule formation, nucleation and polymerization and by
CC inhibiting microtubule catastrophe in neurons. Inhibits microtubule
CC catastrophe by binding both to microtubules and to tubulin, leading to
CC enhanced microtubule stability along the axon. Plays a role in
CC metaphase spindle orientation. 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. Plays a
CC role in primary cilia formation. {ECO:0000250|UniProtKB:Q14203}.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:23648839). 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 MAPRE2 and MAPRE3. Interacts with FBXL5. Interacts with
CC ECPAS and SNX6. Interacts with CLIP1. Interacts with CLN3 and DYNAP.
CC Interacts with MISP; this interaction regulates its distribution at the
CC cell cortex. Interacts with CEP131 (By similarity). Interacts (via CAP-
CC Gly domain) with the C-terminus of MAPRE1, forming a heterotetramer
CC (PubMed:23648839). Interacts with dynein intermediate chain and dynein
CC heavy chain. Interacts with PLK1 (via POLO-box domain). Binds
CC preferentially to tyrosinated microtubules than to detyrosinated
CC microtubules. Interacts with TBCB, PARD6A, HPS6, KIF3A. Interacts with
CC BICD2. Identified in a complex with MREG and RILP (By similarity).
CC Interacts with BCCIP. Interacts with DCDC1 (By similarity). Interacts
CC with AKNA (By similarity). Interacts with DYNC1I2 (By similarity).
CC {ECO:0000250|UniProtKB:O08788, ECO:0000250|UniProtKB:Q14203,
CC ECO:0000269|PubMed:23648839}.
CC -!- INTERACTION:
CC P28023; P28023: Dctn1; NbExp=2; IntAct=EBI-7894970, EBI-7894970;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14203}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q14203}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q14203}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:Q14203}. Note=Localizes to microtubule plus
CC ends. Localizes preferentially to the ends of tyrosinated microtubules.
CC Localization at centrosome is regulated by SLK-dependent
CC phosphorylation. Localizes to centrosome in a PARKDA-dependent manner.
CC PLK1-mediated phosphorylation at Ser-179 is essential for its
CC localization in the nuclear envelope. Localizes to the subdistal
CC appendage region of the centriole in a KIF3A-dependent manner.
CC {ECO:0000250|UniProtKB:O08788, ECO:0000250|UniProtKB:Q14203}.
CC -!- TISSUE SPECIFICITY: Ubiquitous with a high level expression observed in
CC the brain (at protein level). {ECO:0000269|PubMed:22777741}.
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:0000250|UniProtKB:Q14203}.
CC -!- PTM: Ubiquitinated by a SCF complex containing FBXL5, leading to its
CC degradation by the proteasome. {ECO:0000250|UniProtKB:Q14203}.
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 and promotes its dissociation from microtubules during early mitosis
CC and positively regulates nuclear envelope breakdown during prophase.
CC {ECO:0000250|UniProtKB:Q14203}.
CC -!- SIMILARITY: Belongs to the dynactin 150 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; X62160; CAA44091.1; -; mRNA.
DR PIR; S16129; S16129.
DR RefSeq; NP_077044.1; NM_024130.1.
DR PDB; 2M02; NMR; -; A=19-107.
DR PDB; 2MPX; NMR; -; C=26-95.
DR PDBsum; 2M02; -.
DR PDBsum; 2MPX; -.
DR AlphaFoldDB; P28023; -.
DR BMRB; P28023; -.
DR SMR; P28023; -.
DR BioGRID; 247848; 7.
DR CORUM; P28023; -.
DR DIP; DIP-44817N; -.
DR IntAct; P28023; 6.
DR MINT; P28023; -.
DR STRING; 10116.ENSRNOP00000059076; -.
DR iPTMnet; P28023; -.
DR PhosphoSitePlus; P28023; -.
DR jPOST; P28023; -.
DR PaxDb; P28023; -.
DR PeptideAtlas; P28023; -.
DR PRIDE; P28023; -.
DR GeneID; 29167; -.
DR KEGG; rno:29167; -.
DR UCSC; RGD:62038; rat.
DR CTD; 1639; -.
DR RGD; 62038; Dctn1.
DR eggNOG; KOG0971; Eukaryota.
DR InParanoid; P28023; -.
DR OrthoDB; 1550378at2759; -.
DR PhylomeDB; P28023; -.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-RNO-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-RNO-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-RNO-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-RNO-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-RNO-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-RNO-6807878; COPI-mediated anterograde transport.
DR Reactome; R-RNO-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-RNO-8854518; AURKA Activation by TPX2.
DR PRO; PR:P28023; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0099738; C:cell cortex region; ISS:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; ISO:RGD.
DR GO; GO:0120103; C:centriolar subdistal appendage; ISO:RGD.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005868; C:cytoplasmic dynein complex; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; ISO:RGD.
DR GO; GO:0035371; C:microtubule plus-end; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008017; F:microtubule binding; IDA:RGD.
DR GO; GO:0051010; F:microtubule plus-end binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0010457; P:centriole-centriole cohesion; ISS:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISS:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB.
DR GO; GO:0032402; P:melanosome transport; ISO:RGD.
DR GO; GO:0034454; P:microtubule anchoring at centrosome; ISS:UniProtKB.
DR GO; GO:0061744; P:motor behavior; ISO:RGD.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR GO; GO:1990535; P:neuron projection maintenance; ISO:RGD.
DR GO; GO:1905515; P:non-motile cilium assembly; ISS:UniProtKB.
DR GO; GO:0051081; P:nuclear membrane disassembly; ISS:UniProtKB.
DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISS:UniProtKB.
DR GO; GO:1904398; P:positive regulation of neuromuscular junction development; ISO:RGD.
DR GO; GO:0060236; P:regulation of mitotic spindle organization; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:RGD.
DR GO; GO:0021517; P:ventral spinal cord development; ISO:RGD.
DR DisProt; DP02910; -.
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; Cell cycle; Cell division; Coiled coil; Cytoplasm;
KW Cytoskeleton; Dynein; Microtubule; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1..1280
FT /note="Dynactin subunit 1"
FT /id="PRO_0000083520"
FT DOMAIN 48..90
FT /note="CAP-Gly"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 910..1280
FT /note="Interaction with HPS6"
FT /evidence="ECO:0000250|UniProtKB:O08788"
FT REGION 1064..1089
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 214..513
FT /evidence="ECO:0000255"
FT COILED 942..1048
FT /evidence="ECO:0000255"
FT COILED 1184..1213
FT /evidence="ECO:0000255"
FT COMPBIAS 1..21
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:0000250|UniProtKB:Q14203"
FT MOD_RES 145
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14203"
FT MOD_RES 146
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14203"
FT MOD_RES 147
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14203"
FT MOD_RES 179
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000250|UniProtKB:Q14203"
FT MOD_RES 212
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q14203"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:2M02"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:2M02"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:2M02"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:2M02"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2MPX"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:2M02"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:2M02"
SQ SEQUENCE 1280 AA; 141930 MW; C9348CF129F4FF5C CRC64;
MAQSKRHMYN RTPSGSRMST EASARPLRVG SRVEVIGKGH RGTVAYVGAT LFATGKWVGV
ILDEAKGKND GTVQGRKYFT CDEGHGIFVR QSQIQVFEDG ADTTSPETPD SSASKILKRE
GADAAAKTSK LRGLKPKKAP TARKTTTRRP KPTRPASTGV AGPSSSLGPS GSASAGELSS
SEPSTPAQTP LAAPIIPTPA LTSPGAAPPL PSPSKEEEGL RDQVRDLEEK LETLRLKRSE
DKAKLKELEK HKIQLEQVQE WKSKMQEQQA DLQRRLKEAK EAKEALEAKE RYMEEMADTA
DAIEMATLDK EMAEERAESL QQEVEALKER VDELTTDLEI LKAEIEEKGS DGAASSYQLK
QLEEQNARLK DALVRMRDLS SSEKQEHVKL QKLMEKKNQE LEVVRQQRER LQEELSQAES
TIDELKEQVD AALGAEEMVE MLTDRNLNLE EKVRELRETV GDLEAMNEMN DELQENARET
ELELREQLDM AGARVREAQK RVEAAQETVA DYQQTIKKYR QLTAHLQDVN RELTNQQEAS
VERQQQPPPE TFDFKIKFAE TKAHAKAIEM ELRQMEVAQA NRHMSLLTAF MPDSFLRPGG
DHDCVLVLLL MPRLICKAEL IRKQAQEKFD LSENCSERPG LRGAAGEQLS FAAGLVYSLS
LLQATLHRYE HALSQCSVDV YKKVGSLYPE MSAHERSLDF LIELLHKDQL DETVNVEPLT
KAIKYYQHLY SIHLAEQPEE STMQLADHIK FTQSALDCMS VEVGRLRAFL QGGQEATDIA
LLLRDLETSC SDIRQFCKKI RRRMPGTDAP GIPAALAFGS QVSDTLLDCR KHLTWVVAVL
QEVAAAAAQL IAPLAENEGL PVAALEELAF KASEQIYGSP SSSPYECLRQ SCSILISTMN
KLATAMQEGE YDAERPPSKP PPVEPWPAAL RAEITDAEGL GLKLEDRETV IKELKKSLKI
KGEELSEANV RLSLLEKKLD SAAKDADERI EKVQTRLEET QTLLRKKEKE FEETMDALQA
DIDQLEAEKT ELKQRLNSQS KRTIEGLRGP PPSGIATLVS GIAGEEQQRG GTPGQAPGAL
PGPGPVKDSP LLLQQISAMR LHISQLQHEN SILRGAQMKA SLAALPPLHV AKFSLPPHEG
PGGNLLSGAL YRKTSQLLEK LNQLSTYTHV VDITRSSPAC KSPSAQLMEQ VAQLKSLSDT
IEKLKDEVLK ETVTQRPGAT VPTDFATFPS SAFLRAKEEQ QDDTVYMGKV TFSCAAGLGQ
RHRLVLTQEQ LHQLHGRLIS
