UniProt:Q14203-2 DCTN1

chain
  • chain:1-1278
checksum 6DCEA5E67856E4BC
comment
  • FUNCTION Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020).SUBUNIT Monomer and homodimer (PubMed:23874158). Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. DCTN1/p150(glued) binds directly to microtubules and to cytoplasmic dynein. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Interacts (via C-terminus) with SNX6. Interacts with CLN3, DYNAP, ECPAS and FBXL5. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131. Interacts with CEP126 (PubMed:24867236). Interacts with CLIP1 (PubMed:17828275, PubMed:17828277, PubMed:20679239, PubMed:26972003). Interacts with dynein intermediate chain and dynein heavy chain (PubMed:25185702). Interacts with PLK1 (via POLO-box domain) (PubMed:20679239). Interacts with TBCB (PubMed:22777741). Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules (PubMed:26968983, PubMed:26972003). Interacts with PARD6A (PubMed:20719959). Interacts with HPS6 (PubMed:25189619). Interacts with KIF3A. Interacts with BICD2 (By similarity). Interacts with DST (isoform 9) (By similarity). Interacts with DST (isoform 1) (By similarity). Identified in a complex with MREG and RILP (By similarity). Interacts with BCCIP (isoform 2/alpha) (PubMed:28394342). Interacts with DCDC1 (PubMed:22159412). Interacts with AKNA (By similarity). Interacts with DYNC1I2 (By similarity). Interacts with RUFY3 and RUFY4 (PubMed:35314674).INTERACTION Localizes to microtubule plus ends (PubMed:17828277, PubMed:22777741, PubMed:25774020). Localizes preferentially to the ends of tyrosinated microtubules (PubMed:26972003). Localization at centrosome is regulated by SLK-dependent phosphorylation (PubMed:23985322). Localizes to centrosome in a PARKDA-dependent manner (PubMed:20719959). Localizes to the subdistal appendage region of the centriole in a KIF3A-dependent manner (PubMed:23386061). PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope (PubMed:20679239).ALTERNATIVE PRODUCTS Brain.DOMAIN The CAP-Gly domain is essential for interactions with microtubules and its binding partners and for its motion along the microtubules. Essential for its preferential binding to tyrosinated microtubules and for promoting the sustained interaction of the dynein motor with microtubules.PTM Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome.PTM Phosphorylation by SLK at Thr-145, Thr-146 and Thr-147 targets DCTN1 to the centrosome. It is uncertain if SLK phosphorylates all three threonines or one or two of them. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope, promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the dynactin 150 kDa subunit family.
crossReference
databaseName UniProt
dbId 146642
description
  • recommendedName: Dynactin subunit 1 alternativeName: 150 kDa dynein-associated polypeptide alternativeName: DAP-150 shortName: DP-150 alternativeName: p135 alternativeName: p150-glued
displayName UniProt:Q14203-2 DCTN1
geneName
  • DCTN1
identifier Q14203
isSequenceChanged false
isoformParent
keyword
  • 3D-structure
  • Alternative splicing
  • Amyotrophic lateral sclerosis
  • Cell cycle
  • Cell division
  • Coiled coil
  • Cytoplasm
  • Cytoskeleton
  • Dynein
  • Microtubule
  • Mitosis
  • Neurodegeneration
  • Neuropathy
  • Nucleus
  • Parkinsonism
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Transport
  • Ubl conjugation
modified [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType Protein
name
  • DCTN1
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceIsoform
secondaryIdentifier
  • DCTN1_HUMAN
  • A8MY36
  • B4DM45
  • E9PFS5
  • E9PGE1
  • G5E9H4
  • O95296
  • Q6IQ37
  • Q9BRM9
  • Q9UIU1
  • Q9UIU2
sequenceLength 1278
species [Species:48887] Homo sapiens
stId uniprot:Q14203-2
url http://purl.uniprot.org/uniprot/Q14203-2
variantIdentifier Q14203-2
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