UniProt functional annotation for P28023



	UniProt functional annotation for P28023

UniProt code: P28023.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: 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. 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. Plays a role in metaphase spindle orientation. 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. Plays a role in primary cilia formation. {ECO:0000250|UniProtKB:Q14203}.

Subunit: Monomer and homodimer (PubMed:23648839). Dynactin is a large macromolecular complex of at least 10 components; p150(glued) binds directly to microtubules and to cytoplasmic dynein. Interacts with the C-terminus of MAPRE2 and MAPRE3. Interacts with FBXL5. Interacts with ECPAS and SNX6. Interacts with CLIP1. Interacts with CLN3 and DYNAP. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131 (By similarity). Interacts (via CAP- Gly domain) with the C-terminus of MAPRE1, forming a heterotetramer (PubMed:23648839). Interacts with dynein intermediate chain and dynein heavy chain. Interacts with PLK1 (via POLO-box domain). Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules. Interacts with TBCB, PARD6A, HPS6, KIF3A. Interacts with BICD2. Identified in a complex with MREG and RILP (By similarity). Interacts with BCCIP. Interacts with DCDC1 (By similarity). Interacts with AKNA (By similarity). Interacts with DYNC1I2 (By similarity). {ECO:0000250|UniProtKB:O08788, ECO:0000250|UniProtKB:Q14203, ECO:0000269|PubMed:23648839}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q14203}. Nucleus envelope {ECO:0000250|UniProtKB:Q14203}. Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q14203}. Note=Localizes to microtubule plus ends. Localizes preferentially to the ends of tyrosinated microtubules. Localization at centrosome is regulated by SLK-dependent phosphorylation. Localizes to centrosome in a PARKDA-dependent manner. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope. Localizes to the subdistal appendage region of the centriole in a KIF3A-dependent manner. {ECO:0000250|UniProtKB:O08788, ECO:0000250|UniProtKB:Q14203}.

Tissue specificity: Ubiquitous with a high level expression observed in the brain (at protein level). {ECO:0000269|PubMed:22777741}.

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. {ECO:0000250|UniProtKB:Q14203}.

Ptm: Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome. {ECO:0000250|UniProtKB:Q14203}.

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 and promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase. {ECO:0000250|UniProtKB:Q14203}.

Similarity: Belongs to the dynactin 150 kDa subunit family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		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. 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. Plays a role in metaphase spindle orientation. 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. Plays a role in primary cilia formation. {ECO:0000250\|UniProtKB:Q14203}.


Subunit:		Monomer and homodimer (PubMed:23648839). Dynactin is a large macromolecular complex of at least 10 components; p150(glued) binds directly to microtubules and to cytoplasmic dynein. Interacts with the C-terminus of MAPRE2 and MAPRE3. Interacts with FBXL5. Interacts with ECPAS and SNX6. Interacts with CLIP1. Interacts with CLN3 and DYNAP. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131 (By similarity). Interacts (via CAP- Gly domain) with the C-terminus of MAPRE1, forming a heterotetramer (PubMed:23648839). Interacts with dynein intermediate chain and dynein heavy chain. Interacts with PLK1 (via POLO-box domain). Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules. Interacts with TBCB, PARD6A, HPS6, KIF3A. Interacts with BICD2. Identified in a complex with MREG and RILP (By similarity). Interacts with BCCIP. Interacts with DCDC1 (By similarity). Interacts with AKNA (By similarity). Interacts with DYNC1I2 (By similarity). {ECO:0000250\|UniProtKB:O08788, ECO:0000250\|UniProtKB:Q14203, ECO:0000269\|PubMed:23648839}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q14203}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250\|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000250\|UniProtKB:Q14203}. Cytoplasm, cytoskeleton, spindle {ECO:0000250\|UniProtKB:Q14203}. Nucleus envelope {ECO:0000250\|UniProtKB:Q14203}. Cytoplasm, cell cortex {ECO:0000250\|UniProtKB:Q14203}. Note=Localizes to microtubule plus ends. Localizes preferentially to the ends of tyrosinated microtubules. Localization at centrosome is regulated by SLK-dependent phosphorylation. Localizes to centrosome in a PARKDA-dependent manner. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope. Localizes to the subdistal appendage region of the centriole in a KIF3A-dependent manner. {ECO:0000250\|UniProtKB:O08788, ECO:0000250\|UniProtKB:Q14203}.
Tissue specificity:		Ubiquitous with a high level expression observed in the brain (at protein level). {ECO:0000269\|PubMed:22777741}.
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. {ECO:0000250\|UniProtKB:Q14203}.
Ptm:		Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome. {ECO:0000250\|UniProtKB:Q14203}.
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 and promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase. {ECO:0000250\|UniProtKB:Q14203}.
Similarity:		Belongs to the dynactin 150 kDa subunit family. {ECO:0000305}.