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FLASH GENE

Symbol

DCTN1

contributors: mct - updated : 03-06-2015

HGNC name	dynactin 1 (p150, glued homolog, Drosophila)
HGNC id	2711

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive salivary gland       highly Nervous brain       highly   nerve         Reproductive male system testis

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	umbilical cord

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal cytoskeleton-associated protein–glycine-rich (CAP-Gly) domain having a critical role in the initiation and persistence of dynein-dependent movement of the mitotic spindle and nucleus, but is otherwise dispensable for dynein-based movement
	the 'GKNDG' binding motif
	three binding domains : microtubules (CAP-Gly domain), dynein and ARP1

mono polymer

heteromer , polymer

HOMOLOGY

interspecies

homolog to Drosophila Glued

Homologene

FAMILY

CATEGORY

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus,chromatin/chromosome,kinetochore
	intracellular,nuclear envelope
text	punctate cytoplasmic structures and centrosomes during interphase, mitotic spindle through cleavage furrow and midbodies of dividing cells
	microtubule plus-ends
	localizes in the nuclear envelope during prophase
	phosphorylation is required only for centrosomal localization of DCTN1

basic FUNCTION	critical functions for NUMA1, DCTN1 and GPSM2 in mammalian development
	NUMA1, DCTN1 and GPSM2 are involved in spindle orientation regulation
	major component of the dynactin complex which facilitates retrograde axonal transport of cargos by the dynein complex
	NDE1 and DCTN1 are likely associated with distinct dynein pools having specific functions
	likely DCTN1 function and microtubule stabilization pathway could act cooperatively for protection of axons against degeneration
	could be activating enzymes involved in the pro-survival signaling cascades that might involve MAP kinases to propagate protective signals against excitotoxicity-induced axon degeneration
	major function of dynactin is minus end-directed transport along microtubules in a complex with dynein motor
	dynactin phosphorylation is involved in Golgi reorientation in polarized cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

REST, DCTN1, HTT, HAP1, and RILP form a complex involved in the translocation of REST into the nucleus and HAP1 controls REST cellular localization in neurons

INTERACTION

DNA

RNA

small molecule

protein	interaction SNX6-DCTN1 for recruitment of the motor complex to the membrane-associated retromer
	PARD6A interacts with the dynactin subunit DCTN1 and is a critical regulator of centrosomal protein recruitment
	interacting with HTT (regulates spindle orientation by ensuring the proper localization of the DCTN1 subunit of dynactin, dynein and NUMA1)
	TRAPPC9 mediates the interaction between DCTN1 and COPII vesicles at the target membrane
	BICD2, DCTN1, and PAFAH1B1 cooperate in regulating dynein recruitment to cellular structures
	AURKA is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of DCTN1

cell & other

REGULATION

Phosphorylated by

SLK, and SLK targets it to the centrosome, where it maintains microtubule radial organization

Other	regulated by ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination and subsequent proteolysis
	phosphorylation by PLK1 that might be one major pathway of nuclear envelope breakdown regulation

ASSOCIATED DISORDERS

corresponding disease(s)

LMND , PERS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       linked to a slowly progressive form of lower motor neuron disease that resembles ALS (Moore 2009) constitutional     --over   with microtubule stabilization, functions cooperatively to protect axons from excitotoxicity-induced degeneration (pMID: 22728878) constitutional     --over   in sporadic amyotrophic lateral sclerosis (SALS) and dependent of age

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Heterozygous G59S-mutant mice are viable, and adults exhibit cellular abnormalities in lower motor neurons that are reminiscent of changes seen with human diseases, including ALS (Moore 2009)