Required for the cytoplasmic dynein-driven retrograde movement of vesicles and organelles along microtubules. Dynein- dynactin interaction is a key component of the mechanism of axonal transport of vesicles and organelles. Defects in DCTN1 are the cause of distal hereditary motor neuronopathy type 7B (HMN7B); also known as progressive lower motor neuron disease (PLMND). HMN7B is a neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. Defects in DCTN1 are a cause of susceptibility to amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disorder affecting upper and lower motor neurons, and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology is likely to be multifactorial, involving both genetic and environmental factors. Defects in DCTN1 are the cause of Perry syndrome (PERRYS); also called parkinsonism with alveolar hypoventilation and mental depression. Perry syndrome is a neuropsychiatric disorder characterized by mental depression not responsive to antidepressant drugs or electroconvulsive therapy, sleep disturbances, exhaustion and marked weight loss. Parkinsonism develops later and respiratory failure occurred terminally. Belongs to the dynactin 150 kDa subunit family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Motility/polarity/chemotaxis; Motor protein; Microtubule binding protein
Molecular Function: dynein binding; protein binding; motor activity
Biological Process: nervous system development; mitosis; unfolded protein response, activation of signaling protein activity; cellular protein metabolic process; unfolded protein response; organelle organization and biogenesis; antigen processing and presentation of exogenous peptide antigen via MHC class II; mitotic cell cycle; G2/M transition of mitotic cell cycle; retrograde transport, endosome to Golgi; melanosome transport
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.