DST
Domain
Its association with epidermal and simple keratins is dependent on the tertiary structure induced by heterodimerization of these intermediate filaments proteins and most likely involves recognition sites located in the rod domain of these keratins.
The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.
Function
Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity).
Isoform 3
Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.
Isoform 6
Required for bundling actin filaments around the nucleus.
Isoform 7
Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport.
Involvement in disease
Neuropathy, hereditary sensory and autonomic, 6
HSAN6
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN6 is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection.
None
The disease is caused by variants affecting the gene represented in this entry.
Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency
EBS3
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS3 is an autosomal recessive disorder characterized by skin blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Isoform 1 is expressed in myoblasts (at protein level). Isoform 3 is expressed in the skin. Isoform 6 is expressed in the brain. Highly expressed in skeletal muscle and cultured keratinocytes.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cytoskeleton
- Stress fiber
- Cell projection
- Axon
- Associates with intermediate filaments, actin and microtubule cytoskeletons. Localizes to actin stress fibers and to actin-rich ruffling at the cortex of cells (By similarity). Associated at the growing distal tip of microtubules.
- Isoform 1
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
- Cytoplasm
- Myofibril
- Sarcomere
- H zone
- Localizes to microtubules and actin microfilaments throughout the cytoplasm and at focal contact attachments at the plasma membrane.
- Isoform 2
- Cytoplasm
- Cytoskeleton
- Colocalizes both cortical and cytoplasmic actin filaments.
- Isoform 3
- Cytoplasm
- Cytoskeleton
- Cell junction
- Hemidesmosome
- Localizes to actin and intermediate filaments cytoskeletons (By similarity). Colocalizes with the epidermal KRT5-KRT14 intermediate filaments network of keratins. Colocalizes with ITGB4 at the leading edge of migrating keratinocytes.
- Isoform 6
- Nucleus
- Nucleus envelope
- Membrane
- Single-pass membrane protein
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cytoskeleton
- Stress fiber
- Localizes to actin and intermediate filaments cytoskeletons. Localizes to central actin stress fibers around the nucleus and is excluded form focal contact sites in myoblast cells. Translocates to the nucleus (By similarity). Associates with actin cytoskeleton in sensory neurons.
- Isoform 7
- Cytoplasm
- Cytoskeleton
- Cell projection
- Axon
- Membrane
- Associates with axonal microtubules and intermediate filaments, but not with actin cytoskeleton, in sensory neurons.
- Isoform 8
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cell cortex
- Cell membrane
- Lipid-anchor
Alternative names
BP230, BP240, BPAG1, DMH, DT, KIAA0728, DST, Dystonin, 230 kDa bullous pemphigoid antigen, 230/240 kDa bullous pemphigoid antigen, Bullous pemphigoid antigen 1, Dystonia musculorum protein, Hemidesmosomal plaque protein, BPA, Bullous pemphigoid antigen