InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DST

Summary

InnateDB Protein

IDBP-382248.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DST

Protein Name

dystonin

Synonyms

BP240; BPA; BPAG1; CATX-15; CATX15; D6S1101; DMH; DT; EBSB2; HSAN6; MACF2;

Species

Homo sapiens

Ensembl Protein

ENSP00000404924

InnateDB Gene

IDBG-91303 (DST)

Protein Structure

UniProt Annotation

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.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. {ECO:0000250}.Isoform 7: regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport.

Subcellular Localization

Cytoplasm, cytoskeleton {ECO:0000269PubMed:11751855, ECO:0000269PubMed:19932097}. Note=Associates with intermediate filaments, acin 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. {ECO:0000250}.Isoform 1: Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm, myofibril, sarcomere, Z line. Cytoplasm, myofibril, sarcomere, H zone {ECO:0000250}. Note=Localizes to microtubules and actin microfilaments throughout the cytoplasm and at focal contact attachments at the plasma membrane. {ECO:0000250}.Isoform 2: Cytoplasm, cytoskeleton {ECO:0000250}. Note=Colocalizes both cortical and cytoplasmic actin filaments. {ECO:0000250}.Isoform 3: Cytoplasm, cytoskeleton. Cell junction, hemidesmosome. Note=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. {ECO:0000250}.Isoform 6: Nucleus {ECO:0000250}. Nucleus envelope {ECO:0000269PubMed:10428034}. Membrane {ECO:0000269PubMed:10428034}; Single-pass membrane protein {ECO:0000269PubMed:10428034}. Endoplasmic reticulum membrane {ECO:0000250}; Single-pass membrane protein {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000269PubMed:10428034}. Note=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. {ECO:0000250}.Isoform 7: Cytoplasm, cytoskeleton {ECO:0000269PubMed:10428034}. Cell projection, axon {ECO:0000269PubMed:10428034}. Membrane {ECO:0000269PubMed:10428034}. Note=Associates with axonal microtubules and intermediate filaments, but not with actin cytoskeleton, in sensory neurons.Isoform 8: Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}.

Disease Associations

Neuropathy, hereditary sensory and autonomic, 6 (HSAN6) [MIM:614653]: 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. {ECO:0000269PubMed:22522446}. Note=The disease is caused by mutations affecting the gene represented in this entry.Epidermolysis bullosa simplex, autosomal recessive 2 (EBSB2) [MIM:615425]: A form of epidermolysis bullosa, a dermatologic disorder characterized by localized blistering on the dorsal, lateral and plantar surfaces of the feet. EBSB2 is characterized by trauma-induced blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques. {ECO:0000269PubMed:20164846, ECO:0000269PubMed:22113475}. Note=The disease is caused by mutations 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. {ECO:0000269PubMed:11751855, ECO:0000269PubMed:19932097, ECO:0000269PubMed:8752219}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 47 experimentally validated interaction(s) in this database.

Experimentally validated
Total	47 [view]
Protein-Protein	45 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005178	integrin binding
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0042803	protein homodimerization activity
GO:0051010	microtubule plus-end binding

Biological Process

GO:0000226	microtubule cytoskeleton organization
GO:0007010	cytoskeleton organization
GO:0007050	cell cycle arrest
GO:0007155	cell adhesion
GO:0007229	integrin-mediated signaling pathway
GO:0009611	response to wounding
GO:0030011	maintenance of cell polarity
GO:0030198	extracellular matrix organization
GO:0031581	hemidesmosome assembly
GO:0045104	intermediate filament cytoskeleton organization
GO:0048870	cell motility

Cellular Component

GO:0005604	basement membrane
GO:0005634	nucleus
GO:0005635	nuclear envelope
GO:0005737	cytoplasm
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005882	intermediate filament
GO:0005938	cell cortex
GO:0009925	basal plasma membrane
GO:0015629	actin cytoskeleton
GO:0015630	microtubule cytoskeleton
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0030018	Z disc
GO:0030056	hemidesmosome
GO:0030424	axon
GO:0031252	cell leading edge
GO:0031673	H zone
GO:0035371	microtubule plus-end
GO:0045111	intermediate filament cytoskeleton
GO:0070062	extracellular vesicular exosome