InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DTNBP1

Summary

InnateDB Protein

IDBP-62937.6

Last Modified

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

Gene Symbol

DTNBP1

Protein Name

dystrobrevin binding protein 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000341680

InnateDB Gene

IDBG-62935 (DTNBP1)

Protein Structure

UniProt Annotation

Function

Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway. {ECO:0000269PubMed:15345706, ECO:0000269PubMed:16837549, ECO:0000269PubMed:17182842, ECO:0000269PubMed:17989303, ECO:0000269PubMed:19094965, ECO:0000269PubMed:20180862, ECO:0000269PubMed:20921223}.

Subcellular Localization

Isoform 1: Cytoplasm {ECO:0000269PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Endosome membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Melanosome membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density {ECO:0000269PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. Nucleus {ECO:0000269PubMed:21390302}. Note=Mainly cytoplasmic but shuttles between the cytoplasm and nucleus. Exported out of the nucleus via its NES in a XPO1-dependent manner. Nuclear localization is required for regulation of the expression of genes such as SYN1. Detected in neuron cell bodies, axons and dendrites. Mainly located to the postsynaptic density. Detected at tubulovesicular elements in the vicinity of the Golgi apparatus and of melanosomes. Occasionally detected at the membrane of pigmented melanosomes in cultured melanoma cells. The BLOC-1 complex associates with the BLOC-2 complex in early endosome-associated tubules.Isoform 2: Cytoplasm {ECO:0000269PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Endosome membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Melanosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. Nucleus {ECO:0000269PubMed:21390302}. Note=Shuttles between the cytoplasm and nucleus. Exported out of the nucleus via its NES in a XPO1-dependent manner. Nuclear localization is required for regulation of the expression of genes such as SYN1. Mainly expressed in the dendritic spine. Predominantly a synaptic vesicle isoform but also highly expressed in the nucleus. The BLOC-1 complex associates with the BLOC-2 complex in early endosome-associated tubules. Associated with the AP-3 complex at presynaptic terminals.Isoform 3: Cytoplasm {ECO:0000269PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Endosome membrane {ECO:0000269PubMed:21390302}; Peripheral membrane protein {ECO:0000269PubMed:21390302}; Cytoplasmic side {ECO:0000269PubMed:21390302}. Melanosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000269PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. Note=Exclusivley cytoplasmic. Predominantly found in the postsynaptic density (PSD). Little association with synaptic vesicles. The BLOC-1 complex associates with the BLOC-2 complex in early endosome-associated tubules. Associated with the AP-3 complex at presynaptic terminals.

Disease Associations

Hermansky-Pudlak syndrome 7 (HPS7) [MIM:614076]: A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. {ECO:0000269PubMed:12923531}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in DTNBP1 are associated with susceptibility to schizophrenia, a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. Genetic mutations lead to alterations in the glutamatergic transmisssion in the brain and modified Akt signaling (PubMed:15345706). Protein levels and expression are reduced in nerve terminals of the hippocampus and there is an increased release of glutamate in schizophrenic patients (PubMed:15124027). Levels of isoform 1 are reduced in the pSTG, but not in HF, by about 48% in 92% of schizophrenic patients. In the HF, there is an average of 33% reduction in synaptic expression of isoform 2 in 67% of cases, and of isoform 3, an average reduction of 35% in 80% of cases. In the dorsolateral prefrontal cortex (DLPFC), significant reductions in levels of isoform 3 are observed about 71% of schizophrenic patients showed an average reduction of this isoform of about 60% (PubMed:19617633). {ECO:0000269PubMed:15124027, ECO:0000269PubMed:15345706, ECO:0000269PubMed:19617633}.

Tissue Specificity

Detected in brain, in neurons and in neuropil. Isoform 1 is expressed in the cerebral cortex, and hippocampal frontal (HF). Specific expression in the posterior half of the superior temporal gyrus (pSTG). Higher expression of isoform 2 and 3 in the HF than in the pSTG while isoform 1 shows no difference in expression in these areas. In the HF, detected in dentate gyrus (DG) and in pyramidal cells of hippocampus CA2 and CA3 (at protein level). Expressed in all principal neuronal populations of the HF, namely pyramidal neurons in the subiculum and CA1-3, granule cells in the dense cell layer of the DG (DGg), and polymorph cells in the hilus of the DG (DGh). Maximal levels in CA2, CA3, and DGh. Isoform 2 not expressed in the cerebral cortex. {ECO:0000269PubMed:16980328}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 45 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

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

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological Process

GO:0001956	positive regulation of neurotransmitter secretion
GO:0006892	post-Golgi vesicle-mediated transport
GO:0006996	organelle organization
GO:0007596	blood coagulation
GO:0008089	anterograde axon cargo transport
GO:0010628	positive regulation of gene expression
GO:0014059	regulation of dopamine secretion
GO:0031175	neuron projection development
GO:0031532	actin cytoskeleton reorganization
GO:0032438	melanosome organization
GO:0048490	anterograde synaptic vesicle transport
GO:0048812	neuron projection morphogenesis
GO:0060155	platelet dense granule organization
GO:0060159	regulation of dopamine receptor signaling pathway
GO:0061024	membrane organization

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0014069	postsynaptic density
GO:0016528	sarcoplasm
GO:0030054	cell junction
GO:0030424	axon
GO:0030426	growth cone
GO:0030672	synaptic vesicle membrane
GO:0031083	BLOC-1 complex
GO:0033162	melanosome membrane
GO:0042383	sarcolemma
GO:0043005	neuron projection
GO:0043197	dendritic spine
GO:0045211	postsynaptic membrane