Protein: Dysbindin (Biogenesis of lysosome-related organelles complex 1 subunit 8) (BLOC-1 subunit 8) (Dysbindin-1) (Dystrobrevin-binding protein 1) (Hermansky-Pudlak syndrome 7 protein) (HPS7 protein) (Q96EV8)
Organism: Homo sapiens (Human)
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.
Subcellular location: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Endosome membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Melanosome membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Postsynaptic density {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. Nucleus {ECO:0000269|PubMed: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.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Endosome membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Melanosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Postsynaptic cell membrane {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. Nucleus {ECO:0000269|PubMed: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.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Endosome membrane {ECO:0000269|PubMed:21390302}; Peripheral membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side {ECO:0000269|PubMed:21390302}. Melanosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Postsynaptic cell membrane {ECO:0000269|PubMed: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.
Interaction partners:
- Biogenesis of lysosome-related organelles complex 1 subunit 6
- Biogenesis of lysosome-related organelles complex 1 subunit 1
- SNARE-associated protein Snapin
- Biogenesis of lysosome-related organelles complex 1 subunit 2
- Biogenesis of lysosome-related organelles complex 1 subunit 3
- Biogenesis of lysosome-related organelles complex 1 subunit 5
- Biogenesis of lysosome-related organelles complex 1 subunit 4
- BLOC-2 complex member HPS5
- BLOC-2 complex member HPS6
- BLOC-2 complex member HPS3
Sequence:
MLETLRERLLSVQQDFTSGLKTLSDKSREAKVKSKPRTVPFLPKYSAGLELLSRYEDTWAALHRRAKDCASAGELVDSEVVMLSAHWEKKKTSLVELQEQLQQLPALIADLESMTANLTHLEASFEEVENNLLHLEDLCGQCELERCKHMQSQQLENYKKNKRKELETFKAELDAEHAQKVLEMEHTQQMKLKERQKFFEEAFQQDMEQYLSTGYLQIAERREPIGSMSSMEVNVDMLEQMDLMDISDQEALDVFLNSGGEENTVLSPALGPESSTCQNEITLQVPNPSELRAKPPSSSSTCTDSATRDISEGGESPVVQSDEEEVQVDTALATSHTDREATPDGGEDSDS