{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q91WZ8","secondaryAccessions":["Q3TWK1","Q6WXQ1","Q80ZN4","Q9CY43"],"uniProtkbId":"DTBP1_MOUSE","entryAudit":{"firstPublicDate":"2003-11-28","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-12-01","entryVersion":173,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Dysbindin"}},"alternativeNames":[{"fullName":{"value":"Biogenesis of lysosome-related organelles complex 1 subunit 8"},"shortNames":[{"value":"BLOC-1 subunit 8"}]},{"fullName":{"value":"Dysbindin-1"}},{"fullName":{"value":"Dystrobrevin-binding protein 1"}},{"fullName":{"value":"Hermansky-Pudlak syndrome 7 protein homolog"},"shortNames":[{"value":"HPS7 protein homolog"}]}]},"genes":[{"geneName":{"value":"Dtnbp1"},"synonyms":[{"value":"Bloc1s8"},{"value":"Sdy"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12923531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15345706"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16448387"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16760431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16837549"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18504299"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18555792"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18984010"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19094965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19428785"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19546860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19887632"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20045719"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20921223"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20956979"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21998198"}],"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11316798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12923531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14688250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16448387"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16837549"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16980328"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17577571"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19142223"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19428785"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19546860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21998198"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22554196"}],"value":"Interacts with AP3M1 and TRIM32. Interacts (isoform 1 and isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK; the interaction phosphorylates DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and XRCC6. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. This BLOC-1 complex also associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may not be a physiological binding partner (PubMed:16448387, PubMed:16980328). Interacts (via its coiled coil domain) with KXD1. Interacts with AP3B2, BLOC1S5, BLOC1S6, CMYA5, PI4K2, RNF151 and SNAPIN/BLOC1S8. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q91WZ8","intActId":"EBI-643186"},"interactantTwo":{"uniProtKBAccession":"Q70KF4","geneName":"Cmya5","intActId":"EBI-782290"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q91WZ8","intActId":"EBI-643186"},"interactantTwo":{"uniProtKBAccession":"Q9D2N4","geneName":"Dtna","intActId":"EBI-296019"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 1","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"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 (By similarity). The BLOC-1 complex associates with the BLOC-2 complex in early endosome-associated tubules. Associated with the AP-3 complex at presynaptic terminals"}]},"subcellularLocations":[{"location":{"value":"Cytoplasm","id":"SL-0086"}},{"location":{"value":"Cytoplasmic vesicle membrane","id":"SL-0089"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"value":"Endosome membrane","id":"SL-0100"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"value":"Melanosome membrane","id":"SL-0160"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"value":"Postsynaptic density","id":"SL-0297"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Endoplasmic reticulum","id":"SL-0095"}},{"location":{"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 3","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Exclusivley cytoplasmic. Predominantly found in the postsynaptic density (PSD). Little association with synaptic vesicles (By similarity). The BLOC-1 complex associates with the BLOC-2 complex in early endosome-associated tubules. Vesicle membranes and microtubules. Associated with the AP-3 complex at presynaptic terminals"}]},"subcellularLocations":[{"location":{"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic vesicle membrane","id":"SL-0089"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane","id":"SL-0260"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Endosome membrane","id":"SL-0100"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Melanosome membrane","id":"SL-0160"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"value":"Postsynaptic cell membrane","id":"SL-0219"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Endoplasmic reticulum","id":"SL-0095"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"Dysbindin 1-A"}],"isoformIds":["Q91WZ8-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q91WZ8-2"],"sequenceIds":["VSP_009024"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"Dysbindin 1-C"}],"isoformIds":["Q91WZ8-3"],"sequenceIds":["VSP_021939"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11316798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12923531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16760431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16980328"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19428785"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19546860"}],"value":"Detected in brain, in hippocampus and dentate gyrus neurons. Detected at axon bundles and axon terminals, notably in the cerebellum and hippocampus. Detected in neuropil in hippocampus, lateral septum, basal ganglia and substantia nigra. Highly expressed in pyramidal cells of hippocampus CA2 and CA3. Detected at the heart and skeletal muscle sarcolemma (at protein level). Ubiquitously expressed. The highest expression is observed in testis, liver, kidney, brain, heart and lung. Expressed at lower levels in stomach and small intestine"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 degradation"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12923531"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18504299"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18555792"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18945333"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18984010"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19220483"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1936982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20921223"}],"value":"Defects in Dtnbp1 are the cause of the sandy (sdy) mutant phenotype, a model for human Hermansky-Pudlak syndrome (HPS). Sdy mice lack dysbindin expression; they have a characteristic sandy coat color and have much fewer melanosomes in the retinal pigment epithelium and choroid. They are fully viable, but present behavioral abnormalities. They have prolonged bleeding times due to platelet storage pool deficiency, and lysosomal storage defects. The number of electron-opaque platelet dense granules is severely reduced, and the platelet serotonin content is strongly reduced. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy mice also display impaired long-term memory retention and working memory and schizophrenia-like behavioral abnormalities. Vesicle morphology and kinetics of transmitter release are affected in both neuroendocrine cells and hippocampal synapses, characterized by larger vesicle size, slower quantal release, fewer release events and reduced readily releasable pool (RRP). Expression levels of SYN1 are lower in both the cortex and the hippocampal formation (HF)"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15345706"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19094965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20956979"}],"value":"Null mice exhibit cognitive abnormalities including schizophrenia-related behaviors such as impaired working memory under stressful conditions. There is higher acoustic startle reactivity to stimuli. Pyramidal neurons are hypoexcitable on dopamine-2 receptor stimulation. There is reduced expression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and CaMKKbeta in the medial prefrontal cortex mPFC. There is increased expression levels of cell surface dopamine receptor D2 in cortical neurons. Expression levels of SYN1 are lower in both cortex and in the hippocampal formation (HF)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the dysbindin family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAH48682.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAE35265.1","note":"Extended N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":352,"modifier":"EXACT"}},"description":"Dysbindin","featureId":"PRO_0000191002"},{"type":"Region","location":{"start":{"value":173,"modifier":"EXACT"},"end":{"value":325,"modifier":"EXACT"}},"description":"Dysbindin"},{"type":"Region","location":{"start":{"value":267,"modifier":"EXACT"},"end":{"value":352,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Coiled coil","location":{"start":{"value":88,"modifier":"EXACT"},"end":{"value":176,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Motif","location":{"start":{"value":243,"modifier":"EXACT"},"end":{"value":256,"modifier":"EXACT"}},"description":"Nuclear export signal","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Compositional bias","location":{"start":{"value":274,"modifier":"EXACT"},"end":{"value":285,"modifier":"EXACT"}},"description":"Polar residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":286,"modifier":"EXACT"},"end":{"value":301,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":11,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96EV8"}]},{"type":"Modified residue","location":{"start":{"value":315,"modifier":"EXACT"},"end":{"value":315,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96EV8"}]},{"type":"Modified residue","location":{"start":{"value":340,"modifier":"EXACT"},"end":{"value":340,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"21183079"}]},{"type":"Modified residue","location":{"start":{"value":343,"modifier":"EXACT"},"end":{"value":343,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"21183079"}]},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":81,"modifier":"EXACT"}},"description":"in isoform 3","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12923531"}],"featureId":"VSP_021939","alternativeSequence":{}},{"type":"Alternative sequence","location":{"start":{"value":171,"modifier":"EXACT"},"end":{"value":222,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11316798"}],"featureId":"VSP_009024","alternativeSequence":{}},{"type":"Sequence conflict","location":{"start":{"value":251,"modifier":"EXACT"},"end":{"value":251,"modifier":"EXACT"}},"description":"in Ref. 3; BAE35265","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Sequence conflict","location":{"start":{"value":280,"modifier":"EXACT"},"end":{"value":280,"modifier":"EXACT"}},"description":"in Ref. 3; BAE35265","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["G"]}}],"keywords":[{"id":"KW-0015","category":"Disease","name":"Albinism"},{"id":"KW-0025","category":"Coding sequence diversity","name":"Alternative splicing"},{"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"id":"KW-0175","category":"Domain","name":"Coiled coil"},{"id":"KW-0963","category":"Cellular component","name":"Cytoplasm"},{"id":"KW-0968","category":"Cellular component","name":"Cytoplasmic vesicle"},{"id":"KW-0256","category":"Cellular component","name":"Endoplasmic reticulum"},{"id":"KW-0967","category":"Cellular component","name":"Endosome"},{"id":"KW-0363","category":"Disease","name":"Hermansky-Pudlak syndrome"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0539","category":"Cellular component","name":"Nucleus"},{"id":"KW-0597","category":"PTM","name":"Phosphoprotein"},{"id":"KW-0628","category":"Cellular component","name":"Postsynaptic cell membrane"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0716","category":"Biological process","name":"Sensory transduction"},{"id":"KW-0770","category":"Cellular component","name":"Synapse"},{"id":"KW-0832","category":"PTM","name":"Ubl conjugation"}],"references":[{"referenceNumber":1,"citation":{"id":"11316798","citationType":"journal article","authors":["Benson M.A.","Newey S.E.","Martin-Rendon E.","Hawkes R.","Blake D.J."],"citationCrossReferences":[{"database":"PubMed","id":"11316798"},{"database":"DOI","id":"10.1074/jbc.m010418200"}],"title":"Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.","publicationDate":"2001","journal":"J. 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