ID DTBP1_HUMAN Reviewed; 351 AA. AC Q96EV8; A8K3V3; Q5THY3; Q5THY4; Q96NV2; Q9H0U2; Q9H3J5; DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 24-JAN-2024, entry version 184. DE RecName: Full=Dysbindin; DE AltName: Full=Biogenesis of lysosome-related organelles complex 1 subunit 8; DE Short=BLOC-1 subunit 8; DE AltName: Full=Dysbindin-1; DE AltName: Full=Dystrobrevin-binding protein 1; DE AltName: Full=Hermansky-Pudlak syndrome 7 protein; DE Short=HPS7 protein; GN Name=DTNBP1; Synonyms=BLOC1S8; ORFNames=My031; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN HPS7. RC TISSUE=Placenta; RX PubMed=12923531; DOI=10.1038/ng1229; RA Li W., Zhang Q., Oiso N., Novak E.K., Gautam R., O'Brien E.P., RA Tinsley C.L., Blake D.J., Spritz R.A., Copeland N.G., Jenkins N.A., RA Amato D., Roe B.A., Starcevic M., Dell'Angelica E.C., Elliott R.W., RA Mishra V., Kingsmore S.F., Paylor R.E., Swank R.T.; RT "Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a RT member of the biogenesis of lysosome-related organelles complex 1 (BLOC- RT 1)."; RL Nat. Genet. 35:84-89(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Jiang Y., Straub R.E., Sullivan P.F., Chen X., O'Neill F.A., Walsh D., RA Kendler K.S., Riley B.P.; RT "Localization and identification of a human DTNBP1 gene from a putative RT schizophrenia susceptibility locus on 6p22.3 by in silico cloning."; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, and Neuroblastoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 109-351 (ISOFORM 1). RC TISSUE=Fetal brain; RA Mao Y.M., Xie Y., Ying K.; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [8] RP ASSOCIATION WITH SCHIZOPHRENIA, AND FUNCTION. RX PubMed=15345706; DOI=10.1093/hmg/ddh280; RA Numakawa T., Yagasaki Y., Ishimoto T., Okada T., Suzuki T., Iwata N., RA Ozaki N., Taguchi T., Tatsumi M., Kamijima K., Straub R.E., RA Weinberger D.R., Kunugi H., Hashimoto R.; RT "Evidence of novel neuronal functions of dysbindin, a susceptibility gene RT for schizophrenia."; RL Hum. Mol. Genet. 13:2699-2708(2004). RN [9] RP ASSOCIATION WITH SCHIZOPHRENIA, TISSUE SPECIFICITY (ISOFORMS 1 AND 2), AND RP SUBCELLULAR LOCATION. RX PubMed=15124027; DOI=10.1172/jci20425; RA Talbot K., Eidem W.L., Tinsley C.L., Benson M.A., Thompson E.W., RA Smith R.J., Hahn C.G., Siegel S.J., Trojanowski J.Q., Gur R.E., Blake D.J., RA Arnold S.E.; RT "Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the RT hippocampal formation in schizophrenia."; RL J. Clin. Invest. 113:1353-1363(2004). RN [10] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=16980328; DOI=10.1093/hmg/ddl246; RA Talbot K., Cho D.S., Ong W.Y., Benson M.A., Han L.Y., Kazi H.A., Kamins J., RA Hahn C.G., Blake D.J., Arnold S.E.; RT "Dysbindin-1 is a synaptic and microtubular protein that binds brain RT snapin."; RL Hum. Mol. Genet. 15:3041-3054(2006). RN [11] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=16837549; DOI=10.1091/mbc.e06-05-0379; RA Di Pietro S.M., Falcon-Perez J.M., Tenza D., Setty S.R., Marks M.S., RA Raposo G., Dell'Angelica E.C.; RT "BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein RT trafficking on endosomes."; RL Mol. Biol. Cell 17:4027-4038(2006). RN [12] RP IDENTIFICATION IN THE BLOC-1 COMPLEX, AND FUNCTION. RX PubMed=17182842; DOI=10.1091/mbc.e06-12-1066; RA Setty S.R., Tenza D., Truschel S.T., Chou E., Sviderskaya E.V., Theos A.C., RA Lamoreux M.L., Di Pietro S.M., Starcevic M., Bennett D.C., RA Dell'Angelica E.C., Raposo G., Marks M.S.; RT "BLOC-1 is required for cargo-specific sorting from vacuolar early RT endosomes toward lysosome-related organelles."; RL Mol. Biol. Cell 18:768-780(2007). RN [13] RP FUNCTION. RX PubMed=17989303; DOI=10.1523/jneurosci.1689-07.2007; RA Iizuka Y., Sei Y., Weinberger D.R., Straub R.E.; RT "Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor RT internalization and signaling but not D1 internalization."; RL J. Neurosci. 27:12390-12395(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-321, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP ASSOCIATION WITH SCHIZOPHRENIA. RX PubMed=19617633; DOI=10.1093/hmg/ddp329; RA Tang J., LeGros R.P., Louneva N., Yeh L., Cohen J.W., Hahn C.G., RA Blake D.J., Arnold S.E., Talbot K.; RT "Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is RT reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA RT expression."; RL Hum. Mol. Genet. 18:3851-3863(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-321, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [17] RP REVIEW. RA Talbot K., Ong W.-Y., Blake D.J., Tang J., Louneva N., Carlson G.C., RA Arnold S.E.; RT "Dysbindin-1 and its protein family with special attention to the potential RT role of dysbindin-1 in neuronal functions and the pathophysiology of RT schizophrenia."; RL (In) Javitt D.C., Kantrowitz J. (eds.); RL Handbook of neurochemistry and molecular neurobiology (3rd ed.), RL pp.27:107-241, Springer Science, New York (2009). RN [18] RP FUNCTION. RX PubMed=19094965; DOI=10.1016/j.bbrc.2008.12.017; RA Kubota K., Kumamoto N., Matsuzaki S., Hashimoto R., Hattori T., Okuda H., RA Takamura H., Takeda M., Katayama T., Tohyama M.; RT "Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal RT organization."; RL Biochem. Biophys. Res. Commun. 379:191-195(2009). RN [19] RP INTERACTION WITH TRIM32, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=19349376; DOI=10.1093/hmg/ddp167; RA Locke M., Tinsley C.L., Benson M.A., Blake D.J.; RT "TRIM32 is an E3 ubiquitin ligase for dysbindin."; RL Hum. Mol. Genet. 18:2344-2358(2009). RN [20] RP INTERACTION WITH AP3M1, AND MUTAGENESIS OF TYR-215. RX PubMed=19428785; DOI=10.1016/j.neuint.2009.01.014; RA Taneichi-Kuroda S., Taya S., Hikita T., Fujino Y., Kaibuchi K.; RT "Direct interaction of dysbindin with the AP-3 complex via its mu RT subunit."; RL Neurochem. Int. 54:431-438(2009). RN [21] RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), RP INTERACTION WITH AP3B2; XRCC5 AND XRCC6 IN THE DNA-DEPENDENT PROTEIN KINASE RP COMPLEX DNA-PK, AND PHOSPHORYLATION. RX PubMed=19142223; DOI=10.1371/journal.pone.0004199; RA Oyama S., Yamakawa H., Sasagawa N., Hosoi Y., Futai E., Ishiura S.; RT "Dysbindin-1, a schizophrenia-related protein, functionally interacts with RT the DNA-dependent protein kinase complex in an isoform-dependent manner."; RL PLoS ONE 4:E4199-E4199(2009). RN [22] RP ASSOCIATION WITH SCHIZOPHRENIA, AND FUNCTION. RX PubMed=20180862; DOI=10.1111/j.1601-183x.2010.00574.x; RA Fallgatter A.J., Ehlis A.C., Herrmann M.J., Hohoff C., Reif A., RA Freitag C.M., Deckert J.; RT "DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in RT schizophrenic patients--support for the glutamate hypothesis of RT schizophrenias."; RL Genes Brain Behav. 9:489-497(2010). RN [23] RP SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH XPO1, AND MUTAGENESIS OF RP 243-LEU--LEU-256. RX PubMed=20921223; DOI=10.1074/jbc.m110.107912; RA Fei E., Ma X., Zhu C., Xue T., Yan J., Xu Y., Zhou J., Wang G.; RT "Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related RT protein, regulates synapsin I expression."; RL J. Biol. Chem. 285:38630-38640(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP ASSOCIATION WITH SCHIZOPHRENIA, TISSUE SPECIFICITY (ISOFORMS 1; 2 AND 3), RP AND SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 3). RX PubMed=21390302; DOI=10.1371/journal.pone.0016886; RA Talbot K., Louneva N., Cohen J.W., Kazi H., Blake D.J., Arnold S.E.; RT "Synaptic dysbindin-1 reductions in schizophrenia occur in an isoform- RT specific manner indicating their subsynaptic location."; RL PLoS ONE 6:E16886-E16886(2011). RN [26] RP IDENTIFICATION IN THE BLOC-1 COMPLEX, AND COMPOSITION OF THE BLOC-1 RP COMPLEX. RX PubMed=22203680; DOI=10.1074/jbc.m111.325746; RA Lee H.H., Nemecek D., Schindler C., Smith W.J., Ghirlando R., Steven A.C., RA Bonifacino J.S., Hurley J.H.; RT "Assembly and architecture of biogenesis of lysosome-related organelles RT complex-1 (BLOC-1)."; RL J. Biol. Chem. 287:5882-5890(2012). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-321, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Component of the BLOC-1 complex, a complex that is required CC for normal biogenesis of lysosome-related organelles (LRO), such as CC platelet dense granules and melanosomes. In concert with the AP-3 CC complex, the BLOC-1 complex is required to target membrane protein CC cargos into vesicles assembled at cell bodies for delivery into CC neurites and nerve terminals. The BLOC-1 complex, in association with CC SNARE proteins, is also proposed to be involved in neurite extension. CC Associates with the BLOC-2 complex to facilitate the transport of TYRP1 CC independent of AP-3 function. Plays a role in synaptic vesicle CC trafficking and in neurotransmitter release. Plays a role in the CC regulation of cell surface exposure of DRD2. May play a role in actin CC cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 CC phosphorylation. Appears to promote neuronal transmission and viability CC through regulating the expression of SNAP25 and SYN1, modulating PI3- CC kinase-Akt signaling and influencing glutamatergic release. Regulates CC the expression of SYN1 through binding to its promoter. Modulates CC prefrontal cortical activity via the dopamine/D2 pathway. CC {ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:16837549, CC ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:17989303, CC ECO:0000269|PubMed:19094965, ECO:0000269|PubMed:20180862, CC ECO:0000269|PubMed:20921223}. CC -!- SUBUNIT: Interacts (via its coiled coil domain) with KXD1. Interacts CC with CMYA5, PI4K2 and RNF151 (By similarity). Component of the CC biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed CC of at least BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, CC DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly in the complex CC with BLOC1S5, BLOC1S6 and SNAPIN/BLOC1S8. The BLOC-1 complex associates CC with the AP-3 protein complex and membrane protein cargos. This BLOC-1 CC complex also associates with the BLOC-2 complex in endosomes. Binds to CC DTNA and DTNB but may not be a physiological binding partner CC (PubMed:16980328). Interacts (isoform 1 and isoform 2 only) with the CC DNA-dependent protein kinase complex DNA-PK; the interaction CC phosphorylates DTNBP1 in vitro. Interacts directly in this complex with CC XRCC5 and XRCC6. Interacts with AP3M1, AP3B2 and TRIM32. Interacts with CC XPO1; the interaction exports DTNBP1 out of the nucleus. {ECO:0000250, CC ECO:0000269|PubMed:16837549, ECO:0000269|PubMed:16980328, CC ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:19142223, CC ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:19428785, CC ECO:0000269|PubMed:20921223, ECO:0000269|PubMed:22203680}. CC -!- INTERACTION: CC Q96EV8; Q8TDH9: BLOC1S5; NbExp=3; IntAct=EBI-465804, EBI-465861; CC Q96EV8; Q9UL45: BLOC1S6; NbExp=9; IntAct=EBI-465804, EBI-465781; CC Q96EV8; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-465804, EBI-2837444; CC Q96EV8; Q8IYE0-2: CCDC146; NbExp=3; IntAct=EBI-465804, EBI-10247802; CC Q96EV8; Q494R4: CCDC153; NbExp=3; IntAct=EBI-465804, EBI-10241443; CC Q96EV8; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-465804, EBI-10175300; CC Q96EV8; O60941: DTNB; NbExp=3; IntAct=EBI-465804, EBI-740402; CC Q96EV8; A1L3X0: ELOVL7; NbExp=3; IntAct=EBI-465804, EBI-10285373; CC Q96EV8; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-465804, EBI-2514791; CC Q96EV8; Q8IY31: IFT20; NbExp=3; IntAct=EBI-465804, EBI-744203; CC Q96EV8; Q7Z3B3: KANSL1; NbExp=3; IntAct=EBI-465804, EBI-740244; CC Q96EV8; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-465804, EBI-2125614; CC Q96EV8; O95678: KRT75; NbExp=3; IntAct=EBI-465804, EBI-2949715; CC Q96EV8; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-465804, EBI-10172876; CC Q96EV8; O43482: OIP5; NbExp=3; IntAct=EBI-465804, EBI-536879; CC Q96EV8; Q7Z4N8: P4HA3; NbExp=3; IntAct=EBI-465804, EBI-10181968; CC Q96EV8; O00560: SDCBP; NbExp=3; IntAct=EBI-465804, EBI-727004; CC Q96EV8; Q9NUL5: SHFL; NbExp=3; IntAct=EBI-465804, EBI-10313866; CC Q96EV8; O95295: SNAPIN; NbExp=7; IntAct=EBI-465804, EBI-296723; CC Q96EV8; A1L4H1: SSC5D; NbExp=3; IntAct=EBI-465804, EBI-10172867; CC Q96EV8; P14373: TRIM27; NbExp=3; IntAct=EBI-465804, EBI-719493; CC Q96EV8; Q8N3L3: TXLNB; NbExp=4; IntAct=EBI-465804, EBI-6116822; CC Q96EV8; Q9Y3C0: WASHC3; NbExp=3; IntAct=EBI-465804, EBI-712969; CC Q96EV8-1; P13010: XRCC5; NbExp=2; IntAct=EBI-16749108, EBI-357997; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Endosome membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Melanosome membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Postsynaptic density CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. CC Nucleus {ECO:0000269|PubMed:21390302}. Note=Mainly cytoplasmic but CC shuttles between the cytoplasm and nucleus. Exported out of the nucleus CC via its NES in a XPO1-dependent manner. Nuclear localization is CC required for regulation of the expression of genes such as SYN1. CC Detected in neuron cell bodies, axons and dendrites. Mainly located to CC the postsynaptic density. Detected at tubulovesicular elements in the CC vicinity of the Golgi apparatus and of melanosomes. Occasionally CC detected at the membrane of pigmented melanosomes in cultured melanoma CC cells. The BLOC-1 complex associates with the BLOC-2 complex in early CC endosome-associated tubules. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, CC synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral CC membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Endosome membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Melanosome membrane {ECO:0000250}; CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side CC {ECO:0000250}. Postsynaptic cell membrane CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. CC Nucleus {ECO:0000269|PubMed:21390302}. Note=Shuttles between the CC cytoplasm and nucleus. Exported out of the nucleus via its NES in a CC XPO1-dependent manner. Nuclear localization is required for regulation CC of the expression of genes such as SYN1. Mainly expressed in the CC dendritic spine. Predominantly a synaptic vesicle isoform but also CC highly expressed in the nucleus. The BLOC-1 complex associates with the CC BLOC-2 complex in early endosome-associated tubules. Associated with CC the AP-3 complex at presynaptic terminals. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Cytoplasmic vesicle, secretory vesicle, CC synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; Peripheral CC membrane protein {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Endosome membrane CC {ECO:0000269|PubMed:21390302}; Peripheral membrane protein CC {ECO:0000269|PubMed:21390302}; Cytoplasmic side CC {ECO:0000269|PubMed:21390302}. Melanosome membrane {ECO:0000250}; CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side CC {ECO:0000250}. Postsynaptic cell membrane CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum {ECO:0000250}. CC Note=Exclusivley cytoplasmic. Predominantly found in the postsynaptic CC density (PSD). Little association with synaptic vesicles. The BLOC-1 CC complex associates with the BLOC-2 complex in early endosome-associated CC tubules. Associated with the AP-3 complex at presynaptic terminals. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=3; CC Name=1; Synonyms=Dysbindin 1-A; CC IsoId=Q96EV8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96EV8-2; Sequence=VSP_009023; CC Name=3; Synonyms=Dysbindin 1-B; CC IsoId=Q96EV8-3; Sequence=VSP_046062; CC -!- TISSUE SPECIFICITY: Detected in brain, in neurons and in neuropil. CC Isoform 1 is expressed in the cerebral cortex, and hippocampal frontal CC (HF). Specific expression in the posterior half of the superior CC temporal gyrus (pSTG). Higher expression of isoform 2 and 3 in the HF CC than in the pSTG while isoform 1 shows no difference in expression in CC these areas. In the HF, detected in dentate gyrus (DG) and in pyramidal CC cells of hippocampus CA2 and CA3 (at protein level). Expressed in all CC principal neuronal populations of the HF, namely pyramidal neurons in CC the subiculum and CA1-3, granule cells in the dense cell layer of the CC DG (DGg), and polymorph cells in the hilus of the DG (DGh). Maximal CC levels in CA2, CA3, and DGh. Isoform 2 not expressed in the cerebral CC cortex. {ECO:0000269|PubMed:16980328}. CC -!- PTM: Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 CC degradation. {ECO:0000269|PubMed:19349376}. CC -!- PTM: Isoforms 1 and 2 highly phosphorylated by PRKDC in vitro. Isoform CC 3 only weakly phosphorylated by PRKDC in vitro. CC {ECO:0000269|PubMed:19142223}. CC -!- DISEASE: Hermansky-Pudlak syndrome 7 (HPS7) [MIM:614076]: A form of CC Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal CC recessive disorder characterized by oculocutaneous albinism, bleeding CC due to platelet storage pool deficiency, and lysosomal storage defects. CC This syndrome results from defects of diverse cytoplasmic organelles CC including melanosomes, platelet dense granules and lysosomes. Ceroid CC storage in the lungs is associated with pulmonary fibrosis, a common CC cause of premature death in individuals with HPS. CC {ECO:0000269|PubMed:12923531}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Defects in DTNBP1 are associated with susceptibility to CC schizophrenia, a mental disorder characterized by a breakdown of CC thought processes and by poor emotional responsiveness. Genetic CC mutations lead to alterations in the glutamatergic transmission in the CC brain and modified Akt signaling (PubMed:15345706). Protein levels and CC expression are reduced in nerve terminals of the hippocampus and there CC is an increased release of glutamate in schizophrenic patients CC (PubMed:15124027). Levels of isoform 1 are reduced in the pSTG, but not CC in HF, by about 48% in 92% of schizophrenic patients. In the HF, there CC is an average of 33% reduction in synaptic expression of isoform 2 in CC 67% of cases, and of isoform 3, an average reduction of 35% in 80% of CC cases. In the dorsolateral prefrontal cortex (DLPFC), significant CC reductions in levels of isoform 3 are observed about 71% of CC schizophrenic patients showed an average reduction of this isoform of CC about 60% (PubMed:19617633). {ECO:0000269|PubMed:15124027, CC ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:19617633}. CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the dysbindin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG43145.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY265460; AAP91870.1; -; mRNA. DR EMBL; AF394226; AAL46636.1; -; mRNA. DR EMBL; AL136637; CAB66572.1; -; mRNA. DR EMBL; AK054593; BAB70770.1; -; mRNA. DR EMBL; AK290718; BAF83407.1; -; mRNA. DR EMBL; AL021978; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL022343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC011912; AAH11912.1; -; mRNA. DR EMBL; AF061734; AAG43145.1; ALT_INIT; mRNA. DR CCDS; CCDS4534.1; -. [Q96EV8-1] DR CCDS; CCDS4535.1; -. [Q96EV8-2] DR RefSeq; NP_001258596.1; NM_001271667.1. [Q96EV8-3] DR RefSeq; NP_001258597.1; NM_001271668.1. DR RefSeq; NP_001258598.1; NM_001271669.1. DR RefSeq; NP_115498.2; NM_032122.4. [Q96EV8-1] DR RefSeq; NP_898861.1; NM_183040.2. [Q96EV8-2] DR AlphaFoldDB; Q96EV8; -. DR SMR; Q96EV8; -. DR BioGRID; 123857; 165. DR ComplexPortal; CPX-1910; BLOC-1 complex. DR CORUM; Q96EV8; -. DR IntAct; Q96EV8; 124. DR MINT; Q96EV8; -. DR STRING; 9606.ENSP00000341680; -. DR GlyGen; Q96EV8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96EV8; -. DR PhosphoSitePlus; Q96EV8; -. DR BioMuta; DTNBP1; -. DR DMDM; 38604971; -. DR EPD; Q96EV8; -. DR jPOST; Q96EV8; -. DR MassIVE; Q96EV8; -. DR MaxQB; Q96EV8; -. DR PaxDb; 9606-ENSP00000341680; -. DR PeptideAtlas; Q96EV8; -. DR ProteomicsDB; 76455; -. [Q96EV8-1] DR ProteomicsDB; 76456; -. [Q96EV8-2] DR Pumba; Q96EV8; -. DR Antibodypedia; 25035; 485 antibodies from 35 providers. DR DNASU; 84062; -. DR Ensembl; ENST00000338950.9; ENSP00000344718.5; ENSG00000047579.20. [Q96EV8-2] DR Ensembl; ENST00000344537.10; ENSP00000341680.6; ENSG00000047579.20. [Q96EV8-1] DR GeneID; 84062; -. DR KEGG; hsa:84062; -. DR MANE-Select; ENST00000344537.10; ENSP00000341680.6; NM_032122.5; NP_115498.2. DR UCSC; uc003nbm.4; human. [Q96EV8-1] DR AGR; HGNC:17328; -. DR CTD; 84062; -. DR DisGeNET; 84062; -. DR GeneCards; DTNBP1; -. DR GeneReviews; DTNBP1; -. DR HGNC; HGNC:17328; DTNBP1. DR HPA; ENSG00000047579; Tissue enhanced (brain, retina). DR MalaCards; DTNBP1; -. DR MIM; 607145; gene. DR MIM; 614076; phenotype. DR neXtProt; NX_Q96EV8; -. DR OpenTargets; ENSG00000047579; -. DR Orphanet; 231531; Hermansky-Pudlak syndrome due to BLOC-1 deficiency. DR PharmGKB; PA27512; -. DR VEuPathDB; HostDB:ENSG00000047579; -. DR eggNOG; ENOG502QRS9; Eukaryota. DR GeneTree; ENSGT00940000156479; -. DR InParanoid; Q96EV8; -. DR OMA; KSWFLLH; -. DR OrthoDB; 5396587at2759; -. DR PhylomeDB; Q96EV8; -. DR TreeFam; TF332997; -. DR PathwayCommons; Q96EV8; -. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR SignaLink; Q96EV8; -. DR SIGNOR; Q96EV8; -. DR BioGRID-ORCS; 84062; 11 hits in 1155 CRISPR screens. DR ChiTaRS; DTNBP1; human. DR GeneWiki; Dysbindin; -. DR GenomeRNAi; 84062; -. DR Pharos; Q96EV8; Tbio. DR PRO; PR:Q96EV8; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q96EV8; Protein. DR Bgee; ENSG00000047579; Expressed in tendon of biceps brachii and 180 other cell types or tissues. DR ExpressionAtlas; Q96EV8; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0031083; C:BLOC-1 complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl. DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0030496; C:midbody; IDA:HPA. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB. DR GO; GO:0016528; C:sarcoplasm; IEA:Ensembl. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0008089; P:anterograde axonal transport; ISS:UniProtKB. DR GO; GO:0048490; P:anterograde synaptic vesicle transport; ISS:UniProtKB. DR GO; GO:0007596; P:blood coagulation; IEA:Ensembl. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0032438; P:melanosome organization; NAS:UniProtKB. DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IEA:Ensembl. DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0060155; P:platelet dense granule organization; IBA:GO_Central. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR GO; GO:0061646; P:positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization; IEA:Ensembl. DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl. DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0014059; P:regulation of dopamine secretion; ISS:UniProtKB. DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IBA:GO_Central. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR InterPro; IPR007531; Dysbindin. DR PANTHER; PTHR16294:SF5; DYSBINDIN; 1. DR PANTHER; PTHR16294; DYSTROBREVIN BINDING PROTEIN 1 DYSBINDIN; 1. DR Pfam; PF04440; Dysbindin; 1. DR Genevisible; Q96EV8; HS. PE 1: Evidence at protein level; KW Albinism; Alternative initiation; Alternative splicing; Cell membrane; KW Coiled coil; Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum; KW Endosome; Hermansky-Pudlak syndrome; Membrane; Nucleus; Phosphoprotein; KW Postsynaptic cell membrane; Reference proteome; Schizophrenia; KW Sensory transduction; Synapse; Ubl conjugation. FT CHAIN 1..351 FT /note="Dysbindin" FT /id="PRO_0000191001" FT REGION 173..331 FT /note="Dysbindin" FT REGION 286..351 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 88..181 FT /evidence="ECO:0000255" FT MOTIF 243..256 FT /note="Nuclear export signal" FT COMPBIAS 286..310 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569" FT MOD_RES 321 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569" FT MOD_RES 349 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91WZ8" FT VAR_SEQ 1..81 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_046062" FT VAR_SEQ 272..351 FT /note="PESSTCQNEITLQVPNPSELRAKPPSSSSTCTDSATRDISEGGESPVVQSDE FT EEVQVDTALATSHTDREATPDGGEDSDS -> RVDKLALAEPGQYRCHSPPKVRRENHL FT PVTYA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039" FT /id="VSP_009023" FT VARIANT 214 FT /note="G -> D (in dbSNP:rs16876589)" FT /id="VAR_053069" FT VARIANT 272 FT /note="P -> S (in dbSNP:rs17470454)" FT /id="VAR_029644" FT MUTAGEN 215 FT /note="Y->A: Reduced interaction with AP3M1." FT /evidence="ECO:0000269|PubMed:19428785" FT MUTAGEN 243..256 FT /note="LMDISDQEALDVFL->AMDASDQEAADVFA: Abolishes FT cytoplasmic location. Increased expression of SYN1." FT /evidence="ECO:0000269|PubMed:20921223" FT CONFLICT 242 FT /note="D -> V (in Ref. 3; CAB66572)" FT /evidence="ECO:0000305" SQ SEQUENCE 351 AA; 39493 MW; 0504C86E12B66C08 CRC64; MLETLRERLL SVQQDFTSGL KTLSDKSREA KVKSKPRTVP FLPKYSAGLE LLSRYEDTWA ALHRRAKDCA SAGELVDSEV VMLSAHWEKK KTSLVELQEQ LQQLPALIAD LESMTANLTH LEASFEEVEN NLLHLEDLCG QCELERCKHM QSQQLENYKK NKRKELETFK AELDAEHAQK VLEMEHTQQM KLKERQKFFE EAFQQDMEQY LSTGYLQIAE RREPIGSMSS MEVNVDMLEQ MDLMDISDQE ALDVFLNSGG EENTVLSPAL GPESSTCQNE ITLQVPNPSE LRAKPPSSSS TCTDSATRDI SEGGESPVVQ SDEEEVQVDT ALATSHTDRE ATPDGGEDSD S //