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 11-NOV-2015, entry version 128. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT dysbindin, a member of the biogenesis of lysosome-related organelles RT complex 1 (BLOC-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 RT putative schizophrenia susceptibility locus on 6p22.3 by in silico RT 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., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA 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., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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 RT project: 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 RT gene for schizophrenia."; RL Hum. Mol. Genet. 13:2699-2708(2004). RN [9] RP ASSOCIATION WITH SCHIZOPHRENIA, TISSUE SPECIFICITY (ISOFORMS 1 AND 2), RP AND 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., RA Blake D.J., 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., RA Kamins J., 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 RT protein 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., RA Theos A.C., 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 RT receptor 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 RT is 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 RT potential role of dysbindin-1 in neuronal functions and the RT pathophysiology of 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., RA Okuda H., Takamura H., Takeda M., Katayama T., Tohyama M.; RT "Dysbindin engages in c-Jun N-terminal kinase activity and RT cytoskeletal 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 RP KINASE 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 RT with the DNA-dependent protein kinase complex in an isoform-dependent RT 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 RT in 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 RP OF 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., RA Buerckstuemmer T., 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 RP 3), 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., RA Steven A.C., Bonifacino J.S., Hurley J.H.; RT "Assembly and architecture of biogenesis of lysosome-related RT organelles complex-1 (BLOC-1)."; RL J. Biol. Chem. 287:5882-5890(2012). RN [27] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Component of the BLOC-1 complex, a complex that is CC required for normal biogenesis of lysosome-related organelles CC (LRO), such as platelet dense granules and melanosomes. In concert CC with the AP-3 complex, the BLOC-1 complex is required to target CC membrane protein cargos into vesicles assembled at cell bodies for CC delivery into neurites and nerve terminals. The BLOC-1 complex, in CC association with SNARE proteins, is also proposed to be involved CC in neurite extension. Associates with the BLOC-2 complex to CC facilitate the transport of TYRP1 independent of AP-3 function. CC Plays a role in synaptic vesicle trafficking and in CC neurotransmitter release. Plays a role in the regulation of cell CC surface exposure of DRD2. May play a role in actin cytoskeleton CC reorganization and neurite outgrowth. May modulate MAPK8 CC phosphorylation. Appears to promote neuronal transmission and CC viability through regulating the expression of SNAP25 and SYN1, CC modulating PI3-kinase-Akt signaling and influencing glutamatergic CC release. Regulates the expression of SYN1 through binding to its CC promoter. Modulates prefrontal cortical activity via the CC dopamine/D2 pathway. {ECO:0000269|PubMed:15345706, CC ECO:0000269|PubMed:16837549, ECO:0000269|PubMed:17182842, CC ECO:0000269|PubMed:17989303, ECO:0000269|PubMed:19094965, CC ECO:0000269|PubMed:20180862, ECO:0000269|PubMed:20921223}. CC -!- SUBUNIT: Interacts (via its coiled coil domain) with KXD1. CC Interacts with CMYA5, PI4K2 and RNF151 (By similarity). Component CC of the biogenesis of lysosome-related organelles complex 1 (BLOC- CC 1) composed of at least BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, CC BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts CC directly in the complex with BLOC1S5, BLOC1S6 and SNAPIN/BLOC1S8. CC The BLOC-1 complex associates with the AP-3 protein complex and CC membrane protein cargos. This BLOC-1 complex also associates with CC the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may CC not be a physiological binding partner (PubMed:16980328). CC Interacts (isoform 1 and isoform 2 only) with the DNA-dependent CC protein kinase complex DNA-PK; the interaction phosphorylates CC DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and CC XRCC6. Interacts with AP3M1, AP3B2 and TRIM32. Interacts with CC XPO1; the interaction exports DTNBP1 out of the nucleus. CC {ECO:0000250, ECO:0000269|PubMed:16837549, CC ECO:0000269|PubMed:16980328, ECO:0000269|PubMed:17182842, CC ECO:0000269|PubMed:19142223, ECO:0000269|PubMed:19349376, CC ECO:0000269|PubMed:19428785, ECO:0000269|PubMed:20921223, CC ECO:0000269|PubMed:22203680}. CC -!- INTERACTION: CC P78537:BLOC1S1; NbExp=3; IntAct=EBI-465804, EBI-348630; CC Q6QNY1:BLOC1S2; NbExp=6; IntAct=EBI-465804, EBI-465872; CC Q6QNY0:BLOC1S3; NbExp=3; IntAct=EBI-465804, EBI-465930; CC Q8TDH9:BLOC1S5; NbExp=3; IntAct=EBI-465804, EBI-465861; CC Q9UL45:BLOC1S6; NbExp=6; IntAct=EBI-465804, EBI-465781; CC Q8WUW1:BRK1; NbExp=3; IntAct=EBI-465804, EBI-2837444; CC Q9NUL5:C19orf66; NbExp=3; IntAct=EBI-465804, EBI-10313866; CC Q8IYE0-2:CCDC146; NbExp=3; IntAct=EBI-465804, EBI-10247802; CC Q494R4:CCDC153; NbExp=3; IntAct=EBI-465804, EBI-10241443; CC Q9Y3C0:CCDC53; NbExp=3; IntAct=EBI-465804, EBI-712969; CC Q8TD31-3:CCHCR1; NbExp=3; IntAct=EBI-465804, EBI-10175300; CC Q5HYH7:DKFZp451B226; NbExp=4; IntAct=EBI-465804, EBI-10173842; CC O60941:DTNB; NbExp=3; IntAct=EBI-465804, EBI-740402; CC A1L3X0:ELOVL7; NbExp=3; IntAct=EBI-465804, EBI-10285373; CC Q96CS2:HAUS1; NbExp=3; IntAct=EBI-465804, EBI-2514791; CC Q8IY31:IFT20; NbExp=3; IntAct=EBI-465804, EBI-744203; CC I3L4J3:KANSL1; NbExp=3; IntAct=EBI-465804, EBI-10178305; CC Q9BVG8:KIFC3; NbExp=3; IntAct=EBI-465804, EBI-2125614; CC Q7Z4N8:P4HA3; NbExp=3; IntAct=EBI-465804, EBI-10181968; CC O00560:SDCBP; NbExp=3; IntAct=EBI-465804, EBI-727004; CC O95295:SNAPIN; NbExp=4; IntAct=EBI-465804, EBI-296723; CC A1L4H1:SSC5D; NbExp=3; IntAct=EBI-465804, EBI-10172867; CC P14373:TRIM27; NbExp=3; IntAct=EBI-465804, EBI-719493; 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}. Cell junction, synapse, CC postsynaptic cell membrane, postsynaptic density CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum CC {ECO:0000250}. Nucleus {ECO:0000269|PubMed:21390302}. Note=Mainly CC cytoplasmic but shuttles between the cytoplasm and nucleus. CC Exported out of the nucleus via its NES in a XPO1-dependent CC manner. Nuclear localization is required for regulation of the CC expression of genes such as SYN1. Detected in neuron cell bodies, CC axons and dendrites. Mainly located to the postsynaptic density. CC Detected at tubulovesicular elements in the vicinity of the Golgi CC apparatus and of melanosomes. Occasionally detected at the CC membrane of pigmented melanosomes in cultured melanoma cells. The CC 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 CC vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; CC Peripheral membrane protein {ECO:0000269|PubMed:21390302}; CC Cytoplasmic side {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}. Cell junction, synapse, postsynaptic cell membrane CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum CC {ECO:0000250}. Nucleus {ECO:0000269|PubMed:21390302}. CC Note=Shuttles between the cytoplasm and nucleus. Exported out of CC the nucleus via its NES in a XPO1-dependent manner. Nuclear CC localization is required for regulation of the expression of genes CC such as SYN1. Mainly expressed in the dendritic spine. CC Predominantly a synaptic vesicle isoform but also highly expressed CC in the nucleus. The BLOC-1 complex associates with the BLOC-2 CC complex in early endosome-associated tubules. Associated with the CC 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 CC vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:21390302}; CC Peripheral membrane protein {ECO:0000269|PubMed:21390302}; CC Cytoplasmic side {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}. Cell junction, synapse, postsynaptic cell membrane CC {ECO:0000269|PubMed:21390302}. Endoplasmic reticulum CC {ECO:0000250}. Note=Exclusivley cytoplasmic. Predominantly found CC in the postsynaptic density (PSD). Little association with CC synaptic vesicles. The BLOC-1 complex associates with the BLOC-2 CC complex in early endosome-associated tubules. Associated with the CC 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 Note=Major isoform.; CC Name=2; CC IsoId=Q96EV8-2; Sequence=VSP_009023; CC Note=May be due to intron retention.; 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 CC frontal (HF). Specific expression in the posterior half of the CC superior temporal gyrus (pSTG). Higher expression of isoform 2 and CC 3 in the HF than in the pSTG while isoform 1 shows no difference CC in expression in these areas. In the HF, detected in dentate gyrus CC (DG) and in pyramidal cells of hippocampus CA2 and CA3 (at protein CC level). Expressed in all principal neuronal populations of the HF, CC namely pyramidal neurons in the subiculum and CA1-3, granule cells CC in the dense cell layer of the DG (DGg), and polymorph cells in CC the hilus of the DG (DGh). Maximal levels in CA2, CA3, and DGh. CC Isoform 2 not expressed in the cerebral cortex. CC {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. CC Isoform 3 only weakly phosphorylated by PRKDC in vitro. CC {ECO:0000269|PubMed:19142223}. CC -!- DISEASE: Hermansky-Pudlak syndrome 7 (HPS7) [MIM:614076]: A form CC of Hermansky-Pudlak syndrome, a genetically heterogeneous CC autosomal recessive disorder characterized by oculocutaneous CC albinism, bleeding due to platelet storage pool deficiency, and CC lysosomal storage defects. This syndrome results from defects of CC diverse cytoplasmic organelles including melanosomes, platelet CC dense granules and lysosomes. Ceroid storage in the lungs is CC associated with pulmonary fibrosis, a common cause of premature CC death in individuals with HPS. {ECO:0000269|PubMed:12923531}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Note=Defects in DTNBP1 are associated with susceptibility CC to schizophrenia, a mental disorder characterized by a breakdown CC of thought processes and by poor emotional responsiveness. Genetic CC mutations lead to alterations in the glutamatergic transmisssion CC in the brain and modified Akt signaling (PubMed:15345706). Protein CC levels and expression are reduced in nerve terminals of the CC hippocampus and there is an increased release of glutamate in CC schizophrenic patients (PubMed:15124027). Levels of isoform 1 are CC reduced in the pSTG, but not in HF, by about 48% in 92% of CC schizophrenic patients. In the HF, there is an average of 33% CC reduction in synaptic expression of isoform 2 in 67% of cases, and CC of isoform 3, an average reduction of 35% in 80% of cases. In the CC dorsolateral prefrontal cortex (DLPFC), significant reductions in CC levels of isoform 3 are observed about 71% of schizophrenic CC patients showed an average reduction of this isoform of about 60% CC (PubMed:19617633). {ECO:0000269|PubMed:15124027, CC ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:19617633}. CC -!- SIMILARITY: Belongs to the dysbindin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG43145.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; 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; AL022343; CAI21976.1; -; Genomic_DNA. DR EMBL; AL021978; CAI21976.1; JOINED; Genomic_DNA. DR EMBL; AL022343; CAI21977.1; -; Genomic_DNA. DR EMBL; AL021978; CAI21977.1; JOINED; Genomic_DNA. DR EMBL; AL021978; CAI42339.1; -; Genomic_DNA. DR EMBL; AL022343; CAI42339.1; JOINED; Genomic_DNA. DR EMBL; AL021978; CAI42340.1; -; Genomic_DNA. DR EMBL; AL022343; CAI42340.1; JOINED; 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 UniGene; Hs.571148; -. DR ProteinModelPortal; Q96EV8; -. DR BioGrid; 123857; 126. DR IntAct; Q96EV8; 49. DR MINT; MINT-1438666; -. DR STRING; 9606.ENSP00000341680; -. DR PhosphoSite; Q96EV8; -. DR BioMuta; DTNBP1; -. DR DMDM; 38604971; -. DR MaxQB; Q96EV8; -. DR PaxDb; Q96EV8; -. DR PRIDE; Q96EV8; -. DR DNASU; 84062; -. DR Ensembl; ENST00000338950; ENSP00000344718; ENSG00000047579. [Q96EV8-2] DR Ensembl; ENST00000344537; ENSP00000341680; ENSG00000047579. [Q96EV8-1] DR GeneID; 84062; -. DR KEGG; hsa:84062; -. DR UCSC; uc003nbl.3; human. [Q96EV8-1] DR UCSC; uc003nbp.3; human. [Q96EV8-2] DR CTD; 84062; -. DR GeneCards; DTNBP1; -. DR GeneReviews; DTNBP1; -. DR HGNC; HGNC:17328; DTNBP1. DR HPA; HPA028053; -. DR HPA; HPA029615; -. DR HPA; HPA029616; -. DR MIM; 607145; gene. DR MIM; 614076; phenotype. DR neXtProt; NX_Q96EV8; -. DR Orphanet; 231531; Hermansky-Pudlak syndrome type 7. DR PharmGKB; PA27512; -. DR eggNOG; ENOG410IF9S; Eukaryota. DR eggNOG; ENOG4111YM1; LUCA. DR GeneTree; ENSGT00390000010667; -. DR HOGENOM; HOG000272621; -. DR HOVERGEN; HBG051416; -. DR InParanoid; Q96EV8; -. DR OMA; MFENFRE; -. DR OrthoDB; EOG72VH6B; -. DR PhylomeDB; Q96EV8; -. DR TreeFam; TF332997; -. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR GeneWiki; Dysbindin; -. DR GenomeRNAi; 84062; -. DR NextBio; 73219; -. DR PRO; PR:Q96EV8; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q96EV8; -. DR CleanEx; HS_DTNBP1; -. DR ExpressionAtlas; Q96EV8; baseline and differential. DR Genevisible; Q96EV8; HS. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0031083; C:BLOC-1 complex; IDA:UniProtKB. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. 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:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. 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:0030672; C:synaptic vesicle membrane; IDA:UniProtKB. DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB. DR GO; GO:0008089; P:anterograde axon cargo 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:0032438; P:melanosome organization; NAS:UniProtKB. DR GO; GO:0061024; P:membrane organization; TAS:Reactome. 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; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; ISS:UniProtKB. DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome. 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:0043506; P:regulation of JUN kinase activity; IEA:Ensembl. DR InterPro; IPR007531; Dysbindin. DR PANTHER; PTHR16294; PTHR16294; 1. DR Pfam; PF04440; Dysbindin; 1. PE 1: Evidence at protein level; KW Albinism; Alternative initiation; Alternative splicing; Cell junction; KW Cell membrane; Coiled coil; Complete proteome; Cytoplasm; KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; KW Hermansky-Pudlak syndrome; Membrane; Nucleus; Phosphoprotein; KW Polymorphism; Postsynaptic cell membrane; Reference proteome; KW Schizophrenia; Sensory transduction; Synapse; Ubl conjugation. FT CHAIN 1 351 Dysbindin. FT /FTId=PRO_0000191001. FT REGION 173 331 Dysbindin. FT COILED 88 181 {ECO:0000255}. FT MOTIF 243 256 Nuclear export signal. FT MOD_RES 316 316 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 321 321 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 349 349 Phosphoserine. FT {ECO:0000250|UniProtKB:Q91WZ8}. FT VAR_SEQ 1 81 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_046062. FT VAR_SEQ 272 351 PESSTCQNEITLQVPNPSELRAKPPSSSSTCTDSATRDISE FT GGESPVVQSDEEEVQVDTALATSHTDREATPDGGEDSDS FT -> RVDKLALAEPGQYRCHSPPKVRRENHLPVTYA (in FT isoform 2). {ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039}. FT /FTId=VSP_009023. FT VARIANT 214 214 G -> D (in dbSNP:rs16876589). FT /FTId=VAR_053069. FT VARIANT 272 272 P -> S (in dbSNP:rs17470454). FT /FTId=VAR_029644. FT MUTAGEN 215 215 Y->A: Reduced interaction with AP3M1. FT {ECO:0000269|PubMed:19428785}. FT MUTAGEN 243 256 LMDISDQEALDVFL->AMDASDQEAADVFA: Abolishes FT cytoplasmic location. Increased FT expression of SYN1. FT {ECO:0000269|PubMed:20921223}. FT CONFLICT 242 242 D -> V (in Ref. 3; CAB66572). FT {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 //