DTBP1_MOUSE
ID DTBP1_MOUSE Reviewed; 352 AA.
AC Q91WZ8; Q3TWK1; Q6WXQ1; Q80ZN4; Q9CY43;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
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 homolog;
DE Short=HPS7 protein homolog;
GN Name=Dtnbp1; Synonyms=Bloc1s8, Sdy;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP INTERACTION WITH DTNA AND DTNB, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Liver;
RX PubMed=11316798; DOI=10.1074/jbc.m010418200;
RA Benson M.A., Newey S.E., Martin-Rendon E., Hawkes R., Blake D.J.;
RT "Dysbindin, a novel coiled-coil-containing protein that interacts with the
RT dystrobrevins in muscle and brain.";
RL J. Biol. Chem. 276:24232-24241(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, ALTERNATIVE SPLICING,
RP TISSUE SPECIFICITY, INTERACTION WITH DTNB; BLOC1S5 AND BLOC1S6, AND
RP DISEASE.
RC STRAIN=DBA/2J; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3; TISSUE=Limb, Liver, and Mammary tumor;
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 [5]
RP DISEASE.
RX PubMed=1936982; DOI=10.1017/s0016672300029608;
RA Swank R.T., Sweet H.O., Davisson M.T., Reddington M., Novak E.K.;
RT "Sandy: a new mouse model for platelet storage pool deficiency.";
RL Genet. Res. 58:51-62(1991).
RN [6]
RP DISRUPTION PHENOTYPE, 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 [7]
RP INTERACTION WITH CMYA5.
RX PubMed=14688250; DOI=10.1074/jbc.m312664200;
RA Benson M.A., Tinsley C.L., Blake D.J.;
RT "Myospryn is a novel binding partner for dysbindin in muscle.";
RL J. Biol. Chem. 279:10450-10458(2004).
RN [8]
RP FUNCTION, AND SUBUNIT.
RX PubMed=16448387; DOI=10.1042/bj20051965;
RA Nazarian R., Starcevic M., Spencer M.J., Dell'Angelica E.C.;
RT "Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of
RT lysosome-related organelles complex-1) as a dystrobrevin-binding protein.";
RL Biochem. J. 395:587-598(2006).
RN [9]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH SNAPIN.
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 [10]
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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16760431; DOI=10.1091/mbc.e06-02-0103;
RA Salazar G., Craige B., Styers M.L., Newell-Litwa K.A., Doucette M.M.,
RA Wainer B.H., Falcon-Perez J.M., Dell'Angelica E.C., Peden A.A., Werner E.,
RA Faundez V.;
RT "BLOC-1 complex deficiency alters the targeting of adaptor protein complex-
RT 3 cargoes.";
RL Mol. Biol. Cell 17:4014-4026(2006).
RN [12]
RP INTERACTION WITH RNF151, AND SUBCELLULAR LOCATION.
RX PubMed=17577571; DOI=10.1016/j.abb.2007.05.013;
RA Nian H., Fan C., Liao S., Shi Y., Zhang K., Liu Y., Han C.;
RT "RNF151, a testis-specific RING finger protein, interacts with dysbindin.";
RL Arch. Biochem. Biophys. 465:157-163(2007).
RN [13]
RP FUNCTION, AND DISEASE.
RX PubMed=18555792; DOI=10.1016/j.bbrc.2008.06.016;
RA Hattori S., Murotani T., Matsuzaki S., Ishizuka T., Kumamoto N., Takeda M.,
RA Tohyama M., Yamatodani A., Kunugi H., Hashimoto R.;
RT "Behavioral abnormalities and dopamine reductions in sdy mutant mice with a
RT deletion in Dtnbp1, a susceptibility gene for schizophrenia.";
RL Biochem. Biophys. Res. Commun. 373:298-302(2008).
RN [14]
RP DISEASE, AND FUNCTION.
RX PubMed=18504299; DOI=10.1083/jcb.200711021;
RA Chen X.W., Feng Y.Q., Hao C.J., Guo X.L., He X., Zhou Z.Y., Guo N.,
RA Huang H.P., Xiong W., Zheng H., Zuo P.L., Zhang C.X., Li W., Zhou Z.;
RT "DTNBP1, a schizophrenia susceptibility gene, affects kinetics of
RT transmitter release.";
RL J. Cell Biol. 181:791-801(2008).
RN [15]
RP DISEASE.
RX PubMed=18945333; DOI=10.1186/1756-6606-1-11;
RA Takao K., Toyama K., Nakanishi K., Hattori S., Takamura H., Takeda M.,
RA Miyakawa T., Hashimoto R.;
RT "Impaired long-term memory retention and working memory in sdy mutant mice
RT with a deletion in Dtnbp1, a susceptibility gene for schizophrenia.";
RL Mol. Brain 1:11-11(2008).
RN [16]
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 [17]
RP DISEASE, AND FUNCTION.
RX PubMed=18984010; DOI=10.1016/j.bbr.2008.10.011;
RA Bhardwaj S.K., Baharnoori M., Sharif-Askari B., Kamath A., Williams S.,
RA Srivastava L.K.;
RT "Behavioral characterization of dysbindin-1 deficient sandy mice.";
RL Behav. Brain Res. 197:435-441(2009).
RN [18]
RP DISRUPTION PHENOTYPE, AND 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 DISEASE.
RX PubMed=19220483; DOI=10.1111/j.1601-183x.2009.00477.x;
RA Cox M.M., Tucker A.M., Tang J., Talbot K., Richer D.C., Yeh L.,
RA Arnold S.E.;
RT "Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a
RT C57BL/6J genetic background.";
RL Genes Brain Behav. 8:390-397(2009).
RN [20]
RP REVIEW ON DISEASE.
RX PubMed=20302821; DOI=10.1016/s0079-6123(09)17910-4;
RA Talbot K.;
RT "The sandy (sdy) mouse: a dysbindin-1 mutant relevant to schizophrenia
RT research.";
RL Prog. Brain Res. 179:87-94(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 AND SER-343, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP DISEASE, AND FUNCTION.
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 [23]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19546860; DOI=10.1038/mp.2009.58;
RA Ghiani C.A., Starcevic M., Rodriguez-Fernandez I.A., Nazarian R.,
RA Cheli V.T., Chan L.N., Malvar J.S., de Vellis J., Sabatti C.,
RA Dell'Angelica E.C.;
RT "The dysbindin-containing complex (BLOC-1) in brain: developmental
RT regulation, interaction with SNARE proteins and role in neurite
RT outgrowth.";
RL Mol. Psychiatry 15:204-215(2010).
RN [24]
RP TISSUE SPECIFICITY, INTERACTION WITH THE AP-C COMPLEX, AND FUNCTION.
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 [25]
RP FUNCTION.
RX PubMed=20045719; DOI=10.1016/j.neulet.2009.12.071;
RA Nagai T., Kitahara Y., Shiraki A., Hikita T., Taya S., Kaibuchi K.,
RA Yamada K.;
RT "Dysfunction of dopamine release in the prefrontal cortex of dysbindin
RT deficient sandy mice: an in vivo microdialysis study.";
RL Neurosci. Lett. 470:134-138(2010).
RN [26]
RP INTERACTION WITH AP3B2.
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 [27]
RP FUNCTION.
RX PubMed=19887632; DOI=10.1073/pnas.0904289106;
RA Ji Y., Yang F., Papaleo F., Wang H.X., Gao W.J., Weinberger D.R., Lu B.;
RT "Role of dysbindin in dopamine receptor trafficking and cortical GABA
RT function.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19593-19598(2009).
RN [28]
RP FUNCTION, ASSOCIATION WITH THE AP-3 COMPLEX, AND INTERACTION WITH PI4K2A.
RX PubMed=21998198; DOI=10.1091/mbc.e11-07-0592;
RA Larimore J., Tornieri K., Ryder P.V., Gokhale A., Zlatic S.A., Craige B.,
RA Lee J.D., Talbot K., Pare J.F., Smith Y., Faundez V.;
RT "The schizophrenia susceptibility factor dysbindin and its associated
RT complex sort cargoes from cell bodies to the synapse.";
RL Mol. Biol. Cell 22:4854-4867(2011).
RN [29]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20956979; DOI=10.1038/mp.2010.106;
RA Papaleo F., Yang F., Garcia S., Chen J., Lu B., Crawley J.N.,
RA Weinberger D.R.;
RT "Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like
RT behaviors via dopamine/D2 pathways.";
RL Mol. Psychiatry 17:85-98(2012).
RN [30]
RP INTERACTION WITH KXD1.
RX PubMed=22554196; DOI=10.1111/j.1600-0854.2012.01375.x;
RA Yang Q., He X., Yang L., Zhou Z., Cullinane A.R., Wei A., Zhang Z., Hao Z.,
RA Zhang A., He M., Feng Y., Gao X., Gahl W.A., Huizing M., Li W.;
RT "The BLOS1-interacting protein KXD1 is involved in the biogenesis of
RT lysosome-related organelles.";
RL Traffic 13:1160-1169(2012).
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:12923531, ECO:0000269|PubMed:15345706,
CC ECO:0000269|PubMed:16448387, ECO:0000269|PubMed:16760431,
CC ECO:0000269|PubMed:16837549, ECO:0000269|PubMed:18504299,
CC ECO:0000269|PubMed:18555792, ECO:0000269|PubMed:18984010,
CC ECO:0000269|PubMed:19094965, ECO:0000269|PubMed:19428785,
CC ECO:0000269|PubMed:19546860, ECO:0000269|PubMed:19887632,
CC ECO:0000269|PubMed:20045719, ECO:0000269|PubMed:20921223,
CC ECO:0000269|PubMed:20956979, ECO:0000269|PubMed:21998198}.
CC -!- SUBUNIT: Interacts with AP3M1 and TRIM32. Interacts (isoform 1 and
CC isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK;
CC the interaction phosphorylates DTNBP1 in vitro. Interacts directly in
CC this complex with XRCC5 and XRCC6. Interacts with XPO1; the interaction
CC exports DTNBP1 out of the nucleus (By similarity). Component of the
CC biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed
CC of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7
CC and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein
CC complex and membrane protein cargos. This BLOC-1 complex also
CC associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB
CC but may not be a physiological binding partner (PubMed:16448387 and
CC PubMed:16980328). Interacts (via its coiled coil domain) with KXD1.
CC Interacts with AP3B2, BLOC1S5, BLOC1S6, CMYA5, PI4K2, RNF151 and
CC SNAPIN/BLOC1S8. Interacts with XPO1; the interaction exports DTNBP1 out
CC of the nucleus. {ECO:0000250, ECO:0000269|PubMed:11316798,
CC ECO:0000269|PubMed:12923531, ECO:0000269|PubMed:14688250,
CC ECO:0000269|PubMed:16448387, ECO:0000269|PubMed:16837549,
CC ECO:0000269|PubMed:16980328, ECO:0000269|PubMed:17577571,
CC ECO:0000269|PubMed:19142223, ECO:0000269|PubMed:19428785,
CC ECO:0000269|PubMed:19546860, ECO:0000269|PubMed:21998198,
CC ECO:0000269|PubMed:22554196}.
CC -!- INTERACTION:
CC Q91WZ8; Q70KF4: Cmya5; NbExp=5; IntAct=EBI-643186, EBI-782290;
CC Q91WZ8; Q9D2N4: Dtna; NbExp=3; IntAct=EBI-643186, EBI-296019;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Cytoplasmic vesicle
CC membrane; Peripheral membrane protein; Cytoplasmic side. Endosome
CC membrane; Peripheral membrane protein; Cytoplasmic side. Melanosome
CC membrane; Peripheral membrane protein; Cytoplasmic side. Postsynaptic
CC density. Endoplasmic reticulum {ECO:0000250}. Nucleus. Note=Mainly
CC cytoplasmic but shuttles between the cytoplasm and nucleus. Exported
CC out of the nucleus via its NES in a XPO1-dependent manner. Nuclear
CC localization is required for regulation of the expression of genes such
CC as SYN1. Detected in neuron cell bodies, axons and dendrites. Mainly
CC located to the postsynaptic density. Detected at tubulovesicular
CC elements in the vicinity of the Golgi apparatus and of melanosomes.
CC Occasionally detected at the membrane of pigmented melanosomes in
CC cultured melanoma cells (By similarity). The BLOC-1 complex associates
CC with the BLOC-2 complex in early endosome-associated tubules.
CC Associated with the AP-3 complex at presynaptic terminals.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Cytoplasmic vesicle
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250};
CC Cytoplasmic side {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Endosome membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Melanosome membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Postsynaptic cell membrane. Endoplasmic reticulum {ECO:0000250}.
CC Note=Exclusivley cytoplasmic. Predominantly found in the postsynaptic
CC density (PSD). Little association with synaptic vesicles (By
CC similarity). The BLOC-1 complex associates with the BLOC-2 complex in
CC early endosome-associated tubules. Vesicle membranes and microtubules.
CC Associated with the AP-3 complex at presynaptic terminals.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Dysbindin 1-A;
CC IsoId=Q91WZ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91WZ8-2; Sequence=VSP_009024;
CC Name=3; Synonyms=Dysbindin 1-C;
CC IsoId=Q91WZ8-3; Sequence=VSP_021939;
CC -!- TISSUE SPECIFICITY: Detected in brain, in hippocampus and dentate gyrus
CC neurons. Detected at axon bundles and axon terminals, notably in the
CC cerebellum and hippocampus. Detected in neuropil in hippocampus,
CC lateral septum, basal ganglia and substantia nigra. Highly expressed in
CC pyramidal cells of hippocampus CA2 and CA3. Detected at the heart and
CC skeletal muscle sarcolemma (at protein level). Ubiquitously expressed.
CC The highest expression is observed in testis, liver, kidney, brain,
CC heart and lung. Expressed at lower levels in stomach and small
CC intestine. {ECO:0000269|PubMed:11316798, ECO:0000269|PubMed:12923531,
CC ECO:0000269|PubMed:16760431, ECO:0000269|PubMed:16980328,
CC ECO:0000269|PubMed:19428785, ECO:0000269|PubMed:19546860}.
CC -!- PTM: Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1
CC degradation. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Dtnbp1 are the cause of the sandy (sdy) mutant
CC phenotype, a model for human Hermansky-Pudlak syndrome (HPS). Sdy mice
CC lack dysbindin expression; they have a characteristic sandy coat color
CC and have much fewer melanosomes in the retinal pigment epithelium and
CC choroid. They are fully viable, but present behavioral abnormalities.
CC They have prolonged bleeding times due to platelet storage pool
CC deficiency, and lysosomal storage defects. The number of electron-
CC opaque platelet dense granules is severely reduced, and the platelet
CC serotonin content is strongly reduced. Secretion of lysosomal enzymes
CC from kidney and from thrombin-stimulated platelets is depressed 2- and
CC 3-fold, and ceroid pigment is present in kidney. Sandy mice also
CC display impaired long-term memory retention and working memory and
CC schizophrenia-like behavioral abnormalities. Vesicle morphology and
CC kinetics of transmitter release are affected in both neuroendocrine
CC cells and hippocampal synapses, characterized by larger vesicle size,
CC slower quantal release, fewer release events and reduced readily
CC releasable pool (RRP). Expression levels of SYN1 are lower in both the
CC cortex and the hippocampal formation (HF).
CC {ECO:0000269|PubMed:12923531, ECO:0000269|PubMed:18504299,
CC ECO:0000269|PubMed:18555792, ECO:0000269|PubMed:18945333,
CC ECO:0000269|PubMed:18984010, ECO:0000269|PubMed:19220483,
CC ECO:0000269|PubMed:1936982, ECO:0000269|PubMed:20921223}.
CC -!- DISRUPTION PHENOTYPE: Null mice exhibit cognitive abnormalities
CC including schizophrenia-related behaviors such as impaired working
CC memory under stressful conditions. There is higher acoustic startle
CC reactivity to stimuli. Pyramidal neurons are hypoexcitable on dopamine-
CC 2 receptor stimulation. There is reduced expression of
CC Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and CaMKKbeta in
CC the medial prefrontal cortex mPFC. There is increased expression levels
CC of cell surface dopamine receptor D2 in cortical neurons. Expression
CC levels of SYN1 are lower in both cortex and in the hippocampal
CC formation (HF). {ECO:0000269|PubMed:15345706,
CC ECO:0000269|PubMed:19094965, ECO:0000269|PubMed:20956979}.
CC -!- SIMILARITY: Belongs to the dysbindin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH48682.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE35265.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ404859; CAC37976.1; -; mRNA.
DR EMBL; AY265461; AAP91871.1; -; mRNA.
DR EMBL; AK010924; BAB27270.2; -; mRNA.
DR EMBL; AK159656; BAE35265.1; ALT_INIT; mRNA.
DR EMBL; BC018350; AAH18350.1; -; mRNA.
DR EMBL; BC048682; AAH48682.1; ALT_FRAME; mRNA.
DR EMBL; BC058574; AAH58574.1; -; mRNA.
DR CCDS; CCDS36647.1; -. [Q91WZ8-1]
DR RefSeq; NP_080048.2; NM_025772.4. [Q91WZ8-1]
DR AlphaFoldDB; Q91WZ8; -.
DR SMR; Q91WZ8; -.
DR BioGRID; 220491; 6.
DR ComplexPortal; CPX-1913; BLOC-1 complex.
DR CORUM; Q91WZ8; -.
DR IntAct; Q91WZ8; 15.
DR MINT; Q91WZ8; -.
DR STRING; 10090.ENSMUSP00000072170; -.
DR iPTMnet; Q91WZ8; -.
DR PhosphoSitePlus; Q91WZ8; -.
DR EPD; Q91WZ8; -.
DR MaxQB; Q91WZ8; -.
DR PaxDb; Q91WZ8; -.
DR PeptideAtlas; Q91WZ8; -.
DR PRIDE; Q91WZ8; -.
DR ProteomicsDB; 279814; -. [Q91WZ8-1]
DR ProteomicsDB; 279815; -. [Q91WZ8-2]
DR ProteomicsDB; 279816; -. [Q91WZ8-3]
DR Antibodypedia; 25035; 449 antibodies from 35 providers.
DR DNASU; 94245; -.
DR Ensembl; ENSMUST00000072329; ENSMUSP00000072170; ENSMUSG00000057531. [Q91WZ8-1]
DR Ensembl; ENSMUST00000222583; ENSMUSP00000152812; ENSMUSG00000057531. [Q91WZ8-3]
DR GeneID; 94245; -.
DR KEGG; mmu:94245; -.
DR UCSC; uc007qgw.1; mouse. [Q91WZ8-1]
DR CTD; 84062; -.
DR MGI; MGI:2137586; Dtnbp1.
DR VEuPathDB; HostDB:ENSMUSG00000057531; -.
DR eggNOG; ENOG502QRS9; Eukaryota.
DR GeneTree; ENSGT00940000156479; -.
DR HOGENOM; CLU_071074_0_0_1; -.
DR InParanoid; Q91WZ8; -.
DR OMA; SRYEESW; -.
DR OrthoDB; 862376at2759; -.
DR PhylomeDB; Q91WZ8; -.
DR TreeFam; TF332997; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR BioGRID-ORCS; 94245; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Dtnbp1; mouse.
DR PRO; PR:Q91WZ8; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q91WZ8; protein.
DR Bgee; ENSMUSG00000057531; Expressed in interventricular septum and 255 other tissues.
DR ExpressionAtlas; Q91WZ8; baseline and differential.
DR Genevisible; Q91WZ8; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032279; C:asymmetric synapse; IDA:SynGO.
DR GO; GO:0030424; C:axon; IDA: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; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
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; IDA:UniProtKB.
DR GO; GO:0016528; C:sarcoplasm; IDA:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
DR GO; GO:0008089; P:anterograde axonal transport; IMP:UniProtKB.
DR GO; GO:0048490; P:anterograde synaptic vesicle transport; IMP:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IMP:MGI.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0032438; P:melanosome organization; IC:ComplexPortal.
DR GO; GO:0007517; P:muscle organ development; TAS:MGI.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:MGI.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:UniProtKB.
DR GO; GO:0006996; P:organelle organization; IDA:UniProtKB.
DR GO; GO:0060155; P:platelet dense granule organization; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0061646; P:positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization; ISO:MGI.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:UniProtKB.
DR GO; GO:0043506; P:regulation of JUN kinase activity; IMP:CACAO.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0060041; P:retina development in camera-type eye; 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 splicing; Cell membrane; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome;
KW Hermansky-Pudlak syndrome; Membrane; Nucleus; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Sensory transduction;
KW Synapse; Ubl conjugation.
FT CHAIN 1..352
FT /note="Dysbindin"
FT /id="PRO_0000191002"
FT REGION 173..325
FT /note="Dysbindin"
FT REGION 267..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 88..176
FT /evidence="ECO:0000255"
FT MOTIF 243..256
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 270..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EV8"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EV8"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..81
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12923531"
FT /id="VSP_021939"
FT VAR_SEQ 171..222
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11316798"
FT /id="VSP_009024"
FT CONFLICT 251
FT /note="A -> T (in Ref. 3; BAE35265)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="E -> G (in Ref. 3; BAE35265)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 352 AA; 39651 MW; EE60FB10ECE95361 CRC64;
MLETLRERLL SVQQDFTSGL KTLSDKSREA KVKGKPRTAP RLPKYSAGLE LLSRYEDAWA
ALHRRAKECA DAGELVDSEV VMLSAHWEKK RTSLNELQGQ LQQLPALLQD LESLMASLAH
LETSFEEVEN HLLHLEDLCG QCELERHKQA QAQHLESYKK SKRKELEAFK AELDTEHTQK
ALEMEHTQQL KLKERQKFFE EAFQQDMEQY LSTGYLQIAE RREPMGSMSS MEVNVDVLEQ
MDLMDISDQE ALDVFLNSGG EDNIVMSPGV EMESNPNQNE MSLQIPSPSE SASQPPASPS
ACTDLDTADA PLIQSDEEEV QVDTALVTLH TDRKSTPGVS DDSDQCDSTQ DI
