DTBP1_RAT
ID DTBP1_RAT Reviewed; 352 AA.
AC Q5M834; Q6GX90;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 89.
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;
GN Name=Dtnbp1; Synonyms=Bloc1s8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16288221; DOI=10.1038/sj.onc.1209210;
RA Iwanaga R., Komori H., Ishida S., Okamura N., Nakayama K., Nakayama K.,
RA Ohtani K.;
RT "Identification of novel E2F1 target genes regulated in cell cycle-
RT dependent and independent manners.";
RL Oncogene 25:1786-1798(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [3]
RP TISSUE SPECIFICITY, AND INTERACTION WITH DTNA AND DTNB.
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH DTNA; DTNB AND BLOC1S6.
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 [5]
RP IDENTIFICATION IN THE BLOC-1 COMPLEX, FUNCTION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
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 [6]
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 [7]
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 [8]
RP IDENTIFICATION IN A COMPLEX WITH AP-3 COMPLEX.
RX PubMed=19010779; DOI=10.1074/jbc.m805991200;
RA Salazar G., Zlatic S., Craige B., Peden A.A., Pohl J., Faundez V.;
RT "Hermansky-Pudlak syndrome protein complexes associate with
RT phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal
RT cells.";
RL J. Biol. Chem. 284:1790-1802(2009).
RN [9]
RP INTERACTION WITH AP3M1, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
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).
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:16448387, ECO:0000269|PubMed:16760431,
CC ECO:0000269|PubMed:17989303, ECO:0000269|PubMed:19428785}.
CC -!- SUBUNIT: Interacts (via its coiled coil domain) with KXD1. Interacts
CC with AP3B2, TRIM32, CMYA5, PI4K2 and RNF151. Interacts with the DNA-
CC dependent protein kinase complex DNA-PK; the interaction phosphorylates
CC DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and
CC XRCC6. Interacts with XPO1; the interaction exports DTNBP1 out of the
CC nucleus (By similarity). Component of the biogenesis of lysosome-
CC related organelles complex 1 (BLOC-1) composed of at least BLOC1S1,
CC BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and
CC SNAPIN/BLOC1S8. Interacts directly in the complex with BLOC1S5, BLOC1S6
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. Interacts with AP3M1.
CC {ECO:0000250, ECO:0000269|PubMed:11316798, ECO:0000269|PubMed:16448387,
CC ECO:0000269|PubMed:16760431, ECO:0000269|PubMed:19010779,
CC ECO:0000269|PubMed:19428785}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. 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:0000269|PubMed:19428785}; Peripheral
CC membrane protein {ECO:0000269|PubMed:19428785}; Cytoplasmic side
CC {ECO:0000269|PubMed:19428785}. Endosome membrane
CC {ECO:0000269|PubMed:19428785}; Peripheral membrane protein
CC {ECO:0000269|PubMed:19428785}; Cytoplasmic side
CC {ECO:0000269|PubMed:19428785}. Melanosome membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Nucleus {ECO:0000250}. Postsynaptic density
CC {ECO:0000269|PubMed:19428785}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:19428785}. Endoplasmic reticulum {ECO:0000250}.
CC Note=Mainly cytoplasmic but shuttles between the cytoplasm and nucleus.
CC Exported out of the nucleus via its NES in a XPO1-dependent manner.
CC Nuclear localization is required for regulation of the expression of
CC genes such as SYN1 (By similarity). Detected in neuron cell bodies,
CC axons and dendrites. Detected at synapses, at postsynaptic density, at
CC presynaptic vesicle membranes and microtubules. Associated with the AP-
CC 3 complex at presynaptic terminals. 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 -!- TISSUE SPECIFICITY: Detected in hippocampus neurons (at protein level).
CC Ubiquitously expressed. The highest expression is observed in testis,
CC liver, kidney, brain, heart and lung. In the brain, found primarily in
CC axon bundles and axon terminals, notably in the cerebellum and
CC hippocampus. Expressed at lower levels in stomach, small intestine and
CC skeletal muscle, where it is detected at the sarcolemma.
CC {ECO:0000269|PubMed:11316798, ECO:0000269|PubMed:16448387,
CC ECO:0000269|PubMed:19428785}.
CC -!- PTM: Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1
CC degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dysbindin family. {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; AY623026; AAT46043.1; -; mRNA.
DR EMBL; BC088267; AAH88267.1; -; mRNA.
DR RefSeq; NP_001032753.1; NM_001037664.1.
DR AlphaFoldDB; Q5M834; -.
DR SMR; Q5M834; -.
DR BioGRID; 566020; 2.
DR IntAct; Q5M834; 3.
DR PaxDb; Q5M834; -.
DR Ensembl; ENSRNOT00000102493; ENSRNOP00000091788; ENSRNOG00000048719.
DR GeneID; 641528; -.
DR KEGG; rno:641528; -.
DR CTD; 84062; -.
DR RGD; 1590759; Dtnbp1.
DR eggNOG; ENOG502QRS9; Eukaryota.
DR GeneTree; ENSGT00940000156479; -.
DR InParanoid; Q5M834; -.
DR OrthoDB; 862376at2759; -.
DR PhylomeDB; Q5M834; -.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR PRO; PR:Q5M834; -.
DR Proteomes; UP000002494; Chromosome 17.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032279; C:asymmetric synapse; ISO:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0031083; C:BLOC-1 complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:RGD.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR GO; GO:0016528; C:sarcoplasm; ISO:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
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 axonal transport; ISS:UniProtKB.
DR GO; GO:0048490; P:anterograde synaptic vesicle transport; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0048813; P:dendrite morphogenesis; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IDA:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0006996; P:organelle organization; ISO:RGD.
DR GO; GO:0060155; P:platelet dense granule organization; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:RGD.
DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0014059; P:regulation of dopamine secretion; ISS:UniProtKB.
DR GO; GO:0043506; P:regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
DR InterPro; IPR007531; Dysbindin.
DR PANTHER; PTHR16294; PTHR16294; 1.
DR Pfam; PF04440; Dysbindin; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Synapse; Ubl conjugation.
FT CHAIN 1..352
FT /note="Dysbindin"
FT /id="PRO_0000267210"
FT REGION 267..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 92..180
FT /evidence="ECO:0000255"
FT MOTIF 243..256
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 267..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..352
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 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WZ8"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WZ8"
SQ SEQUENCE 352 AA; 39742 MW; 95AA237E22897390 CRC64;
MLETLRERLL SVQQDFTSGL KTLSDKSKEA KVKSRPRTAP YLPKYSAGLD LLSRYEDTWA
ALHRRAKECA DAGELVDSEV VMLSAHWEKK RTSLAELQEQ LQQLPALLQD VESLMASLAH
LETSFEEVEN HLLHLEDLCG QCELERHKQA HARHLEDYKK SKRKELEAFK AELDTEHAQK
ILEMEHTQQL KLKERQKFFE EAFQQDMEQY LSTGHLQIAE RREPMGSMSS MEVNVDVLEQ
MDLMDLSDQE ALDVFLNSGG EDNTVISPGL EMESNPSQNE MNLQIPNPSE SASQPPASPS
ACTDLDTADA PLIQADEEEV QVDTALVTLN TDRKSTPGVS DDSDQCDSTQ DI
