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Protein

Dysbindin

Gene

DTNBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway.7 Publications

GO - Biological processi

Keywordsi

Biological processSensory transduction

Enzyme and pathway databases

ReactomeiR-HSA-432722. Golgi Associated Vesicle Biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Dysbindin
Alternative name(s):
Biogenesis of lysosome-related organelles complex 1 subunit 8
Short name:
BLOC-1 subunit 8
Dysbindin-1
Dystrobrevin-binding protein 1
Hermansky-Pudlak syndrome 7 protein
Short name:
HPS7 protein
Gene namesi
Name:DTNBP1
Synonyms:BLOC1S8
ORF Names:My031
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000047579.19.
HGNCiHGNC:17328. DTNBP1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Hermansky-Pudlak syndrome 7 (HPS7)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
See also OMIM:614076
Defects in DTNBP1 are associated with susceptibility to schizophrenia, a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. Genetic mutations lead to alterations in the glutamatergic transmission in the brain and modified Akt signaling (PubMed:15345706). Protein levels and expression are reduced in nerve terminals of the hippocampus and there is an increased release of glutamate in schizophrenic patients (PubMed:15124027). Levels of isoform 1 are reduced in the pSTG, but not in HF, by about 48% in 92% of schizophrenic patients. In the HF, there is an average of 33% reduction in synaptic expression of isoform 2 in 67% of cases, and of isoform 3, an average reduction of 35% in 80% of cases. In the dorsolateral prefrontal cortex (DLPFC), significant reductions in levels of isoform 3 are observed about 71% of schizophrenic patients showed an average reduction of this isoform of about 60% (PubMed:19617633).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi215Y → A: Reduced interaction with AP3M1. 1 Publication1
Mutagenesisi243 – 256LMDIS…LDVFL → AMDASDQEAADVFA: Abolishes cytoplasmic location. Increased expression of SYN1. 1 PublicationAdd BLAST14

Keywords - Diseasei

Albinism, Hermansky-Pudlak syndrome, Schizophrenia

Organism-specific databases

DisGeNETi84062.
GeneReviewsiDTNBP1.
MalaCardsiDTNBP1.
MIMi614076. phenotype.
OpenTargetsiENSG00000047579.
Orphaneti231531. Hermansky-Pudlak syndrome type 7.
PharmGKBiPA27512.

Polymorphism and mutation databases

BioMutaiDTNBP1.
DMDMi38604971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001910011 – 351DysbindinAdd BLAST351

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11PhosphoserineCombined sources1
Modified residuei316PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1
Modified residuei349PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 degradation.1 Publication
Isoforms 1 and 2 highly phosphorylated by PRKDC in vitro. Isoform 3 only weakly phosphorylated by PRKDC in vitro.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96EV8.
MaxQBiQ96EV8.
PaxDbiQ96EV8.
PeptideAtlasiQ96EV8.
PRIDEiQ96EV8.

PTM databases

iPTMnetiQ96EV8.
PhosphoSitePlusiQ96EV8.

Expressioni

Tissue specificityi

Detected in brain, in neurons and in neuropil. Isoform 1 is expressed in the cerebral cortex, and hippocampal frontal (HF). Specific expression in the posterior half of the superior temporal gyrus (pSTG). Higher expression of isoform 2 and 3 in the HF than in the pSTG while isoform 1 shows no difference in expression in these areas. In the HF, detected in dentate gyrus (DG) and in pyramidal cells of hippocampus CA2 and CA3 (at protein level). Expressed in all principal neuronal populations of the HF, namely pyramidal neurons in the subiculum and CA1-3, granule cells in the dense cell layer of the DG (DGg), and polymorph cells in the hilus of the DG (DGh). Maximal levels in CA2, CA3, and DGh. Isoform 2 not expressed in the cerebral cortex.1 Publication

Gene expression databases

BgeeiENSG00000047579.
CleanExiHS_DTNBP1.
ExpressionAtlasiQ96EV8. baseline and differential.
GenevisibleiQ96EV8. HS.

Organism-specific databases

HPAiHPA028053.
HPA029615.
HPA029616.

Interactioni

Subunit structurei

Interacts (via its coiled coil domain) with KXD1. Interacts with CMYA5, PI4K2 and RNF151 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of at least BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly in the complex with BLOC1S5, BLOC1S6 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. This BLOC-1 complex also associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may not be a physiological binding partner (PubMed:16980328). Interacts (isoform 1 and isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK; the interaction phosphorylates DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and XRCC6. Interacts with AP3M1, AP3B2 and TRIM32. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus.By similarity8 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi123857. 134 interactors.
CORUMiQ96EV8.
IntActiQ96EV8. 57 interactors.
MINTiMINT-1438666.
STRINGi9606.ENSP00000341680.

Structurei

3D structure databases

ProteinModelPortaliQ96EV8.
SMRiQ96EV8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni173 – 331DysbindinAdd BLAST159

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili88 – 181Sequence analysisAdd BLAST94

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi243 – 256Nuclear export signalAdd BLAST14

Sequence similaritiesi

Belongs to the dysbindin family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IF9S. Eukaryota.
ENOG4111YM1. LUCA.
GeneTreeiENSGT00390000010667.
HOGENOMiHOG000272621.
HOVERGENiHBG051416.
InParanoidiQ96EV8.
KOiK20189.
OMAiNYNAGAD.
OrthoDBiEOG091G0ZXL.
PhylomeDBiQ96EV8.
TreeFamiTF332997.

Family and domain databases

InterProiView protein in InterPro
IPR007531. Dysbindin.
PANTHERiPTHR16294. PTHR16294. 1 hit.
PfamiView protein in Pfam
PF04440. Dysbindin. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q96EV8-1) [UniParc]FASTAAdd to basket
Also known as: Dysbindin 1-A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLETLRERLL SVQQDFTSGL KTLSDKSREA KVKSKPRTVP FLPKYSAGLE
60 70 80 90 100
LLSRYEDTWA ALHRRAKDCA SAGELVDSEV VMLSAHWEKK KTSLVELQEQ
110 120 130 140 150
LQQLPALIAD LESMTANLTH LEASFEEVEN NLLHLEDLCG QCELERCKHM
160 170 180 190 200
QSQQLENYKK NKRKELETFK AELDAEHAQK VLEMEHTQQM KLKERQKFFE
210 220 230 240 250
EAFQQDMEQY LSTGYLQIAE RREPIGSMSS MEVNVDMLEQ MDLMDISDQE
260 270 280 290 300
ALDVFLNSGG EENTVLSPAL GPESSTCQNE ITLQVPNPSE LRAKPPSSSS
310 320 330 340 350
TCTDSATRDI SEGGESPVVQ SDEEEVQVDT ALATSHTDRE ATPDGGEDSD

S
Note: Major isoform.
Length:351
Mass (Da):39,493
Last modified:December 1, 2001 - v1
Checksum:i0504C86E12B66C08
GO
Isoform 2 (identifier: Q96EV8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     272-351: PESSTCQNEI...TPDGGEDSDS → RVDKLALAEPGQYRCHSPPKVRRENHLPVTYA

Note: May be due to intron retention.
Show »
Length:303
Mass (Da):34,831
Checksum:i7AF6611B9F6D46BD
GO
Isoform 3 (identifier: Q96EV8-3) [UniParc]FASTAAdd to basket
Also known as: Dysbindin 1-B

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.

Show »
Length:270
Mass (Da):30,387
Checksum:iC945FAB1BB01B410
GO

Sequence cautioni

The sequence AAG43145 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti242D → V in CAB66572 (PubMed:11230166).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053069214G → D. Corresponds to variant dbSNP:rs16876589Ensembl.1
Natural variantiVAR_029644272P → S. Corresponds to variant dbSNP:rs17470454Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0460621 – 81Missing in isoform 3. CuratedAdd BLAST81
Alternative sequenceiVSP_009023272 – 351PESST…EDSDS → RVDKLALAEPGQYRCHSPPK VRRENHLPVTYA in isoform 2. 2 PublicationsAdd BLAST80

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY265460 mRNA. Translation: AAP91870.1.
AF394226 mRNA. Translation: AAL46636.1.
AL136637 mRNA. Translation: CAB66572.1.
AK054593 mRNA. Translation: BAB70770.1.
AK290718 mRNA. Translation: BAF83407.1.
AL022343, AL021978 Genomic DNA. Translation: CAI21976.1.
AL022343, AL021978 Genomic DNA. Translation: CAI21977.1.
AL021978, AL022343 Genomic DNA. Translation: CAI42339.1.
AL021978, AL022343 Genomic DNA. Translation: CAI42340.1.
BC011912 mRNA. Translation: AAH11912.1.
AF061734 mRNA. Translation: AAG43145.1. Different initiation.
CCDSiCCDS4534.1. [Q96EV8-1]
CCDS4535.1. [Q96EV8-2]
RefSeqiNP_001258596.1. NM_001271667.1. [Q96EV8-3]
NP_001258597.1. NM_001271668.1.
NP_001258598.1. NM_001271669.1.
NP_115498.2. NM_032122.4. [Q96EV8-1]
NP_898861.1. NM_183040.2. [Q96EV8-2]
UniGeneiHs.571148.

Genome annotation databases

EnsembliENST00000338950; ENSP00000344718; ENSG00000047579. [Q96EV8-2]
ENST00000344537; ENSP00000341680; ENSG00000047579. [Q96EV8-1]
GeneIDi84062.
KEGGihsa:84062.
UCSCiuc003nbm.4. human. [Q96EV8-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDTBP1_HUMAN
AccessioniPrimary (citable) accession number: Q96EV8
Secondary accession number(s): A8K3V3
, Q5THY3, Q5THY4, Q96NV2, Q9H0U2, Q9H3J5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: December 1, 2001
Last modified: September 27, 2017
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families