DRD4

DRD4
Identifikatori
AliasiDRD4
Vanjski ID-jeviOMIM: 126452 MGI: 94926 HomoloGene: 20215 GeneCards: DRD4
Lokacija gena (čovjek)
Hromosom 11 (čovjek)
Hrom.Hromosom 11 (čovjek)[1]
Hromosom 11 (čovjek)
Genomska lokacija za DRD4
Genomska lokacija za DRD4
Bend11p15.5Početak637,269 bp[1]
Kraj640,706 bp[1]
Lokacija gena (miš)
Hromosom 7 (miš)
Hrom.Hromosom 7 (miš)[2]
Hromosom 7 (miš)
Genomska lokacija za DRD4
Genomska lokacija za DRD4
Bend7 F5|7 86.6 cMPočetak140,871,919 bp[2]
Kraj140,876,377 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• signal transducer activity
• potassium channel regulator activity
• SH3 domain binding
• vezivanje identičnih proteina
• dopamine neurotransmitter receptor activity
• G protein-coupled receptor activity
• GO:0001948, GO:0016582 vezivanje za proteine
• dopamine binding
• dopamine neurotransmitter receptor activity, coupled via Gi/Go
• epinephrine binding
• norepinephrine binding
• vezivanje iona metala
• G protein-coupled serotonin receptor activity
• neurotransmitter receptor activity
Ćelijska komponenta• integral component of membrane
• integral component of plasma membrane
• membrana
• ćelijska membrana
• postsynapse
• glutamatergic synapse
• dendrit
Biološki proces• response to amphetamine
• ritmički proces
• arachidonic acid secretion
• regulation of circadian rhythm
• positive regulation of dopamine uptake involved in synaptic transmission
• GO:0072468 Transdukcija signala
• fear response
• dopamine metabolic process
• behavioral response to ethanol
• behavioral response to cocaine
• positive regulation of sodium:proton antiporter activity
• cellular calcium ion homeostasis
• positive regulation of kinase activity
• adult locomotory behavior
• inhibitory postsynaptic potential
• negative regulation of protein secretion
• socijalno ponašanje
• negative regulation of voltage-gated calcium channel activity
• regulation of dopamine metabolic process
• response to histamine
• behavioral fear response
• dopamine receptor signaling pathway
• G protein-coupled receptor signaling pathway
• adenylate cyclase-inhibiting dopamine receptor signaling pathway
• regulation of postsynaptic neurotransmitter receptor internalization
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• chemical synaptic transmission
• G protein-coupled serotonin receptor signaling pathway
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

1815

13491

Ensembl

ENSG00000069696
ENSG00000276825

ENSMUSG00000025496

UniProt

P21917

P51436

RefSeq (mRNK)

NM_000797

NM_007878

RefSeq (bjelančevina)

NP_000788

NP_031904

Lokacija (UCSC)Chr 11: 0.64 – 0.64 MbChr 7: 140.87 – 140.88 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Dopaminski receptor D4 je dopaminski D2-liki G-protein spregnuti receptor koji je kodiran genom DRD4 sa hromosoma 11, regija 11p15.5.[5]

Nedavno je objavljena struktura DRD4 u kombinaciji s antipsihotskim lijekom nemonaprid.[6]

Kao i kod drugih podtipova dopaminskih receptora, receptor D4 aktivira neurotransmiter dopamin. Povezan je s mnogim neurvnim i psihijatrijskim stanjima [7] uključujući shizofreniju i bipolarni poremećaj,[8] ADHD,[9][10] addiktivna ponašanja,[11] Parkinsnsonovu bolest,[12] i poremećaj ishrane kao što je anoreksija nervoza.[13] Nađena je slaba povezanost između DRD4 i graničnog poremećaja ličnosti.

Također je meta lijekova koji liječe shizofreniju i Parkinsonovu bolest.[14] Receptor D4 smatra se sličnim D2, u kojem aktivirani receptor inhibira enzim adenilat-ciklaza, čime se smanjuje unutarćelijska koncentracija drugog glasnika cAMPa.[15]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 467 aminokiselina, a molekulska težina 48.361 Da.[16].

1020304050
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLA
GNSLVCVSVATERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGA
WLLSPRLCDALMAMDVMLCTASIFNLCAISVDRFVAVAVPLRYNRQGGSR
RQLLLIGATWLLSAAVAAPVLCGLNDVRGRDPAVCRLEDRDYVVYSSVCS
FFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSGPGPPSPTPPA
PRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPGLPPDPCGPDCAPPAPG
LPQDPCGPDCAPPAPGLPRGPCGPDCAPPAPGLPQDPCGPDCAPPAPGLP
PDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVV
GAFLLCWTPFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTV
FNAEFRNVFRKALRACC

Genetika

Ljudski protein je kodiran DRD4 na hromosom 11 nalazi sw na sekvenci u 11p15,5.[17]

Postoje male varijacije (mutacije/polimorfizmi) u ljudskom genu:

Mutacije u ovom genu povezane su s različitim fenotipovima ponašanja, uključujući disfunkciju autonomnog nervnog sistema, poremećaj pažnje/hiperaktivnosti,[20] shizofreniju[21] and the personality trait of novelty seeking.[22]

Također pogledajte

Reference

  1. ^ a b c ENSG00000276825 GRCh38: Ensembl release 89: ENSG00000069696, ENSG00000276825 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025496 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (april 1991). "Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine". Nature. 350 (6319): 610–4. Bibcode:1991Natur.350..610V. doi:10.1038/350610a0. PMID 1840645. S2CID 4244670.
  6. ^ Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL (oktobar 2017). "D4 dopamine receptor high-resolution structures enable the discovery of selective agonists". Science. 358 (6361): 381–386. Bibcode:2017Sci...358..381W. doi:10.1126/science.aan5468. PMC 5856174. PMID 29051383.
  7. ^ Ptácek R, Kuzelová H, Stefano GB (septembar 2011). "Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders". Medical Science Monitor. 17 (9): RA215–20. doi:10.12659/MSM.881925. PMC 3560519. PMID 21873960.
  8. ^ Domschke K (juli 2013). "Clinical and molecular genetics of psychotic depression". Schizophrenia Bulletin. 39 (4): 766–75. doi:10.1093/schbul/sbt040. PMC 3686457. PMID 23512949.
  9. ^ LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (maj 1996). "Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder". Molecular Psychiatry. 1 (2): 121–4. PMID 9118321.
  10. ^ Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA, Asarnow JR, Woodward JA, Ramsey C, Nelson SF (septembar 1998). "Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder". Molecular Psychiatry. 3 (5): 427–30. doi:10.1038/sj.mp.4000457. PMID 9774776.
  11. ^ McGeary J (septembar 2009). "The DRD4 exon 3 VNTR polymorphism and addiction-related phenotypes: a review". Pharmacology Biochemistry and Behavior. 93 (3): 222–9. doi:10.1016/j.pbb.2009.03.010. PMC 2706302. PMID 19336242.
  12. ^ Cormier F, Muellner J, Corvol JC (april 2013). "Genetics of impulse control disorders in Parkinson's disease". Journal of Neural Transmission. 120 (4): 665–71. doi:10.1007/s00702-012-0934-4. PMID 23232665. S2CID 21967333.
  13. ^ Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB (mart 2010). "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake". Brain Research Reviews. 62 (2): 147–64. doi:10.1016/j.brainresrev.2009.10.007. PMID 19931559. S2CID 37635456.
  14. ^ Ptáček R, Kuželová H, Stefano GB, Raboch J, Kream RM (april 2013). "Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development". Current Drug Targets. 14 (4): 507–12. doi:10.2174/1389450111314040012. PMID 23469923.
  15. ^ Neve KA, Seamans JK, Trantham-Davidson H (august 2004). "Dopamine receptor signaling". Journal of Receptor and Signal Transduction Research. 24 (3): 165–205. CiteSeerX 10.1.1.465.5011. doi:10.1081/RRS-200029981. PMID 15521361. S2CID 12407397.
  16. ^ "UniProt, P21917". Pristupljeno 21. 8. 2021.
  17. ^ Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V (juli 1992). "Multiple dopamine D4 receptor variants in the human population". Nature. 358 (6382): 149–52. Bibcode:1992Natur.358..149T. doi:10.1038/358149a0. PMID 1319557. S2CID 4345839.
  18. ^ Catalano M, Nobile M, Novelli E, Nöthen MM, Smeraldi E (oktobar 1993). "Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients". Biological Psychiatry. 34 (7): 459–64. doi:10.1016/0006-3223(93)90236-7. PMID 8268330. S2CID 34841647.
  19. ^ Rondou P, Haegeman G, Van Craenenbroeck K (juni 2010). "The dopamine D4 receptor: biochemical and signalling properties". Cellular and Molecular Life Sciences. 67 (12): 1971–86. doi:10.1007/s00018-010-0293-y. PMID 20165900. S2CID 21432517.
  20. ^ Thapar A, Langley K, Owen MJ, O'Donovan MC (decembar 2007). "Advances in genetic findings on attention deficit hyperactivity disorder". Psychological Medicine. 37 (12): 1681–92. doi:10.1017/S0033291707000773. PMID 17506925.
  21. ^ Gene Overview of All Published Schizophrenia-Association Studies for DRD4 Arhivirano 21. 2. 2009. na Wayback Machine – SzGene database at Schizophrenia Research Forum.
  22. ^ Munafò MR, Yalcin B, Willis-Owen SA, Flint J (januar 2008). "Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data". Biological Psychiatry. 63 (2): 197–206. doi:10.1016/j.biopsych.2007.04.006. PMID 17574217. S2CID 28997438.

Vanjski linkovi

Šablon:G-protein spregnuti receptori

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