KEGG   PATHWAY: oor04726
Entry
oor04726                    Pathway                                
Name
Serotonergic synapse - Orcinus orca (killer whale)
Description
Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endocrine secretion, as well as in pathological states including abnormal mood and cognition. Once released from presynaptic axonal terminals, 5-HT binds to receptors, which have been divided into 7 subfamilies on the basis of conserved structures and signaling mechanisms. These families include the ionotropic 5-HT3 receptors and G-protein-coupled 5-HT receptors, the 5-HT1 (Gi /Go -coupled), 5-HT2(Gq-coupled), 5-HT4/6/7 (Gs-coupled) and 5-HT5 receptors. Presynaptically localized 5-HT1B receptors are thought to be the autoreceptors that suppress excess 5-HT release. 5-HT's actions are terminated by transporter- mediated reuptake into neurons, leading to catabolism by monoamine oxidase.
Class
Organismal Systems; Nervous system
Pathway map
oor04726  Serotonergic synapse
oor04726

Other DBs
GO: 0007210
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101273510  TPH1; tryptophan 5-hydroxylase 1 [KO:K00502] [EC:1.14.16.4]
101271217  TPH2; tryptophan 5-hydroxylase 2 isoform X2 [KO:K00502] [EC:1.14.16.4]
101290071  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
101285599  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
101279274  SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155]
101272740  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X7 [KO:K04850]
101276749  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101281199  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X11 [KO:K04853]
101275416  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
101271859  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
101284631  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
101286066  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
101279781  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101274558  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270548  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270961  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101281417  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X9 [KO:K05858] [EC:3.1.4.11]
101282737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101281155  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101280894  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101276350  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101277002  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101276418  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101269805  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101270052  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
101286206  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
101270543  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
117195357  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
101280390  cytochrome P450 2C23-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101281073  LOW QUALITY PROTEIN: cytochrome P450 2C18 [KO:K07413] [EC:1.14.14.1]
101276966  LOW QUALITY PROTEIN: cytochrome P450 2D14 [KO:K07414] [EC:1.14.14.1]
101287985  cytochrome P450 2J2 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101283796  ALOX5; polyunsaturated fatty acid 5-lipoxygenase isoform X1 [KO:K00461] [EC:1.13.11.34]
101279538  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 isoform X3 [KO:K00458] [EC:1.13.11.31]
101281563  ALOX15; LOW QUALITY PROTEIN: polyunsaturated fatty acid lipoxygenase ALOX15 [KO:K00460] [EC:1.13.11.33]
101281720  polyunsaturated fatty acid lipoxygenase ALOX15B isoform X2 [KO:K08022] [EC:1.13.11.33 1.13.11.-]
101274585  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
101270299  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
101269648  LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 3C-like [KO:K04819]
101270067  LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 3C-like [KO:K04819]
101289245  HTR3A; 5-hydroxytryptamine receptor 3A isoform X1 [KO:K04819]
101287229  HTR3B; 5-hydroxytryptamine receptor 3B [KO:K04819]
101277127  HTR4; 5-hydroxytryptamine receptor 4 isoform X3 [KO:K04160]
101285093  HTR6; 5-hydroxytryptamine receptor 6 [KO:K04162]
101272540  HTR7; 5-hydroxytryptamine receptor 7 isoform X2 [KO:K04163]
101286834  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
101282939  neuroendocrine secretory protein 55-like [KO:K04632]
101283178  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101277663  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943]
101287959  KCND2; potassium voltage-gated channel subfamily D member 2 [KO:K04892]
101277502  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
101278238  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
101288822  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
101278657  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X5 [KO:K08014]
101270984  APP; amyloid-beta precursor protein isoform X1 [KO:K04520]
101279054  HTR1A; 5-hydroxytryptamine receptor 1A [KO:K04153]
101285522  HTR1B; 5-hydroxytryptamine receptor 1B [KO:K04153]
101271652  HTR1E; 5-hydroxytryptamine receptor 1E [KO:K04153]
101272099  HTR1F; 5-hydroxytryptamine receptor 1F [KO:K04153]
117198714  HTR1D; 5-hydroxytryptamine receptor 1D [KO:K04153]
101290496  HTR5A; 5-hydroxytryptamine receptor 5A [KO:K04161]
101276500  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101277471  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101271719  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101284566  guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101282575  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101277504  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101286052  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
101277343  GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538]
101270085  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X2 [KO:K04539]
101270764  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101282693  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101271265  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101276063  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
117197871  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
117202102  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
117202794  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
117198830  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
117201789  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
105747741  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
117202637  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545]
101290360  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101281533  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
117201513  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101269282  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
117197734  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101289847  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101278083  DUSP1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
101271947  GTPase HRas-like isoform X4 [KO:K02833]
101286301  HRAS; GTPase HRas isoform X2 [KO:K02833]
101281897  KRAS; GTPase KRas isoform X2 [KO:K07827]
101276138  NRAS; GTPase NRas [KO:K07828]
101271966  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
101277195  BRAF; serine/threonine-protein kinase B-raf isoform X4 [KO:K04365] [EC:2.7.11.1]
101272984  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101286388  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101275783  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
101272416  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
101288928  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101271724  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101289618  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X1 [KO:K05002]
101287172  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
101274365  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
101289059  SLC6A4; sodium-dependent serotonin transporter isoform X1 [KO:K05037]
101272484  MAOB; amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
101272725  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
Compound
C00076  Calcium cation
C00078  L-Tryptophan
C00165  Diacylglycerol
C00219  Arachidonate
C00238  Potassium cation
C00427  Prostaglandin H2
C00575  3',5'-Cyclic AMP
C00584  Prostaglandin E2
C00639  Prostaglandin F2alpha
C00643  5-Hydroxy-L-tryptophan
C00696  Prostaglandin D2
C00780  Serotonin
C00909  Leukotriene A4
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C02165  Leukotriene B4
C02166  Leukotriene C4
C02198  Thromboxane A2
C04822  8(R)-HPETE
C05356  5(S)-HPETE
C05635  5-Hydroxyindoleacetate
C05953  Prostaglandin A2
C05954  Prostaglandin B2
C05955  Prostaglandin C2
C05956  Prostaglandin G2
C05957  Prostaglandin J2
C05963  Thromboxane B2
C05964  11-Dehydro-thromboxane B2
C05965  12(S)-HPETE
C05966  15(S)-HPETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
C14772  5,6-DHET
C14773  8,9-DHET
C14774  11,12-DHET
C14775  14,15-DHET
C14812  12(R)-HPETE
C14820  11(R)-HPETE
C14821  9(S)-HPETE
C14823  8(S)-HPETE
Reference
PMID:18676031
  Authors
Millan MJ, Marin P, Bockaert J, Mannoury la Cour C
  Title
Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions.
  Journal
Trends Pharmacol Sci 29:454-64 (2008)
DOI:10.1016/j.tips.2008.06.007
Reference
PMID:16896947
  Authors
Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P
  Title
Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation.
  Journal
Cell Tissue Res 326:553-72 (2006)
DOI:10.1007/s00441-006-0286-1
Reference
PMID:11916537
  Authors
Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN
  Title
Multiplicity of mechanisms of serotonin receptor signal transduction.
  Journal
Pharmacol Ther 92:179-212 (2001)
DOI:10.1016/S0163-7258(01)00169-3
Reference
PMID:15034221
  Authors
Noda M, Higashida H, Aoki S, Wada K
  Title
Multiple signal transduction pathways mediated by 5-HT receptors.
  Journal
Mol Neurobiol 29:31-9 (2004)
DOI:10.1385/MN:29:1:31
Reference
PMID:20561690
  Authors
Daubert EA, Condron BG
  Title
Serotonin: a regulator of neuronal morphology and circuitry.
  Journal
Trends Neurosci 33:424-34 (2010)
DOI:10.1016/j.tins.2010.05.005
Reference
PMID:16826372
  Authors
Chameau P, van Hooft JA
  Title
Serotonin 5-HT(3) receptors in the central nervous system.
  Journal
Cell Tissue Res 326:573-81 (2006)
DOI:10.1007/s00441-006-0255-8
Reference
PMID:9651340
  Authors
Tournois C, Mutel V, Manivet P, Launay JM, Kellermann O
  Title
Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism.
  Journal
J Biol Chem 273:17498-503 (1998)
DOI:10.1074/jbc.273.28.17498
Reference
PMID:19545642
  Authors
Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ
  Title
Epoxyeicosanoid signaling in CNS function and disease.
  Journal
Prostaglandins Other Lipid Mediat 91:68-84 (2010)
DOI:10.1016/j.prostaglandins.2009.06.004
Reference
PMID:12676358
  Authors
Adayev T, Ray I, Sondhi R, Sobocki T, Banerjee P
  Title
The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha.
  Journal
Biochim Biophys Acta 1640:85-96 (2003)
DOI:10.1016/S0167-4889(03)00023-5
Reference
PMID:11701344
  Authors
Albert PR, Tiberi M
  Title
Receptor signaling and structure: insights from serotonin-1 receptors.
  Journal
Trends Endocrinol Metab 12:453-60 (2001)
DOI:10.1016/S1043-2760(01)00498-2
Reference
PMID:9658404
  Authors
Durham PL, Russo AF
  Title
Serotonergic repression of mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer.
  Journal
Mol Endocrinol 12:1002-9 (1998)
DOI:10.1210/mend.12.7.0135
Reference
PMID:15710402
  Authors
Robert S, Maillet M, Morel E, Launay JM, Fischmeister R, Mercken L, Lezoualc'h F
  Title
Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac.
  Journal
FEBS Lett 579:1136-42 (2005)
DOI:10.1016/j.febslet.2005.01.010
Reference
PMID:12543273
  Authors
Lezoualc'h F, Robert SJ
  Title
The serotonin 5-HT4 receptor and the amyloid precursor protein processing.
  Journal
Exp Gerontol 38:159-66 (2003)
DOI:10.1016/S0531-5565(02)00157-2
Reference
PMID:11043573
  Authors
Durham PL, Russo AF
  Title
Differential regulation of mitogen-activated protein kinase-responsive genes by the duration of a calcium signal.
  Journal
Mol Endocrinol 14:1570-82 (2000)
DOI:10.1210/mend.14.10.0529
Reference
PMID:9542727
  Authors
Hagberg GB, Blomstrand F, Nilsson M, Tamir H, Hansson E
  Title
Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.
  Journal
Neurochem Int 32:153-62 (1998)
DOI:10.1016/S0197-0186(97)00087-9
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Related
pathway
oor00380  Tryptophan metabolism
oor00590  Arachidonic acid metabolism
oor04020  Calcium signaling pathway
oor04721  Synaptic vesicle cycle
oor04976  Bile secretion
KO pathway
ko04726   
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