Opioid signaling (Homo sapiens)

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11, 20, 2532, 50353728, 31, 3317, 19395, 463582, 15, 27, 29147, 16485343, 44, 4721, 384226, 39139940244285212, 363939223923, 4113306, 10, 515318, 3445, 49cytosolnucleoplasmendoplasmic reticulum lumencAMP:PKA regulatorysubunitPPP3CB POMC(237-267) CALM1:4xCa2+ADCY2 p-T75,S137-PPP1R1B PDYN(226-230) Ca2+ GNG13 PLC-betaADCY5 GNG3 Mg2+ GNAT3 Adenylate cyclase(Mg2+ cofactor)GNG12 GNB5 GTP GTP ADCY8 GNAI2 ADCY1 GNG10 GNAI1 GNAZ Adenylate cyclase(Mg2+ cofactor)H2OADPGNAI2 H2OCa2+ ADCY3 PRKACG ADCY9 GNG8 ITPR1 POMC(237-267) p-T75-DARPP32s(Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)G-protein alpha (i):GTPGNG11 GNG4 2-Lysophosphatidylcholinep-T75-PPP1R1B OPRM1 ADCY2 Mg2+ POMC(237-241) phospho-CaMKIV:CalmodulinPRKAR2B PPP3R1 GNAI1 Mg2+ ADCY7 GTP ADPCALM1 GNAI1 ADCY8 GNAL GNAI2 GNAI2 ADCY6 GDPFe3+ POMC(237-267) ADCY7 p-S102-PPP1R1B GNAI2 DARPP-32 (and/orphosphorylated)GNAT3 GNAO1 GNGT1 ADCY7 GDP GNB1 GNG3 PP2B catalytic(Fe3+, Zn2+)GNAT2 ADCY2 ADCY3 GRK2:calmodulinADCY8 GNAT3 I(1,4,5)P3 PRKACA PDYN(226-230) p-S505,S727-PLA2G4Ap-T34-PPP1R1B ADCY4 p-S12,S13-CAMK4 ADCY5 ADCY6 ADCY7 ADPADCY9 G-protein beta-gammacomplexADCY8 ADCY5 GNGT1 G alpha-olf:GDPcomplexp-T75,S102-PPP1R1B ADCY6 GNAO1 p-T75,S102,S137-PPP1R1B GNB2 GNB3 GTP PPP1CA GTPGDP Mg2+ Zn2+ ADCY9 GNAT2 GDP PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMGNAI2 ADCY7 PDYN(226-230) Mg2+ ADCY6 GTP CAMK4 GNB5 PPP1R1B H2OADCY5 GNAT2 GNAI2 CALM1 GNAT3 ADCY3 CREB1AHCYL1 p-T34,T75,S102,S137-PPP1R1B DARPP-32 (for CDK5phosphorylation)GDP GNAT3 p-T34,T75-PPP1R1B GNGT2 ADCY8 GNGT2 ADCY8 PRKACB GNAT1 Ca2+ GNAI2 PPP2R5D GNAI2 ADCY6 ATPp-T34,S102,S137-PPP1R1B p-T34,S137-PPP1R1B GNAI3 GTP GNAO1 GNAI1 GNAI3 GNG12 PiCa2+ p-T75,S102-PPP1R1B GNG4 PI(4,5)P2Fe3+ GNAI2 ADCY1 GNG3 PDE4B GNAI2 POMC(237-267) PRKACA p-T75,S102,S137-PPP1R1B PRKACG GNG12 Ca2+ OPRM1 GNAL I(1,4,5)P3 GNAT3 PRKACB POMC(237-241) ADCY3 GNG5 Protein Kinase A,catalytic subunitsAMPGNAO1 PPiGNAO1 p-T34,T75-PPP1R1B p-T34,T75,S102-PPP1R1B PRKAR1B ATPp-T34,S102-PPP1R1B cAMPGNAI3 p-T34,S102-PPP1R1B ADCY9 GNG12 p-T34,T75,S102,S137-PPP1R1B ATPPPP3CA IP3 receptorhomotetramerPKA tetramerOpioid:MOR:G-proteincomplexPOMC(237-267) PKA catalyticsubunitADCY2 ADCY7 PRKACA GNAI3 ADCY6 GNAT3 GNG5 Mg2+ PRKAR1A GNG13 GNAL GNG11 G-protein alpha(i):GTP:AdenylatecyclaseADCY3 p-S102,S137-PPP1R1B GNAT3 GNAI1 cAMPADCY8 ADCY9 ADCY8 ADCY5 GNAI3 PDYN(226-230) Calmodulin:CaMK IVPKA catalyticsubunitCAMK4Fe2+ p-S137-PPP1R1B GNG10 CALM1 GNAI1 GNG3 GNB5 GNAT1 ADCY3 ADCY4 cAMP(Gialpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)GDP p-T34,T75,S102,S137-PPP1R1B p-T34,S102,S137-PPP1R1B GNG11 ADCY1 ADRBK1 GNAO1 Ca2+GNAI3 GNAT3 ADCY8 p-T34,T75,S137-PPP1R1B PDE1C Zn2+ GNAL PPP3CC Mg2+ GNAT1 GNAT2 p-T34,S137-PPP1R1B GNB4 p-S54-PDE4BGNAT3 ADCY1 GNG5 ADCY4 GNGT1 PPP3CA ITPR2 ADCY9 GNAL p-T34,T75,S137-PPP1R1B H2OGNAI3 GNAZ AMPG-protein alpha:GDPOPRM1 Adenylate cyclase(Mg2+ cofactor)GTP GTPGDP PRKACAPiPPP2CA PRKCD PCp-T34,T75-PPP1R1B ADCY2 ADPADCY2 GTP (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)PKA catalyticsubunitPDE1A Calmodulin:CaMK IVGTP GNG8 CALM1 PCG-protein alpha(i):GDPPOMC(237-241) p-T75,S137-PPP1R1B GNB3 p-T185,Y187-MAPK1ADCY4 GNAL GNAI1 GNG12 GNAT3 GNAT2 PPP3CB GNAI2 DAGsH2OGNB1 PPP2R1B GNG7 ITPR3 p-T34,S102-PPP1R1B p-T34-PPP1R1B GNAO1 G protein alpha:GTPcomplexGNAT2 p-T34,T75,S102-PPP1R1B PPiGNB4 Opioid:MOR:Gprotein-GTP complexGNG8 p-T34-PPP1R1B GNG5 PRKAR2A ITPR3 active PKC (alpha,gamma, delta)PRKACG CALM1 ADCY5 ADCY2 GNAI1 Ca2+GNAT3 ADCY1 PRKAR2B GNG2 CDK5ATPADCY5 GDP GNG5 GNB2 GNAI2 PLCB2 GNAI3 ADCY7 CALM1PLCB4 PC GNAI3 GNAT3 Ca2+ ADCY7 ATPPDYN(226-230) ADCY5 ADCY7 GNAT1 GNG10 ADCY7 GNG7 PRKACA GNG4 GNAT2 GNAZ ADCY1 GNAL PPP3CB H2OADCY5 p-T75,S137-PPP1R1B PDE1A PRKACB GDPPPP2CB Galpha-olf:GDP:Adenylate cyclase (active) complexOPRM1 PiGNAI3 GNGT2 GNG7 p-T34,S102,S137-PPP1R1B G protein alpha:GTPcomplexGNAT1 Zn2+ ADCY3 PP2A-ABdeltaCcomplexGDP GNB1 GNAI1 PDE1B GNG10 GNAI1 PPP3CC PiGNAT1 PPP2R1A p-S29-ADRBK1PRKCG GNAI1 PLCB3 GNB4 Opioid:MORGNAT1 DARPP-32phosporylated onT34PDE4C p-T75-PPP1R1B Ca2+ GNAZ PRKACB ITPR:I(1,4,5)P3tetramerGNG11 ADCY6 ITPR2 GNAZ GNB5 PRKAR1A ADCY2 GNGT1 GNAT1 p-T34,T75,S137-PPP1R1B cAMPPRKAR2A Cam-PDE 1 homodimerGNAT2 GNB2 p-T34,T75,S102,S137-PPP1R1B GNAT3 GNAT2 p-T34,T75,S137-PPP1R1B OPRM1ADCY1 GNAI1 Activated PLC beta1/4GNG2 ADCY2 Galpha-olf:GTP:Adenylate cyclase (active) complexp-T34,S137-PPP1R1B PRKACG ADCY9 ARAp-S133-CREB1GNB4 p-T34,T75-PPP1R1B GNB3 PLA2G4AGNG13 GNAI2 ADPPDE 4GNG3 GNGT1 ADCY4 GNGT2 ADCY8 ADCY9 GNB5 GNB2 GNAI3 GNB1 Mn2+ GNB1 GNB3 GTP GDP GNG4 PRKACG Mg2+ GNG13 GNAO1 ADRBK1Opioid:MOR:Gprotein-GDP complexPRKAR1B GNG4 p-S133-CREB1 GNAZ GNAT3 PDE1C H2OCa2+ Fe3+ ITPR2 ITPR1 PRKCA Opioid peptideGNAT1 G alpha-olf:GDPcomplexGNG2 ADCY6 ATPGNAI1 PLCB2 phospho-CREB dimerPhosphorylated (T34)DARPP-32:PP1AI(1,4,5)P3ADCY3 p-S505,S727-PLA2G4A ITPR3 GTP ADCY6 GNAI3 Mg2+ GNAO1 PLCB3 ADCY4 active Cam-PDE 1GNAI1 GNG8 ADCY4 GNAZ PLCB1 GNB2 GNAI3 p-S102,S137-PPP1R1B p-S102-PPP1R1B GDP POMC(237-241) ADCY4 PPP1CAGNAI2 GNG13 PLCB1 GNG7 G-protein alpha(i/o/z/t) subunitPLCB4 G protein-GDPcomplexCALM1 CAMK4 GNAI3 ActivePLA2:phosphatidylcholineGNG7 GNB4 GNG11 GNAI3 ADCY9 ADCY9 p-T75,S102-PPP1R1B ATPATPp-T34,T75,S102-PPP1R1B PDE4A ADCY4 GNG8 PiADCY3 CALM1 PDE1B ADCY2 p-T75-DARPP32s:PRKACAGNG2 PPP3CC ADPcAMP PPP3 complexAHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerGNAI1 p-T75-PPP1R1B ADCY6 PDE4D GNAL PPP3CA PDE4Bp-T34,T75,S102-PPP1R1B GNGT2 ADCY3 NAD+ GNG10 ADCY5 p-T75,S102,S137-PPP1R1B G alpha-olf:GTPGNB3 GNAZ DNA POMC(237-241) Adenylate cyclase(Mg2+ cofactor)ADCY1 GNAZ ITPR1 PRKACB p-S137-PPP1R1B PRKACA GNG2 PPP1R1B PRKACA ADCY1 ADCY1 ADCY4 Mg2+ 3


Description

Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP). View original pathway at:Reactome.

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History

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CompareRevisionActionTimeUserComment
116415view09:08, 7 May 2021EweitzModified title
115086view17:03, 25 January 2021ReactomeTeamReactome version 75
113528view12:00, 2 November 2020ReactomeTeamReactome version 74
112726view16:12, 9 October 2020ReactomeTeamReactome version 73
101642view11:50, 1 November 2018ReactomeTeamreactome version 66
101178view21:37, 31 October 2018ReactomeTeamreactome version 65
100704view20:10, 31 October 2018ReactomeTeamreactome version 64
100254view16:55, 31 October 2018ReactomeTeamreactome version 63
99807view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99353view12:48, 31 October 2018ReactomeTeamreactome version 62
93848view13:40, 16 August 2017ReactomeTeamreactome version 61
93406view11:22, 9 August 2017ReactomeTeamreactome version 61
88062view14:04, 25 July 2016RyanmillerOntology Term : 'chemical compound signaling pathway' added !
88061view14:04, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86494view09:19, 11 July 2016ReactomeTeamreactome version 56
83304view10:42, 18 November 2015ReactomeTeamVersion54
81440view12:58, 21 August 2015ReactomeTeamVersion53
76919view08:19, 17 July 2014ReactomeTeamFixed remaining interactions
76624view11:59, 16 July 2014ReactomeTeamFixed remaining interactions
75955view10:01, 11 June 2014ReactomeTeamRe-fixing comment source
75657view10:55, 10 June 2014ReactomeTeamReactome 48 Update
75012view13:52, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74656view08:43, 30 April 2014ReactomeTeamReactome46
56299view16:38, 5 January 2013EgonwData typed a ChEBI metabolite as such.
42186view23:51, 4 March 2011MaintBotModified categories
42185view23:51, 4 March 2011MaintBot
42184view23:50, 4 March 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170656 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170659 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ComplexR-HSA-170683 (Reactome)
2-LysophosphatidylcholineMetaboliteCHEBI:17504 (ChEBI)
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ADRBK1 ProteinP25098 (Uniprot-TrEMBL)
ADRBK1ProteinP25098 (Uniprot-TrEMBL)
AHCYL1 ProteinO43865 (Uniprot-TrEMBL)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerComplexR-HSA-5226920 (Reactome)
AMPMetaboliteCHEBI:16027 (ChEBI)
ARAMetaboliteCHEBI:15843 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PLC beta 1/4ComplexR-HSA-111856 (Reactome)
Active PLA2:phosphatidylcholineComplexR-HSA-111860 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CALM1:4xCa2+ComplexR-HSA-74294 (Reactome)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
CAMK4ProteinQ16566 (Uniprot-TrEMBL)
CDK5ProteinQ00535 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calmodulin:CaMK IVComplexR-HSA-111900 (Reactome)
Calmodulin:CaMK IVComplexR-HSA-112281 (Reactome)
Cam-PDE 1 homodimerComplexR-HSA-111952 (Reactome)
DAGsMetaboliteCHEBI:18035 (ChEBI)
DARPP-32

phosporylated on

T34
ComplexR-HSA-180075 (Reactome)
DARPP-32 (and/or phosphorylated)ComplexR-HSA-180056 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ComplexR-HSA-180044 (Reactome)
DNA R-NUL-29428 (Reactome)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
G alpha-olf:GDP:Adenylate cyclase (active) complexComplexR-HSA-170679 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexComplexR-HSA-170655 (Reactome)
G alpha-olf:GDP complexComplexR-HSA-170669 (Reactome)
G alpha-olf:GTPComplexR-HSA-170661 (Reactome)
G protein alpha:GTP complexComplexR-HSA-167438 (Reactome)
G protein-GDP complexComplexR-HSA-167418 (Reactome)
G-protein alpha (i):GDPComplexR-HSA-392164 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ComplexR-HSA-396910 (Reactome)
G-protein alpha (i/o/z/t) subunitComplexR-HSA-167413 (Reactome)
G-protein alpha (i): GTPComplexR-HSA-392161 (Reactome)
G-protein alpha:GDPComplexR-HSA-111864 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAL ProteinP38405 (Uniprot-TrEMBL)
GNAO1 ProteinP09471 (Uniprot-TrEMBL)
GNAT1 ProteinP11488 (Uniprot-TrEMBL)
GNAT2 ProteinP19087 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (Uniprot-TrEMBL)
GNAZ ProteinP19086 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GRK2:calmodulinComplexR-HSA-111965 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IP3 receptor homotetramerComplexR-HSA-169686 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
ITPR:I(1,4,5)P3 tetramerComplexR-HSA-169696 (Reactome)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
Mn2+ MetaboliteCHEBI:29035 (ChEBI)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
OPRM1 ProteinP35372 (Uniprot-TrEMBL)
OPRM1ProteinP35372 (Uniprot-TrEMBL)
Opioid peptideComplexR-HSA-167443 (Reactome)
Opioid:MOR:G protein-GDP complexComplexR-HSA-167403 (Reactome)
Opioid:MOR:G protein-GTP complexComplexR-HSA-167426 (Reactome)
Opioid:MOR:G-protein complexComplexR-HSA-167436 (Reactome)
Opioid:MORComplexR-HSA-112039 (Reactome)
PC MetaboliteCHEBI:16110 (ChEBI)
PCMetaboliteCHEBI:16110 (ChEBI)
PDE 4ComplexR-HSA-111960 (Reactome) cAMP selective hydrolase
PDE1A ProteinP54750 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1B ProteinQ01064 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1C ProteinQ14123 (Uniprot-TrEMBL)
PDE4A ProteinP27815 (Uniprot-TrEMBL)
PDE4B ProteinQ07343 (Uniprot-TrEMBL)
PDE4BProteinQ07343 (Uniprot-TrEMBL)
PDE4C ProteinQ08493 (Uniprot-TrEMBL)
PDE4D ProteinQ08499 (Uniprot-TrEMBL)
PDYN(226-230) ProteinP01213 (Uniprot-TrEMBL)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PKA catalytic subunitComplexR-HSA-111920 (Reactome)
PKA tetramerComplexR-HSA-111922 (Reactome)
PLA2G4AProteinP47712 (Uniprot-TrEMBL)
PLC-betaComplexR-HSA-111854 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 ProteinQ15147 (Uniprot-TrEMBL)
POMC(237-241) ProteinP01189 (Uniprot-TrEMBL)
POMC(237-267) ProteinP01189 (Uniprot-TrEMBL)
PP2A-ABdeltaC complexComplexR-HSA-165961 (Reactome)
PP2B catalytic (Fe3+, Zn2+)ComplexR-HSA-201779 (Reactome)
PPP1CA ProteinP62136 (Uniprot-TrEMBL)
PPP1CAProteinP62136 (Uniprot-TrEMBL)
PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
PPP2CA ProteinP67775 (Uniprot-TrEMBL)
PPP2CB ProteinP62714 (Uniprot-TrEMBL)
PPP2R1A ProteinP30153 (Uniprot-TrEMBL)
PPP2R1B ProteinP30154 (Uniprot-TrEMBL)
PPP2R5D ProteinQ14738 (Uniprot-TrEMBL)
PPP3 complexComplexR-HSA-201788 (Reactome)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMComplexR-HSA-201762 (Reactome)
PPP3CB ProteinP16298 (Uniprot-TrEMBL)
PPP3CC ProteinP48454 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA ProteinP17612 (Uniprot-TrEMBL)
PRKACAProteinP17612 (Uniprot-TrEMBL)
PRKACB ProteinP22694 (Uniprot-TrEMBL)
PRKACG ProteinP22612 (Uniprot-TrEMBL)
PRKAR1A ProteinP10644 (Uniprot-TrEMBL)
PRKAR1B ProteinP31321 (Uniprot-TrEMBL)
PRKAR2A ProteinP13861 (Uniprot-TrEMBL)
PRKAR2B ProteinP31323 (Uniprot-TrEMBL)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
PRKCD ProteinQ05655 (Uniprot-TrEMBL)
PRKCG ProteinP05129 (Uniprot-TrEMBL)
Phosphorylated (T34) DARPP-32:PP1AComplexR-HSA-180025 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
Protein Kinase A, catalytic subunitsComplexR-HSA-111917 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
active Cam-PDE 1ComplexR-HSA-111953 (Reactome)
active PKC (alpha, gamma, delta)ComplexR-HSA-112002 (Reactome)
cAMP MetaboliteCHEBI:17489 (ChEBI)
cAMP:PKA regulatory subunitComplexR-HSA-111923 (Reactome)
cAMPMetaboliteCHEBI:17489 (ChEBI)
p-S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S12,S13-CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
p-S133-CREB1 ProteinP16220 (Uniprot-TrEMBL)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S29-ADRBK1ProteinP25098 (Uniprot-TrEMBL)
p-S505,S727-PLA2G4A ProteinP47712 (Uniprot-TrEMBL)
p-S505,S727-PLA2G4AProteinP47712 (Uniprot-TrEMBL)
p-S54-PDE4BProteinQ07343 (Uniprot-TrEMBL)
p-T185,Y187-MAPK1ProteinP28482 (Uniprot-TrEMBL)
p-T34,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75-DARPP32s:PRKACAComplexR-HSA-180050 (Reactome)
p-T75-DARPP32sComplexR-HSA-180026 (Reactome)
p-T75-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
phospho-CREB dimerComplexR-HSA-111911 (Reactome)
phospho-CaMK IV:CalmodulinComplexR-HSA-111904 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170686 (Reactome)
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)R-HSA-170674 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ArrowR-HSA-170671 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170686 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170686 (Reactome)
2-LysophosphatidylcholineArrowR-HSA-111883 (Reactome)
ADPArrowR-HSA-111898 (Reactome)
ADPArrowR-HSA-111915 (Reactome)
ADPArrowR-HSA-111919 (Reactome)
ADPArrowR-HSA-111970 (Reactome)
ADPArrowR-HSA-177275 (Reactome)
ADPArrowR-HSA-177284 (Reactome)
ADRBK1R-HSA-111966 (Reactome)
ADRBK1R-HSA-111970 (Reactome)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerTBarR-HSA-169683 (Reactome)
AMPArrowR-HSA-111955 (Reactome)
AMPArrowR-HSA-111962 (Reactome)
ARAArrowR-HSA-111883 (Reactome)
ATPR-HSA-111898 (Reactome)
ATPR-HSA-111915 (Reactome)
ATPR-HSA-111919 (Reactome)
ATPR-HSA-111930 (Reactome)
ATPR-HSA-111970 (Reactome)
ATPR-HSA-170676 (Reactome)
ATPR-HSA-177275 (Reactome)
ATPR-HSA-177284 (Reactome)
Activated PLC beta 1/4ArrowR-HSA-111870 (Reactome)
Activated PLC beta 1/4R-HSA-112037 (Reactome)
Activated PLC beta 1/4mim-catalysisR-HSA-111879 (Reactome)
Active PLA2:phosphatidylcholineArrowR-HSA-111881 (Reactome)
Active PLA2:phosphatidylcholinemim-catalysisR-HSA-111883 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170674 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170677 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-170672 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-392206 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisR-HSA-111930 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisR-HSA-170672 (Reactome)
CALM1:4xCa2+ArrowR-HSA-111956 (Reactome)
CALM1:4xCa2+ArrowR-HSA-74448 (Reactome)
CALM1:4xCa2+R-HSA-111913 (Reactome)
CALM1:4xCa2+R-HSA-201783 (Reactome)
CALM1R-HSA-111966 (Reactome)
CALM1R-HSA-74448 (Reactome)
CAMK4R-HSA-111913 (Reactome)
CDK5mim-catalysisR-HSA-180047 (Reactome)
CREB1R-HSA-111919 (Reactome)
Ca2+ArrowR-HSA-169683 (Reactome)
Ca2+R-HSA-111881 (Reactome)
Ca2+R-HSA-169683 (Reactome)
Ca2+R-HSA-74448 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-111913 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-112282 (Reactome)
Calmodulin:CaMK IVR-HSA-111915 (Reactome)
Calmodulin:CaMK IVR-HSA-112282 (Reactome)
Calmodulin:CaMK IVmim-catalysisR-HSA-111915 (Reactome)
Cam-PDE 1 homodimerR-HSA-111956 (Reactome)
DAGsArrowR-HSA-111879 (Reactome)
DARPP-32

phosporylated on

T34
ArrowR-HSA-177275 (Reactome)
DARPP-32

phosporylated on

T34
R-HSA-180038 (Reactome)
DARPP-32

phosporylated on

T34
R-HSA-201787 (Reactome)
DARPP-32 (and/or phosphorylated)ArrowR-HSA-201787 (Reactome)
DARPP-32 (and/or phosphorylated)R-HSA-177275 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ArrowR-HSA-201790 (Reactome)
DARPP-32 (for CDK5 phosphorylation)R-HSA-180047 (Reactome)
G alpha-olf:GDP:Adenylate cyclase (active) complexArrowR-HSA-170685 (Reactome)
G alpha-olf:GDP:Adenylate cyclase (active) complexR-HSA-170677 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexArrowR-HSA-170672 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexR-HSA-170685 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexmim-catalysisR-HSA-170676 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexmim-catalysisR-HSA-170685 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170674 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170677 (Reactome)
G alpha-olf:GTPR-HSA-170671 (Reactome)
G alpha-olf:GTPR-HSA-170672 (Reactome)
G protein alpha:GTP complexArrowR-HSA-112271 (Reactome)
G protein alpha:GTP complexR-HSA-111870 (Reactome)
G protein alpha:GTP complexR-HSA-167415 (Reactome)
G protein-GDP complexArrowR-HSA-167433 (Reactome)
G protein-GDP complexR-HSA-167408 (Reactome)
G-protein alpha (i):GDPArrowR-HSA-170674 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ArrowR-HSA-392206 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
R-HSA-170671 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisR-HSA-167415 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisR-HSA-167429 (Reactome)
G-protein alpha (i): GTPR-HSA-392206 (Reactome)
G-protein alpha:GDPArrowR-HSA-112037 (Reactome)
G-protein alpha:GDPArrowR-HSA-167415 (Reactome)
G-protein alpha:GDPR-HSA-167433 (Reactome)
G-protein beta-gamma complexArrowR-HSA-112271 (Reactome)
G-protein beta-gamma complexR-HSA-167433 (Reactome)
GDPArrowR-HSA-167419 (Reactome)
GDPR-HSA-167415 (Reactome)
GRK2:calmodulinArrowR-HSA-111966 (Reactome)
GTPArrowR-HSA-167415 (Reactome)
GTPR-HSA-167429 (Reactome)
H2OR-HSA-111879 (Reactome)
H2OR-HSA-111883 (Reactome)
H2OR-HSA-111955 (Reactome)
H2OR-HSA-111962 (Reactome)
H2OR-HSA-112037 (Reactome)
H2OR-HSA-201787 (Reactome)
H2OR-HSA-201790 (Reactome)
I(1,4,5)P3ArrowR-HSA-111879 (Reactome)
I(1,4,5)P3ArrowR-HSA-169683 (Reactome)
I(1,4,5)P3R-HSA-169680 (Reactome)
IP3 receptor homotetramerR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramerArrowR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-169683 (Reactome)
OPRM1ArrowR-HSA-167427 (Reactome)
OPRM1R-HSA-112042 (Reactome)
Opioid peptideArrowR-HSA-167427 (Reactome)
Opioid peptideR-HSA-112042 (Reactome)
Opioid:MOR:G protein-GDP complexArrowR-HSA-167408 (Reactome)
Opioid:MOR:G protein-GDP complexR-HSA-167419 (Reactome)
Opioid:MOR:G protein-GTP complexArrowR-HSA-167429 (Reactome)
Opioid:MOR:G protein-GTP complexR-HSA-112271 (Reactome)
Opioid:MOR:G-protein complexArrowR-HSA-167419 (Reactome)
Opioid:MOR:G-protein complexR-HSA-167429 (Reactome)
Opioid:MORArrowR-HSA-112042 (Reactome)
Opioid:MORArrowR-HSA-112271 (Reactome)
Opioid:MORR-HSA-167408 (Reactome)
Opioid:MORR-HSA-167427 (Reactome)
Opioid:MORmim-catalysisR-HSA-167408 (Reactome)
PCR-HSA-111881 (Reactome)
PCR-HSA-111883 (Reactome)
PDE 4mim-catalysisR-HSA-111962 (Reactome)
PDE4BR-HSA-177284 (Reactome)
PI(4,5)P2R-HSA-111879 (Reactome)
PKA catalytic subunitArrowR-HSA-111925 (Reactome)
PKA catalytic subunitR-HSA-111924 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-177275 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-177284 (Reactome)
PKA tetramerR-HSA-111925 (Reactome)
PLA2G4AR-HSA-111898 (Reactome)
PLC-betaArrowR-HSA-112037 (Reactome)
PLC-betaR-HSA-111870 (Reactome)
PP2A-ABdeltaC complexmim-catalysisR-HSA-201790 (Reactome)
PP2B catalytic (Fe3+, Zn2+)R-HSA-201783 (Reactome)
PPP1CAR-HSA-180038 (Reactome)
PPP3 complexmim-catalysisR-HSA-201787 (Reactome)
PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMArrowR-HSA-201783 (Reactome)
PPiArrowR-HSA-111930 (Reactome)
PPiArrowR-HSA-170676 (Reactome)
PRKACAR-HSA-180073 (Reactome)
Phosphorylated (T34) DARPP-32:PP1AArrowR-HSA-180038 (Reactome)
Phosphorylated (T34) DARPP-32:PP1Amim-catalysisR-HSA-180038 (Reactome)
PiArrowR-HSA-112037 (Reactome)
PiArrowR-HSA-170666 (Reactome)
PiArrowR-HSA-170685 (Reactome)
PiArrowR-HSA-170686 (Reactome)
PiArrowR-HSA-201787 (Reactome)
PiArrowR-HSA-201790 (Reactome)
Protein Kinase A, catalytic subunitsArrowR-HSA-111924 (Reactome)
Protein Kinase A, catalytic subunitsmim-catalysisR-HSA-111919 (Reactome)
R-HSA-111870 (Reactome) The active form of G protein alpha subunit q (Gq-alpha) was found to activate phospholipase C beta-1 (PLC-beta1), in investigations using bovine membranes. Subsequently, all 4 human isoforms have been shown to be activated by Gq, though activation of PLCbeta-4 is limited. In recombinant assays, several activated rat G alpha q family members were found to stimulate human PLC-beta isoforms with the same rank order of decreasing potency. PLC-beta1 stimulation was slightly more than for PLC-beta3; PLC-beta3 stimulation was 10-fold greater than for beta-2. PLC-beta2 is expressed specifically in hematopoietic cells. PLC-beta acts directly on Gq to accelerate hydrolysis of bound GTP, thus PLC-betas are GTPase activating proteins (GAPs). The crystal structure of the C-terminal region from Turkey PLC-beta, revealed a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The extent of the dimer interface and gel exclusion chromatography data suggest that PLC-betas are functionally dimeric.
R-HSA-111879 (Reactome) The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. One type, PLC-beta1, hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions.
R-HSA-111881 (Reactome) The 85kDa cytosolic phospholipase A2 (cPLA2 - PLA2G4A) is involved in cell signalling processes and inflammatory response and is regulated by phosphorylation and calcium concentrations. cPLA2 is phosphorylated at Ser727 and by a MAPK at Ser505. When phosphorylation is coupled with an influx of calcium ions, PLA2 becomes stimulated and translocates to the membrane where it releases arachidonic acid (AA) from membrane phospholipids. Calcium does not itself activate cPLA2. cPLA2 contains an N-terminal calcium-dependent phospholipid binding domain (CaLB) which shares homology with C2 domains (plays roles in signal transduction and membrane trafficking) and binds it to the membrane. Arachidonic acid is both a signalling molecule and the precursor for other signalling molecules termed eicosanoids (e.g., prostaglandins, leukotrienes and platelet-activating factor). A strict regulation of the activity of phospholipase enzyme is essential.
R-HSA-111883 (Reactome) Once bound to the membrane, cPLA2 hydrolyzes phosphatidylcholine to produce arachidonic acid (AA), a precursor to inflammatory mediators. While several phospholipases can catalyze this reaction in cells overexpressing the enzymes, PLA2G4A is the major enzyme that catalyzes this reaction in vivo (Reed et al. 2011). At the same time, possible physiological roles have been described for soluble phospholipases (sPLA) in the mobilization of arachidonic acid in some cell types or under some physiological conditions (Murakami et al. 2011). Here, the major role of PLA2G4A has been annotated.
R-HSA-111898 (Reactome) ERK2 phosphorylates cPLA2, increasing enzymatic activity. The site of cPLA2 phosphorylation by ERK2 is Ser-505, the major site of cPLA2 phosphorylation observed in phorbol ester-treated cells.
R-HSA-111913 (Reactome) CaMKIV becomes fully activated after a three-step mechanism: Upon a transient increase in intracellular calcium, calcium-bound calmodulin (Ca2+/CaM) binds to its autoregulatory domain, which relieves intersteric inhibition. An activating protein kinase, calcium/calmodulin-dependent protein kinase kinase (CaMKK), binds to the Ca2+/CaM:CaMKIV complex and phosphorylates CaMKIV on a threonine residue in the activation loop. After full activation by the three-step mechanism mentioned above, the activity of CaMKIV becomes autonomous and no longer requires bound Ca2+/CaM. This activity is required for CaMKIV-mediated transcriptional regulation. The CaMKIV-associated PP2A then dephosphorylates CaMKIV, thereby terminating autonomous activity and CaMKIV-mediated gene transcription.
R-HSA-111915 (Reactome) Autophosphorylation of the N-terminus Ser12-Ser13 is required for full activation after Ca2+/calmodulin binding and phosphorylation of the Ca2+/calmodulin-bound enzyme on Thr200 by a Ca2+/calmodulin-dependent protein kinase kinase.
R-HSA-111916 (Reactome) CREB readily dimerizes.
R-HSA-111919 (Reactome) cAMP-dependent protein kinase A (PKA) phosphorylates in vitro CREB at a specific residue, serine 133; Phosphorylation of Ser133 is required for signal-induced transcription in vivo.
R-HSA-111924 (Reactome) When cAMP level rises, the PKA catalytic subunit (C subunit) released from the holoenzyme enters the nucleus by passive diffusion whereas termination of signaling to the nucleus involves an active mechanism. In the nucleus, the C subunit binds to the heat-stable protein kinase inhibitor (PKI), and this binding not only inactivates the C subunit but also by conformational change unveils a nuclear export signal in PKI which leads to export of the C-PKI complex from the nucleus.
R-HSA-111925 (Reactome) The four protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The specific isoform activated in response to glucagon signalling is not known. The PKA kinase is a tetramer of two regulatory and two catalytic. The regulatory subunits block the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
R-HSA-111930 (Reactome) Adenylate cyclase is responsive to calcium and calmodulin and produces cAMP. One important physiological role for Calmodulin is the regulation of adenylylcyclases. Four of the ten known adenylylcyclases are calcium sensitive, in particular type 8 (AC8).
R-HSA-111955 (Reactome) Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP, inactivating these second messengers.
R-HSA-111956 (Reactome) Increased Ca2+ levels, acting via calmodulin, can activate PDE which can then act upon cAMP.
R-HSA-111962 (Reactome) PDE4 hydrolyzes cAMP to AMP.
R-HSA-111966 (Reactome) GRK2 is a Serine/Threonine kinase. G-protein-coupled receptor kinases (GRKs) are important regulators of G-protein-coupled receptor function. Binding of calmodulin to GRK2 results in inhibition of the kinase activity. This inhibition is almost completely abolished when GRK2 is phosphorylated by PKC.
R-HSA-111970 (Reactome) GRK2 is phosphorylated at serine 29 in vitro and in vivo by the alpha, gamma and delta isoforms of PKC. PKC-mediated phosphorylation at Ser29 increases GRK2 kinase activity towards GPCR substrates, contributing to GPCR desensitization. Phosphorylation at Ser29, which falls within the calmodulin-binding region of GRK2, abolishes the inhibitory effect of calmodulin on GRK2 kinase activity.
R-HSA-112037 (Reactome) PLC-beta1 is a GTPase-activating protein (GAP) for Gq-alpha, exchanging GTP for GDP and releasing the alpha subunit to cycle back to the membrane and reassociate with the beta-gamma subunits. Between itself and the receptor, they regulate the amplitude of the PLC signal and the rates of signal initiation and termination.
R-HSA-112042 (Reactome) The binding of an opiate peptide to the mu opiate receptor stabilises the receptor conformation in a state of high affinity, both for the ligand itself, and for the G-protein.
R-HSA-112271 (Reactome) The ternary complex neurotransmitter:receptor:G-protein dissociates. Both the alpha-i subunit and beta:gamma complex become active, by conformational transition and surface exposure, and both are free to activate downstream effectors.
R-HSA-112282 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
R-HSA-167408 (Reactome) The high affinity complex beta-endorphin:mu opioid receptor binds to the heterotrimeric G-protein. This binding stabilises a conformation of the G-protein alpha i subunit presenting a low affinity for GDP, but a high affinity for GTP
R-HSA-167415 (Reactome) Slow intrisinc GTPase activity results in an inactivation of the alpha-i subunit by hydrolyzing GTP to GDP.
R-HSA-167419 (Reactome) G proteins are inactive in the GDP-bound state. The ternary complex neurotransmitter:receptor:G-protein releases GDP.
R-HSA-167427 (Reactome) Different ligands of the MOR receptor can promote MOR phosphorylation, uncoupling, endocytosis or inactivation. For example, the endogenous peptide ligands at the MOR induce rapid desensitization, endocytosis and rapid receptor recycling. By contrast, morphine induces little to no endocytosis, tolerance and dependence. The agonist-dependent phosphorylation of opioid receptors changes the receptor conformation and increases the affinity of the receptors for cytosolic beta-arrestin proteins. This results in an uncoupling of G protein signalling and recruitment of the endocytotic machinery leading to receptor internalization and rapid resensitization. By contrast, PKC phosphorylation by non internalizing opioid ligands (e.g., morphine) cause receptors to remain inactivated in the plasma membrane, leading to signaling desensitization and opioid tolerance. In this case receptors appear to require activity of a phosphatase to be resensitized.
R-HSA-167429 (Reactome) The ternary complex neurotransmitter:receptor:G-protein binds GTP, resulting in activation of G protein.
R-HSA-167433 (Reactome) Gbetagamma rebinds Galpha-olfactory:GDP, stopping its activity
R-HSA-169680 (Reactome) The IP3 receptor (IP3R) is an IP3-gated calcium channel. It is a large, homotetrameric protein, similar to other calcium channel proteins such as ryanodine. The four subunits form a 'four-leafed clover' structure arranged around the central calcium channel. Binding of ligands such as IP3 results in conformational changes in the receptor's structure that leads to channel opening.
R-HSA-169683 (Reactome) IP3 promotes the release of intracellular calcium.
R-HSA-170666 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170671 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
R-HSA-170672 (Reactome) G alpha-olf:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it.
R-HSA-170674 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-i dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170676 (Reactome) Once activated, adenylate cyclase utilizes one molecule of ATP to synthesize one molecule of cyclic AMP and pyrophosphate.
R-HSA-170677 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-olf dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170685 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170686 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-177275 (Reactome) DARPP-32 is phosphorylated by cAMP-dependent protein kinase (PKA) on a single threonine residue, Thr34, resulting in its conversion into a potent inhibitor of protein phosphatase-1.
R-HSA-177284 (Reactome) The phosphorylation of the phosphodiesterase increases its activity, forming a negative feedback loop of the cAMP signal.
R-HSA-180038 (Reactome) DARPP-32 is phosphorylated by cAMP-dependent protein kinase (PKA) on a single threonine residue, Thr34, resulting in its conversion into a potent inhibitor of protein phosphatase-1.
R-HSA-180047 (Reactome) The amino-acid sequence of DARPP-32 contains consensus phosphorylation sites for proline-directed kinases, including Cdk5, a cyclin-dependent kinase family member which is present in post-mitotic neurons expressing high levels of DARPP-32.
R-HSA-180073 (Reactome) DARPP-32 is converted into an inhibitor of protein kinase A (PKA) when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5) in brain cells.
R-HSA-201783 (Reactome) PP2B (calcineurin) is a calcium-dependent, calmodulin-stimulated protein phosphatase. It comprises of two components; a catalytic subunit and a regulatory subunit which confers calcium sensitivity to the complex. PP2B is in equilibrium between active and inactive forms. Because the affinity of calmodulin for the active form is higher than for the inactive form, it stabilises PP2B.
R-HSA-201787 (Reactome) Calcineurin has been identified as a Ca2+- and calmodulin-dependent phosphoprotein phosphatase. The concentration of the enzyme is relatively high in mammalian brain.
R-HSA-201790 (Reactome) PP2A is ubiquitously expressed in eukaryotic cells, existing as a heterotrimeric enzyme composed of a 36-kDa catalytic C subunit, a 64-kDa scaffolding A subunit, and multiple regulatory B subunits. The B subunits are thought to influence enzyme activity, substrate specificity, and subcellular localization. PKA phosphorylates PP2A thereby activating the enzyme and is responsible for dopamine/cAMP-dependent dephosphorylation of Thr-75 of DARPP-32.
R-HSA-392206 (Reactome) G-proteins in the Gi class inhibit adenylate cyclase activity, decreasing the production of cAMP from ATP, which has many consequences but classically results in decreased activity of Protein Kinase A (PKA). cAMP also activates the cyclic nucleotide-gated ion channels, a process that is particularly important in olfactory cells.
R-HSA-74448 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
active Cam-PDE 1ArrowR-HSA-111956 (Reactome)
active Cam-PDE 1mim-catalysisR-HSA-111955 (Reactome)
active PKC (alpha, gamma, delta)mim-catalysisR-HSA-111970 (Reactome)
cAMP:PKA regulatory subunitArrowR-HSA-111925 (Reactome)
cAMPArrowR-HSA-111930 (Reactome)
cAMPArrowR-HSA-170676 (Reactome)
cAMPR-HSA-111925 (Reactome)
cAMPR-HSA-111955 (Reactome)
cAMPR-HSA-111962 (Reactome)
p-S133-CREB1ArrowR-HSA-111919 (Reactome)
p-S133-CREB1R-HSA-111916 (Reactome)
p-S29-ADRBK1ArrowR-HSA-111970 (Reactome)
p-S505,S727-PLA2G4AArrowR-HSA-111898 (Reactome)
p-S505,S727-PLA2G4AR-HSA-111881 (Reactome)
p-S54-PDE4BArrowR-HSA-177284 (Reactome)
p-T185,Y187-MAPK1mim-catalysisR-HSA-111898 (Reactome)
p-T75-DARPP32s:PRKACAArrowR-HSA-180073 (Reactome)
p-T75-DARPP32sArrowR-HSA-180047 (Reactome)
p-T75-DARPP32sR-HSA-180073 (Reactome)
p-T75-DARPP32sR-HSA-201790 (Reactome)
p-T75-DARPP32sTBarR-HSA-177284 (Reactome)
p-T75-DARPP32smim-catalysisR-HSA-180073 (Reactome)
phospho-CREB dimerArrowR-HSA-111916 (Reactome)
phospho-CaMK IV:CalmodulinArrowR-HSA-111915 (Reactome)
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