Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)

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372215, 422143, 449538, 53293220, 25, 35, 67332493, 13, 17, 19, 24...326051, 527, 1416, 50, 58101, 11, 28, 45277, 143737343262126651, 5236214573621595640263630395518, 23128, 656463CaMKII alpha/beta subunits G alpha-olfGDP complex CaMKII RasGRF RasGRF CaMKII alpha/beta subunits O-acteylcholine bound to calcium permeable postsynaptic nicotinic acetylcholine receptors Adenylate cyclase Adenylate cyclase RasGDP CaMKII PLC-beta 1/2/3 NR2 interacting proteins G alpha-olfGDP complex AMPA receptors containing GluR1 and GluR2 Acetylcholine receptors alpha2CaMKII alpha/beta subunits NR2 interacting proteins AMPA receptors containing GluR2 CaMKII alpha/beta subunits NR1 interacting proteins GABAB receptorGABA acetylcholine receptor alpha6 aplha4 beta3 Ca impermeable AMPA receptors G-protein alpha NMDA receptor complex Acetylcholine Receptor CaMKII GRIK 3 homomer G-protein beta-gamma complex Ca permeable AMPA receptors CaMKII delta/gamma subunits Adenylate cyclase Adenylate cyclase G-protein alpha Adenylate cyclase TARP-PSD95-Mdm2 G-protein alpha NR1 interacting proteins Gamma subunit of VGCC kaiante Receptors AMPA receptors containing GluR2 GABRA2ARHGEF9 GRIK 2 homomer AMPA receptors containing GluR1 RasGTP-B raf compex Kainate receptor-glutamate complex G alpha-olfGTP Edited Kainate receptors G-protein alpha Acetylcholine receptor alpha3GRIA3,GRIA4 CaMKII delta/gamma Adenylate cyclase G-protein alpha GRIA3,GRIA4 Kainate receptor-glutamate-Gprotein complex GRIK1, GRIK2, GRIK3 NR2 subunits Edited Kainate Receptor-glutamate complex GABRAs Acetylcholine receptor alpha3-beta2-aplha5 G-protein beta subunits O-Acetylcholine bound to Acetylcholine receptor GRIK4 heteromer with GRIK1/2/3 Acetylcholine receptor alpha3-beta4 G-protein Gamma subunits Active Calmodulin Acetylcholine receptor alpha3-beta4-apha5 GABA B receptor G-protein beta-gamma and Kir3 channel complex AP2 complex G-protein alpha GABA B receptor G-protein beta-gamma complex Gamma subunit of VGCC Acetylcholine Receptor Kir3.x channels NR2 subunits GRIK5 heteromer with GRIk1/2/3 AMPA receptors containing GluR2 0-acteylcholine bound to calcium permeable nictonic acteylcholine receptor complex NR2 interacting proteins NMDA receptor ligand complex CalmodulinCaMK IV active Calmodulin GRIK2 interacting proteins CaMKII delta/gamma subunits active Calmodulin CalmodulinCaMK IV NMDA receptor complex Edited GRIK1 and GRIK2 heteroteramer GABRBs NMDA receptor-Mg complex Ca impermeable AMPA receptors Kir3 heterotetramer CaMKII NMDA receptor complex Acetylcholine Receptor alpha4GRIK1 homomer CaMKII alpha/beta subunits CaMKII subunits alpha/beta GRIK1 and 2 heterotetramer CaMKII alpha/beta subunits NR1 interacting proteins GRIK 3 homomer 2GABRA2GABRBGABRGGABA CaMKII CaMKII delta/gamma subunits Edited Kainate receptors NMDA receptor complex NR2 subunits CaMKII-Ca2+/Calmodulin Adenylate cyclase Edited GRIK1 and GRIK2 heteroteramer G-protein alpha Highly calcium permeable postsynaptic nicotinic acetylcholine receptors Active Calmodulin G-protein alpha G-protein beta-gammaPLC beta 1/2/3 phospho-CaMK IVCalmodulin G-protein alpha CaMKII delta/gamma subunits AMPA receptors containing GluR2 Acetylcholine Receptors alpha4Delta, epsilon, gamma subunits of acetylcholine receptor NR2 interacting proteins GABAB receptor G alpha-olfGTP CaMKII NMDA receptor ligand complex AMPA receptors containing GluR1 and GluR2 Adenylate cyclase G-protein beta-gamma complex TARP-PSD95-Mdm2 Edited GRIK1 homomer CaMKII G-protein beta-gamma subunits GABAB receptor Acetylcholine receptor containing alpha7 subunit CaMKII CaMKII delta/gamma subunits Kir heterotetramers G-protein alpha NR2 subunits cytosolActivated B-raf complex G-protein alpha GABRR1-3 CaMKII alpha/beta R-Ras-GTP CaMKII alpha/beta subunits GRIK4 interacting proteins CaMKII delta/gamma subunits NR2 interacting proteins Ca impermeable AMPA receptor ligand complex nucleoplasmG-protein alpha endocytic vesicle membraneKir4.2Kir5.1 heterotetramer CaMKII delta/gamma subunits GABRGs R-Ras-GTP NMDA receptor ligand complex CaMKII gamma/delta subunits NR1 interacting proteins GRIK 3 homomer GRIA3,GRIA4 Edited GRIK1 homomer Active Calmodulin GABRR pentamerGABA G-protein alpha NMDA receptor complex GRIK 3 homomer Adenylate cyclase Highly calcium permeable nicotinic acetylcholine receptors RasGTP G-protein alpha NR1 interacting proteins G-protein alpha Highly sodium permeable nicotinic acetylcholine receptors Acetylcholine receptor alpha6 beta3 beta4 GluR1 receptors acetylcholine receptor subunits Adenylate cyclase Kir2.1Kirx.x heterotetramer Kirx.x that interacts with Kir2.1 Kir4.1Kir5.1 heterotetramer NR2 subunits GABAB receptor CaMKII subunits delta/gamma active Calmodulin GRIK3 homomer glutamate complex G alpha-olfGDP complex G-protein beta-gammaPLC beta 1/2/3 GRIK3 homomer glutamate complex Edited GRIK2 homomer GABAB receptorGABA Ca permeable AMPA receptor ligand complex CaMKII alpha/beta subunits RasGRFCa/calmodulin CaMKII CaMKII AP2A PLC-beta 1/2/3 Edited GRIK2 homomer GRIK4 Mg2+Edited Kainate receptorsADCY6 ADCY9 CALM1p-T287-CAMK2D CAMK4GTP GRIA2 ADCY4 p-T287-CAMK2G ADCY7 p-T287-CAMK2G PPiGNAI3ADP GNAI2GRIA2 NEFL ACTN2 GNG2 GABBR1 PLCB2 GNAI1GRIA3 Ca2+Mg2+ Mg2+ GRIN2D GRIA1 phospho-CaMK IVCalmodulinADCY4 CaMKIIKCNJ12 NMDA receptor ligand complexCHRNA6 Glup-T287-CAMK2D GRIK2 CHRNB4 Ca2+GABRA4 GRIN2B GABAB receptorGABACa2+p-T286-CAMK2A ADCY5 Mg2+ GNALp-T287-CAMK2D DLG4 KCNJ9 KCNJ10 GRIN2Cp-T286-CAMK2A Glu AcCho Edited GRIK 1 GABA Mg2+ Activated conventional protein kinase CCACNG3 p-T287-CAMK2B Cl- Na+ATPADCY6 GABBR2 CHRNB3 K+Ca impermeable AMPA receptors KCNJ6 GABA GABBR1 GRIN2A RRAS GABRB2 GABRR1 GRIP1/GRIP2ADCY4 3',5'-Cyclic AMPGluGABBR2 CACNG2 MDM2 GNAI3Activated B-raf complexCl- KCNJ5 GluGRIN2D CaMKII-Ca2+/CalmodulinGNAI3Ca impermeable AMPA receptorsGlyGNG8CHRNB2 Ca2+p-T287-CAMK2D GDP GABRA2 ADPNEFL Glu GABRR3 GNAT3AKAP9 NMDA receptor complexGNAT3ARHGEF9 GRIN2B CHRNA5 DLG1 AP2AATPCALM1 DLG4 CALM1 Cl-GNGT1 GNAI1ADCY1 Ca permeable AMPA receptorsACTN2 GRIN1 EPB41L1ATPp-T286-CAMK2A ATPAKAP9 Edited GRIK 1 ADCY6 p-T287-CAMK2G KCNJ15 HRASGNAI1G-protein alpha GRIA4 NCALD GABRR2 DLG4 GRIN1 GABRB3 NSFADPRasGRFAP2 complexDLG3 PiCl- MYO6ADCY7 Cl- CHRNA4 GNAI3GRIK3 GNAI2GNAI2GABRA1 ACTN2 ADCY6 GTP Glu GRIK3 homomer glutamate complexPiRasGTPCACNG8 GluTARP-PSD95-Mdm2AP2B1-1 GNG4 RasGTP-B raf compexKainate receptor-glutamate-Gprotein complexCa/calmodulin activated Adenylate CyclaseATPCaMKIIACTN2 ADPGRIK3 PhosphoKCNJ2 GRIA1 GNG5 GNAI3GDP GRIN2A K+GNG10 BRAF GNAT3GRIA1 CHRNB2 CALM1 CHRNB4 GNAI1GNAT3PhosphoGly RASGRF2 GluGRIN2CADPAcChoGABRB1 ATPATPADCY6 GNALADCY9 PhosphoGNG12 Edited GRIK2 HRASp-S12,S13-CAMK4 GNB1 PiADCY1 Na+ADCY4 ADCY9 AKAP9 GDP AP2M1-2 PICK1AKAP5p-T287-CAMK2G GNALATPGTP Glu ATPGRIN1 CAMKK1ADP ADCY2 MYO6ADCY8 CHRNA5 p-T287-CAMK2D GlyGRIK3 Ca2+GRIN2D GTP CALM1 ADCY5 ADCY1 p-T287-CAMK2B ADPp-T287-CAMK2D GNAI1PICK1GNB2 PLCB3CHRNA2 Ca2+ADCY3 CHRNA2 Glu p-T286-CAMK2A ADCY9 PICK1p-S133-CREB1ADCY8 CHRNA9 MDM2 NMDA receptor-Mg complexGRIN1 p-CAMKK1AKAP5p-T287-CAMK2D CREB1Ca impermeable AMPA receptorsGRIN1 CACNG3 ADCY7 G alpha-olfGDP complexp-T286-CAMK2A CACNG8 CALM1 GABA PiGABRG3 ATPNa+DLG4 GTP RASGRF1 Glu CACNG2 Edited GRIK2 CHRNA1 GNAT3p-T287-CAMK2B CHRNA1 Ca2+GRIA4 GNALGNB3 GABRG2 MAPK1EPB41L1GRIN2D p-T286-CAMK2A GTP 2GABRA2GABRBGABRGGABACl- p-T287-CAMK2G Ca2+ GRIP1/GRIP2NMDA receptor ligand complexCa2+ DLG1CHRNA3 GNGT2 Glup-T287-CAMK2B CHRNA3 p-T286-CAMK2A CHRNA4 NEFL p-S338-RAF1Ca2+Mg2+ GABBR1 ATPAcCho PLCB1 CHRNB3 GRIA3 ADCY2 p-T286-CAMK2A CACNG4 GRIA4 RASGRF2 GNAI1Ca2+ ADCY7 ADPAKAP9 p-T287-CAMK2B CHRNA3 GABRA6 p-T287-CAMK2D TARP-PSD95-Mdm2CALM1 GRIN2B Ca impermeable AMPA receptorsADCY8 GNAI2AP2A2-3 ADCY2 AcCho PLCB1 p-T286-CAMK2A RasGDPDLG4 GRIK5 PDPK1p-T287-CAMK2D CACNG4 GDP O-acteylcholine bound to calcium permeable postsynaptic nicotinic acetylcholine receptorsCa2+CHRNA7 p-T286-CAMK2A Mg2+ PRKACBADCY2 Ca impermeable AMPA receptor ligand complexGABRA3 RRAS p-T287-CAMK2G GABAB receptorGABA GNAI2GRIK1 CHRNB2 Ca2+ Na+GluADCY5 GRIN2A NEFL Ca2+CHRNE GTP GRIN2CPiGRIN2B ADCY9 ATPG alpha-olfGTPGRIN2CGlu GRIP1/GRIP2GNAI2Glu ACTN2 GABRA5 CaMKIIGRIN2D PLCB2 GNG3 GRIN2A CALM1 Edited Kainate Receptor-glutamate complexGlu RasGRFCa/calmodulinkaiante Receptorsp-S338-BRAF CHRNA4 Highly calcium permeable postsynaptic nicotinic acetylcholine receptorsO-Acetylcholine bound to Acetylcholine receptorDLG4 p-T287-CAMK2D ADPCa2+ADCY3 RASGRF1 GTP Ca2+ Na+ADCY4 Highly calcium permeable nicotinic acetylcholine receptorsCAMK4 Gly CREB10-acteylcholine bound to calcium permeable nictonic acteylcholine receptor complexCHRNB4 DLG4 p-T287-CAMK2B CHRNG Ribosomal S6 kinaseGNG7 Ca2+ Ca impermeable AMPA receptorsCa permeable AMPA receptor ligand complexCaMKIIGly ADPADCY2 G-protein alpha p-T287-CAMK2G Adenylate cyclase Na+AP2S1-1 ATPCl-ADCY3 p-T287-CAMK2G CalmodulinCaMK IVp-T185,Y187-MAPK1CAMK4 GRIA3 Highly sodium permeable nicotinic acetylcholine receptorsCHRND AP2A1 CalmodulinCaMK IVNEFL DLG4 p-T287-CAMK2B ADCY8 ADCY3 ADCY1 PLCB3ADCY8 GNAI3KCNJ3 GRIN2A ADCY5 Cl- Na+KCNJ4 GDP GRIN2B ADCY5 GRIK 3 homomerp-T287-CAMK2B ADPGABRR pentamerGABAADCY1 GNAT3ADPGNALAKAP9 KCNJ16 GRIN2CDLG1GABA B receptor G-protein beta-gamma and Kir3 channel complexADCY7 CHRNA6 Ca permeable AMPA receptorsp-T287-CAMK2B Active CalmodulinKainate receptor-glutamate complexp-T287-CAMK2G GABBR2 p-T287-CAMK2B p-T287-CAMK2G GRIK3 ADCY3 ADPGTP ADPGDP G-protein beta-gammaPLC beta 1/2/3G-protein alpha GABA48266


Description

The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=112314

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
118519view10:04, 28 May 2021EweitzOntology Term : 'neuron-to-neuron signaling pathway via the chemical synapse' added !
114633view16:09, 25 January 2021ReactomeTeamReactome version 75
113081view11:14, 2 November 2020ReactomeTeamReactome version 74
112315view15:23, 9 October 2020ReactomeTeamReactome version 73
101214view11:11, 1 November 2018ReactomeTeamreactome version 66
100752view20:36, 31 October 2018ReactomeTeamreactome version 65
100296view19:13, 31 October 2018ReactomeTeamreactome version 64
99842view15:57, 31 October 2018ReactomeTeamreactome version 63
99399view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94502view09:18, 14 September 2017Mkutmonreactome version 61
86651view09:23, 11 July 2016ReactomeTeamreactome version 56
83166view10:15, 18 November 2015ReactomeTeamVersion54
81530view13:04, 21 August 2015ReactomeTeamVersion53
77001view08:29, 17 July 2014ReactomeTeamFixed remaining interactions
76706view12:07, 16 July 2014ReactomeTeamFixed remaining interactions
76032view10:09, 11 June 2014ReactomeTeamRe-fixing comment source
75741view11:22, 10 June 2014ReactomeTeamReactome 48 Update
75091view14:04, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74738view08:49, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
0-acteylcholine bound to calcium permeable nictonic acteylcholine receptor complexComplexREACT_23302 (Reactome)
2GABRA

2GABRB GABRG

GABA		ComplexREACT_26202 (Reactome)
3',5'-Cyclic AMPMetaboliteCHEBI:17489 (ChEBI)
ACTN2 ProteinP35609 (Uniprot-TrEMBL)
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)
ADP MetaboliteCHEBI:16761 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
AKAP5ProteinP24588 (Uniprot-TrEMBL)
AKAP9 ProteinQ99996 (Uniprot-TrEMBL)
AP2 complexComplexREACT_18535 (Reactome)
AP2A1 ProteinO95782 (Uniprot-TrEMBL)
AP2A2-3 ProteinO94973-3 (Uniprot-TrEMBL)
AP2AProteinREACT_19022 (Reactome)
AP2B1-1 ProteinP63010-1 (Uniprot-TrEMBL)
AP2M1-2 ProteinQ96CW1-2 (Uniprot-TrEMBL)
AP2S1-1 ProteinP53680-1 (Uniprot-TrEMBL)
ARHGEF9 ProteinO43307 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
AcCho MetaboliteCHEBI:15355 (ChEBI)
AcChoMetaboliteCHEBI:15355 (ChEBI)
Activated B-raf complexComplexREACT_25467 (Reactome)
Activated conventional protein kinase CREACT_4434 (Reactome)
Active CalmodulinComplexREACT_3178 (Reactome)
Adenylate cyclase ComplexREACT_17689 (Reactome)
BRAF ProteinP15056 (Uniprot-TrEMBL)
CACNG2 ProteinQ9Y698 (Uniprot-TrEMBL)
CACNG3 ProteinO60359 (Uniprot-TrEMBL)
CACNG4 ProteinQ9UBN1 (Uniprot-TrEMBL)
CACNG8 ProteinQ8WXS5 (Uniprot-TrEMBL)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
CAMK4ProteinQ16566 (Uniprot-TrEMBL)
CAMKK1ProteinQ8N5S9 (Uniprot-TrEMBL)
CHRNA1 ProteinP02708 (Uniprot-TrEMBL)
CHRNA2 ProteinQ15822 (Uniprot-TrEMBL)
CHRNA3 ProteinP32297 (Uniprot-TrEMBL)
CHRNA4 ProteinP43681 (Uniprot-TrEMBL)
CHRNA5 ProteinP30532 (Uniprot-TrEMBL)
CHRNA6 ProteinQ15825 (Uniprot-TrEMBL)
CHRNA7 ProteinP36544 (Uniprot-TrEMBL)
CHRNA9 ProteinQ9UGM1 (Uniprot-TrEMBL)
CHRNB2 ProteinP17787 (Uniprot-TrEMBL)
CHRNB3 ProteinQ05901 (Uniprot-TrEMBL)
CHRNB4 ProteinP30926 (Uniprot-TrEMBL)
CHRND ProteinQ07001 (Uniprot-TrEMBL)
CHRNE ProteinQ04844 (Uniprot-TrEMBL)
CHRNG ProteinP07510 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
Ca impermeable AMPA receptor ligand complexComplexREACT_18924 (Reactome)
Ca impermeable AMPA receptors ComplexREACT_19016 (Reactome)
Ca impermeable AMPA receptorsComplexREACT_18797 (Reactome)
Ca impermeable AMPA receptorsComplexREACT_19064 (Reactome)
Ca permeable AMPA receptor ligand complexComplexREACT_18904 (Reactome)
Ca permeable AMPA receptorsComplexREACT_18563 (Reactome)
Ca permeable AMPA receptorsComplexREACT_18763 (Reactome)
Ca/calmodulin activated Adenylate CyclaseREACT_20929 (Reactome)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
CaMKII-Ca2+/CalmodulinComplexREACT_20912 (Reactome)
CaMKIIComplexREACT_18980 (Reactome) CaMKII is composed of a homo or hetero dodecamer of four subunits apha, beta, delta and gamma. In a heteromultimer the ratio of alpha to beta may vary from 6;1, 3:1 or 1:1.
CaMKIIComplexREACT_20828 (Reactome)
CaMKIIComplexREACT_21044 (Reactome)
CaMKIIComplexREACT_21174 (Reactome) CaMKII is composed of a homo or hetero dodecamer of four subunits apha, beta, delta and gamma. In a heteromultimer the ratio of alpha to beta may vary from 6;1, 3:1 or 1:1.
Calmodulin CaMK IVComplexREACT_15739 (Reactome)
Calmodulin CaMK IVComplexREACT_15747 (Reactome)
Cl- MetaboliteCHEBI:17996 (ChEBI)
Cl-MetaboliteCHEBI:17996 (ChEBI)
DLG1 ProteinQ12959 (Uniprot-TrEMBL)
DLG1ProteinQ12959 (Uniprot-TrEMBL)
DLG3 ProteinQ92796 (Uniprot-TrEMBL)
DLG4 ProteinP78352 (Uniprot-TrEMBL)
EPB41L1ProteinQ9H4G0 (Uniprot-TrEMBL)
Edited GRIK 1 ProteinP39086 (Uniprot-TrEMBL) Glutamine at position 636 is replaced by arginine in an editing step which occurs posttranscriptionally.
Edited GRIK2 ProteinQ13002 (Uniprot-TrEMBL) GRIK2 is edited at the Q/R site at 621 where the glutamine is edited to arginine. GRIK2 is also edited at 571 (Y/C) where a tyrosine residue is changed to cysteine and 567 (I/V) where an isoleucine is changed to valine. All three sites are edited postranscriptionally. A fully edited GRIK2 at all three sites is totally impermeable to calcium ions.
Edited Kainate Receptor-glutamate complexComplexREACT_21503 (Reactome)
Edited Kainate receptorsComplexREACT_21924 (Reactome) Kainate receptors are formed by the assembly of four subunits. GluR5-7 (GRIK, glutamate receptor, ionotropic Kainate 1-3) form functional homomers whereas, KA1 and KA2 or GRIK4,5 form functional heteromers with GRIK1/2/3. Kainate receptor subunits bind Cl- ion in the anion binding site in the ligand binding domain. The dimer is stabilized by the presence of one Cl- ion which binds within the dimer interface.
G alpha-olf GDP complexComplexREACT_17352 (Reactome)
G alpha-olf GTPComplexREACT_16015 (Reactome)
G-protein alpha ComplexREACT_19580 (Reactome)
G-protein alpha ComplexREACT_19806 (Reactome)
G-protein alpha ComplexREACT_19914 (Reactome)
G-protein beta-gamma PLC beta 1/2/3ComplexREACT_19982 (Reactome)
GABA B receptor G-protein beta-gamma and Kir3 channel complexComplexREACT_26489 (Reactome)
GABA MetaboliteCHEBI:16865 (ChEBI)
GABAB receptor GABAComplexREACT_18601 (Reactome)
GABAB receptorComplexREACT_18843 (Reactome)
GABAMetaboliteCHEBI:16865 (ChEBI)
GABBR1 ProteinQ9UBS5 (Uniprot-TrEMBL)
GABBR2 ProteinO75899 (Uniprot-TrEMBL)
GABRA1 ProteinP14867 (Uniprot-TrEMBL)
GABRA2 ProteinP47869 (Uniprot-TrEMBL)
GABRA3 ProteinP34903 (Uniprot-TrEMBL)
GABRA4 ProteinP48169 (Uniprot-TrEMBL)
GABRA5 ProteinP31644 (Uniprot-TrEMBL)
GABRA6 ProteinQ16445 (Uniprot-TrEMBL)
GABRB1 ProteinP18505 (Uniprot-TrEMBL)
GABRB2 ProteinP47870 (Uniprot-TrEMBL)
GABRB3 ProteinP28472 (Uniprot-TrEMBL)
GABRG2 ProteinP18507 (Uniprot-TrEMBL)
GABRG3 ProteinQ99928 (Uniprot-TrEMBL)
GABRR pentamer GABAComplexREACT_26162 (Reactome)
GABRR1 ProteinP24046 (Uniprot-TrEMBL)
GABRR2 ProteinP28476 (Uniprot-TrEMBL)
GABRR3 ProteinA8MPY1 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GNAI1ProteinP63096 (Uniprot-TrEMBL)
GNAI2ProteinP04899 (Uniprot-TrEMBL)
GNAI3ProteinP08754 (Uniprot-TrEMBL)
GNALProteinP38405 (Uniprot-TrEMBL)
GNAT3ProteinA8MTJ3 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GRIA1 ProteinP42261 (Uniprot-TrEMBL)
GRIA2 ProteinP42262 (Uniprot-TrEMBL)
GRIA3 ProteinP42263 (Uniprot-TrEMBL)
GRIA4 ProteinP48058 (Uniprot-TrEMBL)
GRIK 3 homomerComplexREACT_22081 (Reactome)
GRIK1 ProteinP39086 (Uniprot-TrEMBL)
GRIK2 ProteinQ13002 (Uniprot-TrEMBL)
GRIK3 ProteinQ13003 (Uniprot-TrEMBL)
GRIK3 homomer glutamate complexComplexREACT_21898 (Reactome)
GRIK4 ProteinQ16099 (Uniprot-TrEMBL)
GRIK5 ProteinQ16478 (Uniprot-TrEMBL)
GRIN1 ProteinQ05586 (Uniprot-TrEMBL)
GRIN2A ProteinQ12879 (Uniprot-TrEMBL)
GRIN2B ProteinQ13224 (Uniprot-TrEMBL)
GRIN2CProteinQ14957 (Uniprot-TrEMBL)
GRIN2D ProteinO15399 (Uniprot-TrEMBL)
GRIP1/GRIP2ProteinREACT_18455 (Reactome)
GRIP1/GRIP2ProteinREACT_18837 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
Glu MetaboliteCHEBI:16015 (ChEBI)
GluMetaboliteCHEBI:16015 (ChEBI)
Gly MetaboliteCHEBI:15428 (ChEBI)
GlyMetaboliteCHEBI:15428 (ChEBI)
HRASProteinP01112 (Uniprot-TrEMBL)
Highly calcium permeable nicotinic acetylcholine receptorsREACT_22488 (Reactome)
Highly calcium permeable postsynaptic nicotinic acetylcholine receptorsREACT_22452 (Reactome)
Highly sodium permeable nicotinic acetylcholine receptorsREACT_23370 (Reactome)
K+MetaboliteCHEBI:29103 (ChEBI)
KCNJ10 ProteinP78508 (Uniprot-TrEMBL)
KCNJ12 ProteinQ14500 (Uniprot-TrEMBL)
KCNJ15 ProteinQ99712 (Uniprot-TrEMBL)
KCNJ16 ProteinQ9NPI9 (Uniprot-TrEMBL)
KCNJ2 ProteinP63252 (Uniprot-TrEMBL)
KCNJ3 ProteinP48549 (Uniprot-TrEMBL)
KCNJ4 ProteinP48050 (Uniprot-TrEMBL)
KCNJ5 ProteinP48544 (Uniprot-TrEMBL)
KCNJ6 ProteinP48051 (Uniprot-TrEMBL)
KCNJ9 ProteinQ92806 (Uniprot-TrEMBL)
Kainate receptor-glutamate complexComplexREACT_22077 (Reactome)
Kainate receptor-glutamate-Gprotein complexComplexREACT_21842 (Reactome)
MAPK1ProteinP28482 (Uniprot-TrEMBL)
MDM2 ProteinQ00987 (Uniprot-TrEMBL)
MYO6ProteinQ9UM54 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
Mg2+MetaboliteCHEBI:18420 (ChEBI)
NCALD ProteinP61601 (Uniprot-TrEMBL)
NEFL ProteinP07196 (Uniprot-TrEMBL)
NMDA receptor complexComplexREACT_20772 (Reactome) NMDAR complex consists of two NR1 subunits and two NR2 subunits. Each subunit has extensive C terminal tail that is modified by series of protein kinases and protein phosphatases. The NR1 subunits binds co-agonist glycine while the NR2 subunit binds glutamate. Hence the activation of NR1/NR2 containing NMDA receptor complexes are activated upon depolarization of the membrane and binding of both glycine and glutamate. The dual requirement of membrane depolarization and agonist binding facilitate coincidence detection by NMDA receptors that ensures activation of both pre-synaptic and post-synaptic cell. NR1/NR2 containing NMDA receptors are highly Ca2+ permeable and subjected to a voltage dependent Mg2+ block.
NMDA receptor ligand complexComplexREACT_21126 (Reactome)
NMDA receptor-Mg complexComplexREACT_20969 (Reactome)
NSFProteinP46459 (Uniprot-TrEMBL)
Na+MetaboliteCHEBI:29101 (ChEBI)
O-Acetylcholine bound to Acetylcholine receptorComplexREACT_23014 (Reactome)
O-acteylcholine bound to calcium permeable postsynaptic nicotinic acetylcholine receptorsComplexREACT_23170 (Reactome)
PDPK1ProteinO15530 (Uniprot-TrEMBL)
PICK1ProteinQ9NRD5 (Uniprot-TrEMBL)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3ProteinQ01970 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACBProteinP22694 (Uniprot-TrEMBL)
PhosphoProteinREACT_20714 (Reactome)
PhosphoProteinREACT_20750 (Reactome)
PhosphoProteinREACT_20941 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
RASGRF1 ProteinQ13972 (Uniprot-TrEMBL)
RASGRF2 ProteinO14827 (Uniprot-TrEMBL)
ComplexREACT_15853 (Reactome)
ComplexREACT_15896 (Reactome)
ComplexREACT_15996 (Reactome)
RRAS ProteinP10301 (Uniprot-TrEMBL)
Ras GDPComplexREACT_21149 (Reactome)
Ras GTPComplexREACT_21235 (Reactome)
RasGRF Ca/calmodulinComplexREACT_21180 (Reactome)
RasGRFComplexREACT_20701 (Reactome)
RasGTP-B raf compexComplexREACT_26693 (Reactome)
Ribosomal S6 kinaseProteinREACT_20775 (Reactome)
TARP-PSD95-Mdm2ComplexREACT_18885 (Reactome)
TARP-PSD95-Mdm2ComplexREACT_19058 (Reactome)
kaiante ReceptorsComplexREACT_21711 (Reactome) Kainate receptors are formed by the assembly of four subunits. GluR5-7 (GRIK, glutamate receptor, ionotropic Kainate 1-3) form functional homomers whereas, KA1 and KA2 or GRIK4,5 form functional heteromers with GRIK1/2/3. Kainate receptor subunits bind Cl- ion in the anion binding site in the ligand binding domain. The dimer is stabilized by the presence of one Cl- ion which binds within the dimer interface.
p-CAMKK1ProteinQ8N5S9 (Uniprot-TrEMBL)
p-S12,S13-CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-S338-BRAF ProteinP15056 (Uniprot-TrEMBL)
p-S338-RAF1ProteinP04049 (Uniprot-TrEMBL)
p-T185,Y187-MAPK1ProteinP28482 (Uniprot-TrEMBL)
p-T286-CAMK2A ProteinQ9UQM7 (Uniprot-TrEMBL)
p-T287-CAMK2B ProteinQ13554 (Uniprot-TrEMBL)
p-T287-CAMK2D ProteinQ13557 (Uniprot-TrEMBL)
p-T287-CAMK2G ProteinQ13555 (Uniprot-TrEMBL)
phospho-CaMK IV CalmodulinComplexREACT_15743 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2GABRA

2GABRB GABRG

GABA		REACT_25130 (Reactome)
3',5'-Cyclic AMPArrowREACT_20564 (Reactome)
ADPArrowREACT_15320 (Reactome)
ADPArrowREACT_18308 (Reactome)
ADPArrowREACT_18320 (Reactome)
ADPArrowREACT_18330 (Reactome)
ADPArrowREACT_18393 (Reactome)
ADPArrowREACT_20503 (Reactome)
ADPArrowREACT_20562 (Reactome)
ADPArrowREACT_20576 (Reactome)
ADPArrowREACT_20578 (Reactome)
ADPArrowREACT_20583 (Reactome)
ADPArrowREACT_20631 (Reactome)
ADPArrowREACT_20635 (Reactome)
ADPArrowREACT_20640 (Reactome)
ADPArrowREACT_20666 (Reactome)
AKAP5ArrowREACT_18393 (Reactome)
AKAP5REACT_18393 (Reactome)
AP2 complexArrowREACT_18330 (Reactome)
AP2 complexREACT_18330 (Reactome)
AP2AArrowREACT_18308 (Reactome)
AP2AREACT_18308 (Reactome)
ATPREACT_15320 (Reactome)
ATPREACT_18308 (Reactome)
ATPREACT_18320 (Reactome)
ATPREACT_18330 (Reactome)
ATPREACT_18393 (Reactome)
ATPREACT_20503 (Reactome)
ATPREACT_20562 (Reactome)
ATPREACT_20564 (Reactome)
ATPREACT_20576 (Reactome)
ATPREACT_20578 (Reactome)
ATPREACT_20583 (Reactome)
ATPREACT_20631 (Reactome)
ATPREACT_20635 (Reactome)
ATPREACT_20640 (Reactome)
ATPREACT_20666 (Reactome)
AcChoREACT_22116 (Reactome)
AcChoREACT_22409 (Reactome)
AcChoREACT_22438 (Reactome)
Activated B-raf complexArrowREACT_20578 (Reactome)
Activated conventional protein kinase CREACT_18308 (Reactome)
Activated conventional protein kinase CREACT_18330 (Reactome)
Active CalmodulinREACT_15339 (Reactome)
Active CalmodulinREACT_20634 (Reactome)
Adenylate cyclase ArrowREACT_15384 (Reactome)
Adenylate cyclase REACT_19222 (Reactome)
ArrowREACT_15335 (Reactome)
ArrowREACT_15495 (Reactome)
CALM1REACT_20670 (Reactome)
CAMK4REACT_15339 (Reactome)
CAMKK1REACT_20635 (Reactome)
CREB1REACT_20503 (Reactome)
CREB1REACT_20576 (Reactome)
CREB1REACT_20583 (Reactome)
CREB1REACT_20666 (Reactome)
Ca impermeable AMPA receptor ligand complexREACT_18434 (Reactome)
Ca impermeable AMPA receptors REACT_18308 (Reactome)
Ca impermeable AMPA receptorsArrowREACT_18308 (Reactome)
Ca impermeable AMPA receptorsArrowREACT_18320 (Reactome)
Ca impermeable AMPA receptorsArrowREACT_18330 (Reactome)
Ca impermeable AMPA receptorsArrowREACT_18434 (Reactome)
Ca impermeable AMPA receptorsArrowREACT_20569 (Reactome)
Ca impermeable AMPA receptorsREACT_18320 (Reactome)
Ca impermeable AMPA receptorsREACT_18330 (Reactome)
Ca impermeable AMPA receptorsREACT_18341 (Reactome)
Ca impermeable AMPA receptorsREACT_18434 (Reactome)
Ca impermeable AMPA receptorsREACT_20500 (Reactome)
Ca impermeable AMPA receptorsREACT_20569 (Reactome)
Ca permeable AMPA receptor ligand complexREACT_18258 (Reactome)
Ca permeable AMPA receptor ligand complexREACT_18378 (Reactome)
Ca permeable AMPA receptorsArrowREACT_18258 (Reactome)
Ca permeable AMPA receptorsArrowREACT_18378 (Reactome)
Ca permeable AMPA receptorsArrowREACT_18393 (Reactome)
Ca permeable AMPA receptorsREACT_18258 (Reactome)
Ca permeable AMPA receptorsREACT_18296 (Reactome)
Ca permeable AMPA receptorsREACT_18378 (Reactome)
Ca permeable AMPA receptorsREACT_18393 (Reactome)
Ca/calmodulin activated Adenylate CyclaseREACT_20564 (Reactome)
Ca2+ArrowREACT_18258 (Reactome)
Ca2+ArrowREACT_20499 (Reactome)
Ca2+ArrowREACT_20564 (Reactome)
Ca2+ArrowREACT_21414 (Reactome)
Ca2+ArrowREACT_22243 (Reactome)
Ca2+ArrowREACT_22354 (Reactome)
Ca2+REACT_18258 (Reactome)
Ca2+REACT_20499 (Reactome)
Ca2+REACT_20564 (Reactome)
Ca2+REACT_20670 (Reactome)
Ca2+REACT_21414 (Reactome)
Ca2+REACT_22243 (Reactome)
Ca2+REACT_22354 (Reactome)
CaMKIIREACT_18393 (Reactome)
CaMKIIREACT_20576 (Reactome)
CaMKIIREACT_20634 (Reactome)
Calmodulin CaMK IVREACT_15320 (Reactome)
Calmodulin CaMK IVREACT_20666 (Reactome)
DLG1ArrowREACT_18393 (Reactome)
DLG1REACT_18393 (Reactome)
EPB41L1ArrowREACT_18393 (Reactome)
EPB41L1REACT_18393 (Reactome)
Edited Kainate Receptor-glutamate complexREACT_21274 (Reactome)
Edited Kainate receptorsArrowREACT_21274 (Reactome)
Edited Kainate receptorsREACT_21274 (Reactome)
Edited Kainate receptorsREACT_21317 (Reactome)
G alpha-olf GDP complexArrowREACT_15384 (Reactome)
G alpha-olf GTPREACT_15435 (Reactome)
G-protein alpha ArrowREACT_15384 (Reactome)
G-protein alpha REACT_15435 (Reactome)
G-protein alpha REACT_19222 (Reactome)
G-protein beta-gamma PLC beta 1/2/3REACT_21309 (Reactome)
GABA B receptor G-protein beta-gamma and Kir3 channel complexREACT_25066 (Reactome)
GABAB receptorREACT_18291 (Reactome)
GABAREACT_18291 (Reactome)
GABRR pentamer GABAREACT_25391 (Reactome)
GRIK 3 homomerREACT_21255 (Reactome)
GRIK3 homomer glutamate complexREACT_21309 (Reactome)
GRIP1/GRIP2ArrowREACT_18308 (Reactome)
GRIP1/GRIP2ArrowREACT_18320 (Reactome)
GRIP1/GRIP2ArrowREACT_18330 (Reactome)
GRIP1/GRIP2REACT_18308 (Reactome)
GRIP1/GRIP2REACT_18320 (Reactome)
GRIP1/GRIP2REACT_18330 (Reactome)
GluArrowREACT_18258 (Reactome)
GluArrowREACT_18378 (Reactome)
GluArrowREACT_18434 (Reactome)
GluArrowREACT_20499 (Reactome)
GluArrowREACT_21274 (Reactome)
GluArrowREACT_21414 (Reactome)
GluREACT_18296 (Reactome)
GluREACT_18341 (Reactome)
GluREACT_20499 (Reactome)
GluREACT_20601 (Reactome)
GluREACT_21255 (Reactome)
GluREACT_21269 (Reactome)
GluREACT_21317 (Reactome)
GlyArrowREACT_20499 (Reactome)
GlyREACT_20499 (Reactome)
GlyREACT_20601 (Reactome)
Highly calcium permeable nicotinic acetylcholine receptorsArrowREACT_22354 (Reactome)
Highly calcium permeable nicotinic acetylcholine receptorsREACT_22354 (Reactome)
Highly calcium permeable nicotinic acetylcholine receptorsREACT_22409 (Reactome)
Highly calcium permeable postsynaptic nicotinic acetylcholine receptorsArrowREACT_22243 (Reactome)
Highly calcium permeable postsynaptic nicotinic acetylcholine receptorsREACT_22116 (Reactome)
Highly calcium permeable postsynaptic nicotinic acetylcholine receptorsREACT_22243 (Reactome)
Highly sodium permeable nicotinic acetylcholine receptorsArrowREACT_22390 (Reactome)
Highly sodium permeable nicotinic acetylcholine receptorsREACT_22390 (Reactome)
Highly sodium permeable nicotinic acetylcholine receptorsREACT_22438 (Reactome)
Kainate receptor-glutamate complexREACT_21414 (Reactome)
MAPK1REACT_20631 (Reactome)
MYO6ArrowREACT_18393 (Reactome)
MYO6REACT_18393 (Reactome)
Mg2+ArrowREACT_20500 (Reactome)
NMDA receptor complexArrowREACT_20499 (Reactome)
NMDA receptor complexArrowREACT_20500 (Reactome)
NMDA receptor complexREACT_20601 (Reactome)
NMDA receptor ligand complexREACT_20499 (Reactome)
NMDA receptor ligand complexREACT_20566 (Reactome)
NMDA receptor ligand complexREACT_20670 (Reactome)
NSFREACT_18320 (Reactome)
Na+ArrowREACT_18378 (Reactome)
Na+ArrowREACT_18434 (Reactome)
Na+ArrowREACT_20569 (Reactome)
Na+ArrowREACT_21274 (Reactome)
Na+ArrowREACT_22390 (Reactome)
Na+REACT_18378 (Reactome)
Na+REACT_18434 (Reactome)
Na+REACT_20569 (Reactome)
Na+REACT_21274 (Reactome)
Na+REACT_22390 (Reactome)
PDPK1REACT_20640 (Reactome)
PICK1ArrowREACT_18308 (Reactome)
PICK1ArrowREACT_18320 (Reactome)
PICK1ArrowREACT_18330 (Reactome)
PICK1REACT_18308 (Reactome)
PICK1REACT_18320 (Reactome)
PICK1REACT_18330 (Reactome)
PPiArrowREACT_20564 (Reactome)
PRKACBREACT_20583 (Reactome)
PhosphoArrowREACT_20562 (Reactome)
PhosphoArrowREACT_20640 (Reactome)
PhosphoREACT_20503 (Reactome)
PhosphoREACT_20640 (Reactome)
PiArrowREACT_15335 (Reactome)
PiArrowREACT_15495 (Reactome)
PiArrowREACT_18308 (Reactome)
PiArrowREACT_18330 (Reactome)
PiArrowREACT_18393 (Reactome)
PiREACT_18320 (Reactome)
REACT_15320 (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.
REACT_15332 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
REACT_15335 (Reactome)
REACT_15339 (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.
REACT_15384 (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.
REACT_15435 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
REACT_15495 (Reactome)
REACT_18258 (Reactome) Each AMPA receptor subunit binds one glutamate molecule in the ligand binding site in the N terminus. Each receptor is capable of binding four glutamate molecule, however, channel opens when two sites are occupied by the ligand and the current increases with increased ligand binding. Ca permeable AMPA receptors containing homomers of GluR1 or heteromers containing GluR1, GluR3 and GluR4 conduct Ca upon glutamate or agonist namely AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding. Calcium permeable AMPA receptors conduct Ca and other cations such as Na. The inonic flux leads to Ca or Na currents that leads to either increase in the intracellular Ca concentration leading to further Ca-dependent signaling or increase in depolarization that opens voltage gated channels such as NMDA receptors that require both membrane depolarization and glutamate binding for activation.
REACT_18291 (Reactome) Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its effects through two ligand-gated channels and a the GPCR GABAB (Kaupmann K et al, 1998), which acts through G proteins to regulate potassium and calcium channels. GABAB can only bind GABA once it forms a heterodimer composed of the GABABR1 and GABABR2 receptors (White JH et al, 1998). The effects of this dimer are mediated by coupling to the G protein alpha i subunit, which inhibits adenylyl cyclase.
REACT_18296 (Reactome) AMPA receptors bind glutamate, released in the synaptic cleft by the presynaptic cell, in the ligand binding region in the N terminal domain.
REACT_18308 (Reactome) GluR2 containing AMPA receptors are constitutively recycled between the endosome membrane and the plasma membrane. GRIP and PICK compete for the binding to the C tail of GluR2. Once the GluR2 containing AMPA receptors are in the plasmamembrane, phosphorylation of GluR2 at S880 by PKC causes disruption of GRIP interaction, but not PICK interaction which facilitates internalization of GluR2 containing AMPA receptors into endosomes.
REACT_18320 (Reactome) Constitutively recycling GluR2 containing AMPA receptors in the plasmamembrane are stabilized by the action of NSF ATPase activity which disassociates PICK from GluR2 thereby retaining AMPA receptors in the plasmamembrane.
REACT_18330 (Reactome) GluR2 containing AMPA receptors are trafficked to the plasmamembrane by the activation of Ca activated PKC that binds PICK.The PICK interaction delivers GluR2 containing AMPA receptors to the Plasmamembrane. This reaction is a part of constitutive recycling of AMPA receptor that delivers the AMPA receptors from the endosome to the plasmamembrane and back to endosome from the plasmamembrane.
REACT_18341 (Reactome) AMPA receptors bind glutamate, released in the synaptic cleft by the presynaptic cell, in the ligand binding region in the N terminal domain.
REACT_18378 (Reactome) Each AMPA receptor subunit binds one glutamate molecule in the ligand binding site in the N terminus. Each receptor is capable of binding four glutamate molecule, however, channel opens when two sites are occupied by the ligand and the current increases with increased ligand binding. Ca permeable AMPA receptors containing homomers of GluR1 or heteromers containing GluR1, GluR3 and GluR4 conduct Ca upon glutamate or agonist namely AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding. Calcium permeable AMPA receptors conduct Ca and other cations such as Na. The inonic flux leads to Ca or Na currents that leads to either increase in the intracellular Ca concentration leading to further Ca-dependent signaling or increase in depolarization that opens voltage gated channels such as NMDA receptors that require both membrane depolarization and glutamate binding for activation.
REACT_18393 (Reactome) GluR1-containing AMPA receptors are delivered to the synapses in an activity dependent manner. GluR1 trafficking is controlled by protein- protein interactions with 4.1N/G protein, SAP97 and by intricate regulation of phosphorylation of GluR1 at several phosphorylation sites in the C tail. GluR1 has four phosphorylation sites; serine 818 (S818) is phosphorylated by PKC, necessary for LTP, serine 831 (S831) is phosphorylated by CaMKII and increases the delivery of receptors to the synapse and also increases their single channel conductance, Threonine (T840) is implicated in LTP and serine 845 (S845) phosphorylated by PKA regulates open channel probability and also by cGKII, a cyclic GMP activated kinase, that increases the surface expression of GluR1. GluR1 insertion into synapse by CaMKII may induce LTP. CaMKII is a Ca/calmodulin dependent kinase that is activated upon increases in the Ca ion concentration during postsynaptic activity through NMDA receptors. The increase in GluR1-containing AMPA receptor population at the synapse results in enhancement of excitatory post synaptic potential (EPSC) which forms the basis of Long term potentiation (LTP). LTP is one form of synaptic plasticity that is involved in memory and learning. The increase in the GluR1 containing AMPA receptors and their activity leads to rise in intracellular Ca which induces signaling pathways that in turn promote switch in the type of AMPA receptors (Ca impermeable) thereby limiting the Ca increase and preventing cell death.
REACT_18434 (Reactome) Each AMPA receptor subunit binds one glutamate molecule in the ligand binding site in the N terminus. Each receptor is capable of binding four glutamate molecules however, channel opens when two sites are occupied by the ligand and the current increases with increased ligand binding. Ca impermeable AMPA receptors containing GluR2 subunit conduct Na currents upon activation by either glutamate binding or agonist, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding. The Na currents mainly lead to depolarization of the membrane leading to activation of voltage gated channels such as NMDA receptors that require both agonist binding and depolarization for their activation.
REACT_19222 (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.
REACT_20499 (Reactome) NMDA receptors are activated upon binding of two ligands, glutamate and glycine.
The activation leads to Ca2+ influx into the post-synaptic cell. The local rise in the Ca2+ ion concentration further leads to activation of several Ca2+ dependent pathways leading to long term changes in the synapse.
REACT_20500 (Reactome) NMDA receptors are activated in a two step mechanism; first by the removal of the voltage dependent Mg2+ block and then by the ligand dependent activation of the unblocked NMDA receptor. At resting membrane potential NMDA receptors can not be activated by ligand alone due to the presence of Mg2+ ion in the pore of the channel. Due to the activation of other membrane resident channels that allow the influx of Na+ the membrane is depolarized which triggers the removal of Mg2+ form the NMDA receptor pore. Once the Mg2+ is expelled NMDA receptors are ready to be activated by the agonist (glutamate) and the co-agonist (glycine).
REACT_20503 (Reactome) CREB is phosphorylated at serine 133 by any of the four isoforms of ribosomal S6 kinase.
REACT_20562 (Reactome) Activated MAPK/ERK activates RSK in its C terminal kinase domain by sequentially phosphorylating T573, S363 and 380.
REACT_20564 (Reactome) Ca2+ fluxes through NMDA receptors in the post-synaptic neuron facilitate binding of Ca2+/Calmodulin to adenylate cyclase type 1, 3 or 8, resulting in its activation. Once activated, cAMP is produced which further activates PKA.
REACT_20566 (Reactome) CaMKII gets activated upon Ca2+ influx through the NMDA receptor and moves from plasma membrane to cytoplasm and then nucleus where it phosphorylates CREB at serine 133.
REACT_20569 (Reactome) Membrane depolarization occurs due to glutamate dependent activation of Ca-impermeable AMPA receptors, which permit the influx of Na+ ions. The depolarization triggers the removal of Mg2+ from the NMDA receptor pore to facilitate its activation. Therefore activation of AMPA receptors by glutamate precedes activation of NMDA receptors.
REACT_20576 (Reactome) CaMKII is an important regulator of neuronal plasticity. CaMKII shows distinct subcellular localization and acts quickly in a spatio-temporal manner. CaMKII shows fast synaptic localization upon synaptic activity and also nuclear localization, where it phosphorylates CREB at serine 133 to activate transcription of set of genes that results in long lasting structural changes at the synapse.
REACT_20578 (Reactome) Raf is a downstream effector of ras. Raf is activated upon phosphorylation at S338, oligomerization and membrane localization. Membrane localization is facilitated by ras. Interaction of ras with raf is a necessary step but not sufficient for raf activation. Other unknown protein partner interactions are required for raf activation. Raf further activates MAP kinase.
REACT_20579 (Reactome) Nuclear targeting of CaMKII depends on several factors including the phosphorylation in the regulatory domain of CaMKII and induction of other signal transduction pathways.
REACT_20583 (Reactome) Protein kinase A has two regulatory subunits and two catalytic subunits which are held together to form the holoenzyme and is activated upon binding of cAMP within the regulatory subunits. Once cAMP binds the regulatory subunits, the catalytic subunits are released to carry out phosphorylation of CREB at serine133.
REACT_20601 (Reactome) NMDA receptors require binding of two ligands; the agonist, glutamate and co-agonist, glycine. The N terminal extracellular ligand binding domain in NR1 subunits binds co-agonist glycine and the N terminal extracellular ligand binding domain in NR2 binds glutamate.
REACT_20612 (Reactome) Binding of RasGRF to Ca2+/Calmodulin in the presence of high Ca2+ leads to the activation of Ras. Activation of Ras involves the exchange of GDP for GTP.
REACT_20631 (Reactome) MAPK/ERK is phosphorylated at threonine 185 and tyrosine 187 by membrane associated activated raf kianse leading to the activation of MAPK/ERK kinase. The activated MAPK/ERK in turn activates ribosomal S6 kinase.
REACT_20634 (Reactome) CaMKII is fully activated upon Ca2+/Calmodulin binding. In addition to Ca2+/Calmodulin activation, CaMKII undergoes multiple autophosphorylation events leading Ca2+/Calmodulin independent activity of the enzyme.
REACT_20635 (Reactome) CaMKK is fully activated upon binding Ca2+/Calmodulin after intracellular Ca2+ levels increase. Once CaMKK binds Ca2+/Calmodulin it autophosphorylates, resulting in activation. CaMKK is negatively regulated by phosphorylation of S74 and T108 by PKA. Once activated CaMKK phosphorylates CaMKIV in a Ca2+/Calmodulin dependent manner.
REACT_20640 (Reactome) PDK1 activates ribosomal S6 kinase (RSK) by phosphorylating S221. The binding site for PDK1 on RSK is available after RSK phosphorylation by MAPK/ERK. PDK1 is present in the activated form at the plasma membrane where the phosphorylation occurs. The activation of RSK occurs in the cytoplasm, plasma membrane and in the nucleus where it finally activates CREB by phosphorylation.
REACT_20666 (Reactome) Activated CaMKIV phosphorylates CREB at S133 thereby initiating the transcription of CREB regulated set of genes leading to protein synthesis and long lasting changes that underlie synaptic plasticity.
REACT_20670 (Reactome) RASGRF is activated upon binding of Ca2+/Calmodulin after Ca2+ influx through the NMDA receptor.
REACT_21255 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
REACT_21269 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
REACT_21274 (Reactome) The activation of Kainate receptors by glutamate in the postsynaptic neuron leads to influx of Na+ ions resulting in depolarization of the postsynaptic membrane.
REACT_21309 (Reactome) Kainate receptor activation activates G protein coupled receptors involving the release of Ca2+ from the intracellular stores. This activity of Kainate receptors is independent of ionic influx and regulates both glutamate release by the pyramidal neurons and gama-aminobutyric acid release by the internuerons.
REACT_21317 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
REACT_21414 (Reactome) Kainate receptors that are assembled with subunits GRIK1-5, are Ca2+ permeable if GRIK1 and GRIK2 are not edited at the Q/R or other sites.
These channels permit Ca2+ upon activation by glutamate or other agonists.
REACT_22116 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
REACT_22243 (Reactome) Acetylcholine binding activates postsynaptic acetylchloine receptors that show Ca2+ currents which facilitate the process of long term potentiation (LTP).
REACT_22354 (Reactome) Nicotinic acetylcholine receptors are activated upon ligand binding which opens the acetylcholine channels and permits Ca2+ and Na+ ion influx depending on the subunit composition and stoichiometry of the subunits. The ratio of Ca2+ to Na+ ion influx varies making the receptors either highly Na+ permeable or Ca2+ permeable.
REACT_22390 (Reactome) Nicotinic acetylcholine receptors containing aplha4(2) beta2 (3) and alpha3(2) beta4(3) are selectively highly Na+ permeable upon activation of these receptors by acetylcholine.
REACT_22409 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
REACT_22438 (Reactome) Nicotinic acetylcholine receptors bind two molecules of ligand, acetylcholine, in the alpha beta interface in receptors containing heteromeric subunits or in the interface of 2 aplha subunits in receptors containing homomeric subunits.
REACT_25066 (Reactome) Binding of G beta gamma activates the GIRK/Kir3 channels that allow the efflux of K+ out of the cell resulting in a hyperpolarized membrane potential. This negative membrane potential prevents the activation of voltage dependent Ca2+ channels.
REACT_25130 (Reactome) The GABA(A) receptor (GABR) family belongs to the ligand-gated ion channel superfamily (LGIC). Its endogenous ligand is gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. There are six alpha subunits (GABRA) (Garrett et al. 1988, Schofield et al. 1989, Hadingham et al. 1993, Edenberg et al. 2004, Hadingham et al. 1993, Yang et al. 1995, Wingrove et al. 1992, Hadingham et al. 1996), three beta subunits (GABRB) (Schofield et al. 1989, Hadingham et al. 1993, Wagstaff et al. 1991) and 2 gamma subunits (GABRG) (Khan et al. 1993, Hadingham et al. 1995) characterized. GABA(A) functions as a heteropentamer, the most common structure being 2 alpha subunits, 2 beta subunits and a gamma subunit (2GABRA:2GABRB:GABRG). Upon binding of GABA, this complex conducts chloride ions through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by reducing the chances of a successful action potential occurring.
REACT_25391 (Reactome) The GABA(A)-rho receptor (GABRR) is expressed in many areas of the brain, but in contrast to other GABA(A) receptors, has especially high expression in the retina. It is functional as a homopentamer and is permeable to chloride ions when GABA binds to it (Cutting et al. 1991, Cutting et al. 1992, Bailey et al. 1990).
RasGRF Ca/calmodulinREACT_20612 (Reactome)
RasGRFREACT_20670 (Reactome)
RasGTP-B raf compexREACT_20578 (Reactome)
Ribosomal S6 kinaseREACT_20562 (Reactome)
TARP-PSD95-Mdm2ArrowREACT_18393 (Reactome)
TARP-PSD95-Mdm2REACT_18393 (Reactome)
kaiante ReceptorsArrowREACT_21414 (Reactome)
kaiante ReceptorsREACT_21269 (Reactome)
kaiante ReceptorsREACT_21414 (Reactome)
p-CAMKK1ArrowREACT_20635 (Reactome)
p-S133-CREB1ArrowREACT_20503 (Reactome)
p-S133-CREB1ArrowREACT_20576 (Reactome)
p-S133-CREB1ArrowREACT_20583 (Reactome)
p-S133-CREB1ArrowREACT_20666 (Reactome)
p-S338-RAF1REACT_20631 (Reactome)
p-T185,Y187-MAPK1ArrowREACT_20631 (Reactome)
p-T185,Y187-MAPK1REACT_20562 (Reactome)
phospho-CaMK IV CalmodulinArrowREACT_15320 (Reactome)
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