Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)

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44, 48163347, 65199575640, 451751192641, 615611347, 131841, 61438202712, 215730, 31, 42, 5024576714, 22, 23, 26, 28...44, 48346056395985, 66136376429, 32, 63253410, 15, 46, 55113CaMKII G-protein alpha NMDA receptor complex NMDA receptor ligand complex NR2 subunits RasGRFCa/calmodulin acetylcholine receptor subunits G-protein alpha G-protein alpha CaMKII active Calmodulin 0-acteylcholine bound to calcium permeable nictonic acteylcholine receptor complex CaMKII delta/gamma subunits Adenylate cyclase AMPA receptors containing GluR2 Highly sodium permeable nicotinic acetylcholine receptors NMDA receptor complex CaMKII delta/gamma subunits NR2 subunits CaMKII CaMKII alpha/beta subunits G-protein Gamma subunits Acetylcholine Receptor alpha4AMPA receptors containing GluR1 and GluR2 Adenylate cyclase NR2 interacting proteins Acetylcholine receptor alpha6 beta3 beta4 NMDA receptor ligand complex PLC-beta 1/2/3 G-protein beta-gammaPLC beta 1/2/3 GluR1 receptors RasGRF G-protein alpha G-protein alpha GABRR1-3 Gamma subunit of VGCC CaMKII alpha/beta subunits CaMKII GRIK 3 homomer AMPA receptors containing GluR2 GABAB receptor GRIK1 homomer Ca impermeable AMPA receptor ligand complex R-Ras-GTP GRIK2 interacting proteins G-protein alpha Edited GRIK2 homomer G-protein alpha O-acteylcholine bound to calcium permeable postsynaptic nicotinic acetylcholine receptors Ca impermeable AMPA receptors NR2 subunits G-protein alpha G-protein alpha NMDA receptor-Mg complex PLC-beta 1/2/3 GRIK 3 homomer CaMKII Edited GRIK1 homomer GABRGs Acetylcholine receptors alpha2Kirx.x that interacts with Kir2.1 Acetylcholine receptor alpha3GRIK5 heteromer with GRIk1/2/3 Highly calcium permeable postsynaptic nicotinic acetylcholine receptors Kir2.1Kirx.x heterotetramer Edited Kainate receptors acetylcholine receptor alpha6 aplha4 beta3 GABAB receptor Ca permeable AMPA receptors G alpha-olfGTP G-protein beta-gamma subunits CaMKII subunits delta/gamma GABRA2ARHGEF9 RasGTP-B raf compex CaMKII GRIK 3 homomer AMPA receptors containing GluR2 Acetylcholine Receptor CaMKII delta/gamma subunits NR1 interacting proteins Active Calmodulin TARP-PSD95-Mdm2 CaMKII gamma/delta subunits GRIK1 and 2 heterotetramer NR1 interacting proteins Active Calmodulin active Calmodulin NR2 interacting proteins Kainate receptor-glutamate complex GABAB receptorGABA NR1 interacting proteins AMPA receptors containing GluR1 and GluR2 Kir4.2Kir5.1 heterotetramer NMDA receptor ligand complex NR2 interacting proteins Delta, epsilon, gamma subunits of acetylcholine receptor GRIK1, GRIK2, GRIK3 NR2 subunits AP2A GRIK4 interacting proteins Active Calmodulin CaMKII alpha/beta subunits Acetylcholine Receptors alpha4GABRBs CalmodulinCaMK IV NR2 subunits TARP-PSD95-Mdm2 Edited GRIK2 homomer NR2 interacting proteins CaMKII CaMKII delta/gamma subunits G alpha-olfGTP Edited Kainate Receptor-glutamate complex G alpha-olfGDP complex Acetylcholine Receptor CaMKII delta/gamma subunits Adenylate cyclase GRIK3 homomer glutamate complex Edited GRIK1 and GRIK2 heteroteramer G alpha-olfGDP complex RasGTP GRIA3,GRIA4 Acetylcholine receptor alpha3-beta4-apha5 Acetylcholine receptor containing alpha7 subunit Adenylate cyclase CaMKII delta/gamma subunits GABAB receptorGABA Adenylate cyclase CaMKII-Ca2+/Calmodulin NR1 interacting proteins NMDA receptor complex GRIK 3 homomer CaMKII subunits alpha/beta Edited Kainate receptors RasGRF Kir heterotetramers GABA B receptor G-protein beta-gamma and Kir3 channel complex 2GABRA2GABRBGABRGGABA AP2 complex CaMKII alpha/beta subunits Kir3 heterotetramer G-protein alpha CaMKII Adenylate cyclase G-protein alpha nucleoplasmNMDA receptor complex Adenylate cyclase Adenylate cyclase CaMKII alpha/beta GRIK3 homomer glutamate complex CaMKII alpha/beta subunits CaMKII delta/gamma subunits GRIA3,GRIA4 Adenylate cyclase Activated B-raf complex CalmodulinCaMK IV GABAB receptor G-protein alpha NR1 interacting proteins CaMKII delta/gamma CaMKII alpha/beta subunits G-protein beta-gammaPLC beta 1/2/3 Ca impermeable AMPA receptors kaiante Receptors phospho-CaMK IVCalmodulin cytosolGABRR pentamerGABA NR2 interacting proteins GRIK4 heteromer with GRIK1/2/3 G-protein alpha Acetylcholine receptor alpha3-beta2-aplha5 CaMKII alpha/beta subunits Adenylate cyclase Gamma subunit of VGCC CaMKII alpha/beta subunits G-protein alpha Acetylcholine receptor alpha3-beta4 O-Acetylcholine bound to Acetylcholine receptor AMPA receptors containing GluR2 GABRAs G-protein alpha Kir3.x channels Kir4.1Kir5.1 heterotetramer R-Ras-GTP CaMKII G-protein beta subunits G alpha-olfGDP complex Ca permeable AMPA receptor ligand complex Edited GRIK1 homomer Highly calcium permeable nicotinic acetylcholine receptors endocytic vesicle membraneKainate receptor-glutamate-Gprotein complex G-protein beta-gamma complex Edited GRIK1 and GRIK2 heteroteramer GABA B receptor G-protein beta-gamma complex GRIA3,GRIA4 RasGDP NMDA receptor complex active Calmodulin CaMKII AMPA receptors containing GluR1 G-protein beta-gamma complex GRIK 2 homomer Ca2+GRIN2A Cl- ADCY1 ADCY8 RASGRF2 Gly CALM1 GNAI2Ca impermeable AMPA receptorsADCY9 Mg2+ADCY5 Glu Ca2+GNAT3Mg2+ GNALGRIN2A p-T286-CAMK2A AKAP9 GNG5 GABA PLCB1 G alpha-olfGTPGRIA1 Ca impermeable AMPA receptor ligand complexADCY4 ADCY4 DLG4 GRIA3 Ca2+ ADCY9 p-T287-CAMK2G KCNJ3 GRIN2CAcCho PLCB2 GRIN2B DLG1 CHRNG PRKACBGABRB1 ACTN2 GABBR2 Glyp-T287-CAMK2D GTP ADCY4 ADCY2 Glyp-T287-CAMK2B K+KCNJ16 NEFL p-T287-CAMK2D 0-acteylcholine bound to calcium permeable nictonic acteylcholine receptor complex2GABRA2GABRBGABRGGABAGlu GNGT1 ADCY4 ADPCaMKIIGRIN1 GRIK4 GRIA3 CALM1 ADCY1 GABBR1 Ca2+ADPPiKCNJ15 GABA B receptor G-protein beta-gamma and Kir3 channel complexGABA GRIN2D Activated B-raf complexGRIN2A GABRG3 GABA AP2M1-2 ADCY9 Ca2+Ca2+GNG3 CACNG8 AKAP5GNAT3ADP AcChoK+GRIA4 DLG4 p-T287-CAMK2G GNAT3ADPGRIN2B GNG12 CHRNA1 CHRNA4 Gly GNAI1GABRA5 ADPp-T286-CAMK2A Na+MYO6GNAI3p-T287-CAMK2G ADCY2 GABRA6 ACTN2 CHRNB3 Cl- ADPCa2+ phospho-CaMK IVCalmodulinp-T287-CAMK2B RasGDPGABRA3 GNG4 GDP GNALPiAKAP9 CALM1 EPB41L1ATPp-T287-CAMK2D CREB1TARP-PSD95-Mdm2p-T287-CAMK2G Edited Kainate Receptor-glutamate complexADCY1 Mg2+ CREB1p-T185,Y187-MAPK1PiADCY3 Ca2+DLG3 ATPGRIK3 NMDA receptor ligand complexGABA Ca impermeable AMPA receptorsADPRasGRFCa/calmodulinAP2S1-1 GRIK1 GDP Cl- ADCY5 G-protein beta-gammaPLC beta 1/2/3CHRNB4 GNAT3GRIK3 Mg2+ G alpha-olfGDP complexARHGEF9 AKAP9 ADCY1 GTP CAMKK1Glu NSFp-S338-RAF1DLG1RASGRF1 CACNG2 AP2A1 GNG8RRAS PLCB3ATPGTP p-T287-CAMK2D AKAP9 ATPGlup-S133-CREB1KCNJ4 GRIN2B GNGT2 GNAT3GTP GRIN2D Mg2+ ATPGNB1 GTP GTP Ca2+CHRND DLG4 CHRNA2 GDP GNALPhosphoCa2+RASGRF2 Na+NEFL RasGTP-B raf compexCHRNB2 GABRG2 ADPGRIP1/GRIP2ADCY1 GNAI1ADCY8 PDPK1GNB2 GluHRASEdited Kainate receptorsKCNJ10 Ca permeable AMPA receptor ligand complexGTP CHRNA7 ADCY9 ADCY8 p-T287-CAMK2G GDP AP2A2-3 AP2 complexDLG4 Glu ADCY2 GluADPGRIA4 ADP GluCalmodulinCaMK IVBRAF ADCY6 GNAI1CHRNB2 p-T287-CAMK2B RasGRFHighly calcium permeable nicotinic acetylcholine receptorsGluDLG4 ADCY3 Edited GRIK 1 GDP GTP Mg2+ PICK1ATPGRIP1/GRIP2G-protein alpha AP2AKCNJ12 PLCB2 CHRNA5 O-Acetylcholine bound to Acetylcholine receptorADCY7 Ca2+Na+p-T287-CAMK2D ADCY8 Ca impermeable AMPA receptorsPPiGNAI1CHRNB4 CACNG4 GRIN2CCa2+ Ca permeable AMPA receptorsp-T286-CAMK2A 3',5'-Cyclic AMPGRIA2 ADPDLG4 ADCY5 GABRR pentamerGABAp-T287-CAMK2G p-T287-CAMK2B p-T286-CAMK2A MYO6GRIP1/GRIP2GABAB receptorCa/calmodulin activated Adenylate CyclaseCALM1p-T287-CAMK2B GNAI2GRIN2B PLCB1 CACNG8 Edited GRIK 1 Cl-ADCY2 CaMKIICHRNB4 Cl- Glu CACNG4 GABRR1 KCNJ2 GABAATPTARP-PSD95-Mdm2DLG4 p-T287-CAMK2D p-S338-BRAF GABRA2 Edited GRIK2 GRIN2A p-S12,S13-CAMK4 Ca impermeable AMPA receptors GRIN2Cp-T286-CAMK2A EPB41L1CHRNE GNB3 kaiante ReceptorsCaMKII-Ca2+/CalmodulinCHRNA6 p-T287-CAMK2D CHRNA3 p-T286-CAMK2A Ribosomal S6 kinaseHRASCACNG2 GNG2 ADPHighly calcium permeable postsynaptic nicotinic acetylcholine receptorsGRIK3 AcCho Glu ADCY6 p-T287-CAMK2D p-T286-CAMK2A NMDA receptor-Mg complexGRIN2CGDP CACNG3 ADCY5 GRIA3 p-T287-CAMK2G GRIN1 CHRNA6 GABRB3 NMDA receptor complexCAMK4 ACTN2 ATPGNAI1PICK1ADCY6 Highly sodium permeable nicotinic acetylcholine receptorsKainate receptor-glutamate-Gprotein complexp-T287-CAMK2D RasGTPp-T287-CAMK2B Ca2+ATPCaMKIIMDM2 GNAI2CHRNA3 GRIK3 CHRNA4 p-T287-CAMK2D ADCY4 CALM1 ADCY6 GRIA2 GABRA4 Adenylate cyclase p-T287-CAMK2B GABAB receptorGABAGABBR1 Mg2+ Glu CHRNA5 Edited GRIK2 Kainate receptor-glutamate complexCa2+GNAI3GRIN2D p-T286-CAMK2A Active CalmodulinNa+GNAI2NEFL AKAP5ACTN2 ADCY8 ATPNEFL GRIN2CCa2+ PiGRIN2B G-protein alpha GluAKAP9 GABRB2 p-T287-CAMK2G DLG4 Cl- GNG7 GRIN2D p-T287-CAMK2B Cl- GRIK 3 homomerGRIN2A CALM1 ADCY2 CHRNA9 CHRNA2 CHRNA3 CACNG3 Gly CAMK4Na+ADCY7 RASGRF1 GNAI2CalmodulinCaMK IVGRIK2 ADCY9 CHRNA4 ATPp-CAMKK1ADPCHRNA1 Cl-p-T287-CAMK2B NMDA receptor ligand complexNa+PhosphoGNG10 p-T287-CAMK2B ATPGRIA1 p-T287-CAMK2G GluADPADCY6 GNAI2ATPADCY3 GRIA4 Ca impermeable AMPA receptorsAP2B1-1 GABRA1 ADCY7 Ca2+ CAMK4 PhosphoCALM1 GRIA1 CHRNB2 AcCho PiCa2+ p-T286-CAMK2A Ca permeable AMPA receptorsGRIN1 GNAI3ADCY7 GTP Glu GNAI3GNAT3KCNJ5 GRIN2D GNAI3Na+O-acteylcholine bound to calcium permeable postsynaptic nicotinic acetylcholine receptorsKCNJ6 GABRR2 ACTN2 GNAI3GRIK3 homomer glutamate complexCALM1 PICK1GABRR3 G-protein alpha GNALRRAS GNALADCY3 p-T287-CAMK2G KCNJ9 NEFL MDM2 GABBR2 ADCY5 CHRNB3 DLG1GRIN1 CaMKIINCALD p-T286-CAMK2A GABBR1 GRIN1 Glu GRIK5 ADCY7 MAPK1Activated conventional protein kinase CADCY3 PLCB3GNAI1GABBR2 49432


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

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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		mim-catalysisREACT_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 Cmim-catalysisREACT_18308 (Reactome)
Activated conventional protein kinase Cmim-catalysisREACT_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)
CAMKK1mim-catalysisREACT_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_20569 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisREACT_18434 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisREACT_20500 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisREACT_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_18296 (Reactome)
Ca permeable AMPA receptorsREACT_18393 (Reactome)
Ca permeable AMPA receptorsmim-catalysisREACT_18258 (Reactome)
Ca permeable AMPA receptorsmim-catalysisREACT_18378 (Reactome)
Ca/calmodulin activated Adenylate Cyclasemim-catalysisREACT_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_20634 (Reactome)
CaMKIImim-catalysisREACT_18393 (Reactome)
CaMKIImim-catalysisREACT_20576 (Reactome)
CaMKIImim-catalysisREACT_20634 (Reactome)
Calmodulin CaMK IVREACT_15320 (Reactome)
Calmodulin CaMK IVmim-catalysisREACT_15320 (Reactome)
Calmodulin CaMK IVmim-catalysisREACT_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_21317 (Reactome)
Edited Kainate receptorsmim-catalysisREACT_21274 (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 complexmim-catalysisREACT_25066 (Reactome)
GABAB receptorREACT_18291 (Reactome)
GABAREACT_18291 (Reactome)
GABRR pentamer GABAmim-catalysisREACT_25391 (Reactome)
GRIK 3 homomerREACT_21255 (Reactome)
GRIK3 homomer glutamate complexREACT_21309 (Reactome)
GRIK3 homomer glutamate complexmim-catalysisREACT_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 nicotinic acetylcholine receptorsmim-catalysisREACT_22354 (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 calcium permeable postsynaptic nicotinic acetylcholine receptorsmim-catalysisREACT_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)
Highly sodium permeable nicotinic acetylcholine receptorsmim-catalysisREACT_22390 (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_20670 (Reactome)
NMDA receptor ligand complexmim-catalysisREACT_20499 (Reactome)
NMDA receptor ligand complexmim-catalysisREACT_20566 (Reactome)
NMDA receptor ligand complexmim-catalysisREACT_20670 (Reactome)
NSFmim-catalysisREACT_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)
PDPK1mim-catalysisREACT_20640 (Reactome)
PICK1ArrowREACT_18308 (Reactome)
PICK1ArrowREACT_18320 (Reactome)
PICK1ArrowREACT_18330 (Reactome)
PICK1REACT_18308 (Reactome)
PICK1REACT_18320 (Reactome)
PICK1REACT_18330 (Reactome)
PPiArrowREACT_20564 (Reactome)
PRKACBmim-catalysisREACT_20583 (Reactome)
PhosphoArrowREACT_20562 (Reactome)
PhosphoArrowREACT_20640 (Reactome)
PhosphoREACT_20640 (Reactome)
Phosphomim-catalysisREACT_20503 (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) 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).
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) 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).
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/calmodulinmim-catalysisREACT_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 Receptorsmim-catalysisREACT_21414 (Reactome)
mim-catalysisREACT_15335 (Reactome)
mim-catalysisREACT_15495 (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-RAF1mim-catalysisREACT_20631 (Reactome)
p-T185,Y187-MAPK1ArrowREACT_20631 (Reactome)
p-T185,Y187-MAPK1mim-catalysisREACT_20562 (Reactome)
phospho-CaMK IV CalmodulinArrowREACT_15320 (Reactome)
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