Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)

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118, 22, 27, 33, 36...6, 10, 15, 19, 543017, 34, 51143, 29582131, 4557161813, 46, 49, 663550, 552659, 41562672130235843434181, 2524, 32446258692043184731, 45532867484250, 5537, 63305238endocytic vesicle membranenucleoplasmcytosolp-T287-CAMK2D GNAI3 NSFPhospho(S221,S363,S380,T573)- ribosomal S6 kinaseGABRB1 KCNJ15 GRIN2A ADCY2 Ca2+Ras:GDPGABAB receptorGABRA6 PiGNGT1 L-Glu GlyGABBR1 GABRA1 GNG10 PICK1ACTN2 AcChoADCY4 ATPG-protein alpha(i):GDPPLCB1 GRIN2B GNGT2 KCNJ4 ARHGEF9 p-T287-CAMK2G ATPGTP AKAP9 Highly sodiumpermeable nicotinicacetylcholinereceptorsPICK1Calmodulin:CaMK IVp-T287-CAMK2D ADCY9 ADCY2 p-T287-CAMK2G p-T287-CAMK2G RASGRF1 CAMK2 heteromerCALM1 GRIN2A Ca2+GRIN2B PRKACB-like proteinsPLCB3 GRIA2 GTP p-T286-CAMK2A GABRG3 ATPADCY3 ADPATPMg2+ CHRNB4 Ca2+DLG4 CACNG4 ADCY5 Ca impermeable AMPAreceptorsp-T287-CAMK2B DLG4 cAMPGRIK3 GABBR2 p-T287-CAMK2B p-T286-CAMK2A Ribosomal S6 kinaseADCY1 PLCB2 Ca2+ CHRNG CHRNA3 Kainatereceptor-glutamate-Gprotein complexGDP PLCB1 Ca impermeable AMPAreceptorsCHRNA1 AP2 complexCl- GNAI2 p-T287-CAMK2B ADCY1 KCNJ6 Mg2+Ca impermeable AMPAreceptor ligandcomplexL-Glu GNAT3 ADCY5 Cl-p-T286-CAMK2A GNAI3 CHRND GRIN2D GRIN1 GNAT3 GNG8 GRIP1/GRIP2CHRNA3 GRIK2 CAMK4 ADCY3 GRIK5 O-acteylcholinebound to calciumpermeablepostsynapticnicotinicacetylcholinereceptorsGNAI2 NEFL CaMKIICa2+G alpha-olf:GTPADCY2 EPB41L1DLG4 ADCY2 p-T287-CAMK2G L-Glu p-T286-CAMK2A p-CAMKK1p-T287-CAMK2G GRIN2C MAPK1ADPADCY1 Cl- Highly calciumpermeable nicotinicacetylcholinereceptorsADCY7 G-protein alpha (i):GTPPiHighly calciumpermeablepostsynaptic nicotinicacetylcholinereceptorsL-Glu AKAP9 AKAP9 PDPK1RRAS CACNG8 GNAI1 EPB41L1CHRNE ADPGABBR1 p-T287-CAMK2B GNAT3 p-T287-CAMK2D ATPGNAI1 ADPGRIK3 homomerglutamate complexCHRNA7 GRIN2B CaMKIICAMK2heteromer:CALM:4xCa2+ADPGABRR1 p-T287-CAMK2G MDM2 GNAL KCNJ5 p-T287-CAMK2B ATPp-S338-BRAF p-T287-CAMK2D GABAB receptor:GABAADCY9 GRIK1 p-T287-CAMK2D KCNJ9 GNB2 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)L-Glu CaMKIINMDA receptor-MgcomplexCHRNA4 CHRNB2 GRIN2D NMDA receptor ligandcomplexCHRNA9 Ca2+ADPCHRNA3 p-T286-CAMK2A p-T286-CAMK2A Ca2+CACNG2 p-T287-CAMK2B CHRNB2 ADCY6 GRIN2A ADPAcCho CHRNB4 AcCho GNG12 TARP-PSD95-Mdm2phospho-CaMKIV:Calmodulinp-T286-CAMK2A CAMK4G-protein alpha(i):GTP:AdenylatecyclaseADCY1 NEFL ADCY3 GRIN2D GRIA4 GRIN2C CHRNA5 p-T287-CAMK2D GRIK3 CHRNA2 GABBR2 GNAI1 ADCY8 DLG4 CHRNA6 PPiPhospho(S363,S380,T573)-ribosomal S6 kinaseGABRR pentamer:GABACHRNA2 K+Edited KainateReceptor-glutamatecomplexGNAI2 GABBR1 ADCY1 GNG2 GRIP1/GRIP2ADCY6 ADCY5 KCNJ10 CHRNB4 CHRNA6 Ca2+ADCY5 Ca2+ CHRNB3 GABRA4 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)CREB1Mg2+ GDP Na+p-T287-CAMK2D Ca impermeable AMPAreceptorsAKAP9 GRIA1 Ca impermeable AMPAreceptorsKCNJ12 ADCY2 ADCY4 GNAT3 Phospho(S363,S380,T573)- ribosomal S6 kinaseGTP GNG3 KCNJ2 CHRNA4 GABBR2 AcCho GRIN2C L-Glu Calmodulin:CaMK IVGABRA5 p-T287-CAMK2B CALM1 MYO6ADPp-T287-CAMK2D GABRR3 GNG5 Kainatereceptor-glutamatecomplexCACNG3 ADCY9 DLG1ADCY8 Ca2+L-Glup-T287-CAMK2G ADCY9 GRIN1 ADCY5 ADCY8 Na+L-GluGNAL Cl- GRIN1 L-Glu Ca permeable AMPAreceptor ligandcomplexADP NEFL p-T287-CAMK2G GNAI1 CREB1DLG1 GABA GlyCaMKIIADPp-T286-CAMK2A GTP GNAL CHRNB3 GRIK3 GRIN2B MDM2 GDP RASGRF1 GABRheteropentamers:GABAGRIK3 p-S133-CREB1RasGRF:Ca/calmodulinp-T185,Y187-MAPK1RASGRF2 NEFL p-S12,S13-CAMK4 CHRNA5 Ca2+p-T287-CAMK2B CAMKK1GRIA4 L-Glu L-GluGRIN2A TARP-PSD95-Mdm2Cl- GNAL Mg2+ GTP Edited GRIK2 (GluR6)ACTN2 ADCY8 ADCY6 CALM1 GABA B receptorG-proteinbeta-gamma and Kir3channel complexPiDLG4 Adenylate cyclase(Mg2+ cofactor)GNAI3 Mg2+ GABRB2 ADCY3 p-T286-CAMK2A NMDA receptorcomplexCa permeable AMPAreceptorsL-Glup-T287-CAMK2D PiGRIK 3 homomerAKAP5ADCY7 GNAI3 GDP GNAT3 Ras:GTPAP2A1 ADCY4 RRAS ADPKCNJ16 CAMK4 GRIN2A p-T286-CAMK2A PICK1AKAP5CALM1 p-T287-CAMK2D p-T287-CAMK2B L-GluGNAI2 Edited GRIK2 (GluR6)CaMKIICl- GNAL ADCY4 GRIN2D ADCY6 GRIK4 GABA CALM1CACNG3 G-proteinbeta-gamma:PLC beta1/2/3L-Glu Mg2+ p-T287-CAMK2G Gly ATPATPGRIA3 K+AP2S1-1 GABRR2 GRIN1 GRIN2B Edited KainatereceptorsADPAP2ACACNG8 GABRB3 ACTN2 GNB3 AP2A2-3 AP2M1-2 AP2B1-1 Mg2+ Na+DLG1GNAI1 Ca2+PiNEFL 0-acteylcholinebound to calciumpermeable nictonicacteylcholinereceptor complexCACNG4 DLG4 ATPCACNG2 Ca2+ ACTN2 Ca2+ ADCY7 GABRA3 Na+Edited GRIK 1(GluR5) Ca2+ GDP p-T287-CAMK2D CALM1 GNAI2 G alpha-olf:GDPcomplexGABA GRIN2C GNG7 GABA ADPHRAS 4xCa2+:CaMADCY9 GNAT3 p-T287-CAMK2G p-S338-RAF1Gly Na+GRIN1 MYO6NCALD DLG4 RASGRF2 Edited GRIK 1(GluR5) GRIN2D CHRNA1 Ca2+RasGRFNa+Na+RasGTP-B raf compexADCY4 GABRA2 DLG3 ADCY7 L-GluGRIP1/GRIP2GDP GRIN2C (Gialpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)GTP CALM1 Ca2+ GNAI2 HRAS p-T286-CAMK2A Ca permeable AMPAreceptorsGRIA1 GABRQ p-T287-CAMK2D KCNJ3 Activated B-rafcomplexDLG4 GNAI3 ATPCHRNB2 AKAP9 ADCY6 GNG4 Ca/calmodulinactivated AdenylateCyclaseCl- O-Acetylcholinebound toAcetylcholinereceptorGNAI3 Ca impermeable AMPAreceptors (withphospho GluR2 S880)ADCY8 GTP p-T287-CAMK2B ADCY7 Gly GNAI1 GABRG2 ATPCl-GTP GNB1 ADCY3 GRIA3 CHRNA4 p-T287-CAMK2B PLCB3 BRAF kaiante ReceptorsACTN2 CALM1 p-T287-CAMK2G PLCB2 Activatedconventionalprotein kinase Cp-T287-CAMK2G p-T287-CAMK2B ADP GTP ATPNMDA receptor ligandcomplexGABAp-T286-CAMK2A L-Glu55312


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. Source:Reactome.

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Bibliography

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  18. Handford CA, Lynch JW, Baker E, Webb GC, Ford JH, Sutherland GR, Schofield PR.; ''The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes.''; PubMed Europe PMC Scholia
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  26. Lee HK.; ''Synaptic plasticity and phosphorylation.''; PubMed Europe PMC Scholia

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

View all...
NameTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170656 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170659 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ComplexR-HSA-170683 (Reactome)
0-acteylcholine

bound to calcium permeable nictonic acteylcholine

receptor complex		ComplexR-HSA-629600 (Reactome)
4xCa2+:CaMComplexR-HSA-74294 (Reactome)
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 complexComplexR-HSA-416629 (Reactome)
AP2A1 ProteinO95782 (Uniprot-TrEMBL)
AP2A2-3 ProteinO94973-3 (Uniprot-TrEMBL)
AP2AR-HSA-416640 (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

conventional

protein kinase C		R-HSA-139830 (Reactome)
Activated B-raf complexComplexR-HSA-1063697 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (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)
CAMK2 heteromer:CALM:4xCa2+ComplexR-HSA-444601 (Reactome)
CAMK2 heteromerComplexR-HSA-432792 (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.
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

complex		ComplexR-HSA-420974 (Reactome)
Ca impermeable AMPA

receptors (with

phospho GluR2 S880)		R-HSA-421001 (Reactome)
Ca impermeable AMPA receptorsR-HSA-399713 (Reactome)
Ca impermeable AMPA receptorsR-HSA-416323 (Reactome)
Ca permeable AMPA

receptor ligand

complex		ComplexR-HSA-420976 (Reactome)
Ca permeable AMPA receptorsR-HSA-399714 (Reactome)
Ca permeable AMPA receptorsR-HSA-416325 (Reactome)
Ca/calmodulin

activated Adenylate

Cyclase		R-HSA-443461 (Reactome)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
CaMKIIComplexR-HSA-417004 (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.
CaMKIIComplexR-HSA-444796 (Reactome)
CaMKIIComplexR-HSA-445374 (Reactome)
Calmodulin:CaMK IVComplexR-HSA-111900 (Reactome)
Calmodulin:CaMK IVComplexR-HSA-112281 (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 (GluR5) ProteinP39086 (Uniprot-TrEMBL) Glutamine at position 636 is replaced by arginine in an editing step which occurs posttranscriptionally.
Edited GRIK2 (GluR6) 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

complex		ComplexR-HSA-451304 (Reactome)
Edited Kainate receptorsComplexR-HSA-451279 (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 complexComplexR-HSA-170669 (Reactome)
G alpha-olf:GTPComplexR-HSA-170661 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3		ComplexR-HSA-398037 (Reactome)
G-protein alpha (i):GDPComplexR-HSA-392164 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase		ComplexR-HSA-396910 (Reactome)
G-protein alpha (i): GTPComplexR-HSA-392161 (Reactome)
GABA B receptor

G-protein beta-gamma and Kir3

channel complex		ComplexR-HSA-1013011 (Reactome)
GABA MetaboliteCHEBI:16865 (ChEBI)
GABAB receptor:GABAComplexR-HSA-420698 (Reactome)
GABAB receptorComplexR-HSA-420748 (Reactome)
GABAMetaboliteCHEBI:16865 (ChEBI)
GABBR1 ProteinQ9UBS5 (Uniprot-TrEMBL)
GABBR2 ProteinO75899 (Uniprot-TrEMBL)
GABR heteropentamers:GABAComplexR-HSA-975268 (Reactome)
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)
GABRQ ProteinQ9UN88 (Uniprot-TrEMBL)
GABRR pentamer:GABAComplexR-HSA-975448 (Reactome)
GABRR1 ProteinP24046 (Uniprot-TrEMBL)
GABRR2 ProteinP28476 (Uniprot-TrEMBL)
GABRR3 ProteinA8MPY1 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAL ProteinP38405 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (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)
GNG8 ProteinQ9UK08 (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 homomerComplexR-HSA-450196 (Reactome)
GRIK1 ProteinP39086 (Uniprot-TrEMBL)
GRIK2 ProteinQ13002 (Uniprot-TrEMBL)
GRIK3 ProteinQ13003 (Uniprot-TrEMBL)
GRIK3 homomer glutamate complexComplexR-HSA-500705 (Reactome)
GRIK4 ProteinQ16099 (Uniprot-TrEMBL)
GRIK5 ProteinQ16478 (Uniprot-TrEMBL)
GRIN1 ProteinQ05586 (Uniprot-TrEMBL)
GRIN2A ProteinQ12879 (Uniprot-TrEMBL)
GRIN2B ProteinQ13224 (Uniprot-TrEMBL)
GRIN2C ProteinQ14957 (Uniprot-TrEMBL)
GRIN2D ProteinO15399 (Uniprot-TrEMBL)
GRIP1/GRIP2R-HSA-416631 (Reactome)
GRIP1/GRIP2R-HSA-416636 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
Gly MetaboliteCHEBI:15428 (ChEBI)
GlyMetaboliteCHEBI:15428 (ChEBI)
HRAS ProteinP01112 (Uniprot-TrEMBL)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors		R-HSA-629581 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors		R-HSA-629586 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors		R-HSA-629576 (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

complex		ComplexR-HSA-451281 (Reactome)
Kainate receptor-glutamate-Gprotein complexComplexR-HSA-500703 (Reactome)
L-Glu MetaboliteCHEBI:16015 (ChEBI)
L-GluMetaboliteCHEBI:16015 (ChEBI)
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 complexComplexR-HSA-419566 (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 complexComplexR-HSA-432783 (Reactome)
NMDA receptor-Mg complexComplexR-HSA-438039 (Reactome)
NSFProteinP46459 (Uniprot-TrEMBL)
Na+MetaboliteCHEBI:29101 (ChEBI)
O-Acetylcholine

bound to Acetylcholine

receptor		ComplexR-HSA-629590 (Reactome)
O-acteylcholine

bound to calcium permeable postsynaptic nicotinic acetylcholine

receptors		ComplexR-HSA-629592 (Reactome)
PDPK1ProteinO15530 (Uniprot-TrEMBL)
PICK1ProteinQ9NRD5 (Uniprot-TrEMBL)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACB-like proteinsR-HSA-4127466 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
Phospho(S221,S363,S380,T573)- ribosomal S6 kinaseR-HSA-444291 (Reactome)
Phospho(S363,S380,T573)- ribosomal S6 kinaseR-HSA-444261 (Reactome)
Phospho(S363,S380,T573)-ribosomal S6 kinaseR-HSA-445403 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
RASGRF1 ProteinQ13972 (Uniprot-TrEMBL)
RASGRF2 ProteinO14827 (Uniprot-TrEMBL)
RRAS ProteinP10301 (Uniprot-TrEMBL)
Ras:GDPComplexR-HSA-206896 (Reactome)
Ras:GTPComplexR-HSA-206946 (Reactome)
RasGRF:Ca/calmodulinComplexR-HSA-442735 (Reactome)
RasGRFComplexR-HSA-442734 (Reactome)
RasGTP-B raf compexComplexR-HSA-1063687 (Reactome)
Ribosomal S6 kinaseR-HSA-444247 (Reactome)
TARP-PSD95-Mdm2ComplexR-HSA-416329 (Reactome)
TARP-PSD95-Mdm2ComplexR-HSA-416851 (Reactome)
cAMPMetaboliteCHEBI:17489 (ChEBI)
kaiante ReceptorsR-HSA-450885 (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:CalmodulinComplexR-HSA-111904 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170686 (Reactome)
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)R-HSA-170674 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ArrowR-HSA-170671 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170686 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170686 (Reactome)
0-acteylcholine

bound to calcium permeable nictonic acteylcholine

receptor complex		ArrowR-HSA-629599 (Reactome)
4xCa2+:CaMR-HSA-111913 (Reactome)
4xCa2+:CaMR-HSA-442725 (Reactome)
ADPArrowR-HSA-111915 (Reactome)
ADPArrowR-HSA-416320 (Reactome)
ADPArrowR-HSA-416639 (Reactome)
ADPArrowR-HSA-416985 (Reactome)
ADPArrowR-HSA-421007 (Reactome)
ADPArrowR-HSA-442724 (Reactome)
ADPArrowR-HSA-442726 (Reactome)
ADPArrowR-HSA-442737 (Reactome)
ADPArrowR-HSA-442739 (Reactome)
ADPArrowR-HSA-442749 (Reactome)
ADPArrowR-HSA-443474 (Reactome)
ADPArrowR-HSA-443475 (Reactome)
ADPArrowR-HSA-443480 (Reactome)
ADPArrowR-HSA-444253 (Reactome)
AKAP5ArrowR-HSA-416320 (Reactome)
AKAP5R-HSA-416320 (Reactome)
AP2 complexArrowR-HSA-416639 (Reactome)
AP2 complexR-HSA-416639 (Reactome)
AP2AArrowR-HSA-421007 (Reactome)
AP2AR-HSA-421007 (Reactome)
ATPR-HSA-111915 (Reactome)
ATPR-HSA-416320 (Reactome)
ATPR-HSA-416639 (Reactome)
ATPR-HSA-416985 (Reactome)
ATPR-HSA-421007 (Reactome)
ATPR-HSA-442715 (Reactome)
ATPR-HSA-442724 (Reactome)
ATPR-HSA-442726 (Reactome)
ATPR-HSA-442737 (Reactome)
ATPR-HSA-442739 (Reactome)
ATPR-HSA-442749 (Reactome)
ATPR-HSA-443474 (Reactome)
ATPR-HSA-443475 (Reactome)
ATPR-HSA-443480 (Reactome)
ATPR-HSA-444253 (Reactome)
AcChoR-HSA-629588 (Reactome)
AcChoR-HSA-629596 (Reactome)
AcChoR-HSA-629599 (Reactome)
Activated

conventional

protein kinase C		mim-catalysisR-HSA-416639 (Reactome)
Activated

conventional

protein kinase C		mim-catalysisR-HSA-421007 (Reactome)
Activated B-raf complexArrowR-HSA-442726 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170674 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-392206 (Reactome)
CALM1R-HSA-442760 (Reactome)
CAMK2 heteromer:CALM:4xCa2+ArrowR-HSA-442725 (Reactome)
CAMK2 heteromerR-HSA-442725 (Reactome)
CAMK2 heteromerR-HSA-445367 (Reactome)
CAMK4R-HSA-111913 (Reactome)
CAMKK1R-HSA-442749 (Reactome)
CAMKK1mim-catalysisR-HSA-442749 (Reactome)
CREB1R-HSA-442724 (Reactome)
CREB1R-HSA-443474 (Reactome)
CREB1R-HSA-443475 (Reactome)
CREB1R-HSA-443480 (Reactome)
Ca impermeable AMPA

receptor ligand

complex		ArrowR-HSA-420975 (Reactome)
Ca impermeable AMPA

receptor ligand

complex		R-HSA-399711 (Reactome)
Ca impermeable AMPA

receptors (with

phospho GluR2 S880)		R-HSA-421007 (Reactome)
Ca impermeable AMPA receptorsArrowR-HSA-399711 (Reactome)
Ca impermeable AMPA receptorsArrowR-HSA-416639 (Reactome)
Ca impermeable AMPA receptorsArrowR-HSA-416985 (Reactome)
Ca impermeable AMPA receptorsArrowR-HSA-421007 (Reactome)
Ca impermeable AMPA receptorsArrowR-HSA-438037 (Reactome)
Ca impermeable AMPA receptorsR-HSA-416639 (Reactome)
Ca impermeable AMPA receptorsR-HSA-416985 (Reactome)
Ca impermeable AMPA receptorsR-HSA-420975 (Reactome)
Ca impermeable AMPA receptorsR-HSA-438037 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisR-HSA-399711 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisR-HSA-432162 (Reactome)
Ca impermeable AMPA receptorsmim-catalysisR-HSA-438037 (Reactome)
Ca permeable AMPA

receptor ligand

complex		ArrowR-HSA-420977 (Reactome)
Ca permeable AMPA

receptor ligand

complex		R-HSA-399712 (Reactome)
Ca permeable AMPA

receptor ligand

complex		R-HSA-420980 (Reactome)
Ca permeable AMPA receptorsArrowR-HSA-399712 (Reactome)
Ca permeable AMPA receptorsArrowR-HSA-416320 (Reactome)
Ca permeable AMPA receptorsArrowR-HSA-420980 (Reactome)
Ca permeable AMPA receptorsR-HSA-416320 (Reactome)
Ca permeable AMPA receptorsR-HSA-420977 (Reactome)
Ca permeable AMPA receptorsmim-catalysisR-HSA-399712 (Reactome)
Ca permeable AMPA receptorsmim-catalysisR-HSA-420980 (Reactome)
Ca/calmodulin

activated Adenylate

Cyclase		mim-catalysisR-HSA-442715 (Reactome)
Ca2+ArrowR-HSA-399712 (Reactome)
Ca2+ArrowR-HSA-432164 (Reactome)
Ca2+ArrowR-HSA-442715 (Reactome)
Ca2+ArrowR-HSA-451311 (Reactome)
Ca2+ArrowR-HSA-622326 (Reactome)
Ca2+ArrowR-HSA-629595 (Reactome)
Ca2+R-HSA-399712 (Reactome)
Ca2+R-HSA-432164 (Reactome)
Ca2+R-HSA-442715 (Reactome)
Ca2+R-HSA-442760 (Reactome)
Ca2+R-HSA-451311 (Reactome)
Ca2+R-HSA-622326 (Reactome)
Ca2+R-HSA-629595 (Reactome)
CaMKIIArrowR-HSA-444792 (Reactome)
CaMKIIArrowR-HSA-445367 (Reactome)
CaMKIIR-HSA-444792 (Reactome)
CaMKIImim-catalysisR-HSA-416320 (Reactome)
CaMKIImim-catalysisR-HSA-442725 (Reactome)
CaMKIImim-catalysisR-HSA-442726 (Reactome)
CaMKIImim-catalysisR-HSA-443475 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-111913 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-112282 (Reactome)
Calmodulin:CaMK IVR-HSA-111915 (Reactome)
Calmodulin:CaMK IVR-HSA-112282 (Reactome)
Calmodulin:CaMK IVmim-catalysisR-HSA-111915 (Reactome)
Calmodulin:CaMK IVmim-catalysisR-HSA-443480 (Reactome)
Cl-ArrowR-HSA-975340 (Reactome)
Cl-ArrowR-HSA-975449 (Reactome)
Cl-R-HSA-975340 (Reactome)
Cl-R-HSA-975449 (Reactome)
DLG1ArrowR-HSA-416320 (Reactome)
DLG1R-HSA-416320 (Reactome)
EPB41L1ArrowR-HSA-416320 (Reactome)
EPB41L1R-HSA-416320 (Reactome)
Edited Kainate

Receptor-glutamate

complex		ArrowR-HSA-451309 (Reactome)
Edited Kainate

Receptor-glutamate

complex		R-HSA-451310 (Reactome)
Edited Kainate receptorsArrowR-HSA-451310 (Reactome)
Edited Kainate receptorsR-HSA-451309 (Reactome)
Edited Kainate receptorsmim-catalysisR-HSA-451310 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170674 (Reactome)
G alpha-olf:GTPR-HSA-170671 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3		R-HSA-500717 (Reactome)
G-protein alpha (i):GDPArrowR-HSA-170674 (Reactome)
G-protein alpha

(i):GTP:Adenylate

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

(i):GTP:Adenylate

cyclase		R-HSA-170671 (Reactome)
G-protein alpha (i): GTPR-HSA-392206 (Reactome)
GABA B receptor

G-protein beta-gamma and Kir3

channel complex		mim-catalysisR-HSA-1013020 (Reactome)
GABAB receptor:GABAArrowR-HSA-420688 (Reactome)
GABAB receptorR-HSA-420688 (Reactome)
GABAR-HSA-420688 (Reactome)
GABR heteropentamers:GABAmim-catalysisR-HSA-975340 (Reactome)
GABRR pentamer:GABAmim-catalysisR-HSA-975449 (Reactome)
GRIK 3 homomerR-HSA-500708 (Reactome)
GRIK3 homomer glutamate complexArrowR-HSA-500708 (Reactome)
GRIK3 homomer glutamate complexR-HSA-500717 (Reactome)
GRIK3 homomer glutamate complexmim-catalysisR-HSA-500717 (Reactome)
GRIP1/GRIP2ArrowR-HSA-416639 (Reactome)
GRIP1/GRIP2ArrowR-HSA-416985 (Reactome)
GRIP1/GRIP2ArrowR-HSA-421007 (Reactome)
GRIP1/GRIP2R-HSA-416639 (Reactome)
GRIP1/GRIP2R-HSA-416985 (Reactome)
GRIP1/GRIP2R-HSA-421007 (Reactome)
GlyArrowR-HSA-432164 (Reactome)
GlyR-HSA-432164 (Reactome)
GlyR-HSA-432172 (Reactome)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors		ArrowR-HSA-629595 (Reactome)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors		R-HSA-629595 (Reactome)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors		R-HSA-629596 (Reactome)
Highly calcium

permeable postsynaptic nicotinic acetylcholine

receptors		mim-catalysisR-HSA-629595 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors		ArrowR-HSA-622326 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors		R-HSA-622326 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors		R-HSA-629599 (Reactome)
Highly calcium

permeable nicotinic acetylcholine

receptors		mim-catalysisR-HSA-622326 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors		ArrowR-HSA-622325 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors		R-HSA-622325 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors		R-HSA-629588 (Reactome)
Highly sodium

permeable nicotinic acetylcholine

receptors		mim-catalysisR-HSA-622325 (Reactome)
K+ArrowR-HSA-1013020 (Reactome)
K+R-HSA-1013020 (Reactome)
Kainate

receptor-glutamate

complex		ArrowR-HSA-451283 (Reactome)
Kainate

receptor-glutamate

complex		R-HSA-451311 (Reactome)
Kainate receptor-glutamate-Gprotein complexArrowR-HSA-500717 (Reactome)
L-GluArrowR-HSA-399711 (Reactome)
L-GluArrowR-HSA-399712 (Reactome)
L-GluArrowR-HSA-420980 (Reactome)
L-GluArrowR-HSA-432164 (Reactome)
L-GluArrowR-HSA-451310 (Reactome)
L-GluArrowR-HSA-451311 (Reactome)
L-GluR-HSA-420975 (Reactome)
L-GluR-HSA-420977 (Reactome)
L-GluR-HSA-432164 (Reactome)
L-GluR-HSA-432172 (Reactome)
L-GluR-HSA-451283 (Reactome)
L-GluR-HSA-451309 (Reactome)
L-GluR-HSA-500708 (Reactome)
MAPK1R-HSA-442737 (Reactome)
MYO6ArrowR-HSA-416320 (Reactome)
MYO6R-HSA-416320 (Reactome)
Mg2+ArrowR-HSA-432162 (Reactome)
NMDA receptor complexArrowR-HSA-432162 (Reactome)
NMDA receptor complexArrowR-HSA-432164 (Reactome)
NMDA receptor complexR-HSA-432172 (Reactome)
NMDA receptor ligand complexArrowR-HSA-432172 (Reactome)
NMDA receptor ligand complexR-HSA-432164 (Reactome)
NMDA receptor ligand complexR-HSA-442760 (Reactome)
NMDA receptor ligand complexmim-catalysisR-HSA-432164 (Reactome)
NMDA receptor ligand complexmim-catalysisR-HSA-442760 (Reactome)
NMDA receptor ligand complexmim-catalysisR-HSA-445367 (Reactome)
NMDA receptor-Mg complexR-HSA-432162 (Reactome)
NSFmim-catalysisR-HSA-416985 (Reactome)
Na+ArrowR-HSA-399711 (Reactome)
Na+ArrowR-HSA-420980 (Reactome)
Na+ArrowR-HSA-432162 (Reactome)
Na+ArrowR-HSA-438037 (Reactome)
Na+ArrowR-HSA-451310 (Reactome)
Na+ArrowR-HSA-622325 (Reactome)
Na+R-HSA-399711 (Reactome)
Na+R-HSA-420980 (Reactome)
Na+R-HSA-438037 (Reactome)
Na+R-HSA-451310 (Reactome)
Na+R-HSA-622325 (Reactome)
O-Acetylcholine

bound to Acetylcholine

receptor		ArrowR-HSA-629588 (Reactome)
O-acteylcholine

bound to calcium permeable postsynaptic nicotinic acetylcholine

receptors		ArrowR-HSA-629596 (Reactome)
PDPK1mim-catalysisR-HSA-442739 (Reactome)
PICK1ArrowR-HSA-416639 (Reactome)
PICK1ArrowR-HSA-416985 (Reactome)
PICK1ArrowR-HSA-421007 (Reactome)
PICK1R-HSA-416639 (Reactome)
PICK1R-HSA-416985 (Reactome)
PICK1R-HSA-421007 (Reactome)
PPiArrowR-HSA-442715 (Reactome)
PRKACB-like proteinsmim-catalysisR-HSA-443474 (Reactome)
Phospho(S221,S363,S380,T573)- ribosomal S6 kinaseArrowR-HSA-442739 (Reactome)
Phospho(S221,S363,S380,T573)- ribosomal S6 kinasemim-catalysisR-HSA-442724 (Reactome)
Phospho(S363,S380,T573)- ribosomal S6 kinaseR-HSA-442739 (Reactome)
Phospho(S363,S380,T573)-ribosomal S6 kinaseArrowR-HSA-444253 (Reactome)
PiArrowR-HSA-170666 (Reactome)
PiArrowR-HSA-170686 (Reactome)
PiArrowR-HSA-416320 (Reactome)
PiArrowR-HSA-416639 (Reactome)
PiArrowR-HSA-421007 (Reactome)
PiR-HSA-416985 (Reactome)
R-HSA-1013020 (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.
R-HSA-111913 (Reactome) CaMKIV becomes fully activated after a three-step mechanism: Upon a transient increase in intracellular calcium, calcium-bound calmodulin (Ca2+/CaM) binds to its autoregulatory domain, which relieves intersteric inhibition. An activating protein kinase, calcium/calmodulin-dependent protein kinase kinase (CaMKK), binds to the Ca2+/CaM:CaMKIV complex and phosphorylates CaMKIV on a threonine residue in the activation loop. After full activation by the three-step mechanism mentioned above, the activity of CaMKIV becomes autonomous and no longer requires bound Ca2+/CaM. This activity is required for CaMKIV-mediated transcriptional regulation. The CaMKIV-associated PP2A then dephosphorylates CaMKIV, thereby terminating autonomous activity and CaMKIV-mediated gene transcription.
R-HSA-111915 (Reactome) Autophosphorylation of the N-terminus Ser12-Ser13 is required for full activation after Ca2+/calmodulin binding and phosphorylation of the Ca2+/calmodulin-bound enzyme on Thr200 by a Ca2+/calmodulin-dependent protein kinase kinase.
R-HSA-112282 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
R-HSA-170666 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170671 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
R-HSA-170674 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-i dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170686 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-392206 (Reactome) G-proteins in the Gi class inhibit adenylate cyclase activity, decreasing the production of cAMP from ATP, which has many consequences but classically results in decreased activity of Protein Kinase A (PKA). cAMP also activates the cyclic nucleotide-gated ion channels, a process that is particularly important in olfactory cells.
R-HSA-399711 (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.
R-HSA-399712 (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.
R-HSA-416320 (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.
R-HSA-416639 (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.
R-HSA-416985 (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.
R-HSA-420688 (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.
R-HSA-420975 (Reactome) AMPA receptors bind glutamate, released in the synaptic cleft by the presynaptic cell, in the ligand binding region in the N terminal domain.
R-HSA-420977 (Reactome) AMPA receptors bind glutamate, released in the synaptic cleft by the presynaptic cell, in the ligand binding region in the N terminal domain.
R-HSA-420980 (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.
R-HSA-421007 (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.
R-HSA-432162 (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).
R-HSA-432164 (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.
R-HSA-432172 (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.
R-HSA-438037 (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.
R-HSA-442715 (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.
R-HSA-442724 (Reactome) CREB is phosphorylated at serine 133 by any of the four isoforms of ribosomal S6 kinase.
R-HSA-442725 (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.
R-HSA-442726 (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.
R-HSA-442732 (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.
R-HSA-442737 (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.
R-HSA-442739 (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.
R-HSA-442749 (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.
R-HSA-442760 (Reactome) RASGRF is activated upon binding of Ca2+/Calmodulin after Ca2+ influx through the NMDA receptor.
R-HSA-443474 (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.
R-HSA-443475 (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.
R-HSA-443480 (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.
R-HSA-444253 (Reactome) Activated MAPK/ERK activates RSK in its C terminal kinase domain by sequentially phosphorylating T573, S363 and 380.
R-HSA-444792 (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.
R-HSA-445367 (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.
R-HSA-451283 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-451309 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-451310 (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.
R-HSA-451311 (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.
R-HSA-500708 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-500717 (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.
R-HSA-622325 (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.
R-HSA-622326 (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.
R-HSA-629588 (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.
R-HSA-629595 (Reactome) Acetylcholine binding activates postsynaptic acetylchloine receptors that show Ca2+ currents which facilitate the process of long term potentiation (LTP).
R-HSA-629596 (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.
R-HSA-629599 (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.
R-HSA-975340 (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), 2 gamma subunits (GABRG) (Khan et al. 1993, Hadingham et al. 1995) and a theta subunit (Bonnert et al. 1999) characterised to date. GABA(A) functions as a heteropentamer, the most common structure being 2 alpha subunits, 2 beta subunits and a gamma subunit (2GABRA:2GABRB:GABRG). An alternative heteropentamer with much less affinity for GABA is 2GABRA:GABRB:GABRG:GABRQ (Bonnert et al. 1999). Upon binding of GABA, both GABR complexes conduct chloride ions through their pore, resulting in hyperpolarisation of the neuron. This causes an inhibitory effect on neurotransmission by reducing the chances of a successful action potential occurring.
R-HSA-975449 (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).
Ras:GDPR-HSA-442732 (Reactome)
Ras:GTPArrowR-HSA-442732 (Reactome)
RasGRF:Ca/calmodulinArrowR-HSA-442760 (Reactome)
RasGRF:Ca/calmodulinmim-catalysisR-HSA-442732 (Reactome)
RasGRFR-HSA-442760 (Reactome)
RasGTP-B raf compexR-HSA-442726 (Reactome)
Ribosomal S6 kinaseR-HSA-444253 (Reactome)
TARP-PSD95-Mdm2ArrowR-HSA-416320 (Reactome)
TARP-PSD95-Mdm2R-HSA-416320 (Reactome)
cAMPArrowR-HSA-442715 (Reactome)
kaiante ReceptorsArrowR-HSA-451311 (Reactome)
kaiante ReceptorsR-HSA-451283 (Reactome)
kaiante Receptorsmim-catalysisR-HSA-451311 (Reactome)
p-CAMKK1ArrowR-HSA-442749 (Reactome)
p-S133-CREB1ArrowR-HSA-442724 (Reactome)
p-S133-CREB1ArrowR-HSA-443474 (Reactome)
p-S133-CREB1ArrowR-HSA-443475 (Reactome)
p-S133-CREB1ArrowR-HSA-443480 (Reactome)
p-S338-RAF1mim-catalysisR-HSA-442737 (Reactome)
p-T185,Y187-MAPK1ArrowR-HSA-442737 (Reactome)
p-T185,Y187-MAPK1mim-catalysisR-HSA-444253 (Reactome)
phospho-CaMK IV:CalmodulinArrowR-HSA-111915 (Reactome)
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