KEGG   PATHWAY: hsa04540Help
Entry
hsa04540                    Pathway                                

Name
Gap junction - Homo sapiens (human)
Description
Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation.
Class
Cellular Processes; Cellular commiunity
BRITE hierarchy
Pathway map
Gap junction
hsa04540

All organismsOrtholog table
Disease
H00606  
Early infantile epileptic encephalopathy
H00838  
Congenital fibrosis of the extraocular muscles (CFEOM)
H01095  
Syndactyly
H01210  
Hypomagnesemia
H01272  
Hypoplastic left heart syndrome (HLHS)
Drug
D00095  
Epinephrine (USP/INN)
D00136  
Haloperidol (JP17/USP/INN)
D00283  
Clozapine (JAN/USP/INN)
D00308  
Droperidol (JP17/USP/INN)
D00374  
Tiotixene (JAN)
D00378  
Timolol (USAN)
D00390  
Triflupromazine (USP/INN)
D00426  
Risperidone (JP17/USAN/INN)
D00454  
Olanzapine (JAN/USAN/INN)
D00458  
Quetiapine fumarate (JP17/USAN)
D00479  
Prochlorperazine maleate (JP17/USP)
D00491  
Paclitaxel (JAN/USP/INN)
D00493  
Prochlorperazine (JAN/USP/INN)
D00503  
Perphenazine (JP17/USP/INN)
D00563  
Mirtazapine (JAN/USAN/INN)
D00570  
Colchicine (JP17/USP)
D00598  
Betaxolol hydrochloride (JP17/USP)
D00599  
Carteolol hydrochloride (JP17/USP)
D00603  
Timolol maleate (JP17/USP)
D00633  
Dopamine hydrochloride (JP17/USP)
D00791  
Fluphenazine hydrochloride (JAN/USP)
D00792  
Fluphenazine enanthate (JP17/USP)
D00793  
Fluphenazine decanoate (JAN/USP)
D00796  
Molindone hydrochloride (USP)
D00797  
Promazine hydrochloride (USP)
D00800  
Triflupromazine hydrochloride (JAN/USP)
D01025  
Levobunolol hydrochloride (JAN/USP)
D01044  
Flupentixol (INN)
D01051  
Spiperone (JAN/USAN)
D01068  
Vinblastine sulfate (JP17/USP)
D01101  
Bromperidol (JAN/USAN/INN)
D01105  
Moperone hydrochloride (JAN)
D01164  
Aripiprazole (JAN/USAN/INN)
D01226  
Sulpiride (JP17/USAN/INN)
D01321  
Zotepine (JAN/INN)
D01348  
Terguride (JAN/INN)
D01468  
Nemonapride (JAN/INN)
D01482  
Pipamperone hydrochloride (JAN)
D01485  
Propericiazine (JAN)
D01520  
Levomepromazine hydrochloride (JAN/USAN)
D01691  
Nipradilol (JAN/INN)
D01742  
Clebopride malate (JP17)
D01745  
Domperidone (JP17/USAN/INN)
D01769  
Vindesine sulfate (JAN/USAN)
D01898  
Haloperidol decanoate (JAN/USAN)
D01902  
Fonazine mesylate (USAN)
D01935  
Vinorelbine ditartrate (JAN)
D02004  
Apomorphine hydrochloride (USP)
D02022  
Prochlorperazine mesilate (JAN)
D02034  
Setiptiline maleate (JAN)
D02035  
Timiperone (JAN)
D02163  
Fluphenazine maleate (JAN)
D02165  
Docetaxel (USAN)
D02197  
Vincristine sulfate (JP17/USP)
D02208  
Sultopride hydrochloride (JAN)
D02211  
Dihydroergotamine mesylate (USP)
D02213  
Metoclopramide hydrochloride (JAN)
D02236  
Flupentixol dihydrochloride (JAN)
D02248  
Levomepromazine maleate (JP17/USAN)
D02357  
Methysergide (USAN/INN)
D02371  
Clocapramine hydrochloride hydrate (JP17)
D02372  
Perospirone hydrochloride hydrate (JAN)
D02605  
Methoxypromazine maleate
D02609  
Prochlorperazine edisylate (USP)
D02612  
Thiothixene hydrochloride (USP)
D02613  
Clopenthixol (USAN)
D02622  
Pipamperone (USAN/INN)
D02623  
Moperone (INN)
D02626  
Bromperidol decanoate (USAN)
D02641  
Butaclamol hydrochloride (USAN)
D02666  
Iloperidone (USAN/INN)
D02670  
Mazapertine succinate (USAN)
D02676  
Oxiperomide (USAN/INN)
D02681  
Piquindone hydrochloride (USAN)
D02682  
Remoxipride (USAN)
D02683  
Remoxipride hydrochloride (USAN)
D02688  
Tiospirone hydrochloride (USAN)
D02775  
Adrogolide hydrochloride (USAN)
D02893  
Amesergide (USAN/INN)
D02995  
Asenapine maleate (JAN/USAN)
D03065  
Becaplermin (USAN/INN)
D03165  
Bromocriptine (USAN/INN)
D03214  
Aplindore fumarate (USAN)
D03494  
Ciladopa hydrochloride (USAN)
D03534  
Clebopride (USAN)
D03891  
Dopexamine (USAN/INN)
D03937  
Ecopipam hydrochloride (USAN)
D04488  
Ibopamine (USAN/INN)
D04710  
Levobetaxolol hydrochloride (USAN)
D04864  
Maytansine (USAN)
D05008  
Metoclopramide hydrochloride (USAN)
D05010  
Metopimazine (USAN/INN)
D05333  
Paclitaxel poliglumex (USAN/INN)
D05339  
Paliperidone (JAN/USAN/INN)
D05340  
Paliperidone palmitate (JAN/USAN)
D05529  
Podofilox (USAN)
D05677  
Quinelorane hydrochloride (USAN)
D05682  
Quinpirole hydrochloride (USAN)
D05690  
Raclopride C11 (USP)
D05768  
Rotigotine (JAN/USAN/INN)
D05832  
Sibenadet hydrochloride (USAN)
D06304  
Vindesine (USAN/INN)
D06623  
Olanzapine pamoate (USAN)
D07217  
Quinagolide (INN/BAN)
D07312  
Levosulpiride (INN)
D07460  
Apomorphine (BAN)
D07526  
Betaxolol (INN)
D07624  
Carteolol (INN)
D07718  
Clocapramine (INN)
D07837  
Dihydroergotamine (INN)
D07838  
Dihydroergotamine tartrate
D07854  
Dimetotiazine (INN)
D07866  
Docetaxel (JAN/INN)
D07868  
Domperidone maleate
D07870  
Dopamine (INN)
D07905  
Ergometrine (INN)
D07906  
Ergotamine (INN)
D07976  
Flupentixol decanoate
D07977  
Fluphenazine (INN)
D08035  
Haloperidol lactate
D08057  
Ibopamine hydrochloride
D08115  
Levobunolol (INN)
D08456  
Quetiapine (INN)
D08457  
Quinagolide hydrochloride (BAN)
D08511  
Setiptiline (INN)
D08549  
Sultopride (INN)
D08590  
Tiapride (INN)
D08675  
Vinblastine (INN)
D08679  
Vincristine (INN)
D08680  
Vinorelbine (INN)
D08914  
Eribulin mesylate (USAN)
D09635  
Linifanib (USAN/INN)
D09939  
Olaratumab (USAN/INN)
D10018  
Necitumumab (USAN/INN)
D10029  
Verubulin (USAN/INN)
D10030  
Verubulin hydrochloride (USAN)
D10364  
Aripiprazole lauroxil (USAN)
D10434  
Vintafolide (USAN/INN)
D10516  
Aripiprazole hydrate (JAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
2697  
GJA1; gap junction protein alpha 1 [KO:K07372]
57369  
GJD2; gap junction protein delta 2 [KO:K07373]
1902  
LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
2770  
GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  
GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  
GNAI2; G protein subunit alpha i2 [KO:K04630]
5154  
PDGFA; platelet derived growth factor subunit A [KO:K04359]
5155  
PDGFB; platelet derived growth factor subunit B [KO:K17386]
56034  
PDGFC; platelet derived growth factor C [KO:K05450]
80310  
PDGFD; platelet derived growth factor D [KO:K05450]
1950  
EGF; epidermal growth factor [KO:K04357]
5156  
PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
5159  
PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
2885  
GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  
SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  
SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
10746  
MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
5607  
MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
5598  
MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
10376  
TUBA1B; tubulin alpha 1b [KO:K07374]
7277  
TUBA4A; tubulin alpha 4a [KO:K07374]
7278  
TUBA3C; tubulin alpha 3c [KO:K07374]
7846  
TUBA1A; tubulin alpha 1a [KO:K07374]
84790  
TUBA1C; tubulin alpha 1c [KO:K07374]
51807  
TUBA8; tubulin alpha 8 [KO:K07374]
112714  
TUBA3E; tubulin alpha 3e [KO:K07374]
113457  
TUBA3D; tubulin alpha 3d [KO:K07374]
79861  
TUBAL3; tubulin alpha like 3 [KO:K07374]
84617  
TUBB6; tubulin beta 6 class V [KO:K07375]
203068  
TUBB; tubulin beta class I [KO:K07375]
81027  
TUBB1; tubulin beta 1 class VI [KO:K07375]
7280  
TUBB2A; tubulin beta 2A class IIa [KO:K07375]
10381  
TUBB3; tubulin beta 3 class III [KO:K07375]
10382  
TUBB4A; tubulin beta 4A class IVa [KO:K07375]
347688  
TUBB8; tubulin beta 8 class VIII [KO:K07375]
347733  
TUBB2B; tubulin beta 2B class IIb [KO:K07375]
10383  
TUBB4B; tubulin beta 4B class IVb [KO:K07375]
1453  
CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
983  
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
7082  
TJP1; tight junction protein 1 [KO:K05701]
153  
ADRB1; adrenoceptor beta 1 [KO:K04141]
1812  
DRD1; dopamine receptor D1 [KO:K04144]
2778  
GNAS; GNAS complex locus [KO:K04632]
1813  
DRD2; dopamine receptor D2 [KO:K04145]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
3356  
HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
3357  
HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
3358  
HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
2911  
GRM1; glutamate metabotropic receptor 1 [KO:K04603]
2915  
GRM5; glutamate metabotropic receptor 5 [KO:K04604]
2767  
GNA11; G protein subunit alpha 11 [KO:K04635]
2776  
GNAQ; G protein subunit alpha q [KO:K04634]
23236  
PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
5578  
PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
2977  
GUCY1A2; guanylate cyclase 1, soluble, alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  
GUCY1A3; guanylate cyclase 1, soluble, alpha 3 [KO:K12318] [EC:4.6.1.2]
2983  
GUCY1B3; guanylate cyclase 1, soluble, beta 3 [KO:K12319] [EC:4.6.1.2]
5592  
PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
5593  
PRKG2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
Compound
C00025  
L-Glutamate
C00076  
Calcium cation
C00165  
Diacylglycerol
C00533  
Nitric oxide
C00547  
L-Noradrenaline
C00575  
3',5'-Cyclic AMP
C00681  
1-Acyl-sn-glycerol 3-phosphate
C00780  
Serotonin
C00942  
3',5'-Cyclic GMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C03758  
Dopamine
Reference
  Authors
Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC.
  Title
Plasma membrane channels formed by connexins: their regulation and functions.
  Journal
Physiol Rev 83:1359-400 (2003)
Reference
  Authors
Warn-Cramer BJ, Lau AF.
  Title
Regulation of gap junctions by tyrosine protein kinases.
  Journal
Biochim Biophys Acta 1662:81-95 (2004)
Reference
PMID:9535909
  Authors
Warn-Cramer BJ, Cottrell GT, Burt JM, Lau AF.
  Title
Regulation of connexin-43 gap junctional intercellular communication by mitogen-activated protein kinase.
  Journal
J Biol Chem 273:9188-96 (1998)
Reference
  Authors
Roerig B, Feller MB.
  Title
Neurotransmitters and gap junctions in developing neural circuits.
  Journal
Brain Res Brain Res Rev 32:86-114 (2000)
Reference
  Authors
Hatton GI.
  Title
Synaptic modulation of neuronal coupling.
  Journal
Cell Biol Int 22:765-80 (1998)
Reference
  Authors
Cruciani V, Mikalsen SO.
  Title
Connexins, gap junctional intercellular communication and kinases.
  Journal
Biol Cell 94:433-43 (2002)
Reference
  Authors
Giepmans BN.
  Title
Gap junctions and connexin-interacting proteins.
  Journal
Cardiovasc Res 62:233-45 (2004)
Reference
  Authors
Laird DW.
  Title
Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation.
  Journal
Biochim Biophys Acta 1711:172-82 (2005)
Reference
  Authors
Peracchia C.
  Title
Chemical gating of gap junction channels; roles of calcium, pH and calmodulin.
  Journal
Biochim Biophys Acta 1662:61-80 (2004)
Reference
  Authors
Bukauskas FF, Verselis VK.
  Title
Gap junction channel gating.
  Journal
Biochim Biophys Acta 1662:42-60 (2004)
KO pathway
 

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