KEGG PATHWAY: hsa04540

PATHWAY: hsa04540

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; Cell communication

Pathway map

hsa04540

Gap junction

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	Adrenaline (JP16)
D00136	Haloperidol (JP16/USP/INN)
D00283	Clozapine (JAN/USP/INN)
D00308	Droperidol (JP16/USP/INN)
D00374	Tiotixene (JAN)
D00378	Timolol (USAN)
D00390	Triflupromazine (USP/INN)
D00426	Risperidone (JP16/USAN/INN)
D00454	Olanzapine (JAN/USAN/INN)
D00458	Quetiapine fumarate (JP16/USAN)
D00479	Prochlorperazine maleate (JP16/USP)
D00491	Paclitaxel (JAN/USP/INN)
D00493	Prochlorperazine (JAN/USP/INN)
D00503	Perphenazine (JP16/USP/INN)
D00563	Mirtazapine (JAN/USAN/INN)
D00570	Colchicine (JP16/USP)
D00598	Betaxolol hydrochloride (JP16/USP)
D00599	Carteolol hydrochloride (JP16/USP)
D00603	Timolol maleate (JP16/USP)
D00633	Dopamine hydrochloride (JP16/USP)
D00791	Fluphenazine hydrochloride (JAN/USP)
D00792	Fluphenazine enanthate (JP16/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 (JP16/USP)
D01101	Bromperidol (JAN/USAN/INN)
D01105	Moperone hydrochloride (JAN)
D01164	Aripiprazole (JAN/USAN/INN)
D01226	Sulpiride (JP16/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 (JP16)
D01745	Domperidone (JP16/USAN/INN)
D01769	Vindesine sulfate (JAN/USAN)
D01898	Haloperidol decanoate (JAN/USAN)
D01902	Dimetotiazine mesilate (JAN)
D01935	Vinorelbine ditartrate (JAN)
D02004	Apomorphine hydrochloride hydrate (JAN)
D02022	Prochlorperazine mesilate (JAN)
D02034	Setiptiline maleate (JAN)
D02035	Timiperone (JAN)
D02163	Fluphenazine maleate (JAN)
D02165	Docetaxel hydrate (JAN)
D02197	Vincristine sulfate (JP16/USP)
D02208	Sultopride hydrochloride (JAN)
D02211	Dihydroergotamine mesilate (JP16)
D02213	Metoclopramide hydrochloride (JAN)
D02236	Flupentixol dihydrochloride (JAN)
D02248	Levomepromazine maleate (JP16/USAN)
D02357	Methysergide (USAN/INN)
D02371	Clocapramine hydrochloride hydrate (JP16)
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 (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 mesilate (JAN)
D09635	Linifanib (USAN/INN)
D09939	Olaratumab (USAN/INN)
D10018	Necitumumab (USAN/INN)
D10029	Verubulin (USAN/INN)
D10030	Verubulin hydrochloride (USAN)

Other DBs

BSID:

83072

GO:

0005921

Organism

Homo sapiens (human) [GN:hsa]

Gene

2697	GJA1; gap junction protein, alpha 1, 43kDa [KO:K07372]
57369	GJD2; gap junction protein, delta 2, 36kDa [KO:K07373]
1902	LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
2770	GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773	GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771	GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
5155	PDGFB; platelet-derived growth factor beta polypeptide [KO:K04359]
5154	PDGFA; platelet-derived growth factor alpha polypeptide [KO:K04359]
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 polypeptide [KO:K04363] [EC:2.7.10.1]
5159	PDGFRB; platelet-derived growth factor receptor, beta polypeptide [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; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [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; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [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-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567	PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568	PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613	PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
3356	HTR2A; 5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled [KO:K04157]
3357	HTR2B; 5-hydroxytryptamine (serotonin) receptor 2B, G protein-coupled [KO:K04157]
3358	HTR2C; 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled [KO:K04157]
2911	GRM1; glutamate receptor, metabotropic 1 [KO:K04603]
2915	GRM5; glutamate receptor, metabotropic 5 [KO:K04604]
2767	GNA11; guanine nucleotide binding protein (G protein), alpha 11 (Gq class) [KO:K04635]
2776	GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
23236	PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [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 (phosphatidylinositol-specific) [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:K02677] [EC:2.7.11.13]
5582	PRKCG; protein kinase C, gamma [KO:K02677] [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:K07376] [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

PMID:14506308

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

PMID:15033580

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

PMID:10751659

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

PMID:10873290

Authors

Hatton GI.

Title

Synaptic modulation of neuronal coupling.

Journal

Cell Biol Int 22:765-80 (1998)

Reference

PMID:12566218

Authors

Cruciani V, Mikalsen SO.

Title

Connexins, gap junctional intercellular communication and kinases.

Journal

Biol Cell 94:433-43 (2002)

Reference

PMID:15094344

Authors

Giepmans BN.

Title

Gap junctions and connexin-interacting proteins.

Journal

Cardiovasc Res 62:233-45 (2004)

Reference

PMID:15955302

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

PMID:15033579

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

PMID:15033578

Authors

Bukauskas FF, Verselis VK.

Title

Gap junction channel gating.

Journal

Biochim Biophys Acta 1662:42-60 (2004)

KO pathway

ko04540

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (1)   
   BioSystems (1)   
Disease (4)   
   KEGG DISEASE (4)   
Drug (136)   
   KEGG DRUG (136)   
Genome (1)   
   KEGG GENOME (1)   
Gene (89)   
   KEGG GENES (89)   
All databases (232)   

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