KEGG   PATHWAY: ko04020Help
Entry
ko04020                     Pathway                                

Name
Calcium signaling pathway
Description
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs).
The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it.
The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
Calcium signaling pathway
ko04020

All organismsOrtholog table
Disease
H00441  
Progressive osseous heteroplasia (POH)
H00608  
46,XY disorders of sex development (Disorders in androgen synthesis or action)
H00627  
Premature ovarian failure
H00699  
Central core disease
H00715  
Darier disease
H00728  
Brugada syndrome (BRS)
H00746  
Hypokalemic periodic paralysis (HypoPP)
H00749  
Episodic ataxias
H00755  
Acrokeratosis verruciformis
H00759  
Waardenburg syndrome (WS)
H00775  
Familial or sporadic hemiplegic migraine
H00787  
Congenital stationary night blindness (CSNB)
H00801  
Familial thoracic aortic aneurysm and dissection (TAAD)
H00823  
ABCD syndrome
H00865  
Lethal congenital contractural syndrome (LCCS)
H00910  
Hirschsprung disease (HD)
H00937  
Precocious puberty
H01019  
Catecholaminergic polymorphic ventricular tachycardia
H01118  
Progressive external ophthalmoplegia (PEO)
H01129  
Brody myopathy
H01307  
Nonsyndromic congenital nail disorder (NDNC)
H01310  
Multi-minicore disease (MmD)
Other DBs
BSID: 
GO: 
Orthology
K05849  
solute carrier family 8 (sodium/calcium exchanger)
K05850  
Ca2+ transporting ATPase, plasma membrane [EC:3.6.3.8]
K04129  
muscarinic acetylcholine receptor M1
K04131  
muscarinic acetylcholine receptor M3
K04133  
muscarinic acetylcholine receptor M5
K04266  
adenosine receptor A2a
K04267  
adenosine receptor A2b
K04141  
adrenergic receptor beta-1
K04142  
adrenergic receptor beta-2
K04143  
adrenergic receptor beta-3
K04144  
dopamine receptor D1
K05840  
dopamine receptor D5
K04150  
histamine receptor H2
K04160  
5-hydroxytryptamine receptor 4
K04161  
5-hydroxytryptamine receptor 5
K04162  
5-hydroxytryptamine receptor 6
K04163  
5-hydroxytryptamine receptor 7
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K04633  
guanine nucleotide-binding protein G(olf) subunit alpha
K08041  
adenylate cyclase 1 [EC:4.6.1.1]
K08042  
adenylate cyclase 2 [EC:4.6.1.1]
K08043  
adenylate cyclase 3 [EC:4.6.1.1]
K08044  
adenylate cyclase 4 [EC:4.6.1.1]
K08047  
adenylate cyclase 7 [EC:4.6.1.1]
K08048  
adenylate cyclase 8 [EC:4.6.1.1]
K08049  
adenylate cyclase 9 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K05852  
phospholamban
K05853  
Ca2+ transporting ATPase, sarcoplasmic/endoplasmic reticulum [EC:3.6.3.8]
K16059  
stromal interaction molecule 1
K18196  
stromal interaction molecule 2
K16056  
calcium release-activated calcium channel protein 1
K16057  
calcium release-activated calcium channel protein 2
K16058  
calcium release-activated calcium channel protein 3
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K04853  
voltage-dependent calcium channel L type alpha-1F
K04857  
voltage-dependent calcium channel L type alpha-1S
K04344  
voltage-dependent calcium channel P/Q type alpha-1A
K04849  
voltage-dependent calcium channel N type alpha-1B
K04852  
voltage-dependent calcium channel R type alpha-1E
K04854  
voltage-dependent calcium channel T type alpha-1G
K04855  
voltage-dependent calcium channel T type alpha-1H
K04856  
voltage-dependent calcium channel T type alpha-1I
K04809  
nicotinic acetylcholine receptor alpha-7
K05215  
P2X purinoceptor 1
K05216  
P2X purinoceptor 2
K05217  
P2X purinoceptor 3
K05218  
P2X purinoceptor 4
K05219  
P2X purinoceptor 5
K05220  
P2X purinoceptor 7
K05221  
P2X purinoceptor 6
K05208  
glutamate receptor ionotropic, NMDA 1
K05209  
glutamate receptor ionotropic, NMDA 2A
K05211  
glutamate receptor ionotropic, NMDA 2C
K05212  
glutamate receptor ionotropic, NMDA 2D
K04961  
ryanodine receptor 1
K04962  
ryanodine receptor 2
K04963  
ryanodine receptor 3
K04322  
cysteinyl leukotriene receptor 1
K04323  
cysteinyl leukotriene receptor 2
K04130  
muscarinic acetylcholine receptor M2
K04135  
adrenergic receptor alpha-1A
K04136  
adrenergic receptor alpha-1B
K04137  
adrenergic receptor alpha-1D
K04166  
angiotensin II receptor type 1
K04197  
endothelin receptor type A
K04198  
endothelin receptor type B
K03914  
coagulation factor II (thrombin) receptor
K04603  
metabotropic glutamate receptor 1
K04604  
metabotropic glutamate receptor 5
K04169  
gastrin-releasing peptide receptor
K04149  
histamine receptor H1
K04157  
5-hydroxytryptamine receptor 2
K04248  
luteinizing hormone/choriogonadotropin receptor
K04211  
neurotensin receptor 1
K04229  
oxytocin receptor
K04226  
arginine vasopressin receptor 1A
K04227  
arginine vasopressin receptor 1B
K04297  
leukotriene B4 receptor 2
K04279  
platelet-activating factor receptor
K04258  
prostaglandin E receptor 1
K04260  
prostaglandin E receptor 3
K04262  
prostaglandin F receptor
K03915  
bradykinin receptor B1
K03916  
bradykinin receptor B2
K04222  
tachykinin receptor 1
K04223  
tachykinin receptor 2
K04224  
tachykinin receptor 3
K04264  
thromboxane A2 receptor
K04282  
thyrotropin-releasing hormone receptor
K04194  
cholecystokinin A receptor
K04195  
cholecystokinin B receptor
K04361  
epidermal growth factor receptor [EC:2.7.10.1]
K05083  
receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05084  
receptor tyrosine-protein kinase erbB-3 [EC:2.7.10.1]
K05085  
receptor tyrosine-protein kinase erbB-4 [EC:2.7.10.1]
K04363  
platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  
platelet-derived growth factor receptor beta [EC:2.7.10.1]
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K04635  
guanine nucleotide-binding protein subunit alpha-11
K04636  
guanine nucleotide-binding protein subunit alpha-14
K04637  
guanine nucleotide-binding protein subunit alpha-15
K10784  
T cell receptor alpha chain V region
K10785  
T-cell receptor beta chain V region
K06856  
immunoglobulin heavy chain
K05857  
phosphatidylinositol phospholipase C, delta [EC:3.1.4.11]
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K01116  
phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K05859  
phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05860  
phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K05861  
phosphatidylinositol phospholipase C, zeta [EC:3.1.4.11]
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K01242  
ADP-ribosyl cyclase 1 [EC:2.4.99.20 3.2.2.6]
K04718  
sphingosine kinase [EC:2.7.1.91]
K05862  
voltage-dependent anion channel protein 1
K15040  
voltage-dependent anion channel protein 2
K15041  
voltage-dependent anion channel protein 3
K05863  
solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K09565  
peptidyl-prolyl isomerase F (cyclophilin D) [EC:5.2.1.8]
K05865  
troponin C, slow skeletal and cardiac muscles
K12042  
troponin C, skeletal muscle
K02183  
calmodulin
K00871  
phosphorylase kinase gamma subunit [EC:2.7.11.19]
K07190  
phosphorylase kinase alpha/beta subunit
K00907  
myosin-light-chain kinase [EC:2.7.11.18]
K04515  
calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K05869  
calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K04348  
serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  
serine/threonine-protein phosphatase 2B regulatory subunit
K13240  
nitric-oxide synthase, brain [EC:1.14.13.39]
K13241  
nitric-oxide synthase, inducible [EC:1.14.13.39]
K13242  
nitric-oxide synthase, endothelial [EC:1.14.13.39]
K13755  
calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase [EC:3.1.4.17]
K05871  
focal adhesion kinase 2 [EC:2.7.10.2]
K00911  
1D-myo-inositol-triphosphate 3-kinase [EC:2.7.1.127]
K02677  
classical protein kinase C [EC:2.7.11.13]
Compound
C00002  
ATP
C00004  
NADH
C00076  
Calcium cation
C00165  
Diacylglycerol
C00575  
3',5'-Cyclic AMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C01330  
Sodium cation
C06124  
Sphingosine 1-phosphate
C13050  
Cyclic ADP-ribose
C13051  
Nicotinic acid adenine dinucleotide phosphate
Reference
  Authors
Berridge MJ, Bootman MD, Roderick HL.
  Title
Calcium signalling: dynamics, homeostasis and remodelling.
  Journal
Nat Rev Mol Cell Biol 4:517-29 (2003)
Reference
  Authors
Berridge MJ, Lipp P, Bootman MD.
  Title
The versatility and universality of calcium signalling.
  Journal
Nat Rev Mol Cell Biol 1:11-21 (2000)
Reference
  Authors
Wang MC, Dolphin A, Kitmitto A.
  Title
L-type voltage-gated calcium channels: understanding function through structure.
  Journal
FEBS Lett 564:245-50 (2004)
Reference
  Authors
Ferrier GR, Howlett SE.
  Title
Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.
  Journal
Am J Physiol Heart Circ Physiol 280:H1928-44 (2001)
Reference
  Authors
Keef KD, Hume JR, Zhong J.
  Title
Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases.
  Journal
Am J Physiol Cell Physiol 281:C1743-56 (2001)
Reference
PMID:8125957
  Authors
Hell JW, Appleyard SM, Yokoyama CT, Warner C, Catterall WA.
  Title
Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini.
  Journal
J Biol Chem 269:7390-6 (1994)
Reference
  Authors
Yunker AM.
  Title
Modulation and pharmacology of low voltage-activated ("T-Type") calcium channels.
  Journal
J Bioenerg Biomembr 35:577-98 (2003)
Reference
PMID:9149541
  Authors
Yakel JL.
  Title
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.
  Journal
Trends Pharmacol Sci 18:124-34 (1997)
Reference
  Authors
Fukunaga K, Miyamoto E.
  Title
A working model of CaM kinase II activity in hippocampal long-term potentiation and memory.
  Journal
Neurosci Res 38:3-17 (2000)
Reference
PMID:9235901
  Authors
Della Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ.
  Title
Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase.
  Journal
J Biol Chem 272:19125-32 (1997)
Reference
PMID:7861177
  Authors
Furuichi T, Mikoshiba K.
  Title
Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain.
  Journal
J Neurochem 64:953-60 (1995)
Reference
  Authors
Bruce JI, Straub SV, Yule DI.
  Title
Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
  Journal
Cell Calcium 34:431-44 (2003)
Reference
  Authors
Lee HC, Munshi C, Graeff R.
  Title
Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes.
  Journal
Mol Cell Biochem 193:89-98 (1999)
Reference
  Authors
Crompton M.
  Title
Mitochondrial intermembrane junctional complexes and their role in cell death.
  Journal
J Physiol 529 Pt 1:11-21 (2000)
Reference
  Authors
Grewal SS, York RD, Stork PJ.
  Title
Extracellular-signal-regulated kinase signalling in neurons.
  Journal
Curr Opin Neurobiol 9:544-53 (1999)
Reference
  Authors
Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV.
  Title
Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes.
  Journal
Mol Cell Biol 23:7068-81 (2003)
Reference
  Authors
Hutchins JR, Dikovskaya D, Clarke PR.
  Title
Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II.
  Journal
Mol Biol Cell 14:4003-14 (2003)
Reference
  Authors
Tornquist K
  Title
Sphingosine 1-phosphate, sphingosine kinase and autocrine calcium signalling in thyroid cells.
  Journal
Acta Physiol (Oxf) 204:151-7 (2012)
Reference
  Authors
Feske S
  Title
Immunodeficiency due to defects in store-operated calcium entry.
  Journal
Ann N Y Acad Sci 1238:74-90 (2011)
Reference
  Authors
Giachini FR, Lima VV, Hannan JL, Carneiro FS, Webb RC, Tostes RC
  Title
STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg.
  Journal
Braz J Med Biol Res 44:1080-7 (2011)
Reference
  Authors
Baba Y, Kurosaki T
  Title
[Regulation of store-operated calcium entry by STIM1].
  Journal
Seikagaku 80:1123-8 (2008)

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