KEGG   PATHWAY: rno04020Help
rno04020                    Pathway                                

Calcium signaling pathway - Rattus norvegicus (rat)
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).
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
rno04020  Calcium signaling pathway

Ortholog table
Other DBs
BSID: 83442
GO: 0019722
Rattus norvegicus (rat) [GN:rno]
29715  Slc8a1; solute carrier family 8 member A1 [KO:K05849]
140447  Slc8a2; solute carrier family 8 member A2 [KO:K05849]
140448  Slc8a3; solute carrier family 8 member A3 [KO:K05849]
29600  Atp2b4; ATPase plasma membrane Ca2+ transporting 4 [KO:K05850] [EC:]
29599  Atp2b3; ATPase plasma membrane Ca2+ transporting 3 [KO:K05850] [EC:]
24215  Atp2b2; ATPase plasma membrane Ca2+ transporting 2 [KO:K05850] [EC:]
29598  Atp2b1; ATPase plasma membrane Ca2+ transporting 1 [KO:K05850] [EC:]
25229  Chrm1; cholinergic receptor, muscarinic 1 [KO:K04129]
24260  Chrm3; cholinergic receptor, muscarinic 3 [KO:K04131]
53949  Chrm5; cholinergic receptor, muscarinic 5 [KO:K04133]
25369  Adora2a; adenosine A2a receptor [KO:K04266]
29316  Adora2b; adenosine A2B receptor [KO:K04267]
24925  Adrb1; adrenoceptor beta 1 [KO:K04141]
24176  Adrb2; adrenoceptor beta 2 [KO:K04142]
25645  Adrb3; adrenoceptor beta 3 [KO:K04143]
24316  Drd1; dopamine receptor D1 [KO:K04144]
25195  Drd5; dopamine receptor D5 [KO:K05840]
25461  Hrh2; histamine receptor H 2 [KO:K04150]
25324  Htr4; 5-hydroxytryptamine receptor 4 [KO:K04160]
25689  Htr5a; 5-hydroxytryptamine receptor 5A [KO:K04161]
79247  Htr5b; 5-hydroxytryptamine (serotonin) receptor 5B [KO:K04161]
64354  Htr6; 5-hydroxytryptamine receptor 6 [KO:K04162]
65032  Htr7; 5-hydroxytryptamine (serotonin) receptor 7, adenylate cyclase-coupled [KO:K04163]
103694905  5-hydroxytryptamine receptor 7 [KO:K04163]
24896  Gnas; GNAS complex locus [KO:K04632]
24611  Gnal; G protein subunit alpha L [KO:K04633]
305509  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:]
81636  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:]
64508  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:]
54223  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:]
84420  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:]
29241  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:]
302950  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:]
25636  Prkaca; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:]
293508  Prkacb; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:]
64672  Pln; phospholamban [KO:K05852]
116601  Atp2a1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:]
29693  Atp2a2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:]
25391  Atp2a3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:]
361618  Stim1; stromal interaction molecule 1 [KO:K16059]
117087  Stim2; stromal interaction molecule 2 [KO:K18196]
304496  Orai1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
304592  Orai2; ORAI calcium release-activated calcium modulator 2 [KO:K16057]
309000  Orai3; ORAI calcium release-activated calcium modulator 3 [KO:K16058]
24239  Cacna1c; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
29716  Cacna1d; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
114493  Cacna1f; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
682930  Cacna1s; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
25398  Cacna1a; calcium voltage-gated channel subunit alpha1 A [KO:K04344]
257648  Cacna1b; calcium voltage-gated channel subunit alpha1 B [KO:K04849]
54234  Cacna1e; calcium voltage-gated channel subunit alpha1 E [KO:K04852]
29717  Cacna1g; calcium voltage-gated channel subunit alpha1 G [KO:K04854]
114862  Cacna1h; calcium voltage-gated channel subunit alpha1 H [KO:K04855]
56827  Cacna1i; calcium voltage-gated channel subunit alpha1 I [KO:K04856]
25302  Chrna7; cholinergic receptor nicotinic alpha 7 subunit [KO:K04809]
25505  P2rx1; purinergic receptor P2X 1 [KO:K05215]
114115  P2rx2; purinergic receptor P2X 2 [KO:K05216]
81739  P2rx3; purinergic receptor P2X 3 [KO:K05217]
29659  P2rx4; purinergic receptor P2X 4 [KO:K05218]
113995  P2rx5; purinergic receptor P2X 5 [KO:K05219]
29665  P2rx7; purinergic receptor P2X 7 [KO:K05220]
25041  P2rx6; purinergic receptor P2X 6 [KO:K05221]
24408  Grin1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
24409  Grin2a; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
24411  Grin2c; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211]
24412  Grin2d; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212]
114207  Ryr1; ryanodine receptor 1 [KO:K04961]
689560  Ryr2; ryanodine receptor 2 [KO:K04962]
170546  Ryr3; ryanodine receptor 3 [KO:K04963]
114099  Cysltr1; cysteinyl leukotriene receptor 1 [KO:K04322]
170926  Cysltr2; cysteinyl leukotriene receptor 2 [KO:K04323]
81645  Chrm2; cholinergic receptor, muscarinic 2 [KO:K04130]
29412  Adra1a; adrenoceptor alpha 1A [KO:K04135]
24173  Adra1b; adrenoceptor alpha 1B [KO:K04136]
29413  Adra1d; adrenoceptor alpha 1D [KO:K04137]
24180  Agtr1a; angiotensin II receptor, type 1a [KO:K04166]
81638  Agtr1b; angiotensin II receptor, type 1b [KO:K04166]
24326  Ednra; endothelin receptor type A [KO:K04197]
50672  Ednrb; endothelin receptor type B [KO:K04198]
25439  F2r; coagulation factor II (thrombin) receptor [KO:K03914]
24414  Grm1; glutamate receptor, metabotropic 1 [KO:K04603]
24418  Grm5; glutamate metabotropic receptor 5 [KO:K04604]
24938  Grpr; gastrin releasing peptide receptor [KO:K04169]
24448  Hrh1; histamine receptor H 1 [KO:K04149]
29595  Htr2a; 5-hydroxytryptamine receptor 2A [KO:K04157]
29581  Htr2b; 5-hydroxytryptamine receptor 2B [KO:K04157]
25187  Htr2c; 5-hydroxytryptamine receptor 2C [KO:K04157]
25477  Lhcgr; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
366274  Ntsr1; neurotensin receptor 1 [KO:K04211]
25342  Oxtr; oxytocin receptor [KO:K04229]
25107  Avpr1a; arginine vasopressin receptor 1A [KO:K04226]
29462  Avpr1b; arginine vasopressin receptor 1B [KO:K04227]
100909648  vasopressin V1b receptor-like [KO:K04227]
114098  Ltb4r2; leukotriene B4 receptor 2 [KO:K04297]
58949  Ptafr; platelet-activating factor receptor [KO:K04279]
25637  Ptger1; prostaglandin E receptor 1 [KO:K04258]
24929  Ptger3; prostaglandin E receptor 3 [KO:K04260]
25652  Ptgfr; prostaglandin F receptor [KO:K04262]
81509  Bdkrb1; bradykinin receptor B1 [KO:K03915]
25245  Bdkrb2; bradykinin receptor B2 [KO:K03916]
24807  Tacr1; tachykinin receptor 1 [KO:K04222]
25007  Tacr2; tachykinin receptor 2 [KO:K04223]
24808  Tacr3; tachykinin receptor 3 [KO:K04224]
24816  Tbxa2r; thromboxane A2 receptor [KO:K04264]
25570  Trhr; thyrotropin releasing hormone receptor [KO:K04282]
252859  Mlnr; motilin receptor [KO:K04282]
24889  Cckar; cholecystokinin A receptor [KO:K04194]
25706  Cckbr; cholecystokinin B receptor [KO:K04195]
24329  Egfr; epidermal growth factor receptor [KO:K04361] [EC:]
24337  Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:]
29496  Erbb3; erb-b2 receptor tyrosine kinase 3 [KO:K05084] [EC:]
59323  Erbb4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:]
25267  Pdgfra; platelet derived growth factor receptor alpha [KO:K04363] [EC:]
24629  Pdgfrb; platelet derived growth factor receptor beta [KO:K05089] [EC:]
81666  Gnaq; G protein subunit alpha q [KO:K04634]
81662  Gna11; guanine nucleotide binding protein, alpha 11 [KO:K04635]
309242  Gna14; G protein subunit alpha 14 [KO:K04636]
89788  Gna15; guanine nucleotide binding protein, alpha 15 [KO:K04637]
100362949  TRAV14S2; mCG140239-like [KO:K10784]
688340  T-cell receptor alpha chain V region PHDS58-like [KO:K10784]
691714  RGD1565478; similar to Immunoglobulin heavy chain (gamma polypeptide) [KO:K06856]
24655  Plcd1; phospholipase C, delta 1 [KO:K05857] [EC:]
287745  Plcd3; phospholipase C, delta 3 [KO:K05857] [EC:]
140693  Plcd4; phospholipase C, delta 4 [KO:K05857] [EC:]
24654  Plcb1; phospholipase C beta 1 [KO:K05858] [EC:]
29322  Plcb3; phospholipase C beta 3 [KO:K05858] [EC:]
85240  Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:]
25031  Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:]
25738  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:]
29337  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:]
114633  Plce1; phospholipase C, epsilon 1 [KO:K05860] [EC:]
497197  Plcz1; phospholipase C, zeta 1 [KO:K05861] [EC:]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
25668  Cd38; CD38 molecule [KO:K01242] [EC:]
308589  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:]
170897  Sphk1; sphingosine kinase 1 [KO:K04718] [EC:]
294560  Mcu; mitochondrial calcium uniporter [KO:K20858]
83529  Vdac1; voltage-dependent anion channel 1 [KO:K05862]
83531  Vdac2; voltage-dependent anion channel 2 [KO:K15040]
83532  Vdac3; voltage-dependent anion channel 3 [KO:K15041]
25176  Slc25a5; solute carrier family 25 member 5 [KO:K05863]
85333  Slc25a4; solute carrier family 25 member 4 [KO:K05863]
689108  Slc25a31; solute carrier family 25 member 31 [KO:K05863]
282819  Ppif; peptidylprolyl isomerase F [KO:K09565] [EC:]
290561  Tnnc1; troponin C1, slow skeletal and cardiac type [KO:K05865]
296369  Tnnc2; troponin C2, fast skeletal type [KO:K12042]
50663  Calm2; calmodulin 2 [KO:K02183]
24242  Calm1; calmodulin 1 [KO:K02183]
24244  Calm3; calmodulin 3 [KO:K02183]
364774  Calml5; calmodulin-like 5 [KO:K02183]
307100  Calml3; calmodulin-like 3 [KO:K02183]
691455  Calml4; calmodulin-like 4 [KO:K02183]
140671  Phkg2; phosphorylase kinase catalytic subunit gamma 2 [KO:K00871] [EC:]
29353  Phkg1; phosphorylase kinase, gamma 1 [KO:K00871] [EC:]
64561  Phka1; phosphorylase kinase, alpha 1 [KO:K07190]
361377  Phkb; phosphorylase kinase regulatory subunit beta [KO:K07190]
678739  Phka2; phosphorylase kinase, alpha 2 [KO:K07190]
288057  Mylk; myosin light chain kinase [KO:K00907] [EC:]
117558  Mylk2; myosin light chain kinase 2 [KO:K00907] [EC:]
291926  Mylk3; myosin light chain kinase 3 [KO:K00907] [EC:]
103689985  myosin light chain kinase family member 4 [KO:K00907] [EC:]
100911165  Mylk4; myosin light chain kinase family, member 4 [KO:K00907] [EC:]
25400  Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:]
24246  Camk2d; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:]
24245  Camk2b; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:]
171140  Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:]
103693838  NEWGENE_621802; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:]
25050  Camk4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:]
24675  Ppp3cb; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:]
171378  Ppp3cc; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:]
29748  Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
29749  Ppp3r2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
24598  Nos1; nitric oxide synthase 1 [KO:K13240] [EC:]
24599  Nos2; nitric oxide synthase 2 [KO:K13241] [EC:]
497963  similar to Nitric oxide synthase, inducible (NOS type II) (Inducible NO synthase) (Inducible NOS) (iNOS) [KO:K13241] [EC:]
24600  Nos3; nitric oxide synthase 3 [KO:K13242] [EC:]
81529  Pde1a; phosphodiesterase 1A [KO:K13755] [EC:]
29691  Pde1b; phosphodiesterase 1B [KO:K13755] [EC:]
81742  Pde1c; phosphodiesterase 1C [KO:K13755] [EC:]
50646  Ptk2b; protein tyrosine kinase 2 beta [KO:K05871] [EC:]
81677  Itpka; inositol-trisphosphate 3-kinase A [KO:K00911] [EC:]
54260  Itpkb; inositol-trisphosphate 3-kinase B [KO:K00911] [EC:]
308451  Itpkc; inositol-trisphosphate 3-kinase C [KO:K00911] [EC:]
24680  Prkca; protein kinase C, alpha [KO:K02677] [EC:]
25023  Prkcb; protein kinase C, beta [KO:K19662] [EC:]
24681  Prkcg; protein kinase C, gamma [KO:K19663] [EC:]
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
Berridge MJ, Bootman MD, Roderick HL.
Calcium signalling: dynamics, homeostasis and remodelling.
Nat Rev Mol Cell Biol 4:517-29 (2003)
Berridge MJ, Lipp P, Bootman MD.
The versatility and universality of calcium signalling.
Nat Rev Mol Cell Biol 1:11-21 (2000)
Wang MC, Dolphin A, Kitmitto A.
L-type voltage-gated calcium channels: understanding function through structure.
FEBS Lett 564:245-50 (2004)
Ferrier GR, Howlett SE.
Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.
Am J Physiol Heart Circ Physiol 280:H1928-44 (2001)
Keef KD, Hume JR, Zhong J.
Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases.
Am J Physiol Cell Physiol 281:C1743-56 (2001)
Hell JW, Appleyard SM, Yokoyama CT, Warner C, Catterall WA.
Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini.
J Biol Chem 269:7390-6 (1994)
Yunker AM.
Modulation and pharmacology of low voltage-activated ("T-Type") calcium channels.
J Bioenerg Biomembr 35:577-98 (2003)
Yakel JL.
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.
Trends Pharmacol Sci 18:124-34 (1997)
Fukunaga K, Miyamoto E.
A working model of CaM kinase II activity in hippocampal long-term potentiation and memory.
Neurosci Res 38:3-17 (2000)
Della Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ.
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.
J Biol Chem 272:19125-32 (1997)
Furuichi T, Mikoshiba K.
Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain.
J Neurochem 64:953-60 (1995)
Bruce JI, Straub SV, Yule DI.
Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
Cell Calcium 34:431-44 (2003)
Lee HC, Munshi C, Graeff R.
Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes.
Mol Cell Biochem 193:89-98 (1999)
Crompton M.
Mitochondrial intermembrane junctional complexes and their role in cell death.
J Physiol 529 Pt 1:11-21 (2000)
Grewal SS, York RD, Stork PJ.
Extracellular-signal-regulated kinase signalling in neurons.
Curr Opin Neurobiol 9:544-53 (1999)
Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV.
Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes.
Mol Cell Biol 23:7068-81 (2003)
Hutchins JR, Dikovskaya D, Clarke PR.
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.
Mol Biol Cell 14:4003-14 (2003)
Tornquist K
Sphingosine 1-phosphate, sphingosine kinase and autocrine calcium signalling in thyroid cells.
Acta Physiol (Oxf) 204:151-7 (2012)
Feske S
Immunodeficiency due to defects in store-operated calcium entry.
Ann N Y Acad Sci 1238:74-90 (2011)
Giachini FR, Lima VV, Hannan JL, Carneiro FS, Webb RC, Tostes RC
STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg.
Braz J Med Biol Res 44:1080-7 (2011)
Baba Y, Kurosaki T
[Regulation of store-operated calcium entry by STIM1].
Seikagaku 80:1123-8 (2008)
KO pathway
LinkDB All DBs

DBGET integrated database retrieval system