KEGG   PATHWAY: aml04961
Entry
aml04961                    Pathway                                
Name
Endocrine and other factor-regulated calcium reabsorption - Ailuropoda melanoleuca (giant panda)
Description
Calcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. In kidney, the late part of the distal convoluted tubule (DCT) and the connecting tubule (CNT) are the site of active Ca2+ transport and precisely regulate Ca2+ reabsorption. Following Ca2+ entry through TRPV5, Ca2+ bound to calbindin-D28K diffuses to the basolateral side, where it is extruded into the blood compartment through NCX1 and to a lesser extent PMCA1b. In the urinary compartment, both klotho and tissue kallikrein (TK) increase the apical abundance of TRPV5. In the blood compartment, PTH, 1,25(OH)2D3 and estrogen increase the transcription and protein expression of the luminal Ca2+ channels, calbindins, and the extrusion systems.
Class
Organismal Systems; Excretory system
Pathway map
aml04961  Endocrine and other factor-regulated calcium reabsorption
aml04961

Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100464757  CLTC; clathrin heavy chain 1 isoform X2 [KO:K04646]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465354  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100465631  PTH1R; parathyroid hormone/parathyroid hormone-related peptide receptor [KO:K04585]
100466002  DNM2; dynamin-2 isoform X8 [KO:K23484]
100466326  AP2A1; AP-2 complex subunit alpha-1 isoform X1 [KO:K11824]
100467417  CLTCL1; clathrin heavy chain 2 isoform X1 [KO:K04646]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468266  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100469080  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100469231  [KO:K04632]
100469610  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469796  [KO:K01538]
100470165  DNM1; dynamin-1 [KO:K01528] [EC:3.6.5.5]
100470517  VDR; vitamin D3 receptor [KO:K08539]
100470875  AP2S1; AP-2 complex subunit sigma [KO:K11827]
100471013  DNM3; dynamin-3 isoform X1 [KO:K01528] [EC:3.6.5.5]
100471755  SLC8A3; sodium/calcium exchanger 3 isoform X2 [KO:K05849]
100472840  AP2M1; AP-2 complex subunit mu isoform X3 [KO:K11826]
100472949  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
100473623  KL; klotho [KO:K14756] [EC:3.2.1.31]
100473680  [KO:K04632]
100474128  CLTA; clathrin light chain A isoform X3 [KO:K04644]
100474541  [KO:K05849]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476682  [KO:K01325] [EC:3.4.21.35]
100476768  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100476932  KLK1; kallikrein-1 [KO:K01325] [EC:3.4.21.35]
100477283  RAB11A; ras-related protein Rab-11A [KO:K07904]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100477585  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100477769  AP2A2; AP-2 complex subunit alpha-2 isoform X1 [KO:K11824]
100477989  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100478344  TRPV5; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 5 [KO:K04974]
100479746  CALB1; calbindin [KO:K14757]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480641  [KO:K01539] [EC:7.2.2.13]
100480890  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100481012  ATP1B4; protein ATP1B4 isoform X3 [KO:K01540]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100482647  BDKRB2; B2 bradykinin receptor [KO:K03916]
100483460  PTH; parathyroid hormone [KO:K05261]
100484018  CLTB; clathrin light chain B isoform X3 [KO:K04645]
100484452  AP2B1; AP-2 complex subunit beta isoform X1 [KO:K11825]
100484518  ESR1; estrogen receptor isoform X1 [KO:K08550]
100484596  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100484762  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
117799551  [KO:K01325] [EC:3.4.21.35]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01673  Calcitriol
Reference
  Authors
Boros S, Bindels RJ, Hoenderop JG
  Title
Active Ca(2+) reabsorption in the connecting tubule.
  Journal
Pflugers Arch 458:99-109 (2009)
DOI:10.1007/s00424-008-0602-6
Reference
  Authors
Lambers TT, Bindels RJ, Hoenderop JG
  Title
Coordinated control of renal Ca2+ handling.
  Journal
Kidney Int 69:650-4 (2006)
DOI:10.1038/sj.ki.5000169
Reference
  Authors
de Groot T, Bindels RJ, Hoenderop JG
  Title
TRPV5: an ingeniously controlled calcium channel.
  Journal
Kidney Int 74:1241-6 (2008)
DOI:10.1038/ki.2008.320
Reference
  Authors
Markadieu N, Bindels RJ, Hoenderop JG
  Title
The renal connecting tubule: Resolved and unresolved issues in Ca(2+) transport.
  Journal
Int J Biochem Cell Biol 43:1-4 (2011)
DOI:10.1016/j.biocel.2010.10.006
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Calcium absorption across epithelia.
  Journal
Physiol Rev 85:373-422 (2005)
DOI:10.1152/physrev.00003.2004
Reference
  Authors
van Abel M, Hoenderop JG, Bindels RJ
  Title
The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease.
  Journal
Naunyn Schmiedebergs Arch Pharmacol 371:295-306 (2005)
DOI:10.1007/s00210-005-1021-2
Reference
  Authors
Nijenhuis T, Hoenderop JG, Bindels RJ
  Title
TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate.
  Journal
Pflugers Arch 451:181-92 (2005)
DOI:10.1007/s00424-005-1430-6
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Epithelial calcium channels: from identification to function and regulation.
  Journal
Pflugers Arch 446:304-8 (2003)
DOI:10.1007/s00424-003-1045-8
Reference
  Authors
Gkika D, Topala CN, Chang Q, Picard N, Thebault S, Houillier P, Hoenderop JG, Bindels RJ
  Title
Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5.
  Journal
EMBO J 25:4707-16 (2006)
DOI:10.1038/sj.emboj.7601357
Reference
  Authors
Schoeber JP, Hoenderop JG, Bindels RJ
  Title
Concerted action of associated proteins in the regulation of TRPV5 and TRPV6.
  Journal
Biochem Soc Trans 35:115-9 (2007)
DOI:10.1042/BST0350115
Reference
  Authors
Renkema KY, Alexander RT, Bindels RJ, Hoenderop JG
  Title
Calcium and phosphate homeostasis: concerted interplay of new regulators.
  Journal
Ann Med 40:82-91 (2008)
DOI:10.1080/07853890701689645
Reference
  Authors
de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels RJ, Hoenderop JG
  Title
Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation.
  Journal
J Am Soc Nephrol 20:1693-704 (2009)
DOI:10.1681/ASN.2008080873
Related
pathway
aml04144  Endocytosis
aml04530  Tight junction
KO pathway
ko04961   

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