KEGG   PATHWAY: hsa04961Help
Entry
hsa04961                    Pathway                                
Name
Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Endocrine and other factor-regulated calcium reabsorption
hsa04961

All organismsOrtholog table
Disease
H00680  
Primary failure of tooth eruption
H00700  
Centronuclear myopathy
H00784  
Localized autosomal recessive hypotrichosis
H00998  
Alternating hemiplegia of childhood
H01143  
Vitamin D-dependent rickets
H01193  
Familial tumoral calcinosis (FTC)
Drug
D00067  
Estrone (JAN/USP/INN)
D00105  
Estradiol (JAN/USP/INN)
D00129  
Calcitriol (JAN/USP/INN)
D00930  
Paricalcitol (JAN/USAN/INN)
D01098  
Maxacalcitol (JAN/USAN/INN)
D01125  
Calcipotriol (JAN)
D01472  
Tacalcitol hydrate (JP16)
D01518  
Alfacalcidol (JAN/INN)
D01662  
Falecalcitriol (JAN/INN)
D02217  
Raloxifene hydrochloride (JAN/USP)
D03062  
Bazedoxifene acetate (JAN/USAN)
D03358  
Teriparatide acetate (JAN)
D03677  
Deltibant (USAN/INN)
D05364  
Parathyroid hormone (human) (USAN)
D06078  
Teriparatide (genetical recombination) (JAN)
D06546  
Teriparatide acetate (USAN)
D07578  
Eldecalcitol (JAN/INN)
D08465  
Raloxifene (INN)
D08554  
Tacalcitol (INN)
D08868  
Becocalcidiol (USAN/INN)
D10008  
Fispemifene (USAN/INN)
D10198  
Calcipotriol hydrate (JAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
5745  
PTH1R; parathyroid hormone 1 receptor [KO:K04585]
2778  
GNAS; GNAS complex locus [KO:K04632]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [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]
7421  
VDR; vitamin D (1,25- dihydroxyvitamin D3) receptor [KO:K08539]
2099  
ESR1; estrogen receptor 1 [KO:K08550]
56302  
TRPV5; transient receptor potential cation channel, subfamily V, member 5 [KO:K04974]
9365  
KL; klotho [KO:K14756] [EC:3.2.1.31]
1759  
DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
1785  
DNM2; dynamin 2 [KO:K01528] [EC:3.6.5.5]
26052  
DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5]
161  
AP2A2; adaptor-related protein complex 2, alpha 2 subunit [KO:K11824]
160  
AP2A1; adaptor-related protein complex 2, alpha 1 subunit [KO:K11824]
163  
AP2B1; adaptor-related protein complex 2, beta 1 subunit [KO:K11825]
1173  
AP2M1; adaptor-related protein complex 2, mu 1 subunit [KO:K11826]
1175  
AP2S1; adaptor-related protein complex 2, sigma 1 subunit [KO:K11827]
1211  
CLTA; clathrin, light chain A [KO:K04644]
1212  
CLTB; clathrin, light chain B [KO:K04645]
1213  
CLTC; clathrin, heavy chain (Hc) [KO:K04646]
8218  
CLTCL1; clathrin, heavy chain-like 1 [KO:K04646]
8766  
RAB11A; RAB11A, member RAS oncogene family [KO:K07904]
793  
CALB1; calbindin 1, 28kDa [KO:K14757]
476  
ATP1A1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
477  
ATP1A2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
478  
ATP1A3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
480  
ATP1A4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
23439  
ATP1B4; ATPase, Na+/K+ transporting, beta 4 polypeptide [KO:K01540]
481  
ATP1B1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
482  
ATP1B2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
483  
ATP1B3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
486  
FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
3817  
KLK2; kallikrein-related peptidase 2 [KO:K01325] [EC:3.4.21.35]
3816  
KLK1; kallikrein 1 [KO:K01325] [EC:3.4.21.35]
624  
BDKRB2; bradykinin receptor B2 [KO:K03916]
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]
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]
490  
ATP2B1; ATPase, Ca++ transporting, plasma membrane 1 [KO:K05850] [EC:3.6.3.8]
6546  
SLC8A1; solute carrier family 8 (sodium/calcium exchanger), member 1 [KO:K05849]
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
C16051  
Parathyroid hormone
Reference
  Authors
Boros S, Bindels RJ, Hoenderop JG
  Title
Active Ca(2+) reabsorption in the connecting tubule.
  Journal
Pflugers Arch 458:99-109 (2009)
Reference
  Authors
Lambers TT, Bindels RJ, Hoenderop JG
  Title
Coordinated control of renal Ca2+ handling.
  Journal
Kidney Int 69:650-4 (2006)
Reference
  Authors
de Groot T, Bindels RJ, Hoenderop JG
  Title
TRPV5: an ingeniously controlled calcium channel.
  Journal
Kidney Int 74:1241-6 (2008)
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)
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Calcium absorption across epithelia.
  Journal
Physiol Rev 85:373-422 (2005)
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)
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)
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)
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)
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)
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)
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)
KO pathway
 
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