KEGG   PATHWAY: umr04961
Entry
umr04961                    Pathway                                
Name
Endocrine and other factor-regulated calcium reabsorption - Ursus maritimus (polar bear)
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
umr04961  Endocrine and other factor-regulated calcium reabsorption
umr04961

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103657073  AP2S1; AP-2 complex subunit sigma [KO:K11827]
103657216  SLC8A2; sodium/calcium exchanger 2 isoform X1 [KO:K05849]
103657261  AP2A1; AP-2 complex subunit alpha-1 [KO:K11824]
103657279  KLK1; kallikrein-1 [KO:K01325] [EC:3.4.21.35]
103657282  [KO:K01325] [EC:3.4.21.35]
103657738  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
103660077  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
103660367  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103661416  CALB1; calbindin isoform X1 [KO:K14757]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103663281  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103664359  KL; klotho [KO:K14756] [EC:3.2.1.31]
103664765  CLTB; clathrin light chain B [KO:K04645]
103665907  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103666963  ESR1; estrogen receptor [KO:K08550]
103667291  AP2B1; AP-2 complex subunit beta isoform X1 [KO:K11825]
103667334  CLTC; clathrin heavy chain 1 isoform X1 [KO:K04646]
103668547  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103668895  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
103668991  TRPV5; transient receptor potential cation channel subfamily V member 5 [KO:K04974]
103669178  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
103669226  DNM3; dynamin-3 isoform X1 [KO:K01528] [EC:3.6.5.5]
103669305  CLTCL1; clathrin heavy chain 2 [KO:K04646]
103669413  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103669556  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
103669660  BDKRB2; B2 bradykinin receptor [KO:K03916]
103670446  DNM1; dynamin-1 isoform X1 [KO:K01528] [EC:3.6.5.5]
103670935  [KO:K04632]
103670936  [KO:K04632]
103671046  AP2A2; AP-2 complex subunit alpha-2 isoform X10 [KO:K11824]
103671551  SLC8A1; sodium/calcium exchanger 1 [KO:K05849]
103672049  [KO:K01539] [EC:7.2.2.13]
103672113  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
103672914  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103673552  [KO:K05858] [EC:3.1.4.11]
103674250  SLC8A3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849]
103674425  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103674426  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103675120  PTH1R; parathyroid hormone/parathyroid hormone-related peptide receptor isoform X1 [KO:K04585]
103675426  VDR; vitamin D3 receptor [KO:K08539]
103675618  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103676085  AP2M1; AP-2 complex subunit mu isoform X1 [KO:K11826]
103678432  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
103678470  CLTA; clathrin light chain A isoform X1 [KO:K04644]
103678718  DNM2; dynamin-2 isoform X1 [KO:K23484]
103679069  RAB11A; ras-related protein Rab-11A [KO:K07904]
103679549  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103679703  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
103680185  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
103680217  ATP1B4; protein ATP1B4 [KO:K01540]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103682370  PTH; parathyroid hormone [KO:K05261]
121099746  [KO:K05858] [EC:3.1.4.11]
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
umr04144  Endocytosis
umr04530  Tight junction
KO pathway
ko04961   

DBGET integrated database retrieval system