Vasopressin regulates renal water homeostasis via Aquaporins (Homo sapiens)

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14, 25, 38, 45, 6118, 4916, 19, 27, 29, 40...7, 10, 32, 46, 51...2, 12, 21, 28, 29, 33...431, 5, 9, 13, 23...435511, 15, 26, 34, 50...56, 5952, 628, 39, 4418, 22, 27, 49, 53...4, 172, 3, 12, 21, 28...cytosolBloodstreamcytosolProximal tubule, descending thin limb of HenleCollecting ductFiltratecytoplasmic vesicle lumenPRKACA cAMP GNG5 PRKACB GNB5 GNAS1 PRKAR1A GNG8 ADCY2 AQP1 GNG13 GNB4 GNG5 GNG8 GNB2 AQP4 tetramerPRKACG AVPR2:AVP:G-alpha(s):GTP:G-beta:G-gammaADCY2 ADCY1 PRKAR2B G-beta:G-gamma(candidates)G alpha (s):GTPPRKAR2B GNG4 GNG3 GTP GNG10 RAB11FIP2 GNGT2 GNB1 H2OGDP GNG3 GNG7 GNG4 AVPR2:AVP:G-alpha(s):GDP:G-beta:G-gammaGNG2 GTP GNG12 GNAS2 GNG3 G-alpha(s):GTP:G-beta:G-gammaAdenylate cyclase(Mg2+ cofactor)PPiGNG10 ADCY4 GNB3 AQP1 tetramercAMP:PKA regulatorysubunitGNG10 GGC-RAB11A GTP PRKAR1A PRKAR2B H2OGNB1 PRKACB GNG12 GNB3 ADCY5 ADCY4 GNG8 GNB2 GNG2 GNG7 GNB2 GNGT1 GNG11 GNB3 GNAS2 MYO5B AVP(20-28) p-S256-AQP2 tetramerGNG12 GNGT2 GNG5 GNG13 AVPR2 GNG8 GNG11 Mg2+ PRKAR1A GNG11 GNG8 GNAS2 ADCY7 GNG10 AVPR2:AVP(20-28)GNB1 GNG2 GNGT1 GNB3 GNB5 GNAS1 GNG7 AQP4 GNGT2 G alpha(s):GTP:AdenylatecyclaseGNG7 AVP(20-28) AVPR2 H2OADCY7 PRKACA H2OAVPR2GNGT2 ATPPRKAR2A ADCY8 GNG3 GNAS2 GNG13 GNB5 AVP(20-28)GNG12 GNG12 ADCY9 ADCY3 PKA catalyticsubunitPRKAR1B GDPH2OGNB1 GNG4 p-S256-AQP2 GNB1 GNB4 AVPR2 GNB5 p-S256-AQP2 tetramerGTP G-alpha(s):GDP:G-beta:G-gammaADCY6 PRKACB p-S256-AQP2 GNG11 PRKAR1B GNG13 PKA tetramerGNB3 GNG10 GNB2 GNAS1 AQP3 ADCY6 GNB2 GNGT1 MYO5B:RABFIP2:RAB11AGNG2 GNB5 AQP2 tetramerGNG5 GNG7 GNG13 GNGT1 AQP2 GNG3 AVP(20-28) GNB4 GNAS1 cAMP Mg2+ PRKAR2A ATPGNGT2 H2OGNAS2 GNGT1 PRKACG PRKACA AQP3 tetramerGNAS1 GNAS2 PRKAR1B ADCY9 PRKACG PRKAR2A GTP PKA tetramer:4xcAMPGNAS1 GTPcAMPADPGNG4 GNB4 H2OADCY3 ADCY8 GDP GNB4 ADCY5 ADCY1 GNG4 GNG11 GNG2 GNG5 156, 276, 27202731, 33, 37


In the kidney water and solutes are passed out of the bloodstream and into the proximal tubule via the slit-like structure formed by nephrin in the glomerulus. Water is reabsorbed from the filtrate during its transit through the proximal tubule, the descending loop of Henle, the distal convoluted tubule, and the collecting duct.
Aquaporin-1 (AQP1) in the proximal tubule and the descending thin limb of Henle is responsible for about 90% of reabsorption (as estimated from mouse knockouts of AQP1). AQP1 is located on both the apical and basolateral surface of epithelial cells and thus transports water through the epithelium and back into the bloodstream.
In the collecting duct epithelial cells have AQP2 on their apical surface and AQP3 and AQP4 on their basolateral surface to transport water across the epithelium. The permeability of the epithelium is regulated by vasopressin, which activates the phosphorylation and subsequent translocation of AQP2 from intracellular vesicles to the plasma membrane. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 432040
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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101617view11:48, 1 November 2018ReactomeTeamreactome version 66
101153view21:34, 31 October 2018ReactomeTeamreactome version 65
100680view20:07, 31 October 2018ReactomeTeamreactome version 64
100230view16:52, 31 October 2018ReactomeTeamreactome version 63
99781view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99336view12:47, 31 October 2018ReactomeTeamreactome version 62
93786view13:36, 16 August 2017ReactomeTeamreactome version 61
93319view11:20, 9 August 2017ReactomeTeamreactome version 61
88349view16:17, 1 August 2016FehrhartOntology Term : 'water transport pathway' added !
88348view16:16, 1 August 2016FehrhartOntology Term : 'vasopressin signaling pathway' added !
86404view09:17, 11 July 2016ReactomeTeamreactome version 56
83089view09:57, 18 November 2015ReactomeTeamVersion54
81747view08:20, 26 August 2015ReactomeTeamVersion53
76842view08:06, 17 July 2014ReactomeTeamFixed remaining interactions
76546view11:53, 16 July 2014ReactomeTeamFixed remaining interactions
75879view09:53, 11 June 2014ReactomeTeamRe-fixing comment source
75579view10:41, 10 June 2014ReactomeTeamReactome 48 Update
74934view13:46, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74578view08:37, 30 April 2014ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AQP1 ProteinP29972 (Uniprot-TrEMBL)
AQP1 tetramerComplexR-HSA-432246 (Reactome)
AQP2 ProteinP41181 (Uniprot-TrEMBL)
AQP2 tetramerComplexR-HSA-432228 (Reactome)
AQP3 ProteinQ92482 (Uniprot-TrEMBL)
AQP3 tetramerComplexR-HSA-432250 (Reactome)
AQP4 ProteinP55087 (Uniprot-TrEMBL)
AQP4 tetramerComplexR-HSA-432252 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
AVP(20-28) ProteinP01185 (Uniprot-TrEMBL)
AVP(20-28)ProteinP01185 (Uniprot-TrEMBL)
AVPR2 ProteinP30518 (Uniprot-TrEMBL)
AVPR2:AVP(20-28)ComplexR-HSA-392261 (Reactome)
AVPR2:AVP:G-alpha(s):GDP:G-beta:G-gammaComplexR-HSA-432197 (Reactome)
AVPR2:AVP:G-alpha(s):GTP:G-beta:G-gammaComplexR-HSA-432187 (Reactome)
AVPR2ProteinP30518 (Uniprot-TrEMBL)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
G alpha


ComplexR-HSA-163622 (Reactome)
G alpha (s):GTPComplexR-HSA-164358 (Reactome)
G-alpha(s):GDP:G-beta:G-gammaComplexR-HSA-432200 (Reactome)
G-alpha(s):GTP:G-beta:G-gammaComplexR-HSA-422322 (Reactome)
G-beta:G-gamma (candidates)ComplexR-HSA-400034 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GGC-RAB11A ProteinP62491 (Uniprot-TrEMBL)
GNAS1 ProteinQ5JWF2 (Uniprot-TrEMBL)
GNAS2 ProteinP63092 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
MYO5B ProteinQ9ULV0 (Uniprot-TrEMBL)
MYO5B:RABFIP2:RAB11AComplexR-HSA-2028701 (Reactome)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
PKA catalytic subunitComplexR-HSA-111920 (Reactome)
PKA tetramer:4xcAMPComplexR-HSA-8951729 (Reactome)
PKA tetramerComplexR-HSA-111922 (Reactome)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA ProteinP17612 (Uniprot-TrEMBL)
PRKACB ProteinP22694 (Uniprot-TrEMBL)
PRKACG ProteinP22612 (Uniprot-TrEMBL)
PRKAR1A ProteinP10644 (Uniprot-TrEMBL)
PRKAR1B ProteinP31321 (Uniprot-TrEMBL)
PRKAR2A ProteinP13861 (Uniprot-TrEMBL)
PRKAR2B ProteinP31323 (Uniprot-TrEMBL)
RAB11FIP2 ProteinQ7L804 (Uniprot-TrEMBL)
cAMP MetaboliteCHEBI:17489 (ChEBI)
cAMP:PKA regulatory subunitComplexR-HSA-111923 (Reactome)
cAMPMetaboliteCHEBI:17489 (ChEBI)
p-S256-AQP2 ProteinP41181 (Uniprot-TrEMBL)
p-S256-AQP2 tetramerComplexR-HSA-432217 (Reactome)
p-S256-AQP2 tetramerComplexR-HSA-432226 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-432232 (Reactome)
AQP1 tetramermim-catalysisR-HSA-432010 (Reactome)
AQP1 tetramermim-catalysisR-HSA-432054 (Reactome)
AQP2 tetramerR-HSA-432232 (Reactome)
AQP3 tetramermim-catalysisR-HSA-445714 (Reactome)
AQP4 tetramermim-catalysisR-HSA-432067 (Reactome)
ATPR-HSA-164377 (Reactome)
ATPR-HSA-432232 (Reactome)
AVP(20-28)R-HSA-392263 (Reactome)
AVPR2:AVP(20-28)ArrowR-HSA-392263 (Reactome)
AVPR2:AVP(20-28)R-HSA-432188 (Reactome)
AVPR2:AVP:G-alpha(s):GDP:G-beta:G-gammaArrowR-HSA-432188 (Reactome)
AVPR2:AVP:G-alpha(s):GDP:G-beta:G-gammaR-HSA-432195 (Reactome)
AVPR2:AVP:G-alpha(s):GTP:G-beta:G-gammaArrowR-HSA-432195 (Reactome)
AVPR2R-HSA-392263 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-163617 (Reactome)
G alpha


ArrowR-HSA-163617 (Reactome)
G alpha


mim-catalysisR-HSA-164377 (Reactome)
G alpha (s):GTPArrowR-HSA-422320 (Reactome)
G alpha (s):GTPR-HSA-163617 (Reactome)
G-alpha(s):GDP:G-beta:G-gammaR-HSA-432188 (Reactome)
G-alpha(s):GTP:G-beta:G-gammaR-HSA-422320 (Reactome)
G-beta:G-gamma (candidates)ArrowR-HSA-422320 (Reactome)
GDPArrowR-HSA-432195 (Reactome)
GTPR-HSA-432195 (Reactome)
H2OArrowR-HSA-432010 (Reactome)
H2OArrowR-HSA-432054 (Reactome)
H2OArrowR-HSA-432065 (Reactome)
H2OArrowR-HSA-432067 (Reactome)
H2OArrowR-HSA-445714 (Reactome)
H2OR-HSA-432010 (Reactome)
H2OR-HSA-432054 (Reactome)
H2OR-HSA-432065 (Reactome)
H2OR-HSA-432067 (Reactome)
H2OR-HSA-445714 (Reactome)
MYO5B:RABFIP2:RAB11Amim-catalysisR-HSA-432237 (Reactome)
PKA catalytic subunitArrowR-HSA-111925 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-432232 (Reactome)
PKA tetramer:4xcAMPArrowR-HSA-8951727 (Reactome)
PKA tetramer:4xcAMPR-HSA-111925 (Reactome)
PKA tetramerR-HSA-8951727 (Reactome)
PPiArrowR-HSA-164377 (Reactome)
R-HSA-111925 (Reactome) The four protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The specific isoform activated in response to glucagon signalling is not known. The PKA kinase is a tetramer of two regulatory and two catalytic. The regulatory subunits block the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
R-HSA-163617 (Reactome) G(s)-alpha:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it.
R-HSA-164377 (Reactome) Activated adenylate cyclase associated with the plasma membrane catalyzes the reaction of cytosolic ATP to form 3',5'-cyclicAMP and pyrophosphate ().
R-HSA-392263 (Reactome) Arginine vasopressin receptor 2 (AVPR2) (Birnbaumer et al. 1992) is expressed in the kidneys and can bind the signal peptide Arg-vasopressin (AVP(20-28)), a cleaved peptide from the precursor AVP protein (Mohr et al. 1985, Sausville et al. 1985). This receptor uses the G protein alpha s subunit as its second messenger system.
R-HSA-422320 (Reactome) The binding of GTP by G(s) alpha causes the heterotrimeric G-protein complex to reorientate, exposing previously bound faces of the G(s) alpha:GTP complex and the G-beta: G-gamma complex. Unlike the case with Gi/o heterotrimers, Gs heterotrimers are not observed to significantly dissociate in living cells.
R-HSA-432010 (Reactome) Aquaporin-1 (AQP1) passively transports water across the plasma membrane according to the osmotic gradient. In the kidney AQP1 is expressed in endothelial cells of the vasa recta, the proximal tubule, and thin descending limb of Henle, where it functions to recover water from filtrate during urine formation. AQP1 is expressed in many other tissues, such as red blood cells, pancreas, and choroid plexus. AQP1 plays a role in forming cerebrospinal fluid.
R-HSA-432054 (Reactome) Aquaporin-1 (AQP1) passively transports water across the plasma membrane according to the osmotic gradient. In the kidney AQP1 is expressed in endothelial cells of the vasa recta, the proximal tubule, and thin descending limb of Henle, where it functions to recover water from filtrate during urine formation. AQP1 is expressed in many other tissues, such as red blood cells, pancreas, and choroid plexus. AQP1 plays a role in forming cerebrospinal fluid.
R-HSA-432065 (Reactome) Aquaporin-2 (AQP2) passively transports water across membranes according to the osmotic gradient. AQP2 is mainly expressed in principal cells of the collecting duct and connecting tubule in the kidney. AQP2 function is acutely regulated by the antidiuretc hormone vasopressin. In the presence of vasopressin AQP is phosphorylated at Ser256, As inferred from rat and mouse Ser261, Ser264, and Thr269 may also be phosphorylated. These phosphorylations are thought to influence AQP2 trafficking and compartmentalization.
R-HSA-432067 (Reactome) Aquaporin-4 (AQP4) passively transports water across the plasma membrane according to the osmotic gradient. AQP4 is expressed in the collecting duct of the kidney and in astroglial cells at the blood-brain barrier and ependymal cells lining the ventricles of the brain.
R-HSA-432188 (Reactome) The vasopressin receptor type 2 (AVPR2) interacts with G-protein alpha s via the third intracellular loop of AVPR2.
R-HSA-432195 (Reactome) The AVP:AVPR2 complex activates G-protein alpha s by causing a conformational change in G-protein alpha s that causes it to release GDP and bind GTP.
R-HSA-432232 (Reactome) Activated Protein Kinase A phosphorylates Aquaporin-2 at Serine 256. The phosphorylated form of AQP2 then traffics from intracellular vesicles to the apical plasma membrane.
R-HSA-432237 (Reactome) Intracellular vesicles bearing phosphorylated Aquaporin-2 tetramers are transported to the plasma membrane by a mechanism that may involve motor activity of myosin VB (inferred from rat, Nedvetsky et al. 2007) and dynein (inferred from toad bladder, Marples et al. 1996).
R-HSA-445714 (Reactome) Aquaporin-3 (AQP3) passively transports water and glycerol across the plasma membrane according to the osmotic gradient. AQP3 is expressed in airway epithelia, secretory glands, skin, the collecting ducts of the kidney, and the basolateral surface of intestinal epithelium..
R-HSA-8951727 (Reactome) Protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The isoform activated in response to glucagon signalling is not known.

PKA kinase is a tetramer of two regulatory and two catalytic subunits. The regulatory subunits block the activity of the catalytic subunits.

cAMP binds the regulatory subunits, which leads to dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
cAMP:PKA regulatory subunitArrowR-HSA-111925 (Reactome)
cAMPArrowR-HSA-164377 (Reactome)
cAMPR-HSA-8951727 (Reactome)
p-S256-AQP2 tetramerArrowR-HSA-432232 (Reactome)
p-S256-AQP2 tetramerArrowR-HSA-432237 (Reactome)
p-S256-AQP2 tetramerR-HSA-432237 (Reactome)
p-S256-AQP2 tetramermim-catalysisR-HSA-432065 (Reactome)
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