AVPR2

Protein identityUniProt · HPA

UniProt accession

P30518

Gene

AVPR2

Ensembl

ENSG00000126895

Chromosome

X

Canonical length

371 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes the vasopressin receptor, type 2, also known as the V2 receptor, which belongs to the seven-transmembrane-domain G protein-coupled receptor (GPCR) superfamily, and couples to Gs thus stimulating adenylate cyclase. The subfamily that includes the V2 receptor, the V1a and V1b vasopressin receptors, the oxytocin receptor, and isotocin and mesotocin receptors in non-mammals, is well conserved, though several members signal via other G proteins. All bind similar cyclic nonapeptide hormones. The V2 receptor is expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts, where its primary property is to respond to the pituitary hormone arginine vasopressin (AVP) by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of this gene is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. The V2 receptor is also expressed outside the kidney although its tissue localization is uncertain. When these 'extrarenal receptors' are stimulated by infusion of a V2 selective agonist (dDAVP), a variety of clotting factors are released into the bloodstream. The physiologic importance of this property is not known - its absence does not appear to be detrimental in NDI patients. The gene expression has also been described in fetal lung tissue and lung cancer associated with alternative splicing. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

371 residues, UniProt reviewed canonical sequence.

>P30518|AVPR2
     1  MLMASTTSAV PGHPSLPSLP SNSSQERPLD TRDPLLARAE LALLSIVFVA VALSNGLVLA
    61  ALARRGRRGH WAPIHVFIGH LCLADLAVAL FQVLPQLAWK ATDRFRGPDA LCRAVKYLQM
   121  VGMYASSYMI LAMTLDRHRA ICRPMLAYRH GSGAHWNRPV LVAWAFSLLL SLPQLFIFAQ
   181  RNVEGGSGVT DCWACFAEPW GRRTYVTWIA LMVFVAPTLG IAACQVLIFR EIHASLVPGP
   241  SERPGGRRRG RRTGSPGEGA HVSAAVAKTV RMTLVIVVVY VLCWAPFFLV QLWAAWDPEA
   301  PLEGAPFVLL MLLASLNSCT NPWIYASFSS SVSSELRSLL CCARGRTPPS LGPQDESCTT
   361  ASSSLAKDTS S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AVPR2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AVPR2.

Disease | AllUniProt

Conditions AVPR2 is implicated in, by any mechanism.

• Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) MIM:300539
• Diabetes insipidus, nephrogenic, 1, X-linked (NDI1) MIM:304800

Disease | GeneticClinVar

110 pathogenic / likely-pathogenic of 427 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Diabetes insipidus, nephrogenic, X-linked
• Nephrogenic diabetes insipidus
• Nephrogenic syndrome of inappropriate antidiuresis
• AVPR2-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.72

gnomAD pLI

0.56

gnomAD missense Z

1.01

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of adenylate cyclase activity
• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• cellular response to hormone stimulus
• G protein-coupled receptor signaling pathway
• hemostasis
• negative regulation of cell population proliferation
• positive regulation of cell population proliferation
• positive regulation of gene expression
• positive regulation of intracellular signal transduction
• positive regulation of systemic arterial blood pressure
• positive regulation of vasoconstriction
• regulation of systemic arterial blood pressure by vasopressin
• renal water absorption
• response to cytokine
• telencephalon development
• renal water retention

Molecular functions

• vasopressin receptor activity

Cellular components

• clathrin-coated endocytic vesicle membrane
• endocytic vesicle
• endoplasmic reticulum
• endosome
• Golgi apparatus
• membrane
• perinuclear region of cytoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Vasopressin receptor
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Vasopressin V2 receptor

KeywordsUniProt

• Cell membrane
• Diabetes insipidus
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Receptor
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of AVPR2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRDC4
• TMEM147