A0A1Z0YU59 · MAMB1_DENAN

Function

function

Selectively interacts with vasopressin V2 receptor (V2R/AVPR2) and fully inhibits three major signaling pathways of this receptor that are GalphaS protein, the interaction with beta-arrestin and activation of MAP kinase (PubMed:28630289, PubMed:35122240).
Inhibits vasopressin binding human V2R in the nanomolar range (Ki=5.02 nM), and also potently inhibits vasopressin-induced cAMP production (IC50=94 nM) (PubMed:35122240).
In vivo, this protein shows an aquaretic effect (PubMed:28630289, PubMed:35122240).
Urine output increases and urine osmolality decreases dramatically under treatment with this protein, without differences observed between healthy mice and the pcy mice model of the autosomal-dominant polycystic kidney disease (ADPKD) (PubMed:28630289).
This protein does not modify electrolyte, protein and urea excretions in the urine samples, but produces a 3-fold decrease of creatinine levels (PubMed:28630289).
Intraperitoneal injection of this protein into the pcy mice significantly reduces the number of renal cysts and the total area of cysts (PubMed:28630289).
This protein also shows high efficacy in preventing hyponatremia in rat models (induced by DAVP) (PubMed:33052234).
Is highly visible in mice liver and kidney after intravenous injection (PubMed:33052234).
Is rapidly eliminated in the liver, whereas it exhibits slow elimination in the kidney due to the high expression of V2R which acts as a reservoir (PubMed:33052234).
In addition, its elimination from blood is rapid (PubMed:33052234).
Fluorescent MQ1 probes could also be used for imaging V2R-overexpressing cancer cells; note that these probes label the three renal cancer cell lines CAKI-2, ACHN and A498 that highly express V2R (PubMed:33052234).
In vivo, does not show any toxicity on animals, even at highest doses tested, such as prostration, spidy coat, appetite or weight loss (PubMed:33052234).

Miscellaneous

Negative results: shows a weak inhibition on trypsin (PRSS1) (IC50=14.8 uM) and Kv1.1/KCNA1 (IC50=8.2 uM). Does not interact with vasopression V1a, V1b and the oxytocin receptors. Does not show activity on potassium (except Kv1.1), sodium, and calcium (Cav1.2) channels. Does not show agonist and antagonist activities on the 156 GPCR tested. Does not activate pathways of the vasopression V2 receptor.

Biotechnology

Is a new promising drug for aquaresis-related diseases, including hyponatremia, and a molecular probe to visualize in vitro and in vivo V2R expressed physiologically or under pathological conditions.
Is a new promising therapeutic agent against polycystic kidney diseases (PKD). It shows renoprotective effect on the murine model for PKD, since the number of renal cysts and the total area of cysts is significantly reduced after treatment with this protein.

GO annotations

AspectTerm
Cellular Componentextracellular region
Molecular Functionserine-type endopeptidase inhibitor activity
Molecular Functiontoxin activity

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Mambaquaretin-1
  • Short names
    MQ-1
    ; MQ1
  • Alternative names
    • Upsilon-Da2a

Organism names

Accessions

  • Primary accession
    A0A1Z0YU59
  • Secondary accessions
    • C0HK15

Subcellular Location

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis1-4No change in affinity for V2R, loss of activity on Kv1.1/KCNA1.
Mutagenesis3Important (26-fold) increase in activity on Kv1.1/KCNA1, no change in affinity for V2R.
Mutagenesis921-fold decrease in affinity for human V2R.
Mutagenesis10106-fold decrease in affinity for human V2R.
Mutagenesis15-16Important increase in trypsin inhibition, 1000-fold decrease in affinity for V2R.
Mutagenesis17730-fold decrease in affinity for human V2R.
Mutagenesis1853-fold decrease in affinity for human V2R.
Mutagenesis3424-fold decrease in affinity for human V2R.
Mutagenesis398-fold increase in affinity for human V2R, but not for rat V2R. No change in diuresis in rat. The analog is 14-fold more specific for human V2R than for rat V2R.
Mutagenesis4414-fold decrease in affinity for human V2R.

PTM/Processing

Features

Showing features for chain, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00004422311-57Mambaquaretin-1
Disulfide bond5↔55
Disulfide bond14↔38
Disulfide bond30↔51

Keywords

Expression

Tissue specificity

Expressed by the venom gland.

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain5-55BPTI/Kunitz inhibitor
Region15-16Important for binding V2R

Domain

Exploits its two major loops and engages more positions in its interaction with V2R (PubMed:35122240).
The pharmacophore defined by numerous amino acids positioned in loop 1 (9 to 18) and loop 2 (34, 39 and 44) may be at the origin of the absolute selectivity of this protein for V2R (Probable)

Sequence similarities

Belongs to the venom Kunitz-type family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    57
  • Mass (Da)
    6,377
  • Last updated
    2017-11-22 v2
  • Checksum
    CA79C78B3506D076
RPSFCNLPVKPGPCNGFFSAFYYSQKTNKCHSFTYGGCKGNANRFSTIEKCRRTCVG

Mass Spectrometry

Molecular mass is 6,367.2 Da. Determined by MALDI.
Molecular mass is 6,366.94 Da. Determined by MALDI. Monoisotopic mass.

Keywords

Similar Proteins

Disclaimer

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