Protein Details: Aquaporin-8

Protein ID

ICDB_Pro_0289

Protein Name

Aquaporin-8

Gene Name

AQP8

Organism

Homo sapiens (Human)

Length

261 amino acids

AlphaFoldDB

AF-O94778-F1-model_v4.pdb

Function

Channel that allows the facilitated permeation of water and uncharged molecules;such as hydrogen peroxide and the neutral form of ammonia (NH3);through cellular membranes such as plasma membrane;inner mitochondrial membrane and endoplasmic reticulum membrane of several tissues. The transport of the ammonia neutral form induces a parallel transport of proton;at alkaline pH when the concentration of ammonia is high (By similarity). However;it is unclear whether the transport of proton takes place via the aquaporin or via an endogenous pathway (By similarity). Also;may transport ammonia analogs such as formamide and methylamine;a transport favourited at basic pH due to the increase of unprotonated (neutral) form;which is expected to favor diffusion . Does not transport urea or glycerol . The water transport mechanism is mercury- and copper-sensitive and passive in response to osmotic driving forces . At the canicular plasma membrane;mediates the osmotic transport of water toward the bile canaliculus and facilitates the cAMP-induced bile canalicular water secretion;a process involved in bile formation . In addition;mediates the hydrogen peroxide release from hepatocyte mitochondria that modulates the SREBF2-mediated cholesterol synthesis and facilitates the mitochondrial ammonia uptake which is metabolized into urea;mainly under glucagon stimulation. In B cells;transports the CYBB-generated hydrogen peroxide from the external leaflet of the plasma membrane to the cytosol to promote B cell activation and differentiation for signal amplification (By similarity). In the small intestine and colon system;mediates water transport through mitochondria and apical membrane of epithelial cells (By similarity). May play an important role in the adaptive response of proximal tubule cells to acidosis possibly by facilitating the mitochondrial ammonia transport .

Sequence

MSGEIAMCEPEFGNDKAREPSVGGRWRVSWYERFVQPCLVELLGSALFIFIGCLSVIENGTDTGLLQPALAHGLALGLVIATLGNISGGHFNPAVSLAAMLIGGLNLVMLLPYWVSQLLGGMLGAALAKAVSPEERFWNASGAAFVTVQEQGQVAGALVAEIILTTLLALAVCMGAINEKTKGPLAPFSIGFAVTVDILAGGPVSGGCMNPARAFGPAVVANHWNFHWIYWLGPLLAGLLVGLLIRCFIGDGKTRLILKAR

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Metabolic Acidosis and Polyhydramnios

Location

Detected in the sperm midpiece (at protein level) (PubMed:28042826). Expressed only in pancreas and colon.

DOI ID

10.1006/geno.1998.5552; 10.1101/gr.2596504; 10.1042/bc20050026; 10.1152/ajpgi.90410.2008; 10.1111/j.1447-0756.2009.01061.x; 10.1152/ajprenal.00226.2012; 10.3390/ijms18010066; 10.1089/ars.2013.5330; 10.1089/ars.2016.6636; 10.1126/sciadv.aar5770; 10.1016/j.freeradbiomed.2018.12.016; 10.1002/bit.27901; 10.1126/science.1133427

RefSeq

NP_001160.2

Feature