Protein Details: P2X purinoceptor 4

Protein ID

ICDB_Pro_1539

Protein Name

P2X purinoceptor 4

Gene Name

P2rx4; P2x4

Organism

Mus musculus (Mouse)

Length

388 amino acids

AlphaFoldDB

AF-Q9JJX6-F1-model_v4.pdb

Function

ATP-gated nonselective transmembrane cation channel permeable to potassium; sodium and calcium. CTP; but not GTP or UTP; functions as a weak affinity agonist for P2RX4 (By similarity). Activated by extracellularly released ATP; it plays multiple role in immunity and central nervous system physiology. Plays a key role in initial steps of T-cell activation and Ca(2+) microdomain formation. Participates also in basal T-cell activity without TCR/CD3 stimulation. Promotes the differentiation and activation of Th17 cells via expression of retinoic acid-related orphan receptor C/RORC (By similarity). Upon activation; drives microglia motility via the PI3K/Akt pathway. Could also function as an ATP-gated cation channel of lysosomal membranes.

Sequence

MAGCCSVLGSFLFEYDTPRIVLIRSRKVGLMNRVVQLLILAYVIGWVFVWEKGYQETDSVVSSVTTKAKGVAVTNTSQLGFRIWDVADYVVPAQEENSLFIMTNMIVTVNQTQGTCPEIPDKTSICDSDANCTLGSSDTHSSGIGTGRCVPFNASVKTCEVAAWCPVENDAGVPTPAFLKAAENFTLLVKNNIWYPKFNFSKRNILPNITTSYLKSCIYNARTDPFCPIFRLGQIVADAGHSFQEMAVEGGIMGIQIKWDCNLDRAASHCLPRYSFRRLDTRDLEHNVSPGYNFRFAKYYRDLAGNEQRTLTKAYGIRFDIIVFGKAGKFDIIPTMINVGSGLALLGVATVLCDVIVLYCMKKRYYYRDKKYKYVEDYEQGLSGEMNQ

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 67; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 67; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 69; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 69; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 186; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 186; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 188; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 293; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 293; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 295; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 295; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 313; /ligand="ATP"; /ligand_id="ChEBI:CHEBI:30616"; /evidence="ECO:0000250|UniProtKB:F8W463"; BINDING 313; /ligand="CTP"; /ligand_id="ChEBI:CHEBI:37563"; /evidence="ECO:0000250|UniProtKB:F8W463"

Disease

Location

DOI ID

10.1002/glia.20489; 10.1016/j.cell.2010.12.001; 10.1016/j.bbrc.2015.10.025; 10.1113/jp271893; 10.1126/sciadv.abl9770