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9.A.14.3.8
Adenosine A2a receptor of 412 aas and 7 TMSs. It is a lipid flippase and a water channel (see below). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.  The crystal structure has been solved revealing a continuous water channel (Yuan et al. 2015).  Tryptophan-246 in TMS6 forms the gate. Conformational changes in TMSs 6 and 7 produce local changes in the lipid bilayer (Yuan et al. 2015).  The protein can function as an ATP-independent phopholipid flippase (scramblase) (Goren et al. 2014). Yuan et al. 2015 found that the conserved W246(6.48) residue in transmembrane helix TM6 performs a key rotamer toggle switch. Agonist binding induces the sidechain of W246(6.48) to fluctuate between two distinct conformations, enabling the diffusion of water molecules from the bulk into the center of the receptor. After passing the W246(6.48) gate, the internal water molecules induce another conserved residue, Y288(7.53), to switch to a distinct rotamer conformation establishing a continuous transmembrane water pathway. Further, structural changes of TM6 and TM7 induce local structural changes of the adjacent lipid bilayer (Yuan et al. 2015). The human A2A adenosine receptor was structurally determined by microcrystal electron diffraction (MicroED) after converting the lipidic cubic phase (LCP) into the sponge phase followed by focused ion-beam milling. Martynowycz et al. 2021 determined the structure of the A2A adenosine receptor to 2.8 Å resolution and resolved an antagonist in its orthosteric ligand-binding site, as well as four cholesterol molecules bound around the receptor. Fusion protein strategies for cryo-EM study of this and other G protein-coupled receptors have been described (Zhang et al. 2022).

Accession Number:P29274
Protein Name:Adenosine receptor A2a
Length:412
Molecular Weight:44707.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate phospholipid, water

Cross database links:

Structure:
2YDO   2YDV   3EML   3PWH   3QAK   3REY   3RFM   3UZA   3UZC   3VG9   [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MPIMGSSVYI TVELAIAVLA ILGNVLVCWA VWLNSNLQNV TNYFVVSLAA ADIAVGVLAI 
61:	PFAITISTGF CAACHGCLFI ACFVLVLTQS SIFSLLAIAI DRYIAIRIPL RYNGLVTGTR 
121:	AKGIIAICWV LSFAIGLTPM LGWNNCGQPK EGKNHSQGCG EGQVACLFED VVPMNYMVYF 
181:	NFFACVLVPL LLMLGVYLRI FLAARRQLKQ MESQPLPGER ARSTLQKEVH AAKSLAIIVG 
241:	LFALCWLPLH IINCFTFFCP DCSHAPLWLM YLAIVLSHTN SVVNPFIYAY RIREFRQTFR 
301:	KIIRSHVLRQ QEPFKAAGTS ARVLAAHGSD GEQVSLRLNG HPPGVWANGS APHPERRPNG 
361:	YALGLVSGGS AQESQGNTGL PDVELLSHEL KGVCPEPPGL DDPLAQDGAG VS