CODSWALLOP

Adenosine receptor A2a

Homo sapiens · seed P29274 · 412 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

559Entries 559Entities 204Constructs 15Organisms 536Ligand-bound
1.70 ÅBest res.
2.89 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

9P1T, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 9P1T
9P1T at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

1206412540 constructs

Constructs, most-used first

204 distinct constructs across 559 entries. 514 polymer entities differ from the UniProt canonical sequence in some way, 90 carry a recognised expression tag and 212 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
88 433 1.84 7IO5 fused to BRIL (internal); residues 1-328; 1 internal deletion; M1P, A54L, T88A +16 more
81 460 2.50 9Q3L 3C/PreScission site; G16R, E27Q, M96T +4 more
19 433 1.70 5NM4 fused to BRIL (internal); residues 1-328; 1 internal deletion; M1P, A54L, T88A +17 more
16 447 1.80 4EIY fused to BRIL (internal); residues 1-330; 2 internal deletions; M1P, A317H, G318H +7 more
10 449 1.94 8RW0 fused to BRIL (internal); residues 1-328; 1 internal deletion; M1P, A54L, T88A +16 more
9 315 2.30 4AMJ residues 31-373; 1 internal deletion; V31M, S32G, R68S +12 more
8 434 1.87 5OLG fused to BRIL (internal); residues 1-328; 1 internal deletion; M1P, A54L, T88A +17 more
8 506 2.40 6PS2 His6; M1L, C54T, C97A +2 more
7 313 2.70 2VT4 residues 31-373; 2 internal deletions; V31M, S32G, R68S +12 more
6 465 3.00 7EJ8 matches the canonical sequence
6 469 2.79 4LDE fused to T4 lysozyme (internal); residues 17-348; 1 internal deletion; 2-residue insertion after 26; S17D, H18Y, A19K +12 more
6 500 2.40 2RH1 fused to T4 lysozyme (internal); residues 1-365; 1 internal deletion; G16R, E27Q, N187E
5 307 2.50 6H7N residues 39-373; 1 internal deletion; Q39A, W40A, E41A +14 more
5 329 3.27 3UZA residues 1-329; A54L, T88A, R107A +16 more
5 336 2.13 6TOS residues 25-399; 2 internal deletions; P25A, D26A, Y27S +21 more
5 368 2.30 6TQ4 residues 25-399; 1 internal deletion; P25A, D26A, Y27S +21 more
5 508 2.50 8DCS FLAG+His5; fused to T4 lysozyme (internal); residues 1-368; 2 internal deletions; M1L, G2F, D3Q +4 more
5 794 2.86 8YH0 His8; fused to GFP; 3C/PreScission site; M1G
4 325 2.60 2YDV residues 1-325; L48A, A54L, T65A +10 more
4 341 2.59 9M2O matches the canonical sequence
4 421 2.30 5ZKC fused to BRIL (internal); 3C/PreScission site; 1 internal deletion; N2D, N3D, N6D +2 more
4 490 2.80 3D4S His6; M1L, R12G, C54T +4 more
3 353 2.63 9EE8 FLAG; TEV site; residues 1-330; 1 internal deletion; M1A, V229C, R291A +9 more
3 395 3.16 7DH5 residues 1-386; M1G, A380E, A381N +5 more
3 455 2.17 6ZFZ His10; M1A, R12G, C54T +5 more

Showing the 25 most-used of 204.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

S277G 67% G318A 66% I108S 65% Q297I 65% T279V 65% G114S 65% V282G 65% S35E 65% H230K 65% N36R 64% V275W 64% A50C 64% F286L 64% A265K 64% F257V 64% A59V 63% A73G 63% N39T 63% W29T 63% G118K 63% N175Q 63% G328H 63% I3V 62% V229H 62% A17V 62% I127M 62% W32A 62% F93E 61% G195F 61% I53L 61%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 333 59.6%
tetrameric4 81 14.5%
pentameric5 75 13.4%
dimeric2 39 7.0%
trimeric3 23 4.1%
hexameric6 8 1.4%

185 entries have the depositor's assembly corroborated by PISA, 340 carry the depositor's word alone and 34 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 11 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 2VT4, 2Y00, 2Y01, 2Y02, 2Y03, 2Y04, 4DAJ, 4U14, 4U15, 5DSG, 5UIG.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHGlutaredoxinRhodopsin 7-helix transmem1.10.530.40Cytochrome c/b562Glycogen Phosphorylase B;SCOP2BG protein-coupled receptorThioredoxin-likeG protein-coupled receptorG protein-coupled receptorG protein-coupled receptorCytochromesLysozyme-likeG protein-coupled receptorG protein-coupled receptorType B glycosyltransferaseFlavoproteinsG protein-coupled receptorG protein-coupled receptorG protein-coupled receptor1206412
DomainSourceSpan (seed)Chains
GlutaredoxinCATH 3.40.30.10 18–124 6
Rhodopsin 7-helix transmembrane proteinsCATH 1.20.1070.10 28–326 95
1.10.530.40CATH 206–364 35
Cytochrome c/b562CATH 1.20.120.10 222–332 11
Glycogen Phosphorylase B;CATH 3.40.50.2000 280–412 5
G protein-coupled receptor-likeSCOP2B 8091190 13–412 186
Thioredoxin-likeSCOP2B 8044359 18–123 6
G protein-coupled receptor-likeSCOP2B 8091152 21–315 20
G protein-coupled receptor-likeSCOP2B 8091160 54–249 9
G protein-coupled receptor-likeSCOP2B 8091150 63–412 41
CytochromesSCOP2B 8057879 219–319 150
Lysozyme-likeSCOP2B 8033861 226–385 41

What binds it

NA NA179 entries G1I G1I81 entries TEP TEP79 entries GTP GTP40 entries ZMA ZMA34 entries SOG SOG18 entries CAU CAU12 entries PGW PGW11 entries ADN ADN10 entries 1WV 1WV10 entries HSM HSM10 entries ACM ACM8 entries
ComponentClassNameEntriesBest (Å)
CLRlipid/detergent Cholesterol 214 1.70
OLAlipid/detergent Oleic Acid 201 1.70
OLClipid/detergent (2r)-2,3-Dihydroxypropyl (9z)-Octadec-9-Enoate 186 1.72
NAcofactor Sodium Ion 179 1.70
G1Iligand (5r,6r)-6-(Methylamino)-5,6,7,8-Tetrahydronaphthalene-1,2,5-Trio 81 2.90
TEPligand Theophylline 79 1.84
PEGcryoprotectant Di(Hydroxyethyl)ether 64 1.80
GTPcofactor Guanosine-5'-Triphosphate 40 2.90
SO4ion Sulfate Ion 37 2.11
ZMAligand 4-{2-[(7-Amino-2-Furan-2-Yl[1,2,4]triazolo[1,5-A][1,3,5]triazin- 34 1.70
OLBlipid/detergent (2s)-2,3-Dihydroxypropyl (9z)-Octadec-9-Enoate 28 1.72
DMScryoprotectant Dimethyl Sulfoxide 23 1.84
SOGligand Octyl 1-Thio-Beta-D-Glucopyranoside 18 2.11
2CVlipid/detergent Hega-10 16 2.30
PLMlipid/detergent Palmitic Acid 14 2.40
PG4cryoprotectant Tetraethylene Glycol 13 2.11
CAUligand (2s)-1-(9h-Carbazol-4-Yloxy)-3-(Isopropylamino)propan-2-Ol 12 2.40
Y01lipid/detergent Cholesterol Hemisuccinate 12 2.50
PGWligand (1r)-2-{[(S)-{[(2s)-2,3-Dihydroxypropyl]oxy}(Hydroxy)phosphoryl] 11 2.11
ADNcofactor Adenosine 10 2.63

How it crystallises

Parsed from the free text 334 depositors typed into _exptl_crystal_grow.pdbx_details, out of 339 entries that recorded anything at all. Median pH 5.5 (range 4.2 to 9.0).

Precipitants

PEG × MPD × Sodium citrate × Sodium chloride × Lithium sulfate × Ammonium sulfate × Magnesium chloride × Ammonium phosphate × Sodium formate × Sodium malonate × Jeffamine × Calcium chloride × Isopropanol × Tacsimate ×

Buffers

MES × Citrate × HEPES × Tris × Bis-Tris propane × Phosphate × Sodium cacodylate × ADA × Sodium acetate × Bis-Tris × Glycine ×

Which entries to trust

559 entries carry a wwPDB validation report: 340 clean, 193 worth a check and 26 with something to explain. Median clashscore 5.26, median RSRZ outliers 5.84%, median R-free minus R-work 0.036. 559 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens473 1.70 452 82%
Meleagris gallopavo30 2.10 29 70%
Tequatrovirus T419 2.50 19 81%
Escherichia coli11 2.71 10 82%
Rattus norvegicus5 2.80 5 34%
Influenza A virus (A/Victoria/3/1975(H3N2))5 2.86 5 79%
Canis lupus familiaris3 3.16 3 70%
Acetivibrio thermocellus ATCC 274053 3.21 3 24%
Mus musculus2 2.92 2 72%
Enterobacteria phage RB592 3.20 2 71%
Ixodes scapularis2 3.39 2 69%
Escherichia coli K-121 2.70 1 70%

Seed sequence

412 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

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

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 An integrated experimental and computational pipeline for crystallographic fragment screening of membrane protein in the lipid cubic phase. Commun Chem doi:10.1038/s42004-026-02059-7
2026 Structural Mechanism of an Efficacy Photoswitch Targeting the beta 2 -adrenergic Receptor. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202517995
2026 A biased allosteric modulator is a molecular glue for beta 2 AR dimerization. Nature doi:10.1038/s41586-026-10892-y
2026 Discovery of MK-1088 as a Potent A 2A /A 2B Adenosine Receptor Dual-Antagonist for Cancer Immunotherapy. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03405
2026 Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent. Signal Transduct Target Ther doi:10.1038/s41392-026-02865-4
2026 Development of a random background to understand ligand optimization. Nature doi:10.1038/s41586-026-11013-5
2026 Mechanistic Basis for 5-HT 2A R Over 5-HT 2B R Activation. Nat Commun doi:10.1038/s41467-026-77659-x
2026 A novel fusion tool to enable G protein-coupled receptor structure determination. Acta Crystallogr D Struct Biol doi:10.1107/S2059798326003785
2026 A negative survival pressure selection system enables GPCR antagonist screening. Cell Discov doi:10.1038/s41421-026-00892-7
2026 Structure-based design of subtype-selective psychedelic analogs. Nat Commun doi:10.1038/s41467-026-77658-y
2026 A GPCR-G protein-beta-arrestin megacomplex enabled by a versatile allosteric modulator. Cell doi:10.1016/j.cell.2025.12.023
2026 Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X26003432
2026 Large Library Docking for Polypharmacology. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03810
2026 Rapid and Label-Free Structural Proteomics Using One-Step Swift Trypsin LiP-MS. Acs Omega doi:10.1021/acsomega.5c11109
2026 Decoding ligand recognition and constitutive activation of histamine H3 and H4 receptors. Acta Pharmacol.Sin. doi:10.1038/s41401-025-01633-4
2026 Cryo-EM structure of a single-chain beta 1-adrenoceptor - AmpC beta-lactamase fusion protein. J.Struct.Biol. doi:10.1016/j.jsb.2026.108349
2025 Identification of nanomolar adenosine A 2A receptor ligands using reinforcement learning and structure-based drug design. Nat Commun doi:10.1038/s41467-025-60629-0
2025 Cryo-EM reveals an extrahelical allosteric binding site at the M 5 mAChR. Nat Commun doi:10.1038/s41467-025-62212-z
2025 Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron. Commun Chem doi:10.1038/s42004-024-01404-y
2025 Structural insights into nonpeptide antagonist inhibition of somatostatin receptor subtype 5. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2522515122
2025 Structure and function of a near fully-activated intermediate GPCR-G alpha beta gamma complex. Nat Commun doi:10.1038/s41467-025-56434-4
2025 Structural insights into ligand recognition and G protein preferences across histamine receptors. Commun Biol doi:10.1038/s42003-025-08363-7
2025 Chemosensation of the pheromone spermine by the olfactory TAAR-like receptor TAAR348. Cell Discov doi:10.1038/s41421-025-00839-4
2025 Structure and dynamics determine G protein coupling specificity at a class A GPCR. Sci Adv doi:10.1126/sciadv.adq3971
2025 Structural insights into the agonist activity of the nonpeptide modulator JR14a on C3aR. Cell Discov doi:10.1038/s41421-024-00765-x
2025 Structural basis of oligomerization-modulated activation and autoinhibition of orphan receptor GPR3. Cell Rep doi:10.1016/j.celrep.2025.115478
2025 Mechanism and function of GPR3 regulated by a negative allosteric modulator. Nat Commun doi:10.1038/s41467-025-63422-1
2025 Systematic metabolite screening identifies functional regulators of the adenosine A2A receptor. Commun Chem doi:10.1038/s42004-025-01825-3
2025 Molecular basis of ligand binding and receptor activation at the human A 3 adenosine receptor. Nat Commun doi:10.1038/s41467-025-62872-x
2025 Extracellular nanobody screening using conformationally stable GPCR variants. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2508879122
2025 Cryo-EM structure of a cell-free synthesized full-length human beta 1-adrenergic receptor in complex with G s . Structure doi:10.1016/j.str.2025.07.020
2025 Structural insights into endogenous agonist selectivity of aminergic receptors from the octopamine beta 2 receptor. Pnas Nexus doi:10.1093/pnasnexus/pgaf376
2025 Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR. Embo J. doi:10.1038/s44318-025-00429-w
2025 Structure-guided engineering of snake toxins for selective modulation of adrenergic and muscarinic receptors. Nat Commun doi:10.1038/s41467-025-61695-0
2025 Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks. Nat.Chem. doi:10.1038/s41557-024-01719-2
2024 Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography. Nat Commun doi:10.1038/s41467-024-55109-w
2024 Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson's disease. Sci.Signal. doi:10.1126/scisignal.ado8741
2024 Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A 2 receptors. Sci China Life Sci doi:10.1007/s11427-023-2459-8
2024 Molecular Mechanism of the beta 3 AR Agonist Activity of a beta-Blocker. Chempluschem doi:10.1002/cplu.202400288
2024 7.10 MAG. A Novel Host Monoacylglyceride for In Meso (Lipid Cubic Phase) Crystallization of Membrane Proteins. Cryst.Growth Des. doi:10.1021/acs.cgd.4c00087