The GPCRome tree
Every human GPCR arranged by classification. Leaf size scales with development interest, colour marks the class. Hover to trace a receptor’s lineage back to its class; click to open it.
How GPCRs are classified
The tree above is not a random arrangement — it follows the standard classification of GPCRs. Two complementary systems are in common use, and Helix7 stores both.
A–F classes (Kolakowski, 1994)
The original scheme, based on shared sequence and structural features. Letters A–F label the classes: A (rhodopsin-like), B (secretin & adhesion), C (glutamate), D and E (non-vertebrate), and F (frizzled). Human receptors fall into classes A, B1, B2, C, and F.
GRAFS (Fredriksson, 2003)
A phylogenetic analysis of the human genome that sorted the family into five groups — Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin. These are the coloured groups in the tree.
| Class | A–F | GRAFS group | What it senses | Human |
|---|---|---|---|---|
| A | Class A | Rhodopsin | By far the largest class. Senses light, amines, nucleotides, lipids, peptides, and chemokines. Home to most drug targets. | 287 |
| B1 | Class B1 | Secretin | Large peptide hormones (GLP-1, glucagon, PTH) captured by a sizeable extracellular domain. | 15 |
| B2 | Class B2 | Adhesion | Huge N-termini with self-cleaving GAIN domains; roles in development, immunity, and cell adhesion. | 33 |
| C | Class C | Glutamate | Obligate dimers with 'Venus-flytrap' ligand domains — metabotropic glutamate, GABA-B, calcium-sensing, sweet/umami taste. | 22 |
| F | Class F | Frizzled | Frizzled and Smoothened receptors transducing Wnt and Hedgehog signalling in development and cancer. | 11 |
| T2 | — | Taste 2 | Bitter taste receptors — grouped with Frizzled under GRAFS, but a distinct family. | 25 |
| O1 | — | Olfactory | Human class I odorant receptors — the ancestral “fish-like” clade (OR51/52/56 families). All human genes. | 57 |
| O2 | — | Olfactory | Human class II (“tetrapod”) odorant receptors — the single largest gene family in the human genome. | 350 |
Reading the tree
Within each class, GPCRdb nests receptors in a hierarchy — class → ligand type → receptor family → receptor. The radial tree follows exactly this nesting: branches spread from the central root out through the class, then the family groupings, to the individual receptors at the tips. Receptors that sit close together share more sequence and, usually, a related endogenous ligand — which is why neighbouring leaves tend to be pharmacological relatives (all the adrenoceptors together, all the opioid receptors together, and so on).