Relationships between G-protein-coupled receptors

It is possible to find links between the rhodopsin and calcitonin/secretin families of G-protein by looking at sequences that are distantly related to opsin, and then using those sequences to re-search the sequence databases. The table below shows a greatly abbreviated summary of a search using human opsin (OPSD_HUMAN) against SwissPROT. In this example, no members of the secretin/calcitonin family are found with expectation values < 10 (results are shown only to 1.0). However,many members of the rhodopsin family have expectation values > 0.1.

The best scores are:                                  s-w Z-score E(43470)
OPSD_HUMAN RHODOPSIN.                                2347 2978.5      0
OPSG_CHICK GREEN-SENSITIVE OPSIN (GREEN CONE PHOTO   1791 2266.9      0
OPSG_HUMAN GREEN-SENSITIVE OPSIN (GREEN CONE PHOTO   1002 1261.9      0
OPS1_DROME OPSIN RH1 (OUTER R1-R6 PHOTORECEPTOR CE    527 658.4 3.1e-30
NK2R_MOUSE SUBSTANCE-K RECEPTOR (SKR) (NEUROKININ     435 540.6 1.1e-23
SSR5_HUMAN SOMATOSTATIN RECEPTOR TYPE 5.              431 538.2 1.5e-23
TXKR_HUMAN PUTATIVE TACHYKININ RECEPTOR.              419 513.8 3.5e-22
5H7_HUMAN 5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7)     283 365.5 6.4e-14
CKR1_HUMAN C-C CHEMOKINE RECEPTOR TYPE 1 (C-C CKR-    280 363.4 8.5e-14
ETBR_RAT ENDOTHELIN B RECEPTOR PRECURSOR (ET-B) (E    278 358.9 1.5e-13
AA2B_RAT ADENOSINE A2B RECEPTOR.                      276 358.6 1.6e-13
GRPR_MOUSE GASTRIN-RELEASING PEPTIDE RECEPTOR (GRP    276 357.4 1.8e-13
A1AC_BOVIN ALPHA-1C ADRENERGIC RECEPTOR.              250 321.1 1.9e-11
AG2R_PIG TYPE-1 ANGIOTENSIN II RECEPTOR (AT1).        247 319.2 2.5e-11
THRR_CRILO THROMBIN RECEPTOR PRECURSOR.               260 316.5 3.4e-11
CB1R_HUMAN CANNABINOID RECEPTOR 1 (CB1) (CB-R).       245 314.3 4.6e-11
D2DR_BOVIN D(2) DOPAMINE RECEPTOR.                    242 310.7 7.2e-11
5H2A_RAT 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A)    242 310.3 7.7e-11
GUSB_BOVIN POSSIBLE GUSTATORY RECEPTOR TYPE B (PPR    240 310.0 8.0e-11
IL8B_MOUSE HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B     240 309.8 8.2e-11
ACM1_MOUSE MUSCARINIC ACETYLCHOLINE RECEPTOR M1.      238 305.1 1.5e-10
...
OLFI_HUMAN OLFACTORY RECEPTOR-LIKE PROTEIN HGMP07I    146 179.9 0.001
OLF7_RAT OLFACTORY RECEPTOR-LIKE PROTEIN I7.          146 179.1 0.002
MC3R_RAT MELANOCORTIN-3 RECEPTOR (MC3-R).             140 177.0 0.002
OLF6_CHICK OLFACTORY RECEPTOR-LIKE PROTEIN COR6.      139 171.0 0.004
MAS_MOUSE MAS PROTO-ONCOGENE.                         133 167.6 0.007
PAFR_MACMU PLATELET ACTIVATING FACTOR RECEPTOR (PA    130 167.0 0.007
OLF2_RAT OLFACTORY RECEPTOR-LIKE PROTEIN F12.         135 165.6 0.009
MAS_RAT MAS PROTO-ONCOGENE.                           131 164.9 0.01
CAR1_DICDI CYCLIC AMP RECEPTOR 1.                     130 162.0 0.01 
OLF2_CHICK OLFACTORY RECEPTOR-LIKE PROTEIN COR2.      129 158.1 0.02
CAR3_DICDI CYCLIC AMP RECEPTOR 3.                     124 152.2 0.05
MAS_HUMAN MAS PROTO-ONCOGENE.                         120 150.2 0.06
OLF1_CHICK OLFACTORY RECEPTOR-LIKE PROTEIN COR1.      117 142.4 0.17
PER2_MOUSE PROSTAGLANDIN E RECEPTOR, EP2 SUBTYPE.     121 140.0 0.23
PER2_HUMAN PROSTAGLANDIN E2 RECEPTOR, EP2 SUBTYPE.    120 139.5 0.25
UL33_HCMVA G-PROTEIN COUPLED RECEPTOR HOMOLOG UL33    117 139.2 0.26
GU58_RAT POSSIBLE GUSTATORY RECEPTOR CLONE PTE58      109 138.2 0.30
CAR2_DICDI CYCLIC AMP RECEPTOR 2.                     111 137.0 0.35
MSHR_MOUSE MELANOCYTE STIMULATING HORMONE RECEPTOR    111 134.9 0.45
MSHR_HUMAN MELANOCYTE STIMULATING HORMONE RECEPTOR    111 134.8 0.46
LIVM_ECOLI HIGH-AFFINITY BRANCHED-CHAIN AMINO ACID    109 133.3 0.55
>>APPC_ECOLI PROBABLE CYTOCHROME OXIDASE SUBUNIT I    110 133.1 0.57 <<
>>BIOX_BACSH BIOX PROTEIN.                            102 131.5 0.69 <<
RTA_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR RTA.      109 131.0 0.74
GU45_RAT POSSIBLE GUSTATORY RECEPTOR CLONE PTE45      102 128.8 0.99
AROP_ECOLI AROMATIC AMINO ACID TRANSPORT PROTEIN A    106 128.7 1.00

Additional searches using a very distantly related member of this family - CAR1_DICDI - show the link between OPSD_HUMAN and the calcitonin/secretin family.

As before, it is easy to show that he BIOX_BACSH protein is not a G-protein-coupled receptor. Additional searches with this sequence do not turn up signficant matches with any members of that family.