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Linking the rhodopisin and calcitonin/secretin families


A search of SwissPROT using CAR1_DICDI is shown below. This sequence seems to bridge the two G-protein coupled receptor families by showing signficant similarity with both the calcitonin/secretin family C/S and the rhodopsin family R.

The best scores are:                               s-w Z-score E(43470)
CAR1_DICDI CYCLIC AMP RECEPTOR 1.                  2678 3208.3  0
CAR3_DICDI CYCLIC AMP RECEPTOR 3.                  1524 1819.9  0
CAR2_DICDI CYCLIC AMP RECEPTOR 2.                  1497 1789.8  0
CALR_HUMAN CALCITONIN RECEPTOR PRECURSOR (CT-R).    167 189.4 0.00042 C/S
IL8B_HUMAN HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B   161 185.1 0.00073 R
CLRA_RAT CALCITONIN RECEPTOR A PRECURSOR (CT-R-A)   162 183.6 0.00087 C/S
CLRB_RAT CALCITONIN RECEPTOR B PRECURSOR (CT-R-B)   162 183.0 0.00095 C/S
DIHR_MANSE DIURETIC HORMONE RECEPTOR (DH-R).        150 170.9 0.0045  C/S
YOW3_CAEEL PROBABLE G PROTEIN-COUPLED RECEPTOR ZK6  151 169.7 0.0052
CALR_PIG CALCITONIN RECEPTOR PRECURSOR (CT-R).      145 163.2 0.012   C/S
GLR_RAT GLUCAGON RECEPTOR PRECURSOR (GL-R).         145 163.1 0.012   C/S
IL8B_RABIT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B   141 161.0 0.016   R
RDC1_HUMAN G PROTEIN-COUPLED RECEPTOR RDC1 HOMOLOG  139 158.5 0.022   R
G10D_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR G10D   133 150.5 0.061   R
>>CYB_CROLA CYTOCHROME B (EC 1.10.2.2).             132 149.6 0.069 <<
NY1R_XENLA NEUROPEPTIDE Y RECEPTOR TYPE 1 (NPY1-R)  131 148.7 0.077   R
OPSD_HUMAN RHODOPSIN.                               130 148.0 0.085   R
VIPR_HUMAN VASOACTIVE INTESTINAL POLYPEPTIDE RECEP  131 146.8 0.098   C/S
OPSD_SPHSP OPSIN.                                   129 146.1 0.11    R
SCRC_RAT SECRETIN RECEPTOR PRECURSOR.               129 144.6 0.13    C/S
IL8A_HUMAN HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A   127 144.3 0.14    R
GLPR_RAT GLUCAGON-LIKE PEPTIDE 1 RECEPTOR PRECURSO  128 143.1 0.16    C/S
AG2S_XENLA TYPE-1-LIKE ANGIOTENSIN II RECEPTOR 2 (  126 142.8 0.16    R
>>CYB_MONDO CYTOCHROME B (EC 1.10.2.2).             126 142.4 0.17  <<
>>CYB_ANGRO CYTOCHROME B (EC 1.10.2.2) (FRAGMENT).  122 141.8 0.19  <<
AG2R_BOVIN TYPE-1 ANGIOTENSIN II RECEPTOR (AT1).    125 141.7 0.19    R
>>CYB_CYPCA CYTOCHROME B (EC 1.10.2.2).             125 141.2 0.20  <<
OPSD_CANFA RHODOPSIN.                               124 140.8 0.21    R
>>CYB_XENLA CYTOCHROME B (EC 1.10.2.2).             122 137.6 0.32  <<
OPRM_RAT MU-TYPE OPIOID RECEPTOR (MOR-1) (OPIOID R  122 137.2 0.34    R
>>GABP_ECOLI GABA PERMEASE (4-NH2 BUTYRATE TRANS)   123 137.0 0.35  <<
OPSD_CRIGR RHODOPSIN.                               120 136.0 0.40    R
OPRM_HUMAN MU-TYPE OPIOID RECEPTOR (MOR-1).         121 136.0 0.40    R
AG2R_RABIT TYPE-1 ANGIOTENSIN II RECEPTOR (AT1).    120 135.7 0.41    R
GRFR_HUMAN GROWTH HORMONE-RELEASING HORMONE RECEPT  121 135.5 0.42    C/S
SSR1_HUMAN SOMATOSTATIN RECEPTOR TYPE 1 (SS1R) (SR  119 133.7 0.53    R
VIPR_RAT VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTO  120 133.5 0.54    C/S
IL8B_RAT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (I  118 133.4 0.55    R
AA3R_RAT ADENOSINE A3 RECEPTOR (TGPCR1).            116 131.9 0.67    R
TA2R_MOUSE THROMBOXANE A2 RECEPTOR (TXA2-R).        116 131.3 0.71    R
GRFR_PIG GROWTH HORMONE-RELEASING HORMONE RECEPTOR  118 131.3 0.72    C/S
TA2R_HUMAN THROMBOXANE A2 RECEPTOR (TXA2-R).        115 130.1 0.84    R
OPSD_BOVIN RHODOPSIN.                               115 130.0  0.85    R
AG2R_HUMAN TYPE-1A ANGIOTENSIN II RECEPTOR (AT1A).  115 129.7 0.88    R
CRFR_RAT CORTICOTROPIN RELEASING FACTOR RECEPTOR P  116 129.6 0.89    C/S
SSR5_RAT SOMATOSTATIN RECEPTOR TYPE 5 (SOMATOSTATI  115 129.6 0.89    R
GRFR_MOUSE GROWTH HORMONE-RELEASING HORMONE RECEPT  116 129.5 0.91    C/S
>>CYB_PARLI CYTOCHROME B (EC 1.10.2.2).             115 129.2 0.94  <<

Note that in this example, there are several cytochrome B sequences (which are not members of the G-protein-coupled reseptor family) that obtain very high similarity scores. Thus, one might be suspicious of the conclusion, since unrelated sequences have expectation values << 1.0. The next table shows the results of searching SwissPROT using the SSEARCH program with very slightly higher gap penalties, -14/-2 instead of -12/-2.


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