Table 1.
GPCR splice variants with altered or deleted transmembrane domains
Receptor | Splicing consequence | General properties of splice variant | Dom/neg? | Refs. |
---|---|---|---|---|
α1A-adrenoceptor |
Truncated 6TM mutants. |
No cell surface expression. |
Yes |
[28] |
Calcitonin receptor (CT receptor) |
Truncated 6TM mutant. |
Rabbit CTRΔe13 is poorly expressed on the cell surface and fails to activate cell signaling. |
Yes |
[29] |
Chemokine receptor 5 (CCR5) |
Severely truncated mutants. Ccr5Δ32 is a 5TM mutant. |
Natural mutants of human chemokine receptor CCR5 lacking the last 3 or 5 TMDs are non-functional. Ccr5Δ32 complexes with CCR5 and retains CCR5 in the ER, thus reducing cell surface expression. |
Yes |
[30,31] |
Dopamine receptor (D3) |
D3nf is a truncated 5TM mutant. |
Human D3nf mutant has a punctuate perinuclear distribution and does not bind DA-ligands. |
Yes |
[32,33] |
GABAB receptor (GABABR1) |
GABABR1c has an additional 31 amino acids in TM5. |
|
No |
[34] |
Gastric inhibitory polypeptide receptor (GIP ) |
Truncated 4TM mutant. |
This inactive mutant receptor inhibited GIP signaling and decreased cell surface expression by retaining WT receptor in the ER. |
Yes |
[35] |
Ghrelin receptor (or GHS-R1a) |
GHS-R1b is a truncated 5TM mutant. |
GHS-R1b is a non-signaling splice variant of GHS-R1a. |
Yes |
[36] |
Gonadotropin-releasing hormone receptor (GnRH receptor) |
Truncated 5TM mutant. |
5TM variant of human GnRH receptor shows decreased cell surface expression, no ligand binding and no signal transduction. |
Yes |
[37] |
Growth hormone-releasing hormone receptor (GHRH-R) |
Truncated 5TM mutant. |
The mutant GHRH-R cannot transduce GHRH signals. |
Yes |
[38] |
Histamine receptor (H3) |
6TM-rH3R is a truncated 6TM mutant. |
Several splice variants of rat H3R do not bind agonist, have an intracellular localization and co-expression with WT receptor decreases cell surface expression and functional responses. |
Yes |
[39] |
Histamine receptor (H4) |
hH4R(302) lacks 88 amino acids from TMD2 to TMD4. hH4R(67) is a ~ 1.5TM truncated mutant. |
These human H4R splice variants were localised predominantly intracellularly when expressed in recombinant cells. No ligand binding or cell signaling detected. |
Yes |
[40] |
Leukotriene B4 receptor (BLT1) |
LTB4R-AS1 lacks TMD2 and part of ECL1 (39 amino acid deletion). |
Both isoforms of human BLT1 (LTB4R) are expressed in human airway smooth muscle cells. |
Yes |
[41] |
LTB4R-AS2 is the 3TMD to C-terminus (lacks 100 amino acids). | ||||
Luteinizing hormone receptor (LH receptor) |
Truncated 5TM mutant. |
The 5TM mutant of human LH receptor binds ligand (limited) but has no signaling activity. |
Yes |
[42] |
μ-opioid receptor (μ-OR) |
Truncated 6TM mutant. |
A 6TM μ-OR variant in mice identified ligands lacking the traditional side effects of classical opiates but maintaining analgesic property. |
No |
[6] |
Motilin receptor |
GPR38-B is a truncated 5TM mutant. |
|
? |
[43] |
Neurokinin 2 receptor (NK2) |
An ICL2-TM4 deletion mutant. |
NK2β splice variant is poorly expressed on the cell membrane and is non-signaling. |
Yes |
[44] |
Neuropeptide Y receptor (Y1) |
A truncated 5TM mutant. |
The putative hY1-related 5TM accessory protein encoded by the non-spliced hY1 mRNA is not involved in facilitating hY1 production. |
No |
[13] |
Neurotensin receptor (NTS2) |
Truncated 5TM mutant with long tail. |
Rat vNTS2 is functionally active and can heterodimerize with NTS2. |
No |
[45] |
Nociceptin receptor (NOP) |
Truncated 4TM mutant. |
The rat truncated NOP receptor is localised to cell membranes but is non-functional. |
Yes |
[46] |
Prostaglandin F2α receptor (FP) |
A 6TM truncated mutant (FPs) |
hFPS is functionally inactive and highly expressed in the perinuclear region. |
Yes |
[47] |
A truncated mutant (PTGFR-v2). |
No distinct functional role identified. |
No |
[48] |
|
Somatostatin receptor (sst5) |
Human sst5TMD5 is a 5TM truncated mutant. |
Identified novel truncated but functional human sst5-variants; present in normal and tumoral tissues. |
No |
[49] |
Human SST5TMD4 is a 4TM truncated mutant. | ||||
Murine sst5TMD4 is a 4TM truncated mutant. |
Three murine variants were functional to mediate ligand-selective-induced variations in Ca2+ and cAMP despite being truncated and displayed a preferential intracellular distribution. |
No |
[50] |
|
Murine sst5TM2 is a 2TM truncated mutant. | ||||
Murine and rat sst5TM1 has just TM1. | ||||
Vasopressin receptor, subtype 2 (V2) | V2b is a truncated 6TM mutant. | V2b is retained in the ER where its C-terminus can be either intracellular or extracellular. | Yes | [51] |