I wonder if there are some GPCRs that have extracellular C-terminus and intracellular N-terminus. I know that adiponectin receptors and insect olfactory receptors are upside down, but I can't find any other examples.
Any help would be appreciated.
The adiponectin receptors belong to a distinct family of ‘upside down’ 7TM’ receptors called the PAQR family. They haven’t been shown to signal through G proteins. The membrane progestin receptor is also a member.
http://www.ncbi.nlm.nih.gov/pubmed/16044242
...but the membrane progestin receptor appears to be the 'right way up' and Gi linked.
The PAQR family is a very ancient family, just like the GPCRs, but its numbers in human (11) is much smaller in GPCR numbers in human (300+).
Are there other family of membrane-bound proteins in human, with 7 transmembrane motifs, has this reverse topology? I don't think so. If there is, we would already have found them as all human genes are known now. You can easily validate my claim here by running a TM model against all human protein sequences, and identify those with 4+ TM domains (so you don't miss any due to TM model's inaccuracy). If you find any other members, that are not GPCR, and not PAQR, I think you get a paper. If that new family has the reverse-orientation to GPCR, then it is another PAQR-like family. Good luck with your hunting.
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