D
IPR053880

GPR180-like, N-terminal domain

InterPro entry
Short nameGPR180-like_N

Description

This entry represents the N-terminal domain of GPR180 and TMEM145.

This entry includes GPR180 (also known as intimal thickness-related receptor, ITR) and TMEM145
[3]
. In vivo analyses of this gene revealed that expression of GPR180 protein increased with intimal thickening induced by cuff placement around murine femoral artery. Furthermore, GPR180-knockout mice were found to be resistant to this experimental intimal thickening
[1]
. GPR180 was first thought to be an orphan Rhodopsin-like GPCR (G protein-coupled receptor) given structural similarities to GPCR transmembrane region, however, it was then confirmed not to signal as a a GPCR
[3, 2]
. This protein is associated with TGF-beta signalling as it regulates the activity of the TGF-beta receptor complex through SMAD3 phosphorylation. Furthermore, GPR180 is also required for the action of Collagen triple helix repeat containing 1 (CTHRC1) to regulate brown and beige adipocyte activity and glucose homeostasis
[2]
.

GPR180 and TMEME145 are homologous to TMEM181 and Wntless (WLS), which have been described as GOST proteins (for GOLD domain seven-transmembrane helix proteins) together with TMEM87A/B, GPR107, and GPR108, given they share the same domain architecture consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain
[3]
.

References

1.Inhibition of experimental intimal thickening in mice lacking a novel G-protein-coupled receptor. Tsukada S, Iwai M, Nishiu J, Itoh M, Tomoike H, Horiuchi M, Nakamura Y, Tanaka T. Circulation 107, 313-9, (2003). View articlePMID: 12538434

2.GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1. Balazova L, Balaz M, Horvath C, Horvath A, Moser C, Kovanicova Z, Ghosh A, Ghoshdastider U, Efthymiou V, Kiehlmann E, Sun W, Dong H, Ding L, Amri EZ, Nuutila P, Virtanen KA, Niemi T, Ukropcova B, Ukropec J, Pelczar P, Lamla T, Hamilton B, Neubauer H, Wolfrum C. Nat Commun 12, 7144, (2021). PMID: 34880217

3.Structure of the GOLD-domain seven-transmembrane helix protein family member TMEM87A. Hoel CM, Zhang L, Brohawn SG. Elife 11, e81704, (2022). PMID: 36373655

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