8.A.250.  The Tubby-related Protein 3 (TULP3) Family 

TULP3 is a negative regulator of the Shh signaling transduction pathway, of 442 aas and possibly one C-terminal TMS. It is recruited to primary cilia via association with the IFT complex A (IFT-A; see family 1.X.1) and is required for recruitment of G protein-coupled receptor GPR161 to cilia, a promoter of PKA-dependent basal repression machinery in Shh signaling. It binds to phosphorylated inositide (phosphoinositide) lipids. Both IFT-A- and phosphoinositide-binding properties are required to regulate ciliary G protein-coupled receptor trafficking. During adipogenesis, regulates ciliary trafficking of FFAR4 in preadipocytes (Santagata et al. 2001). The tubby family adapter protein TULP3, mediates the transport of most membrane cargoes into cilia (Reddy Palicharla and Mukhopadhyay 2024).


 

References:

Reddy Palicharla, V. and S. Mukhopadhyay. (2024). Molecular and structural perspectives on protein trafficking to the primary cilium membrane. Biochem Soc Trans 52: 1473-1487.
Santagata, S., T.J. Boggon, C.L. Baird, C.A. Gomez, J. Zhao, W.S. Shan, D.G. Myszka, and L. Shapiro. (2001). G-protein signaling through tubby proteins. Science 292: 2041-2050.
Examples:

TC#NameOrganismal TypeExample
8.A.250.1.1

Tubby related protein 3, TULP3, of 442 aas and possibly 1 C-terminal TMS.  The tubby family adapter protein, TULP3, mediates the transport of membrane protein cargoes into cilia. Cryo-EM  provided fundamental insight into these molecular players. Reddy Palicharla and Mukhopadhyay 2024 reviewed the molecular players mediating cargo delivery into the ciliary membrane through the lens of structural biology. These mechanistic insights into ciliary transport provide a framework for understanding of disease variants in ciliopathies, enable precise manipulation of cilia-mediated pathways, and provide a platform for the development of targeted therapeutics.

TULP3 of Homo sapiens

 
8.A.250.1.2

TUB-like protein, TULP3, of 467 aas and possibly 1 C-terminal TMS.

TULP3 of Anas platyrhynchos platyrhynchos (Northern mallard)