Transmembrane O-mannosyltransferase targeting cadherins 2 (TMTC2)

Transmembrane O-mannosyltransferase targeting cadherins 2 (TMTC2) is an integral membrane enzyme located in the endoplasmic reticulum that transfers mannosyl residues to the hydroxyl groups of serine and threonine residues on cadherin proteins and other targets, such as PDIA3[1][3][4][10]. TMTC2 belongs to a protein family featuring tetratricopeptide repeats (TPR), which mediate protein–protein interactions and target cadherin domains for O-linked mannosylation at specific regions[2][5]. The protein plays a key role in calcium homeostasis within the ER—binding the calcium uptake pump SERCA2B and the chaperone calnexin[1][9]. Disruptions of TMTC2 are associated with diseases including muscular dystrophy-dystroglycanopathy, familial temporal lobe epilepsy, certain forms of non-syndromic hearing loss, and immune/metabolic disorders, pointing to pleiotropic functions in neurological, immune, and metabolic regulation[2]. No drugs are currently described as directly targeting TMTC2, nor are validated biomarkers established for clinical use[1][2].

Other names

Protein O-mannosyl-transferase TMTC2TMTC2DKFZp762A217Transmembrane and tetratricopeptide repeat-containing 2IBDBP1Transmembrane and TPR repeat-containing protein 2EC 2.4.1.1098430438D04RIKD330034A10RikRGD1309848