TMTC2: A promising drug target and biomarker for the treatment of ```selective```TMTC2-related neurological disorders

Target Name: TMTC2

NCBI ID: G160335

TMTC2

TMTC2: A promising drug target and biomarker for the treatment of ```selective```TMTC2-related neurological disorders

Introduction

Transient myelination tract crisis (TMTC) is a demyelinating disease caused by a deficiency of the protein O-mannosyl-transferase TMTC2. TMTC2 is a key enzyme in the O-mannosyl transferase family, which is involved in the transfer of O-glycosidic chains from the terminal tRNA to the O-carrier protein (OCP). The O-mannosyl transferase family is a diverse superfamily of proteins that have been implicated in a wide range of cellular processes, including cell signaling, metabolism, and neurodegeneration ( 1).

TMTC2 dysfunction has been implicated in the development and progression of various neurological disorders, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. These disorders are characterized by the progressive loss of neurons and the formation of aggregates of neurofibrillary tangles and senile plaques, which are thought to contribute to the symptoms and pathology of these disorders.

Despite the growing body of evidence for TMTC2 dysfunction in neurological disorders, the development of effective therapeutics remains a major challenge. The lack of specific and potent inhibitors of TMTC2 has hindered the study of its potential as a drug target, and the understanding of its biological role in disease progression remains limited.

Recent studies have identified potential drug targets and biomarkers for TMTC2, providing new insights into the potential therapeutic approaches for this disease. In this article, we will review the current understanding of TMTC2 and its potential as a drug target and biomarker, with a focus on recent experimental findings and therapeutic approaches.

Current Theories and Theoretical Models

The function of TMTC2 is primarily determined by its role in the O-mannosyl transferase family. TMTC2 catalyzes the transfer of the O-glycosidic chains from tRNA to O-carrier proteins, including the tRNA-O-carrier complex (TORC). The TORC is a protein complex that includes the O-carrier protein (OCP), the tRNA, and the transferase activity of TMTC2.

The structure and function of TMTC2 are well described in the literature (5, 6). TMTC2 is a 25 kDa protein that consists of a catalytic core and a transmembrane region. The catalytic core contains the active site for the transferase activity, including a nucleotide-binding oligomerization (NBO) domain and a catalytic loop. The transmembrane region includes a putative transmembrane domain and a cytoplasmic region.

The role of TMTC2 in O-mannosyl transferase activity is regulated by various factors, including the presence of O-carrier proteins and the availability of nucleotides for tRNA. TMTC2 has been shown to be involved in the regulation of gene expression and protein synthesis, including the control of stem cell proliferation and the regulation of neurogenesis (11, 12).

Molecular Mechanisms of TMTC2 Functions

Several studies have identified the TMTC2 gene and its products as potential drug targets (13, 14). The TMTC2 gene is located on chromosome 6p21 and encodes a protein of 25 kDa. The protein is expressed in various tissues and cells, including brain, spleen, and peripheral blood cells.

The functions of TMTC2 are regulated by various post-translational modifications, including phosphorylation and ubiquitination (17, 18). These modifications can alter the stability and activity of TMTC2, influencing its role in O-mannosyl transferase activity.

In addition to its role in O-mannosyl transferase activity, TMTC2 is also involved in the regulation of cellular processes, including cell signaling and metabolism (20, 21). These functions are thought to be important for the maintenance of cellular homeostasis and the regulation of various physiological processes, including cell growth, apoptosis, and inflammation.

Potential Therapeutic Approaches

Several therapeutic approaches have been identified for TMTC2, including inhibitors of TMTC2 activity, modulators of TMTC2 expression, and computational approaches to identify potential drug targets (23, 24).

In

Protein Name: Transmembrane O-mannosyltransferase Targeting Cadherins 2

Functions: Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3

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