Write a 100-350 word essay about the enzyme human DPM2. Provide information related to enzyme: i) function, ii) reaction pathways, ii) Location, and iv) diseases. In writing include these four subheadings

### Function

Human DPM2 (dolichyl-phosphate mannosyltransferase subunit 2) is a regulatory subunit of the dolichyl-phosphate mannosyltransferase (DPM) complex, which is crucial for glycosylation. DPM2 stabilizes the catalytic subunit DPM1 and enhances its activity. Additionally, DPM2 is essential for the binding of dolichol phosphate, a lipid carrier molecule necessary for transferring mannose to glycoproteins, glycolipids, and GPI anchors. This process is vital for the proper folding, stability, and function of many proteins and lipids in the cell.

### Reaction Pathways

DPM2 is involved in the synthesis of dolichol-phosphate-mannose (Dol-P-Man), an essential mannose donor in several glycosylation pathways, including N-glycosylation, O-mannosylation, C-mannosylation, and GPI-anchor biosynthesis. It works in concert with DPM1 and DPM3 to form the functional DPM synthase complex. This complex facilitates the transfer of mannose from GDP-mannose to dolichol phosphate, forming Dol-P-Man, which is then utilized in the glycosylation of proteins and lipids within the endoplasmic reticulum (ER)【32:0†source】.

### Location

DPM2 is localized in the endoplasmic reticulum membrane. This localization is crucial as it positions DPM2 optimally to interact with DPM1 and DPM3 and participate in the glycosylation processes that occur in the ER. The ER is the site of synthesis for many proteins and lipids that require glycosylation, making the presence of the DPM synthase complex in the ER membrane essential for cellular function.

### Diseases

Mutations or deficiencies in the DPM2 gene can lead to congenital disorders of glycosylation (CDG), specifically CDG-Ie. These disorders result from defects in glycoprotein biosynthesis, leading to a wide range of symptoms including developmental delays, intellectual disability, hypotonia, and other severe multisystemic issues. Additionally, DPM2 mutations have been linked to muscular dystrophies, particularly dystroglycanopathies, which involve improper glycosylation of alpha-dystroglycan, affecting muscle function and integrity. These conditions underscore the critical role of DPM2 in maintaining normal cellular and physiological processes【32:2†source】.

In summary, DPM2 is a key regulatory subunit of the DPM synthase complex, essential for glycosylation pathways in the ER. Its proper function is critical for the stability and activity of the complex, and its deficiencies can lead to severe congenital disorders, highlighting its importance in human health.