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Tubulin polyglutamylase complex subunit 2 (TPGS2)
- Target
- TPGS2
- Molecular classification
- Enzyme, Modifier of post-translational tubulin modification, Polyglutamylase complex subunit
01
Overview
Tubulin polyglutamylase complex subunit 2 (TPGS2) is a non-catalytic subunit of the neuronal polyglutamylase complex responsible for the addition of polyglutamate chains to the C-terminal tails of tubulin. This post-translational modification regulates microtubule functions, cilia and flagella biogenesis and motility, and modulates interactions with microtubule-associated proteins. TPGS2 is linked to cancer pathophysiology and can serve as a prognostic and immunotherapeutic biomarker. Genetic disruptions in TPGS2 are associated with Hypotrichosis 2 and may affect multiple cellular and organelle structures dependent on microtubule dynamics
- Other names
- C18orf10HMFN0601L17PGs2DKFZP586M1523HsT3006polyglutamylase subunit 2
02
Mechanism of action
Drugs targeting TPGS2 would likely involve inhibition or modulation of tubulin polyglutamylation, affecting microtubule stabilization, ciliary/flagellar function, and possibly immune response and cell proliferation. However, there are no approved drugs directly acting on TPGS2 to date.
03
Biological functions
Polyglutamylation of tubulinRegulation of cilia and flagella assembly and motilityMicrotubule stabilization and functionModulation of microtubule-associated protein interactionsPossibly involved in neuronal differentiation and immune cell infiltration in the tumor microenvironment
04
Disease associations
Cancer (biomarker and association with tumor microenvironment, especially colon and stomach adenocarcinoma)Hypotrichosis 2 (genetic disorder)Possible roles in neurodegenerative diseases and other microtubule-related disorders (inferred, see references to cilia/motility defects)
05
Safety considerations
Modulating TPGS2/polyglutamylase activity could disrupt cilia/flagella biogenesis, neuronal function, and cause side effects related to impaired microtubule functions such as infertility, neurodegeneration, motility defects, or altered immune response
06
Interacting drugs
None known specifically targeting TPGS2 as of current evidence
07
Biomarkers
TPGS2 expression level is a potential biomarker for prognosis and immune cell infiltration in various cancers, notably colon adenocarcinoma and stomach adenocarcinoma
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