TTLL12

Last update 08 May 2025

Basic Info

Synonyms

Inactive tubulin--tyrosine ligase-like protein 12, KIAA0153, TTLL12

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Introduction

Negatively regulates post-translational modifications of tubulin, including detyrosination of the C-terminus and polyglutamylation of glutamate residues (PubMed:20162578, PubMed:23251473). Also, indirectly promotes histone H4 trimethylation at 'Lys-20' (H4K20me3) (PubMed:23251473). Probably by controlling tubulin and/or histone H4 post-translational modifications, plays a role in mitosis and in maintaining chromosome number stability (PubMed:20162578, PubMed:23251473). During RNA virus-mediated infection, acts as a negative regulator of the RIG-I pathway by preventing MAVS binding to TBK1 and IKBKE (PubMed:28011935).

100 Clinical Results associated with TTLL12

100 Translational Medicine associated with TTLL12

0 Patents (Medical) associated with TTLL12

Literatures (Medical) associated with TTLL12

01 Mar 2025·Reproductive BioMedicine Online

Characterization of tubulin post-translational modifications and their enzymes during human oocyte meiosis

Article

Author: Vernos, Isabelle ; Ferrer-Vaquer, Anna ; Vassena, Rita ; Barragan, Montserrat ; Karamtzioti, Paraskevi ; Tiscornia, Gustavo

RESEARCH QUESTIONWhat are the profiles of tubulin post-translational modifications (PTM) in the meiotic spindles of oocytes with different developmental competence: in-vivo matured MII oocytes (IVO) versus cumulus-free in-vitro matured germinal vesicles (IVM)?DESIGNCumulus-free germinal vesicles were matured in vitro and compared with IVO in terms of their tubulin PTM, characterizing tubulin PTM patterns (acetylation, tyrosination, detyrosination, D2-tubulin formation and polyglutamylation) of their meiotic spindles by immunofluorescence and by evaluation of the expression levels of the enzymes involved by quantitative reverse transcription polymerase chain reaction.RESULTSLevels of D2-tubulin, tyrosination and polyglutamylation were similar in IVO and IVM oocytes; acetylation displayed different patterns in both groups, whereas detyrosination was detected only in MII oocytes matured in vivo. The PTM enzyme RNA expression levels in germinal vesicles, IVO and IVM were analysed, as well as in oocytes that failed to mature. Of the 24 PTM enzyme transcripts tested, 17 were present in at least one of the groups under study (aΤΑΤ1, NAA50, HDAC6, SIRT2, TTL, TTLL1, TTLL2, TTLL4, TTLL5, TTLL6, TTLL9, TTLL11, TTLL12, CCP1, CCP5, CCP6, VASH1), of which three were differentially expressed (NAA50, TTLL12, CCP1).CONCLUSIONAll modifications studied were present in human oocytes regardless of whether their meiotic maturation occurred in vivo or in vitro, except for detyrosination, which was found at low levels in the IVO group, but not in the IVM group. This suggests that the presence of tubulin PTMs may play a role in human oocyte maturation, completion of meiosis and developmental competence.

01 Jul 2024·Neuropsychopharmacology

Identifying novel proteins for suicide attempt by integrating proteomes from brain and blood with genome-wide association data

Article

Author: Guo, Lan ; Han, Xue ; Zhang, Huimin ; Liao, Yuhua ; Fan, Beifang ; Wang, Wanxin ; Zhao, Hao ; Liu, Yifeng ; Zhang, Xuening ; Lu, Ciyong

AbstractGenome-wide association studies (GWASs) have identified risk loci for suicide attempt (SA), but deciphering how they confer risk for SA remains largely unknown. This study aims to identify the key proteins and gain insights into SA pathogenesis. We integrated data from the brain proteome (N = 376) and blood proteome (N = 35,559) and combined it with the largest SA GWAS summary statistics to date (N = 518,612). A comprehensive set of methods was employed, including Mendelian randomization (MR), Steiger filtering, Bayesian colocalization, proteome‑wide association studies (PWAS), transcript-levels, cell-type specificity, correlation, and protein-protein interaction (PPI) network analysis. Validation was performed using other protein datasets and the SA dataset from FinnGen study. We identified ten proteins (GLRX5, GMPPB, B3GALTL, FUCA2, TTLL12, ADCK1, MMAA, HIBADH, ACP1, DOC2A) associated with SA in brain proteomics. GLRX5, GMPPB, and FUCA2 showed strong colocalization evidence and were supported by PWAS and transcript-level analysis, and were predominantly expressed in glutamatergic neuronal cells. In blood proteomics, one significant protein (PEAR1) and three near-significant proteins (NDE1, EVA1C, B4GALT2) were identified, but lacked colocalization evidence. Moreover, despite the limited correlation between the same protein in brain and blood, the PPI network analysis provided new insights into the interaction between brain and blood in SA. Furthermore, GLRX5 was associated with the GSTP1, the target of Clozapine. The comprehensive analysis provides strong evidence supporting a causal association between three genetically determined brain proteins (GLRX5, GMPPB, and FUCA2) with SA. These findings offer valuable insights into SA’s underlying mechanisms and potential therapeutic approaches.

01 Dec 2023·Mucosal Immunology

Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin D

Article

Author: Sposito, Francesca ; Pennington, Shaun H ; Biagini, Giancarlo A ; McNamara, Paul S ; Northey, Sarah ; Duggan, Jack ; Hedrich, Christian M ; Liptrott, Neill J ; David, Christopher A W ; Charras, Amandine

Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at the air-liquid interface with and without vitamin D. Gene expression and DNA methylation were investigated. Surface protein expression was confirmed by immunofluorescence while vitamin D receptor recruitment to the DNA was analysed through chromatin immunoprecipitation. HEp-2 cells were used for protein co-immunoprecipitation and luciferase reporter assays. Compared to children, airway epithelia from adults show higher viral RNA recovery following infection. This was associated with higher ANPEP/CD13, reduced type I interferon expression, and differential DNA methylation. In cells from adults, exposure to vitamin D reduced TTLL-12 expression, a negative regulator of the interferon response. This was mediated by vitamin D receptor recruitment to TTLL12, where it instructs DNA methylation through DNA methyltransferase 1. This study links age-dependent differential expression of CD13 and type I interferon to variable infection of upper airway epithelia. Furthermore, it provides molecular evidence for vitamin D reducing viral replication by inhibiting TTLL-12.

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TTLL12

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