SEMA6A

Last update 08 May 2025

Basic Info

Synonyms

HT018, KIAA1368, SEMA

+ [9]

Introduction

Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation. (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium.

100 Clinical Results associated with SEMA6A

100 Translational Medicine associated with SEMA6A

0 Patents (Medical) associated with SEMA6A

146

Literatures (Medical) associated with SEMA6A

22 Apr 2025·Proceedings of the National Academy of Sciences

Semaphorin 6A phase separation sustains a histone lactylation–dependent lactate buildup in pathological angiogenesis

Article

Author: Li, Chenxin ; Ju, Rong ; Wang, Can ; Jiang, Shuxin ; Wei, Yanhong ; Xie, Lijing ; Huang, Shuting ; Zhang, Feng ; Hao, Yu ; Wu, Mingjuan ; Cao, Xiaolian ; Ma, Ya ; Li, Junru ; Guo, Dianlei ; Chu, Yu ; Zhong, Xiali ; Zhang, Zhuyi ; Liu, Chunqiao

Ischemic retinal diseases are major causes of blindness worldwide and are characterized by pathological angiogenesis. Epigenetic alterations in response to metabolic shifts in endothelial cells (ECs) suffice to underlie excessive angiogenesis. Lactate accumulation and its subsequent histone lactylation in ECs contribute to vascular disorders. However, the regulatory mechanism of establishing and sustaining lactylation modification remains elusive. Here, we showed that lactate accumulation induced histone lactylations on H3K9 and H3K18 in neovascular ECs in the proliferative stage of oxygen-induced retinopathy. Joint CUT&Tag and scRNA-seq analyses identified Prmt5 as a target of H3K9la and H3K18la in isolated retinal ECs. EC-specific deletion of Prmt5 since the early stage of revascularization suppressed a positive feedback loop of lactate production and histone lactylation, thus inhibiting neovascular tuft formation. Mechanistically, the C-terminal intrinsically disorder region (IDR) of the transmembrane semaphorin 6A (SEMA6A) forms liquid–liquid phase separation condensates to recruit RHOA and P300, facilitating P300 phosphorylation and histone lactylation cycle. Deletion of endothelial Sema6A reduced H3K9la and H3K18la at the promoter of PRMT5 and diminished its expression. The induction of histone lactylation by SEMA6A-IDR and its pro-angiogenic effect were abrogated by deletion of Prmt5 . Our study illustrates a sustainable histone lactylation machinery driven by phase separation-dependent lactyltransferase activation in dysregulated vascularization.

15 Mar 2025·Mutagenesis

Genetic and environmental associations of nonspecific chromosomal aberrations

Review

Author: Vodicka, Pavel ; Hemminki, Kari ; Niazi, Yasmeen ; Försti, Asta ; Vodickova, Ludmila

AbstractNonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation is believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study in healthy individuals in relation to occupational and smoking-related exposure compared to nonexposed referents. The associations (at P < 10–5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS, and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis, and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, the expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

01 Mar 2025·Genomics

ELF5 gene promotes milk lipid synthesis in goat mammary epithelial cells by transcriptomic analysis

Article

Author: Zhong, Jintao ; Zhang, Yunhai ; Song, Ning ; Cui, Shuangshuang ; Ma, Cunxia ; Guo, Yuzhu ; Liu, Hongyu ; Tu, Tongtong

E74-like factor 5 (ELF5) is an Ets transcription factor of epithelial development, while the function of ELF5 gene in goat milk fat synthesis remains to be elucidated. In goat mammary epithelial cells, we performed RNA sequencing and analyzed differentially expressed genes (DEGs) after ELF5 gene overexpression. ELF5 gene significantly up-regulated the synthesis of triglyceride, total cholesterol, free fatty acid, and lipid droplets. We obtained 929 DEGs after ELF5 gene overexpression in GMECs. Among the DEGs, SPP1, ELOVL1, PNPLA2, FOXO1, PTGS2, SEMA6A, ACSL5, and GPNMB genes that are related to lipid metabolism were identified. Enrichment analysis showed MAPK and FoxO signaling pathways were up-regulated by ELF5 gene overexpression in GMECs. These findings offer evidence that ELF5 gene could be a candidate gene for the regulation of milk lipid synthesis in goats, and provide molecular targets for the breeding of goats with high milk fat.

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SEMA6A

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