TM4SF20

Last update 08 May 2025

Basic Info

Synonyms

FLJ22800, TCCE518, TM4SF20

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Introduction

Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis (PubMed:25310401, PubMed:27499293). In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1 (PubMed:27499293). Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein (PubMed:27499293).

100 Clinical Results associated with TM4SF20

100 Translational Medicine associated with TM4SF20

0 Patents (Medical) associated with TM4SF20

Literatures (Medical) associated with TM4SF20

28 Apr 2023·Journal of thoracic disease

A new prognostic model for RHOV, ABCC2, and CYP4B1 to predict the prognosis and association with immune infiltration of lung adenocarcinoma.

Article

Author: Song, Yong-Xiang ; Chen, Cheng ; Luo, Qian ; Jiang, Ni ; Li, Qiao ; Ke, Xi-Xian ; Luo, Xiang-Yu ; Han, Hao ; Liu, Xiao-Li ; Guo, Qiang ; Li, Qian-Yun

BackgroundLymph node metastasis is one of the important factors affecting the prognosis of lung adenocarcinoma (LUAD) patients. The key molecules in lymph node metastasis have not yet been fully revealed. Therefore, we aimed to construct a prognostic model based on lymph node metastasis-related genes to evaluate the prognosis of LUAD patients.MethodsThe differentially expressed genes (DEGs) in the process of LUAD metastasis were identified in The Cancer Genome Atlas (TCGA) database, and the biological roles of the DEGs were depicted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a protein-protein interaction (PPI) network. Survival analysis and Cox regression analysis were used to identify the genes related to the prognosis of patients with LUAD, and a nomogram and a prognostic model were constructed. The potential prognostic value, immune escape, and regulatory mechanisms of the prognostic model in LUAD progression were explored through survival analysis and gene set enrichment analysis (GSEA).ResultsA total of 75 genes were upregulated, and 138 genes were downregulated in tissues of lymph node metastasis. The expression levels of STC1, CYP17A1, RHOV, GUCA2B, TM4SF20, DEFB1, CRHR2, ABCC2, CYP4B1, KRT16, and NTS were revealed as risk factors for a poor prognosis in LUAD patients. High-risk LUAD patients had a poor prognosis in the prognostic model based on RHOV, ABCC2, and CYP4B1. The clinical stage and the risk score were found to be independent risk factors for a poor prognosis in LUAD patients, and the risk score was associated with the tumor purity, T cell, natural killer (NK) cell, and other immune cells. The prognostic model might affect the progression of LUAD using DNA replication, the cell cycle, P53, and other signaling pathways.ConclusionsLymph node metastasis-related genes RHOV, ABCC2, and CYP4B1 are associated with a poor prognosis in LUAD. A prognostic model based on RHOV, ABCC2, and CYP4B1 might predict the prognosis of LUAD patients and be associated with immune infiltration.

01 Apr 2023·Cell Reports

Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence

Article

Author: Ye, Jin ; Wang, Jingcheng ; Han, Sungwon

Transmembrane proteins must adopt proper topology to perform their functions. We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. Accompanying this retrotranslocation, the C terminus of the protein is relocated from cytosol to lumen. Ceramide delays the retrotranslocation process, causing accumulation of the protein that is originally synthesized. Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins.

01 Dec 2021·Meta Gene

Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment

Article

Author: Andres, Erin M ; Neely, Heather L ; Yasmin, Tahira ; Kausar, Farzana ; Raza, Muhammad Hashim ; Hafeez, Huma ; Basra, M Asim Raza

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions and genes of interest, though very few studies have focused on rare variant analysis in non-English speaking or non-European samples. We selected four candidate genes (TM4SF20, NFXL1, CNTNAP2 and ATP2C2) strongly suggested for specific language impairment (SLI), a subtype of LI, and investigated rare protein coding variants through Sanger sequencing of probands with LI ascertained from Pakistan. The probands and their family members completed a speech and language family history questionnaire and a vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, the national language of Pakistan. Our study aimed to determine the significance of rare variants in these SLI candidate genes through segregation analysis in a novel population with a high rate of consanguinity. In total, we identified 16 rare variants (according to the rare MAF in the global population in gnomAD v2.1.1 database exomes), including eight variants with a MAF <0.5 % in the South Asian population. Most of the identified rare variants aggregated in proband's families, one rare variant (c.*9T>C in CNTNAP2) co-segregated in a small family (PKSLI-64) and another (c.2465C>T in ATP2C2) co-segregated in the proband branch (PKSLI-27). The lack of complete co-segregation of most of the identified rare variants indicates that while these genes could be involved in overall risk for LI, other genes are likely involved in LI in this population. Future investigation of these consanguineous families has the potential to expand our understanding of gene function related to language acquisition and impairment.

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TM4SF20

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