LRRC39

Last update 08 May 2025

Basic Info

Synonyms

leucine rich repeat containing 39, Leucine-rich repeat-containing protein 39, LRRC39

+ [3]

Introduction

Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress. May regulate expression of other M-band proteins via an SRF-dependent pathway. Important for normal contractile function in heart.

100 Clinical Results associated with LRRC39

100 Translational Medicine associated with LRRC39

0 Patents (Medical) associated with LRRC39

Literatures (Medical) associated with LRRC39

01 May 2023·Clinical Immunology

TET2-mediated upregulation of 5-hydroxymethylcytosine in LRRC39 promoter promotes Th1 response in association with downregulated Treg response in Vogt-Koyanagi-Harada disease

Article

Author: Su, Guannan ; Cao, Qingfeng ; Lai, Yujie ; Luo, Xiang ; Yang, Peizeng ; Liu, Yaning ; Zhang, Wanyun ; Zhang, Yinan ; Deng, Yang ; Pu, Yanlin ; Chen, Zhijun ; Yi, Kun

DNA 5-Hydroxymethylcytosine (5-hmC), an oxidative reaction mediated by the ten-eleven translocation (TET) family, has been reported to play an essential role in the progression of auto-inflammatory and autoimmune diseases. By far, little is known about the effect of DNA 5-hmC and the TET family on the development of Vogt-Koyanagi-Harada (VKH) disease. In this study, we discovered that the global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET2 at both mRNA and protein levels in CD4⁺T cells from active VKH patients compared to healthy controls. Integrated analysis of DNA 5-hmC pattern and transcription profile of CD4⁺ T cells revealed that 6 candidate target genes were involved in the development of VKH disease. The promoter 5-hmC and mRNA levels of leucine rich repeat containing 39 (LRRC39) were verified to be elevated in active VKH patients. Functional experiments showed that TET2 could up-regulate LRRC39 mRNA expression by increasing the promoter 5-hmC level of LRRC39 in CD4⁺ T cells from active VKH patients. Up-regulated LRRC39 expression could increase the frequencies of IFN-γ⁺ and IL-17⁺ CD4⁺ T cells as well as the secretions of IFN-γ and IL-17 in association with the decreased frequency of CD4⁺CD25⁺FOXP3⁺ regulatory T (Treg) cells and the reduced production of IL-10. Additionally, restoration of LRRC39 rescued TET2-silencing-mediated reduced frequency of IFN-γ⁺ CD4⁺ T cells and increased frequency of CD4⁺CD25⁺FOXP3⁺ Treg cells. Collectively, our study reveals a novel axis, the TET2-5-hmC-LRRC39-Th1/Treg responses axis, in the pathogenesis of VKH and provides a potential target for further investigation into the epigenetic therapy of this disease.

01 Sep 2022·Journal of Proteomics

Comparative proteomics reveals genetic mechanisms of body weight in Hu sheep and Dorper sheep

Article

Author: Yang, Xiaobin ; Li, Wenxin ; Xu, Dan ; Cheng, Jiangbo ; Cui, Panpan ; Zhang, Deyin ; Zhao, Yuan ; Zhang, Xiaoxue ; Ma, Zongwu ; Wang, Weimin ; Lin, Changchun ; Zhang, Yukun ; Wang, Jianghui ; Zhao, Liming ; Li, Xiaolong

Body weight (BW) is a critical economic trait for meat production in sheep, and it is a complex trait affected by numerous elements. The aim of this study was to investigate the genetic mechanisms of sheep BW by a label-free proteomics approach. The result showed, a total of 27, 14, 61, and 65 differentially abundant proteins (DAPs) were identified in the Hu_HBW vs. Hu_LBW, DP_HBW vs. DP_LBW, Hu_HBW vs. DP_HBW, and Hu_LBW vs. DP_LBW comparisons, respectively. Five proteins (including ILK, AHCYL2, MLIP, CYB5A, and SMTNL1) related to fat synthesis and muscle development were detected in the Hu sheep group. In the Dorper sheep group, the screened DAPs strictly related to muscle development and fat synthesis were significantly enriched in MAP kinase activity (MAPK12), Arachidonic acid metabolism, and Steroid hormone biosynthesis (PGFS, LOC101107119) pathways. Several DAPs related to immune responses (SERPINA1, FGG, SERPINC1, and LOC101108131), fat deposition (APOH, GC, AHSG, SKP1, ACSL1, ACAT1, and ACADS), and muscle development (LMOD3 and LRRC39) were detected in the Hu vs. Dorper sheep comparison. These analyses indicated that the BW of sheep is regulated via a variety of pathways, and these DAPs can be further investigated as candidate markers for predicting the BW of sheep. SIGNIFICANCE: Body weight is one of the key traits in sheep and involves multiple coordinated regulatory mechanisms, but the genetic mechanism of BW is still unclear in sheep. In the current study, the label-free method was used to identify the proteins and pathways related to BW using LT muscle of Hu sheep and Dorper sheep with different BW. These findings will provide new candidate proteins and vital pathways into the molecular mechanisms involved growth traits in sheep.

12 Nov 2010·Circulation ResearchQ1 · MEDICINE

Myomasp/LRRC39, a Heart- and Muscle-Specific Protein, Is a Novel Component of the Sarcomeric M-Band and Is Involved in Stretch Sensing

Q1 · MEDICINE

Article

Author: Will, Rainer D. ; Hansen, Arne ; Korn, Bernhard ; Eden, Matthias ; Frey, Norbert ; Rottbauer, Wolfgang ; Frank, Derk ; Eder, Alexandra ; Kuhn, Christian ; Just, Steffen ; Katus, Hugo A. ; Oehl, Ulrike ; Wiemann, Stefan ; Koegl, Manfred ; Eschenhagen, Thomas ; Seeger, Thalia S.

Rationale and Objective:The M-band represents a transverse structure in the center of the sarcomeric A-band and provides an anchor for the myosin-containing thick filaments. In contrast to other sarcomeric structures, eg, the Z-disc, only few M-band–specific proteins have been identified to date, and its exact molecular composition remains unclear.Methods and Results: Using a bioinformatic approach to identify novel heart- and muscle-specific genes, we found a leucine rich protein, myomasp ( Myo sin-interacting, M -band- a ssociated s tress-responsive p rotein)/LRRC39. RT-PCR and Northern and Western blot analyses confirmed a cardiac-enriched expression pattern, and immunolocalization of myomasp revealed a strong and specific signal at the sarcomeric M-band. Yeast 2-hybrid screens, as well as coimmunoprecipitation experiments, identified the C terminus of myosin heavy chain (MYH)7 as an interaction partner for myomasp. Knockdown of myomasp in neonatal rat ventricular myocytes (NRVCMs) led to a significant upregulation of the stretch-sensitive genes GDF-15 and BNP. Conversely, the expression of MYH7 and the M-band proteins myomesin-1 and -2 was found to be markedly reduced. Mechanistically, knockdown of myomasp in NRVCM led to a dose-dependent suppression of serum response factor–dependent gene expression, consistent with earlier observations linking the M-band to serum response factor–mediated signaling. Finally, downregulation of myomasp/LRRC39 in spontaneously beating engineered heart tissue constructs resulted in significantly lower force generation and reduced fractional shortening. Likewise, knockdown of the myomasp/LRRC39 ortholog in zebrafish resulted in severely impaired heart function and cardiomyopathy in vivo. Conclusions:These findings reveal myomasp as a previously unrecognized component of an M-band–associated signaling pathway that regulates cardiomyocyte gene expression in response to biomechanical stress.

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LRRC39

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