SLMAP Membrane Protein Introduction

Introduction of SLMAP

Sarcolemmal membrane-associated protein (SLMAP) is encoded by the gene SLMAP that is located on chromosome 3p14.3-21.2, encoding several isoforms of SLMAP by alternative splicing. SLMAP consists of several functional domains, including the fork-related domain, the RecN domain, two leucine zipper domains, and the tail anchor domain represented as a mutually exclusive TM1 or TM2 domain. The tail anchor domain plays a key role in the subcellular targeting of SLMAP. The ubiquitously expressed isoform SLMAP3 is encoded by an open reading frame from the start codon of exon 1, while the other isoforms SLMAP1 and SLMAP2 are abundantly expressed in striated muscle and encoded by other overlapping reading frames from different start codons. SLMAP is conservative from yeast to humans.

Function of SLMAP Membrane Protein

SLMAP is a tail-anchored protein that was first discovered in cardiomyocytes. In mammals, this protein is involved in myoblast fusion during embryonic development, excitation-contraction coupling and cell cycle progression in cardiomyocytes. In addition, SLMAP is identified as a disease gene for Brugada syndrome (BrS) (a heart disease). The functional diversity of SLMAP relies on alternative splicing, resulting in at least four different protein isoforms. Gene expression analysis indicates that SLMAP expression is associated with diabetes, chromosomal aberrations, and endothelial dysfunction in cancer. Currently, SLMAP is a target for the treatment of drug-resistant cancer cells based on lectin. Like many BrS-associated accessory proteins, SLMAP-mediated BrS is the most common pathogenic mechanism of BrS, which is a loss of sodium current function.

Fig.1 (A) Human SLMAP forkhead-associated (FHA) crystal structure diagram. Cyan represents SLMAP FHA. (B) Crystal structure diagram of human SLMAP FHA complexed with pMST2 peptide. Wheat color and yellow represent SLMAP FHA and pMST2 polypeptides, respectively. (Bae, 2017)

Application of SLMAP Membrane Protein Literature

1. Suriyonplengsaeng C., et al. Immunohistochemistry of sarcolemmal membrane-associated proteins in formalin-fixed and paraffin-embedded skeletal muscle tissue: a promising tool for the diagnostic evaluation of common muscular dystrophies. Diagnostic Pathology. 2017, 12(1): 19. PubMed ID: 28219397
   
   

   This study establishes an immunohistochemical method for sarcolemmal membrane-associated proteins in formalin-fixed and paraffin-embedded skeletal muscle tissues, which may be a promising tool for the diagnosis of some common muscular dystrophy.

2. Nordzieke S., et al. A fungal sarcolemmal membrane-associated protein (SLMAP) homolog plays a fundamental role in development and localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. Eukaryotic Cell. 2015, 14(4): 345-58. PubMed ID: 25527523
   
   

   This article demonstrates that the human SLMAP homolog STRIPAK subunit PRO45 is required for sexual and intercellular fusion, and its fork-related (FHA) domain is essential for these processes.

3. Chen K., et al. Pinelliapedatisecta Agglutinin Targets Drug Resistant K562/ADR Leukemia Cells through Binding with Sarcolemmal Membrane Associated Protein and Enhancing Macrophage Phagocytosis. Plos One. 2013, 8(9): e74363. PubMed ID: 24019967
   
   

   This article suggests that pinelliapedatisecta agglutinin binds to sarcolemmal membrane-associated proteins to enhance macrophage phagocytosis of targeted K562/ADR leukemia cells.

4. Ishikawa T., et al. A novel disease gene for Brugada syndrome: sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5. CircArrhythmElectrophysiol. 2012, 5(6): 1098-107. PubMed ID: 23064965
   
   

   This article finds that mutations in SLMAP may cause Brugada syndrome by modulating intracellular trafficking of the hNav1.5 channel.

5. Ochrietor J.D., et al. The 2M6 antigen is a Müller cell-specific intracellular membrane associated. Molecular vision. 2013, 16: 961-9. PubMed ID: 20577597
   
   

   This article suggests that members of the sarcolemmal membrane-associated proteins family are involved in structural and functional roles associated with the cytoskeletal and internal storage of Ca²⁺ release.

SLMAP Preparation Options

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Reference

1. Bae S J, et al. (2017). SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. Elife. 6: e30278.

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