SLC44A4 Membrane Protein Introduction

Introduction of SLC44A4

SLC44A4, also known as CTL4 or NG22, is a sodium-dependent transmembrane transport protein which belongs to the CTL (choline transporter-like) family. It is encoded by SLC44A4 gene and has 4 isoforms produced by alternative splicing. The longest isoform has 710 acid amino acid residues with 10 transmembrane helixes, 6 cytoplasmic domains, and 5 extracellular domains. SLC44A4 is highly expressed in colon, prostate, trachea, and lung.

Function of SLC44A4 Membrane Protein

SLC44A4 is a sodium-dependent transmembrane transport protein that plays a role in the choline-acetylcholine system involved in the uptake of choline in cholinergic neurons. It has been revealed that SLC44A4 is involved in the efferent innervation of hair cells in the olivocochlear bundle to maintain the physiological function of outer hair cells and protect hair cells from acoustic damage. Besides, SLC44A4 is also regarded as thiamine pyrophosphate (TPP) transport protein in the colon, involved in regulation of microbiota-generated thiamine pyrophosphate absorption and promoting the homeostasis of host thiamine. Recent studies have revealed that the variants in SLC44A4 gene are associated with the susceptibility of ulcerative colitis, with the genetic heterogeneity among north Indian, Japanese and Dutch groups. Furthermore, SLC44A4 is a pathogenic gene of autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss. In the zebrafish model, the decreased expression of SLC44A4 leads to significant abnormalities in the inner ear and lateral line neuromasts and may result in the disorders in hearing and balance.

Fig.1 SLC44A4 expression in prostate and pancreatic adenocarcinoma. A: low-grade prostate adenocarcinoma. B: high-grade prostate adenocarcinoma. C: metastatic prostate adenocarcinoma in bone. D: low-grade pancreatic ductal adenocarcinoma. E: high-grade pancreatic ductal adenocarcinoma. (Mattie, 2016)

Application of SLC44A4 Membrane Protein in Literature

1. Wu J., et al. Evaluating the association of common variants of the SLC44A4 gene with ulcerative colitis susceptibility in the Han Chinese population. Genet Test Mol Biomarkers. 2017, 21(9):555-559. PubMed ID: 28753073
   
   

   The authors prove that the SNP rs2736428 in SLC44A4 gene is associated with the ulcerative colitis susceptibility in Han Chinese population.

2. Gupta A. and Thelma B.K. Identification of critical variants within SLC44A4, an ulcerative colitis susceptibility gene identified in a GWAS in north Indians. Genes & Immunity. 2016, 17(2):105-109. PubMed ID: 26741288
   
   

   The genome-wide association study (GWAS) study identifies the key genetic polymorphisms in SLC44A4 gene, an ulcerative colitis susceptibility gene, in North Indians.

3. Nabokina S.M., et al. Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells. American Journal of Physiology Cell Physiology. 2015, 308(9):C750-7. PubMed ID: 25715703
   
   

   This study represents the first characterization of the SLC44A4 promoter and reveals the important role of both ELF3 and CREB-1 transcription factors in the maintenance of basal promoter activity in colonic epithelial cells.

4. Gupta A., et al. A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility. European Journal of Human Genetics. 2016, 25(1):111-122. PubMed ID: 27759029
   
   

   The study reveals the apparent allelic heterogeneity in CFB and genetic heterogeneity in SLC44A4 among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case-control genotype data.

5. Song P., et al. Choline transporter-like protein 4 (CTL4) links to non-neuronal acetylcholine synthesis. Journal of Neurochemistry. 2013, 126(4):451-461. PubMed ID: 23651124
   
   

   The study suggests that CTL4 regulates ACh synthesis in non-neuronal cell lines and displays a mechanism to target ACh synthesis in non-neuron without influencing the synthesis of neuronal ACh.

SLC44A4 Preparation Options

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Reference

1. Mattie M, et al. (2016). The discovery and preclinical development of ASG-5ME, an antibody drug conjugate targeting SLC44A4 positive epithelial tumors including pancreatic and prostate cancer. Molecular Cancer Therapeutics. 15(11), 2679-87.

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