Protein transport protein Sec16B also known as regucalcin gene promoter region-related protein p117 (RGPR-p117) and leucine zipper transcription regulator 2 (LZTR2) is a protein that in humans is encoded by the SEC16B gene. [5] [6] [7]
Protein transport protein Sec16B also known as regucalcin gene promoter region-related protein p117 (RGPR-p117) and leucine zipper transcription regulator 2 (LZTR2) is a protein that in humans is encoded by the SEC16B gene. [5] [6] [7]
RGPR-p117, which was named as a regucalcin gene promoter region-related protein, was originally discovered as a novel transcription factor that specifically binds to a nuclear factor I (NFI) consensus motif TTGGC(N)6CC that is located on the 5’-flanking region of the regucalcin gene (rgn) in 2001. [6] [8] This gene is a highly conserved a leucine zipper motif, and it was also named as the leucine zipper transcription regulator 2 (LZTR2). In 2007, RGPR-p117 was also renamed as Sec16 homologue B (SEC16B), an endoplasmic reticulum export factor. [9]
The gene consists of 26 exons spanning approximately 4.1 kbp and is localized on human chromosome 1q25.2. [6] This gene expression is stimulated through various signaling factors in cells. [10] [11] RGPR-p117 is present in the plasma membranes, cytoplasm, mitochondria, microsomes and nucleus of the cells. [11] Cytoplasm RGPR-p117 is translocated to nucleus. [10] Phosphorylated RGPR-p117 specifically binds to the TTGGC motif in the promoter region of various genes to enhance the gene expression of various proteins, and plays a crucial role as a transcription factor in the cells. [11] [12] [13]
In the role in the regulation of cell regulation, RGPR-p117 possesses protective effects on apoptotic cell death induced by various signaling factors. [12] Overexpression of RGPR-p117 did not cause an alteration of cell proliferation and led to significant decreases in protein and DNA contents in cloned normal rat kidney proximal tubular epithelial NRK52E cells. [14] It also plays a role as an endoplasmic reticulum export factor to deliver to newly synthesized proteins and lipids to the Golgi. [9] [15] [16] RGPR-p117/SEC16B may be involved in human obesity to possess an association between single nucleotide polymorphisms and different measures of obesity. [17] [18] [19]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal [20] |
| Haematology | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Salmonella infection | Normal [21] |
| Citrobacter infection | Normal [22] |
| All tests and analysis from [23] [24] |
Model organisms have been used in the study of SEC16B function. A conditional knockout mouse line, called Sec16btm1a(KOMP)Wtsi [25] [26] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. [27] [28] [29]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [23] [30] Twenty one tests were carried out on mutant mice and one significant abnormality was observed: homozygote mutants had decreased circulating cholesterol levels. [23]
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