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HighlightsZinc transporter ZIP9 (SLC39A9) is one of the 14 members of the ZIP (ZRT-and Irt-like Protein, SLC39A) family that regulates zinc homeostasis by transporting zinc across cell and organelle membranes into the cytoplasm. Besides, SLC39A9 is also identified as a novel membrane androgen receptor. It is coupled to different G proteins for signaling transduction, such as the Gs protein in granulosa cells, Gi protein in cancer cells, and Gnα11 in spermatogenic cells. SLC39A9 is widely expressed in different human tissues. Structurally, human SLC39A9 protein is predicted to have 8 transmembrane domains with extracellular C termini.
| Basic Information of SLC39A9 | |
| Protein Name | Zinc transporter ZIP9 |
| Gene Name | SLC39A9 |
| Aliases | Solute carrier family 39 member 9, Zrt- and Irt-like protein 9, ZIP9 |
| Organism | Homo sapiens (Human) |
| UniProt ID | Q9NUM3 |
| Transmembrane Times | 8 |
| Length (aa) | 307 |
| Sequence | MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVHALYEDILEGKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFMLLVDQIGNSHVHSTDDPEAARSSNSKITTTLGLVVHAAADGVALGAAASTSQTSVQLIVFVAIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVMSMVTYLGLSKSSKEALSEVNATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDATGGRGLSRLEVAALVLGCLIPLILSVGHQH |
As SLC39A9 is a membrane androgen receptor and a zinc transporter, it functions by binding to androgen and can mediate zinc homeostasis. Upon binding to testosterone, apoptosis can be induced via SLC39A9 protein in croaker granulosa and human cancer cells (breast and prostate cancer cells). Besides, SLC39A9 is up-regulated in malignant breast and prostate tissues, suggesting that it is a potential therapeutic target for treating breast and prostate cancers. Moreover, SLC39A9 also mediates testosterone regulation of tight junction formation in Sertoli cells and non-classical testosterone signaling in spermatogenic cells.
Using triple-negative human breast cancer MDA-MB-468 cells that expressed moderate levels of ZIP9 and nAR-negative PC-3 human prostate cells that expressed lower levels of ZIP9, this study investigated whether human ZIP9 functioned as a membrane androgen receptor. The results showed that in both cell types, human ZIP9 functioned as an mAR and zinc transporter, and mediated testosterone-induced apoptosis via MAPK- and zinc-dependent pathways.
This study reported that in the spermatogenic cell line GC-2, the non-classical signaling pathway of testosterone was mediated by the ZIP9 zinc transporter.
Using a cell line that lacked the classical androgen receptor, this study showed that ZIP9-mediated phosphorylation of Erk1/2, CREB, or ATF-1, as well as expression of claudin-5 and zonula occludens-1 by testosterone, can be completely antagonized by bicalutamide, which was an anti-androgen of significant clinical impact.
This study investigated the underlying mechanisms of ZIP9 in the croaker ovarian cell apoptosis. The results showed that ZIP9 induced apoptosis of croaker ovarian cells via stimulatory G protein α subunit and MAP kinase signaling.
The effects of chronic hypoxia exposure of female Atlantic croaker on oogenesis and apoptosis of ovarian follicles as well as the ovarian expression and functions of the membrane steroid receptors, ZIP9, mPRα, and GPER were investigated.
Creative Biolabs has established a leading technology platform - Magic™ Membrane Protein Production Platform - that offers a wide range of strategies for your membrane protein expression, solubilization, reconstitution, and characterization. Specialized in producing high-quality membrane protein products for various applications, our scientists can prepare your target proteins in detergent micelles, liposomes, nanodiscs, and polymers.
Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC39A9 antibody development services.
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