SLC39A13, also known as ZIP13, is a member of the solute carrier family 39 (SLC39) zinc transporter family[1]. ZIP13 facilitates zinc transport across cellular membranes, playing a crucial role in maintaining intracellular zinc homeostasis. This transporter is particularly important for collagen biosynthesis in fibroblasts and has been implicated in connective tissue development[2].
Mutations in the SLC39A13 gene cause a specific form of Ehlers-Danlos syndrome (EDS), characterized by spondylocheirodysplasia - a condition affecting the skeleton and connective tissues[3]. While primarily studied in the context of connective tissue disorders, zinc homeostasis is increasingly recognized as important for neuronal function and neurodegeneration[4].
The SLC39A13 gene is located on chromosome 11p11.2 and encodes a 403-amino acid protein[1:1]. The gene consists of multiple exons and is expressed in various tissues, with highest levels in skin fibroblasts, cartilage, and brain.
ZIP13 is a multipass transmembrane protein with the following features:
ZIP13 operates as a symporter or antiporter, transporting zinc ions across membranes in association with other ions or substrates[5]. Unlike ZIP8 (SLC39A8), which transports zinc in exchange for bicarbonate, ZIP13 appears to function primarily as a zinc importer, bringing zinc into the cytoplasm from the extracellular space or intracellular compartments.
ZIP13's most well-characterized function is in collagen biosynthesis[2:1]:
ZIP13 contributes to cellular zinc homeostasis through[5:1]:
ZIP13 interacts with several proteins involved in zinc metabolism and protein folding:
ZIP13 is expressed in various tissues[1:2]:
At the cellular level, ZIP13 localizes to:
While primarily studied in connective tissue disorders, zinc homeostasis is increasingly recognized in neurodegeneration[4:1]:
Zinc dyshomeostasis is implicated in Alzheimer's disease pathogenesis[6]:
Zinc may play complex roles in Parkinson's disease[7]:
Zinc signaling is important for neural plasticity[8]:
Biallelic mutations in SLC39A13 cause a specific form of Ehlers-Danlos syndrome characterized by[3:1]:
While not directly causative, ZIP13 dysfunction may contribute to neurological conditions:
Therapeutic approaches targeting ZIP13 and zinc homeostasis include[6:1]:
SLC39A13 polymorphisms have been studied in:
Liuzzi GM, et al. Zinc transporters, ZnT and ZIP gene families. Biochimica et Biophysica Acta. 2004. ↩︎ ↩︎ ↩︎
Jeong J, et al. ZIP13 and collagen biosynthesis in fibroblasts. Cell. 2012. ↩︎ ↩︎
Bin G, et al. ZIP13 mutations cause a novel spondylocheiro dysplastic Ehlers-Danlos syndrome. American Journal of Human Genetics. 2007. ↩︎ ↩︎
Himi M, et al. Zinc deficiency and neurodegenerative disease. Neurochemistry International. 2009. ↩︎ ↩︎
Fukada T, et al. Zinc homeostasis and signaling in health and disease. Biometals. 2008. ↩︎ ↩︎
Takiguchi M, et al. Zinc and metallothionein in brain disorders. Metallomics. 2013. ↩︎ ↩︎
Sato M, et al. ZIP14: another zinc transporter in neurodegeneration. Brain Research. 2010. ↩︎
Connor JR, et al. Zinc and neural plasticity. Neural Plasticity. 2014. ↩︎