Recombinant Human Zinc transporter 10 (SLC30A10), partial

Function

Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange (PubMed:30755481). Required for intracellular manganese homeostasis, an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. Manganese can also be cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis (PubMed:22341972, PubMed:25319704, PubMed:26728129, PubMed:27226609, PubMed:27307044). Could also have an intracellular zinc ion transporter activity, directly regulating intracellular zinc ion homeostasis and more indirectly various signaling pathway and biological processes (PubMed:22427991, PubMed:26728129)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Golgi apparatus membrane (Multi-pass membrane protein); Recycling endosome membrane; Early endosome membrane (Multi-pass membrane protein)

Disease Association

Hypermanganesemia with dystonia 1 (HMNDYT1) : A metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Specifically expressed in fetal liver and fetal brain (PubMed:15154973). Expressed in adult tissues with relative levels small intestine > liver > testes > brain > ovary > colon > cervix > prostate > placenta (PubMed:22706290). Expressed in liver and neurons of the nervous system (at protein level) (PubMed:22341971)

Subunit

Forms homodimers. Forms heterodimers and high-molecular weight oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is mediated by covalent-bound tyrosine residues, occurs probably in a tissue-specific manner and could mediate the intracellular zinc transport activity into early endosomes and recycling endosomes

• Huang L. et al. Characterization of a novel mammalian zinc transporter, ZNT8. (JAN-)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Seve M. et al. In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression. — BMC Genomics (2004)
• Tuschl K. et al. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. — Am. J. Hum. Genet. (2012)
• Quadri M. et al. Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. — Am. J. Hum. Genet. (2012)
• Bosomworth H.J. et al. Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis. — Metallomics (2012)