Recombinant Mouse Metal cation symporter ZIP14 (Slc39a14) Protein

Function

Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15863613, PubMed:16950869, PubMed:18270315, PubMed:19179618, PubMed:21653899, PubMed:28673968). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (PubMed:18270315). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:18270315). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (PubMed:25428902). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (PubMed:21445361). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (PubMed:28673968). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (By similarity). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (PubMed:28536273). Also functions in the extracellular uptake of free iron (PubMed:16950869, PubMed:19179618, PubMed:21653899, PubMed:23110240, PubMed:26028554). May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (By similarity)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Apical cell membrane (Multi-pass membrane protein); Basolateral cell membrane (Multi-pass membrane protein); Early endosome membrane (Multi-pass membrane protein); Late endosome membrane (Multi-pass membrane protein); Lysosome membrane (Multi-pass membrane protein)

Tissue Specificity

More strongly expressed in liver, kidney and duodenum

Subunit

Homotrimer

• Tominaga K. et al. SLC39A14, a LZT protein, is induced in adipogenesis and transports zinc. — FEBS J. (2005)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Okazaki N. et al. Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. — DNA Res. (2003)
• Liuzzi J.P. et al. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. — Proc. Natl. Acad. Sci. U.S.A. (2005)
• Liuzzi J.P. et al. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. — Proc. Natl. Acad. Sci. U.S.A. (2006)
• Kobayashi K. et al. Induction of metallothionein by manganese is completely dependent on interleukin-6 production. — J. Pharmacol. Exp. Ther. (2007)
• Girijashanker K. et al. Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. — Mol. Pharmacol. (2008)