FUNCTION Selective transporter that mediates the uptake of Zn(2+) (PubMed:17202136, PubMed:22242765, PubMed:27321477, PubMed:28875161, PubMed:31164399, PubMed:31914589, PubMed:31979155, PubMed:33837739, PubMed:36473915). Plays an essential role for dietary zinc uptake from small intestine (By similarity). The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). Also exhibits polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (PubMed:22242765, PubMed:31914589).CATALYTIC ACTIVITY Zn(2+)(in) = Zn(2+)(out)ACTIVITY REGULATION The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). Extracellular acidification stimulated SLC39A4-dependent Zn(2+) uptake (PubMed:31979155).BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 5.SUBUNIT Homodimer; homodimerization is mediated by the transmembrane domain.SUBCELLULAR LOCATION Colocalized with TFRC in the recycling endosomes. Cycles between endosomal compartments and the plasma membrane in response to Zn(2+) availability. Zn(2+) deficiency promotes accumulation of SLC39A4 on the surface membrane, whereas high extracellular Zn(2+) levels induce internalization of SLC39A4, but also trigger drastic removal of cellular SLC39A4 via proteasomal and lysosomal degradation pathways.ALTERNATIVE PRODUCTS Highly expressed in kidney, small intestine, stomach, colon, jejunum and duodenum.DOMAIN The N-terminal extracellular domain is required for high efficient zinc transport.DOMAIN The two metal binding sites M1 and M2 that are halfway through the membrane form a binuclear metal center. M1 is essential to Zn(2+) transport, while the other, M2 appears to have an auxiliary role presumably by acting as an additional transport site that can modulate the properties of the primary transport site (PubMed:28875161, PubMed:31914589). The binuclear metal center plays a key role in Zn(2+) sensing (PubMed:32348750).PTM The extracellular N-terminal ectodomain is cleaved when cells are Zn(2+) deficient, N-terminally cleaved SLC39A4 is internalized at a faster rate.PTM Under excess Zn(2+) conditions, SLC39A4 on the cell surface is rapidly endocytosed, ubiquitinated and degraded.PTM Glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ZIP transporter (TC 2.A.5) family.
recommendedName: Zinc transporter ZIP4 alternativeName: Solute carrier family 39 member 4 alternativeName: Zrt- and Irt-like protein 4 shortName: ZIP-4