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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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Zn(2+)(in) = Zn(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29351"},{"database":"ChEBI","id":"CHEBI:29105"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17202136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22242765"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27321477"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28875161"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31164399"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31914589"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31979155"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33837739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36473915"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17202136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31979155"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32348750"}],"value":"The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). 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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)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q78IQ7"}],"value":"The extracellular N-terminal ectodomain is cleaved when cells are Zn(2+) deficient, N-terminally cleaved SLC39A4 is internalized at a faster rate"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17202136"}],"value":"Under excess Zn(2+) conditions, SLC39A4 on the cell surface is rapidly endocytosed, ubiquitinated and degraded"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17202136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27321477"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33837739"}],"value":"Glycosylated"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Acrodermatitis enteropathica, zinc-deficiency type","diseaseAccession":"DI-00027","acronym":"AEZ","description":"A rare autosomal recessive disease caused by the inability to absorb sufficient zinc. 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