SLC39A8
entrez
64116
canonical
uniprot
Q9C0K1
canonical
ensembl
ENSG00000138821
resolver
ensp
ENSP00000349174
resolver
ensp
ENSP00000378310
resolver
ensp
ENSP00000526347
resolver
ensp
ENSP00000526350
resolver
ensp
ENSP00000778842
resolver
ensp
ENSP00000778843
resolver
genesymbol
SLC39A8
resolver
genesymbol_syn
BIGM103
resolver
genesymbol_syn
ZIP8
resolver
hgnc
HGNC:20862
resolver
uniprot
B4E2H3
resolver
uniprot
Q96SM9
resolver
uniprot
Q9BVC0
resolver
uniprot
Q9NSA4
resolver
uniprot_entry
S39A8_HUMAN
resolver
uniprot_sec
B4E2H3
resolver
uniprot_sec
Q96SM9
resolver
uniprot_sec
Q9BVC0
resolver
uniprot_sec
Q9NSA4
resolver
amino_acid_sequence
MAPGRAVAGLLLLAAAGLGGVAEGPGLAFSEDVLSVFGANLSLSAAQLQHLLEQMGAASRVGVPEPGQLHFNQCLTAEEIFSLHGFSNATQITSSKFSVICPAVLQQLNFHPCEDRPKHKTRPSHSEVWGYGFLSVTIINLASLLGLILTPLIKKSYFPKILTFFVGLAIGTLFSNAIFQLIPEAFGFDPKVDSYVEKAVAVFGGFYLLFFFERMLKMLLKTYGQNGHTHFGNDNFGPQEKTHQPKALPAINGVTCYANPAVTEANGHIHFDNVSVVSLQDGKKEPSSCTCLKGPKLSEIGTIAWMITLCDALHNFIDGLAIGASCTLSLLQGLSTSIAILCEEFPHELGDFVILLNAGMSTRQALLFNFLSACSCYVGLAFGILVGNNFAPNIIFALAGGMFLYISLADMFPEMNDMLREKVTGRKTDFTFFMIQNAGMLTGFTAILLITLYAGEIELE
uniprot
proteins
disease_involvement
DISEASE: Congenital disorder of glycosylation 2N (CDG2N) [MIM:616721]: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:26637978, ECO:0000269|PubMed:26637979, ECO:0000269|PubMed:29453449}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Rare variants in SLC39A8 may be a cause of Leigh-like mitochondrial syndrome characterized by profound developmental delay, dystonia, seizures and failure to thrive. {ECO:0000269|PubMed:27995398}.
uniprot
proteins
function
FUNCTION: Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity (PubMed:12504855, PubMed:22898811, PubMed:23403290, PubMed:26637978, PubMed:29337306, PubMed:29453449). Transports an electroneutral complex composed of a divalent metal cation and two bicarbonate anions or alternatively a bicarbonate and a selenite anion (PubMed:27166256, PubMed:31699897). Thereby, it also contributes to the cellular uptake of selenium, an essential trace metal and micronutrient (PubMed:27166256). Also imports cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:27466201). May also transport iron and cobalt through membranes (PubMed:22898811). Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:29337306). Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450). Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290, PubMed:28056086). Protects, for instance, cells from injury and death at the onset of inflammation (PubMed:18390834). By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (By similarity). Reclaims manganese from the bile at the apical membrane of hepatocytes, thereby regulating the activity of the manganese-dependent enzymes through the systemic levels of the nutrient (PubMed:28481222). Also participates in manganese reabsorption in the proximal tubule of the kidney (PubMed:26637978). By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain (PubMed:26637978, PubMed:31699897). With manganese cellular uptake also participates in mitochondrial proper function (PubMed:29453449). Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR-mediated T cell activation (PubMed:19401385). {ECO:0000250|UniProtKB:Q91W10, ECO:0000269|PubMed:12504855, ECO:0000269|PubMed:18390834, ECO:0000269|PubMed:19401385, ECO:0000269|PubMed:22898811, ECO:0000269|PubMed:23403290, ECO:0000269|PubMed:26637978, ECO:0000269|PubMed:27166256, ECO:0000269|PubMed:27466201, ECO:0000269|PubMed:28056086, ECO:0000269|PubMed:28481222, ECO:0000269|PubMed:29337306, ECO:0000269|PubMed:29453449, ECO:0000269|PubMed:29927450, ECO:0000269|PubMed:31699897}.
uniprot
proteins
mass_dalton
49631
uniprot
proteins
post_translational_modification
PTM: N-glycosylated (PubMed:18390834). N-glycosylation is not required for proper iron and zinc transport (By similarity). {ECO:0000250|UniProtKB:Q5FVQ0, ECO:0000269|PubMed:18390834}.
uniprot
proteins
protein_family
ZIP transporter (TC 2.A.5) family
uniprot
proteins
pubmed
12504855
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
18390834
uniprot
proteins
pubmed
19401385
uniprot
proteins
pubmed
22898811
uniprot
proteins
pubmed
23403290
uniprot
proteins
pubmed
26637978
uniprot
proteins
pubmed
26637979
uniprot
proteins
pubmed
27166256
uniprot
proteins
pubmed
27466201
uniprot
proteins
pubmed
27995398
uniprot
proteins
pubmed
28056086
uniprot
proteins
pubmed
28481222
uniprot
proteins
pubmed
29337306
uniprot
proteins
pubmed
29453449
uniprot
proteins
pubmed
29927450
uniprot
proteins
pubmed
31699897
uniprot
proteins
sequence_length
460
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12504855, ECO:0000269|PubMed:18390834, ECO:0000269|PubMed:29337306, ECO:0000269|PubMed:31699897}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:12504855, ECO:0000269|PubMed:18390834, ECO:0000269|PubMed:19401385}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:31699897}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:31699897}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to the lysosome of activated T-cells (PubMed:19401385). A large fraction of the protein is found intracellularly in microvascular capillary endothelial cells that constitute the blood-brain barrier (PubMed:31699897). Localized and functional at both apical and basolateral membranes of microvascular capillary endothelial cells that constitute the blood-brain barrier (PubMed:31699897). {ECO:0000269|PubMed:19401385, ECO:0000269|PubMed:31699897}.
uniprot
proteins
transmembrane_region
TRANSMEM 133..153; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 161..181; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 192..212; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 366..386; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 389..409; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 430..450; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins