Zinc transporter ZIP8

SLC39A8
Identifiers
Aliases	SLC39A8 , BIGM103, LZT-Hs6, ZIP8, PP3105, CDG2N, solute carrier family 39 member 8
External IDs	OMIM: 608732 MGI: 1914797 HomoloGene: 11155 GeneCards: SLC39A8
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q24 Start 102,251,080 bp [1] End 102,431,258 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3 G3|3 63.04 cM Start 135,531,040 bp [2] End 135,594,333 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland lower lobe of lung visceral pleura germinal epithelium upper lobe of lung parietal pleura upper lobe of left lung right lung rectum body of pancreas Top expressed in molar right lung lobe left lung left lung lobe hair follicle conjunctival fornix yolk sac belly cord primitive streak atrium More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion transmembrane transporter activity zinc ion transmembrane transporter activity Cellular component organelle membrane integral component of membrane plasma membrane membrane integral component of plasma membrane Biological process metal ion transport zinc ion transport ion transport cadmium ion transmembrane transport cellular zinc ion homeostasis zinc ion import across plasma membrane transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64116 67547 Ensembl ENSG00000138821 ENSMUSG00000053897 UniProt Q9C0K1 Q91W10 RefSeq (mRNA) NM_001135146 NM_001135147 NM_001135148 NM_022154 NM_001135149 NM_001135150 NM_026228 RefSeq (protein) NP_001128618 NP_001128619 NP_001128620 NP_071437 NP_001128621 NP_001128622 NP_080504 Location (UCSC) Chr 4: 102.25 – 102.43 Mb Chr 3: 135.53 – 135.59 Mb PubMed search [3] [4]
Wikidata
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Zinc transporter ZIP8 is a cation/bicarbonate symporter protein which in humans is encoded by the SLC39A8 gene. ^{[5] [6] [7]}

Function

This transmembrane protein is responsible for the influx of zinc, manganese, iron, and cadmium. ^[8] ZIP8 is distributed among the embryo, placenta, and yolk sac during development. ^[9] Within the embryo, the concentration of ZIP8 is highest during the developmental period of different organ systems, specifically the heart where is it localized in the endothelial cells. Cardiac development is a zinc-dependent event. Beginning around mouse E8.0, the heart is in a tubular form with an outer myocardium layer and an inner endocardium layer, separated by cardiac jelly. ^[10] As development continues, trabeculation, the protrusion of cardiomyocytes into the cardiac jelly, begins and facilitates nutrient and oxygen exchange prior to the establishment of coronary vessels. Simultaneous with coronary circulation development, the trabeculae then collapse into the ventricular wall in a process known as compaction. Cardiomyocyte differentiation, proliferation, and trabeculae patterning is regulated through Notch 1 signaling, which is upregulated by the ECM. ADAMTS 1, 5, 7, 15, and 19 are zinc metalloenzymes responsible for degrading the ECM prior to compaction. ^[11] Many studies have analyzed the effects of Slc39a8-/- on fetal heart development and have shown a decrease in zinc influx leading to an increase in cardiomyocyte proliferation through BMP10, hypertrabeculation through the upregulation of Notch1, and ventricular non-compaction due to the persistence of the ECM.

References

1. GRCh38: Ensembl release 89: ENSG00000138821 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000053897 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "SLC39A8 solute carrier family 39 member 8 [Homo sapiens (human)] – Gene – NCBI". www.ncbi.nlm.nih.gov. National Center for Biotechnology Information, U.S. National Library of Medicine . Retrieved 19 April 2019.
6. Park JH, Hogrebe M, Grüneberg M. "SLC39A8 deficiency is a novel treatable disorder of manganese metabolism and glycosylation". ResearchGate. Retrieved 19 April 2019.
7. Gálvez-Peralta M, He L, Jorge-Nebert LF, Wang B, Miller ML, Eppert BL, Afton S, Nebert DW (2012). "ZIP8 zinc transporter: indispensable role for both multiple-organ organogenesis and hematopoiesis in utero". PLOS ONE. 7 (5): e36055. Bibcode:2012PLoSO...736055G. doi: 10.1371/journal.pone.0036055 . PMC   3341399 . PMID   22563477.
8. Wang B, He L, Dong H, Dalton TP, Nebert DW (July 2011). "Generation of a Slc39a8 hypomorph mouse: markedly decreased ZIP8 Zn²⁺/(HCO₃⁻)₂ transporter expression". Biochemical and Biophysical Research Communications. 410 (2): 289–94. doi:10.1016/j.bbrc.2011.05.134. PMC   3136049 . PMID   21658371.
9. Chen J, Gálvez-Peralta M, Zhang X, Deng J, Liu Z, Nebert DW (July 2018). "In utero gene expression in the Slc39a8(neo/neo) knockdown mouse". Scientific Reports. 8 (1): 10703. Bibcode:2018NatSR...810703C. doi:10.1038/s41598-018-29109-y. PMC   6048144 . PMID   30013175.
10. Lin W, Li D (June 2018). "Zinc and Zinc Transporters: Novel Regulators of Ventricular Myocardial Development". Pediatric Cardiology. 39 (5): 1042–1051. doi:10.1007/s00246-018-1859-y. PMID   29536133. S2CID   3861584.
11. Lin W, Li D, Cheng L, Li L, Liu F, Hand NJ, Epstein JA, Rader DJ (February 2018). "Zinc transporter Slc39a8 is essential for cardiac ventricular compaction". The Journal of Clinical Investigation. 128 (2): 826–833. doi:10.1172/JCI96993. PMC   5785267 . PMID   29337306.