Zinc transporter 10

Details

Name

Zinc transporter 10

Synonyms

• Manganese transporter SLC30A10
• Solute carrier family 30 member 10
• ZnT-10
• ZNT10
• ZNT8

Gene Name

SLC30A10

Organism

Humans

Amino acid sequence

>lcl|BSEQ0052361|Zinc transporter 10
MGRYSGKTCRLLFMLVLTVAFFVAELVSGYLGNSIALLSDSFNMLSDLISLCVGLSAGYI
ARRPTRGFSATYGYARAEVVGALSNAVFLTALCFTIFVEAVLRLARPERIDDPELVLIVG
VLGLLVNVVGLLIFQDCAAWFACCLRGRSRRLQQRQQLAEGCVPGAFGGPQGAEDPRRAA
DPTAPGSDSAVTLRGTSVERKREKGATVFANVAGDSFNTQNEPEDMMKKEKKSEALNIRG
VLLHVMGDALGSVVVVITAIIFYVLPLKSEDPCNWQCYIDPSLTVLMVIIILSSAFPLIK
ETAAILLQMVPKGVNMEELMSKLSAVPGISSVHEVHIWELVSGKIIATLHIKYPKDRGYQ
DASTKIREIFHHAGIHNVTIQFENVDLKEPLEQKDLLLLCNSPCISKGCAKQLCCPPGAL
PLAHVNGCAEHNGGPSLDTYGSDGLSRRDAREVAIEVSLDSCLSDHGQSLNKTQEDQCYV
NRTHF

Number of residues

485

Molecular Weight

52683.46

Theoretical pI

Not Available

GO Classification

Functions

manganese ion transmembrane transporter activity

Processes

cellular response to angiotensin / epidermal growth factor receptor signaling pathway / manganese ion transmembrane transport / manganese ion transport / negative regulation of cellular senescence / negative regulation of neuron apoptotic process / negative regulation of reactive oxygen species biosynthetic process / positive regulation of ERK1 and ERK2 cascade / regulation of cellular response to manganese ion / regulation of zinc ion transport / zinc ion transport

Components

early endosome / Golgi apparatus / integral component of membrane / plasma membrane / recycling endosome

General Function

Plays a pivotal role in manganese transport. Manganese is an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. However, elevated levels of manganese are cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Acts as manganese efflux transporter and confers protection against manganese-induced cell death (PubMed:22341972, PubMed:22341971, PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc transporter involved in zinc homeostasis. Seems to mediate zinc transport into early endosomes and recycling endosomes to prevent zinc toxicity; the function may be regulated by heterodimerization with other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10 heterodimer is involved in zinc transport-dependent regulation of the EGFR/ERK transduction pathway in endosomes. May be involved in regulation of zinc-dependent senescence of vascular smooth muscle cells (PubMed:22706290, PubMed:22427991, PubMed:26728129).

Specific Function

Manganese ion transmembrane transporter activity

Pfam Domain Function

• Cation_efflux (PF01545)

Transmembrane Regions

11-31 41-61 82-102 114-134 245-265 279-299

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0052362|Zinc transporter 10 (SLC30A10)
ATGGGCCGCTACTCTGGCAAGACGTGCCGGCTGCTCTTCATGCTGGTGCTCACCGTCGCC
TTCTTCGTGGCGGAGCTGGTCTCCGGCTACCTGGGCAACTCCATCGCGCTGCTCTCCGAC
TCCTTCAACATGCTCTCCGACCTGATCTCGCTGTGCGTGGGCCTGAGCGCCGGCTACATC
GCCCGGCGCCCCACCCGGGGCTTCAGCGCCACCTACGGCTACGCCCGCGCCGAGGTGGTG
GGCGCGCTGAGCAACGCGGTCTTCCTCACCGCGCTCTGCTTCACCATCTTCGTGGAGGCC
GTGCTGCGCCTGGCCCGGCCCGAGCGCATCGATGACCCCGAGCTGGTGCTCATCGTCGGC
GTCCTGGGGCTGTTGGTCAACGTGGTGGGGCTGCTCATCTTCCAGGACTGCGCCGCCTGG
TTCGCGTGCTGCCTCCGGGGACGCAGTCGCCGCCTGCAGCAGCGGCAGCAGCTGGCGGAG
GGCTGTGTCCCCGGCGCTTTCGGGGGGCCTCAGGGCGCGGAGGACCCGCGGCGCGCGGCG
GACCCGACAGCCCCAGGCTCGGACTCGGCCGTAACCCTCCGGGGGACCTCGGTGGAAAGG
AAGCGGGAGAAGGGGGCGACCGTGTTCGCAAACGTAGCAGGTGATTCCTTCAACACCCAG
AATGAGCCAGAAGACATGATGAAAAAAGAGAAAAAGTCTGAAGCTCTGAATATCAGAGGT
GTACTTTTGCATGTGATGGGAGATGCCCTGGGGTCCGTGGTTGTGGTCATCACGGCCATC
ATATTCTATGTGCTTCCCCTGAAGAGTGAGGACCCGTGTAACTGGCAGTGTTACATTGAC
CCCAGCCTGACTGTCCTCATGGTCATCATCATTTTGTCATCTGCCTTCCCGCTTATCAAG
GAGACCGCTGCCATTCTGCTACAGATGGTCCCAAAAGGAGTCAACATGGAAGAGCTGATG
AGTAAACTCTCTGCTGTGCCTGGAATTAGCAGTGTACATGAAGTGCACATCTGGGAACTT
GTAAGTGGAAAGATTATTGCCACCCTGCACATCAAGTATCCTAAGGACAGGGGATATCAA
GATGCCAGCACAAAAATTCGAGAAATCTTCCACCATGCGGGAATCCACAATGTGACCATC
CAGTTTGAAAATGTGGACTTGAAGGAACCCCTGGAGCAGAAGGACTTACTGTTGCTCTGC
AACTCACCCTGCATCTCCAAGGGCTGTGCTAAGCAGCTGTGTTGTCCCCCCGGGGCACTG
CCTCTGGCTCACGTCAATGGCTGTGCTGAGCACAATGGTGGGCCCTCTCTAGACACATAC
GGAAGTGATGGCCTCAGTAGAAGAGACGCAAGAGAAGTGGCTATTGAAGTGTCTTTGGAT
AGCTGTCTGAGTGACCACGGACAAAGTCTTAACAAAACTCAGGAGGACCAATGTTATGTC
AACAGAACGCATTTTTAA

Chromosome Location

1

Locus

1q41

External Identifiers

Resource	Link
UniProtKB ID	Q6XR72
UniProtKB Entry Name	ZNT10_HUMAN
HGNC ID	HGNC:25355

General References

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2. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
4. Seve M, Chimienti F, Devergnas S, Favier A: In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression. BMC Genomics. 2004 May 23;5(1):32. doi: 10.1186/1471-2164-5-32. [Article]
5. Tuschl K, Clayton PT, Gospe SM Jr, Gulab S, Ibrahim S, Singhi P, Aulakh R, Ribeiro RT, Barsottini OG, Zaki MS, Del Rosario ML, Dyack S, Price V, Rideout A, Gordon K, Wevers RA, Chong WK, Mills PB: Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet. 2012 Mar 9;90(3):457-66. doi: 10.1016/j.ajhg.2012.01.018. Epub 2012 Feb 16. [Article]
6. Quadri M, Federico A, Zhao T, Breedveld GJ, Battisti C, Delnooz C, Severijnen LA, Di Toro Mammarella L, Mignarri A, Monti L, Sanna A, Lu P, Punzo F, Cossu G, Willemsen R, Rasi F, Oostra BA, van de Warrenburg BP, Bonifati V: Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. Am J Hum Genet. 2012 Mar 9;90(3):467-77. doi: 10.1016/j.ajhg.2012.01.017. Epub 2012 Feb 16. [Article]
7. Bosomworth HJ, Thornton JK, Coneyworth LJ, Ford D, Valentine RA: Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis. Metallomics. 2012 Aug;4(8):771-9. doi: 10.1039/c2mt20088k. Epub 2012 Jun 18. [Article]
8. Patrushev N, Seidel-Rogol B, Salazar G: Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PLoS One. 2012;7(3):e33211. doi: 10.1371/journal.pone.0033211. Epub 2012 Mar 12. [Article]
9. Leyva-Illades D, Chen P, Zogzas CE, Hutchens S, Mercado JM, Swaim CD, Morrisett RA, Bowman AB, Aschner M, Mukhopadhyay S: SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. J Neurosci. 2014 Oct 15;34(42):14079-95. doi: 10.1523/JNEUROSCI.2329-14.2014. [Article]
10. Ogo OA, Tyson J, Cockell SJ, Howard A, Valentine RA, Ford D: The zinc finger protein ZNF658 regulates the transcription of genes involved in zinc homeostasis and affects ribosome biogenesis through the zinc transcriptional regulatory element. Mol Cell Biol. 2015 Mar;35(6):977-87. doi: 10.1128/MCB.01298-14. Epub 2015 Jan 12. [Article]
11. Nishito Y, Tsuji N, Fujishiro H, Takeda TA, Yamazaki T, Teranishi F, Okazaki F, Matsunaga A, Tuschl K, Rao R, Kono S, Miyajima H, Narita H, Himeno S, Kambe T: Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 Protein as a Manganese Transporter. J Biol Chem. 2016 Jul 8;291(28):14773-87. doi: 10.1074/jbc.M116.728014. Epub 2016 May 10. [Article]
12. Zogzas CE, Aschner M, Mukhopadhyay S: Structural Elements in the Transmembrane and Cytoplasmic Domains of the Metal Transporter SLC30A10 Are Required for Its Manganese Efflux Activity. J Biol Chem. 2016 Jul 29;291(31):15940-57. doi: 10.1074/jbc.M116.726935. Epub 2016 Jun 15. [Article]
13. Zhao Y, Feresin RG, Falcon-Perez JM, Salazar G: Differential Targeting of SLC30A10/ZnT10 Heterodimers to Endolysosomal Compartments Modulates EGF-Induced MEK/ERK1/2 Activity. Traffic. 2016 Mar;17(3):267-88. doi: 10.1111/tra.12371. Epub 2016 Feb 12. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB14533	Zinc chloride	approved, investigational	unknown	substrate	Details
DB14548	Zinc sulfate, unspecified form	approved, experimental	unknown	substrate	Details