Metal cation symporter ZIP8

Details

Name

Metal cation symporter ZIP8

Kind

protein

Synonyms

• BCG-induced integral membrane protein in monocyte clone 103 protein
• BIGM103
• LIV-1 subfamily of ZIP zinc transporter 6
• LZT-Hs6
• Solute carrier family 39 member 8
• ZIP-8
• ZIP8
• Zrt- and Irt-like protein 8

Gene Name

SLC39A8

UniProtKB Entry

Q9C0K1Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0052365|Metal cation symporter ZIP8
MAPGRAVAGLLLLAAAGLGGVAEGPGLAFSEDVLSVFGANLSLSAAQLQHLLEQMGAASR
VGVPEPGQLHFNQCLTAEEIFSLHGFSNATQITSSKFSVICPAVLQQLNFHPCEDRPKHK
TRPSHSEVWGYGFLSVTIINLASLLGLILTPLIKKSYFPKILTFFVGLAIGTLFSNAIFQ
LIPEAFGFDPKVDSYVEKAVAVFGGFYLLFFFERMLKMLLKTYGQNGHTHFGNDNFGPQE
KTHQPKALPAINGVTCYANPAVTEANGHIHFDNVSVVSLQDGKKEPSSCTCLKGPKLSEI
GTIAWMITLCDALHNFIDGLAIGASCTLSLLQGLSTSIAILCEEFPHELGDFVILLNAGM
STRQALLFNFLSACSCYVGLAFGILVGNNFAPNIIFALAGGMFLYISLADMFPEMNDMLR
EKVTGRKTDFTFFMIQNAGMLTGFTAILLITLYAGEIELE

Number of residues

460

Molecular Weight

49630.175

Theoretical pI

Not Available

GO Classification

Functions

monoatomic cation / zinc

Processes

arginine metabolic process / bicarbonate transport / cartilage homeostasis / cellular detoxification of cadmium ion / cobalt ion transport / DNA-templated transcription / extracellular matrix organization / intracellular manganese ion homeostasis / intracellular monoatomic cation homeostasis / intracellular zinc ion homeostasis / iron ion import across plasma membrane / leukocyte adhesion to arterial endothelial cell / manganese ion transmembrane transport / mercury ion transport / mitochondrial manganese ion transmembrane transport / negative regulation of canonical NF-kappaB signal transduction / negative regulation of inflammatory response / plasma membrane selenite transport / protein N-linked glycosylation / regulation of DNA-templated transcription / regulation of membrane potential / zinc ion transmembrane transport

Components

apical plasma membrane / basolateral plasma membrane / lysosomal membrane

General 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)

Specific Function

Monoatomic cation

Pfam Domain Function

• Zip (PF02535)

Signal Regions

1-22

Transmembrane Regions

133-153 161-181 192-212 366-386 389-409 430-450

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0052366|Zinc transporter ZIP8 (SLC39A8)
ATGGCCCCGGGTCGCGCGGTGGCCGGGCTCCTGTTGCTGGCGGCCGCCGGCCTCGGAGGA
GTGGCGGAGGGGCCAGGGCTAGCCTTCAGCGAGGATGTGCTGAGCGTGTTCGGCGCGAAT
CTGAGCCTGTCGGCGGCGCAGCTCCAGCACTTGCTGGAGCAGATGGGAGCCGCCTCCCGC
GTGGGCGTCCCGGAGCCTGGCCAGCTGCACTTCAACCAGTGTTTAACTGCTGAAGAGATC
TTTTCCCTTCATGGCTTTTCAAATGCTACCCAAATAACCAGCTCCAAATTCTCTGTCATC
TGTCCAGCAGTCTTACAGCAATTGAACTTTCACCCATGTGAGGATCGGCCCAAGCACAAA
ACAAGACCAAGTCATTCAGAAGTTTGGGGATATGGATTCCTGTCAGTGACGATTATTAAT
CTGGCATCTCTCCTCGGATTGATTTTGACTCCACTGATAAAGAAATCTTATTTCCCAAAG
ATTTTGACCTTTTTTGTGGGGCTGGCTATTGGGACTCTTTTTTCAAATGCAATTTTCCAA
CTTATTCCAGAGGCATTTGGATTTGATCCCAAAGTCGACAGTTATGTTGAGAAGGCAGTT
GCTGTGTTTGGTGGATTTTACCTACTTTTCTTTTTTGAAAGAATGCTAAAGATGTTATTA
AAGACATATGGTCAGAATGGTCATACCCACTTTGGAAATGATAACTTTGGTCCTCAAGAA
AAAACTCATCAACCTAAAGCATTACCTGCCATCAATGGTGTGACATGCTATGCAAATCCT
GCTGTCACAGAAGCTAATGGACATATCCATTTTGATAATGTCAGTGTGGTATCTCTACAG
GATGGAAAAAAAGAGCCAAGTTCATGTACCTGTTTGAAGGGGCCCAAACTGTCAGAAATA
GGGACGATTGCCTGGATGATAACGCTCTGCGATGCCCTCCACAATTTCATCGATGGCCTG
GCGATTGGGGCTTCCTGCACCTTGTCTCTCCTTCAGGGACTCAGTACTTCCATAGCAATC
CTATGTGAGGAGTTTCCCCACGAGTTAGGAGACTTTGTGATCCTACTCAATGCAGGGATG
AGCACTCGACAAGCCTTGCTATTCAACTTCCTTTCTGCATGTTCCTGCTATGTTGGGCTA
GCTTTTGGCATTTTGGTGGGCAACAATTTCGCTCCAAATATTATATTTGCACTTGCTGGA
GGCATGTTCCTCTATATTTCTCTGGCAGATATGTTTCCAGAGATGAATGATATGCTGAGA
GAAAAGGTAACTGGAAGAAAAACCGATTTCACCTTCTTCATGATTCAGAATGCTGGAATG
TTAACTGGATTCACAGCCATTCTACTCATTACCTTGTATGCAGGAGAAATCGAATTGGAG
TAA

Chromosome Location

4

Locus

4q24

External Identifiers

Resource	Link
UniProtKB ID	Q9C0K1
UniProtKB Entry Name	S39A8_HUMAN
GeneCard ID	SLC39A8
HGNC ID	HGNC:20862
KEGG ID	hsa:64116
NCBI Gene ID	64116

General References

1. Begum NA, Kobayashi M, Moriwaki Y, Matsumoto M, Toyoshima K, Seya T: Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures. Genomics. 2002 Dec;80(6):630-45. doi: 10.1006/geno.2002.7000. [Article]
2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
3. Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J: Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15724-9. Epub 2004 Oct 21. [Article]
4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
5. 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]
6. Boycott KM, Beaulieu CL, Kernohan KD, Gebril OH, Mhanni A, Chudley AE, Redl D, Qin W, Hampson S, Kury S, Tetreault M, Puffenberger EG, Scott JN, Bezieau S, Reis A, Uebe S, Schumacher J, Hegele RA, McLeod DR, Galvez-Peralta M, Majewski J, Ramaekers VT, Nebert DW, Innes AM, Parboosingh JS, Abou Jamra R: Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8. Am J Hum Genet. 2015 Dec 3;97(6):886-93. doi: 10.1016/j.ajhg.2015.11.002. [Article]
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Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Zinc chloride	approved, investigational	unknown	transporter	substrate	Details
Zinc sulfate, unspecified form	approved, experimental	unknown	transporter	substrate	Details