Proton-coupled zinc antiporter SLC30A5

Details

Name

Proton-coupled zinc antiporter SLC30A5

Kind

protein

Synonyms

• hZTL1
• Solute carrier family 30 member 5
• Zinc transporter 5
• ZnT-5
• ZnT-like transporter 1
• ZNT5
• ZNTL1
• ZTL1

Gene Name

SLC30A5

UniProtKB Entry

Q8TAD4Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0052359|Proton-coupled zinc antiporter SLC30A5
MEEKYGGDVLAGPGGGGGLGPVDVPSARLTKYIVLLCFTKFLKAVGLFESYDLLKAVHIV
QFIFILKLGTAFFMVLFQKPFSSGKTITKHQWIKIFKHAVAGCIISLLWFFGLTLCGPLR
TLLLFEHSDIVVISLLSVLFTSSGGGPAKTRGAAFFIIAVICLLLFDNDDLMAKMAEHPE
GHHDSALTHMLYTAIAFLGVADHKGGVLLLVLALCCKVGFHTASRKLSVDVGGAKRLQAL
SHLVSVLLLCPWVIVLSVTTESKVESWFSLIMPFATVIFFVMILDFYVDSICSVKMEVSK
CARYGSFPIFISALLFGNFWTHPITDQLRAMNKAAHQESTEHVLSGGVVVSAIFFILSAN
ILSSPSKRGQKGTLIGYSPEGTPLYNFMGDAFQHSSQSIPRFIKESLKQILEESDSRQIF
YFLCLNLLFTFVELFYGVLTNSLGLISDGFHMLFDCSALVMGLFAALMSRWKATRIFSYG
YGRIEILSGFINGLFLIVIAFFVFMESVARLIDPPELDTHMLTPVSVGGLIVNLIGICAF
SHAHSHAHGASQGSCHSSDHSHSHHMHGHSDHGHGHSHGSAGGGMNANMRGVFLHVLADT
LGSIGVIVSTVLIEQFGWFIADPLCSLFIAILIFLSVVPLIKDACQVLLLRLPPEYEKEL
HIALEKIQKIEGLISYRDPHFWRHSASIVAGTIHIQVTSDVLEQRIVQQVTGILKDAGVN
NLTIQVEKEAYFQHMSGLSTGFHDVLAMTKQMESMKYCKDGTYIM

Number of residues

765

Molecular Weight

84045.73

Theoretical pI

Not Available

GO Classification

Functions

antiporter activity / metal ion binding / zinc / zinc efflux transmembrane transporter activity

Processes

GPI anchor biosynthetic process / insulin processing / intracellular zinc ion homeostasis / zinc ion import across plasma membrane / zinc ion import into Golgi lumen / zinc ion import into organelle / zinc ion transmembrane transport

Components

cytoplasmic vesicle / endoplasmic reticulum membrane / ER to Golgi transport vesicle membrane / Golgi cis cisterna membrane / Golgi membrane / plasma membrane / trans-Golgi network membrane

General Function

Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway (PubMed:11904301, PubMed:15525635, PubMed:15994300, PubMed:19366695, PubMed:22529353). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (PubMed:15525635, PubMed:15994300, PubMed:16636052, PubMed:35525268). Through the transport of zinc into secretory granules of pancreatic beta-cells, plays an important role in the storage and secretion of insulin (PubMed:11904301)

Specific Function

Antiporter activity

Pfam Domain Function

• Cation_efflux (PF01545)

Signal Regions

Not Available

Transmembrane Regions

33-53 57-77 99-119 121-141 153-173 194-214 239-259 268-288 304-324 343-363 419-439 449-469 484-504 521-541 593-613 618-638

Cellular Location

Golgi apparatus, Golgi stack membrane

Gene sequence

>lcl|BSEQ0052360|Zinc transporter 5 (SLC30A5)
ATGGAGGAGAAATACGGCGGGGACGTGCTGGCCGGCCCCGGCGGCGGCGGCGGCCTTGGG
CCGGTGGACGTACCCAGCGCTCGATTAACAAAATATATTGTGTTACTATGTTTCACTAAA
TTTTTGAAGGCTGTGGGACTTTTCGAATCATATGATCTCCTAAAAGCTGTTCACATTGTT
CAGTTCATTTTTATATTAAAACTTGGGACTGCATTTTTTATGGTTTTGTTTCAAAAGCCA
TTTTCTTCTGGGAAAACTATTACCAAACACCAGTGGATCAAAATATTTAAACATGCAGTT
GCTGGGTGTATTATTTCACTCTTGTGGTTTTTTGGCCTCACTCTTTGTGGACCACTAAGG
ACTTTGCTGCTATTTGAGCACAGTGATATTGTTGTCATTTCACTACTCAGTGTTTTGTTC
ACCAGTTCTGGAGGAGGACCAGCAAAGACAAGGGGAGCTGCTTTTTTCATTATTGCTGTG
ATCTGTTTATTGCTTTTTGACAATGATGATCTCATGGCTAAAATGGCTGAACACCCTGAA
GGACATCATGACAGTGCTCTAACTCATATGCTTTACACAGCCATTGCCTTCTTAGGTGTG
GCAGATCACAAGGGTGGAGTATTATTGCTAGTACTGGCTTTGTGTTGTAAAGTTGGTTTT
CATACAGCTTCCAGAAAGCTCTCTGTCGACGTTGGTGGAGCTAAACGTCTTCAAGCTTTA
TCTCATCTTGTTTCTGTGCTTCTCTTGTGCCCATGGGTCATTGTTCTTTCTGTGACAACT
GAGAGTAAAGTGGAGTCTTGGTTTTCTCTCATTATGCCTTTTGCAACGGTTATCTTTTTT
GTCATGATCCTGGATTTCTACGTGGATTCCATTTGTTCAGTCAAAATGGAAGTTTCCAAA
TGTGCTCGTTATGGATCCTTTCCCATTTTTATTAGTGCTCTCCTTTTTGGAAATTTTTGG
ACACATCCAATAACAGACCAGCTTCGGGCTATGAACAAAGCAGCACACCAGGAGAGCACT
GAACACGTCCTGTCTGGAGGAGTGGTAGTGAGTGCTATATTCTTCATTTTGTCTGCCAAT
ATCTTATCATCTCCCTCTAAGAGAGGACAAAAAGGTACCCTTATTGGATATTCTCCTGAA
GGAACACCTCTTTATAACTTCATGGGTGATGCTTTTCAGCATAGCTCTCAATCGATCCCT
AGGTTTATTAAGGAATCACTAAAACAAATTCTTGAGGAGAGTGACTCTAGGCAGATCTTT
TACTTCTTGTGCTTGAATCTGCTTTTTACCTTTGTGGAATTATTCTATGGCGTGCTGACC
AATAGTCTGGGCCTGATCTCGGATGGATTCCACATGCTTTTTGACTGCTCTGCTTTAGTC
ATGGGACTTTTTGCTGCCCTGATGAGTAGGTGGAAAGCCACTCGGATTTTCTCCTATGGG
TACGGCCGAATAGAAATTCTGTCTGGATTTATTAATGGACTTTTTCTAATAGTAATAGCG
TTTTTTGTGTTTATGGAGTCAGTGGCTAGATTGATTGATCCTCCAGAATTAGACACTCAC
ATGTTAACACCAGTCTCAGTTGGAGGGCTGATAGTAAACCTTATTGGTATCTGTGCCTTT
AGCCATGCCCATAGCCATGCCCATGGAGCTTCTCAAGGAAGCTGTCACTCATCTGATCAC
AGCCATTCACACCATATGCATGGACACAGTGACCATGGGCATGGTCACAGCCACGGATCT
GCGGGTGGAGGCATGAATGCTAACATGAGGGGTGTATTTCTACATGTTTTGGCAGATACA
CTTGGCAGCATTGGTGTGATCGTATCCACAGTTCTTATAGAGCAGTTTGGATGGTTCATC
GCTGACCCACTCTGTTCTCTTTTTATTGCTATATTAATATTTCTCAGTGTTGTTCCACTG
ATTAAAGATGCCTGCCAGGTTCTACTCCTGAGATTGCCACCAGAATATGAAAAAGAACTA
CATATTGCTTTAGAAAAGATACAGAAAATTGAAGGATTAATATCATACCGAGACCCTCAT
TTTTGGCGTCATTCTGCTAGTATTGTGGCAGGAACAATTCATATACAGGTGACATCTGAT
GTGCTAGAACAAAGAATAGTACAGCAGGTTACAGGAATACTTAAAGATGCTGGAGTAAAC
AATTTAACAATTCAAGTGGAAAAGGAGGCATACTTTCAACATATGTCTGGCCTAAGTACT
GGATTTCATGATGTTCTGGCTATGACAAAACAAATGGAATCCATGAAATACTGCAAAGAT
GGTACTTACATCATGTGA

Chromosome Location

5

Locus

5q13.1-q13.2

External Identifiers

Resource	Link
UniProtKB ID	Q8TAD4
UniProtKB Entry Name	ZNT5_HUMAN
GeneCard ID	SLC30A5
HGNC ID	HGNC:19089
KEGG ID	hsa:64924
NCBI Gene ID	64924

General References

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2. Cragg RA, Christie GR, Phillips SR, Russi RM, Kury S, Mathers JC, Taylor PM, Ford D: A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane. J Biol Chem. 2002 Jun 21;277(25):22789-97. doi: 10.1074/jbc.M200577200. Epub 2002 Apr 5. [Article]
3. Devergnas S, Chimienti F, Naud N, Pennequin A, Coquerel Y, Chantegrel J, Favier A, Seve M: Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study. Biochem Pharmacol. 2004 Aug 15;68(4):699-709. [Article]
4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [Article]
5. 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]
6. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
7. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
8. 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]
9. Suzuki T, Ishihara K, Migaki H, Ishihara K, Nagao M, Yamaguchi-Iwai Y, Kambe T: Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells. J Biol Chem. 2005 Sep 2;280(35):30956-62. doi: 10.1074/jbc.M506902200. Epub 2005 Jul 1. [Article]
10. Suzuki T, Ishihara K, Migaki H, Matsuura W, Kohda A, Okumura K, Nagao M, Yamaguchi-Iwai Y, Kambe T: Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane. J Biol Chem. 2005 Jan 7;280(1):637-43. doi: 10.1074/jbc.M411247200. Epub 2004 Nov 2. [Article]
11. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
12. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
13. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
14. 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]

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