Zinc transporter ZIP9

Last updated
SLC39A9
Identifiers
Aliases SLC39A9 , ZIP-9, ZIP9, solute carrier family 39 member 9
External IDs MGI: 1914820; HomoloGene: 6935; GeneCards: SLC39A9; OMA:SLC39A9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55334

328133

Ensembl

ENSG00000029364

ENSMUSG00000048833

UniProt

Q9NUM3

Q8BFU1

RefSeq (mRNA)

NM_026244

RefSeq (protein)

NP_080520

Location (UCSC) Chr 14: 69.4 – 69.46 Mb Chr 12: 80.69 – 80.73 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zinc transporter ZIP9, also known as Zrt- and Irt-like protein 9 (ZIP9) and solute carrier family 39 member 9, is a protein that in humans is encoded by the SLC39A9 gene. [5] This protein is the 9th member out of 14 ZIP family proteins, which is a membrane androgen receptor (mAR) coupled to G proteins, and also classified as a zinc transporter protein. [5] [6] [7] [8] ZIP family proteins transport zinc metal from the extracellular environment into cells through cell membrane. [6]

Contents

Classification and nomenclature

Mammalian cells have two major groups of zinc transporter proteins; the ones that export zinc from the cytoplasm to the extracellular space (efflux), which are called ZnT (SLC30 family), and ZIP (SLC39 family) proteins [9] whose functions are in the opposite direction (influx). [10] ZIP family proteins are named as Zrt- and Irt-like proteins because of their similarities to Zrt and Irt proteins which are respectively zinc and iron -regulated transporter proteins in yeast and Arabidopsis that were discovered earlier than ZIP and ZnT proteins. [10] ZIP family consists of four subfamilies (I, II, LIV-1, and gufA), and ZIP9 is the only member of subfamily I. [11]

Isoforms

ZIP9 can be present as 3 different isoforms in human cells. The canonical isoform of this protein has a length of 307 amino acids, with a molecular mass of 32251  Da . In the second isoform, amino acids 135-157 are missing, so its length and molecular weight are respectively reduced to 284 amino acids and 29931  Da . In the third isoform the amino acids 233-307 are missing, so the isoform only has 232 amino acids and its molecular mass is 24626  Da . Additionally, the last amino acid of isoform 3, which is usually serine, is replaced with aspartic acid. [12]

ZIP9 Isoforms and Sizes [12]
Isoformnumber of amino acidssize (Da)transformationmissing amino acids
isoform 130732251N/AN/A
isoform 228429931N/A135-157
isoform 323224626S -----> D233-307

Discovery

ZIP9 membrane androgen receptor was first discovered in Atlantic croaker (Micropogonias undulatus) brain, ovary and testicular tissues and named "AR2" in 1999, together with another androgen receptor which was found only in brain tissue, and it was named "AR1" in that time. [13] AR1 and AR2 were first thought to be nuclear androgen receptors (nAR), however, further studies on their biochemical and functional features in 2003 illustrated that they were involved in non-genomic mechanisms in the plasma membrane of the cells and were membrane androgen receptors. [14] In 2005, the similarities between the nucleotide and amino acid sequences of AR2 and ZIP family proteins were discovered in other vertebrates, suggesting that AR2 is from this family of proteins. [15] A study in 2014 utilised the latest research technologies to clone and express a particular cDNA of the female Atlantic croaker ovaries, which encoded a protein showing the characteristics of the canonical isoform of ZIP9, as a novel membrane androgen receptor(mAR). [7]

The seven-transmembrane a-helix structure of a G protein-coupled receptor, with intracellular C-terminus PDB 1hzx 7TM Sketch Membrane.png
The seven-transmembrane α-helix structure of a G protein–coupled receptor, with intracellular C-terminus

Structure

Unlike other ZIP subfamilies that are consisted of 8 transmembrane (TM) domains with an extracellular C-terminal, ZIP9 consists of a 7 TM structure with an intracellular C-terminus. [7] ZIP9 is shorter than other ZIP proteins, and only has about 307 amino acids within its structure, however, like other ZIP proteins, between its domains III and IV, within the intracellular loop, it contains histidine-rich clusters. [7] ZIP9 and other ZIP proteins have polar or charged amino acids in their TM domains which probably play important roles in making ion transfer channels and therefore in importing zinc ions into cytoplasm. [15]

Location, expression and function

The image illustrates the location of different zinc transporters in a cell, including ZIP9, which is located at Golgi here. Fphar-05-00033-g002.jpg
The image illustrates the location of different zinc transporters in a cell, including ZIP9, which is located at Golgi here.

ZIP9 influxes zinc ions into the cytosol and its gene is expressed almost in every tissue of human body. [8] The sub-cellular location of ZIP9 is in plasma, nucleus, endoplasmic reticulum and mitochondrial membrane. [8] One of the responsibilities of ZIP9 is the homeostasis of zinc in the secretory pathway, during which this protein stays within the Trans Golgi Network regardless of the change in the concentrations of zinc. [11]

ZIP9 is the only ZIP protein that signals through G protein binding, and pharmaceutical agents decrease its ligand binding once ZIP9 is uncoupled from G proteins. [5] ZIP9 is also the only member of ZIP family with mAR characteristics. [5]

Ligands

Testosterone has high affinity for ZIP9 with a Kd of 14 nM and acts as an agonist of the receptor. [5] In contrast, the other endogenous androgens dihydrotestosterone (DHT) and androstenedione show low affinity for the receptor with less than 1% of that of testosterone, although DHT is still effective in activating the receptor at sufficiently high concentrations. [5] Moreover, the synthetic androgens mibolerone and metribolone (R-1881), the endogenous androgen 11-ketotestoterone, and the other steroid hormones estradiol and cortisol are all ineffective competitors for the receptor. [5] Since mibolerone and metribolone bind to and activate the nuclear androgen receptor (AR) but not ZIP9, they could potentially be employed to differentiate between AR- and ZIP9-mediated responses of testosterone. [5] The nonsteroidal antiandrogen bicalutamide has been identified as an antagonist of ZIP9. [17]

Clinical significance

Zinc homeostasis is very important in human health, because zinc is present in the structure of some proteins like zinc-dependent metalloenzymes and zinc-finger-containing transcriptional factors. [18] In addition, zinc is involved in signalling for cell growth, proliferation, division and apoptosis. [18] [19] As a result, any dysfunction of zinc transporter proteins can be harmful for the cells, and some of them are associated with different cancers, diabetes and inflammation. [18] For instance, through activation of ZIP9, testosterone has been found to increase intracellular zinc levels in breast cancer, prostate cancer, and ovarian follicle cells and to induce apoptosis in these cells, an action which may be mediated partially or fully by increased zinc concentrations. [5] [20]

Gene mutations

Mutations in the SLC39A9 gene can occur due to genetic deletion of the q24.1-24.3 band of base pairs within the human chromosome 14. This interstitial deletion mutation deletes the SLC39A9 gene along with 18 other genes found close to the SLC39A9 gene on chromosome 14 Although specific gene associated diseases have not been determined, the deletion of this band causes diseases such as congenital heart defects, mild intellectual disability, brachydactyly, and all patients with band deletion had hypertelorism and a broad nasal bridge. Patient specific clinical issues included ectopic organs, undescended testes, also called cryptorchidism, and malrotation of the small intestine. Deletion mutation involving the SLC39A9 gene has also been reported in 23 cases of patients with circulation related cancers such as B-cell lymphoma and B-cell chronic lymphocytic leukaemia (CLL). [21] [22] Chimeric genes are a result of faulty DNA replication, and arise when two or more coding sequences of the same or different chromosome combine in order to produce a single new gene. SLC39A9 forms a chimeric gene product with a gene called PLEKHD1, that codes for an intracellular protein found within the cerebellum. A study done in Seattle, USA, established the presence of the fusion protein product of the SLC39A9-PLEKHD1 gene to be present in 124 cases of schizophrenia and was closely related to the pathophysiology of disease. [23] [24] The fusion protein had features from both the parent genes and also possessed the ability to interact with cellular signalling pathways involving kinases such as Akt and Erk, leading to their increased phosphorylation within the brain and a consequent onset of schizophrenia. [23] [24] SLC39A9 gene also forms a fusion transcript with another gene called MAP3K9, that encodes for MAP3 kinase enzyme. This SLC39A9-MAP3K9 fusion gene has a repetitive occurrence in breast cancers, demonstrated by a study done on 120 primary breast cancer samples from Korean women in 2015. [25] [26]

Cancer

Breast and prostate

A study in 2014, elucidated the intermediary role of ZIP9 in causing human breast and prostate cancer, as it induced the apoptosis in the presence of testosterone in breast and prostate cancerous cells. [8] unlike ZIP1, 2 and 3, ZIP9 mRNA expression was increased in human prostate and breast malignant biopsy cancer cells, which probably was because cells that divide rapidly require more zinc. [8]

Brain

Treatment of glioblastoma cells with TPEN showed that upregulation of ZIP9 in glioblastoma cells enhances cell migration in brain cancer by influencing P53 and GSK-3ß, and also ERK and AKT signalling pathways in phosphorylation after activation of B-cell receptors. [18] [27]

Diabetes

Zinc must be constantly supplied to Pancreatic β-cells to function normally and maintain glycaemic control. [19] The insulin secretory pathway in humans is highly dependent on zinc activities. [28] The cells lose many zinc ions during the secretion of insulin, and need to receive more zinc, and expression of ZIP9 mRNA during this process increases. [29] As a result, ZIP9, which is involved in importing zinc into the cells, is potentially a target for therapeutic studies in the future regarding diabetes type2. [29]

See also

Related Research Articles

A hormone receptor is a receptor molecule that binds to a specific hormone. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ligands, such as fatty acids and prostaglandins. Hormone receptors are of mainly two classes. Receptors for peptide hormones tend to be cell surface receptors built into the plasma membrane of cells and are thus referred to as trans membrane receptors. An example of this is Actrapid. Receptors for steroid hormones are usually found within the protoplasm and are referred to as intracellular or nuclear receptors, such as testosterone. Upon hormone binding, the receptor can initiate multiple signaling pathways, which ultimately leads to changes in the behavior of the target cells.

Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen and 3-ketosteroids. In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.

<span class="mw-page-title-main">Estrogen receptor</span> Proteins activated by the hormone estrogen

Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).

<span class="mw-page-title-main">Sex hormone-binding globulin</span> Human glycoprotein that binds to androgens and estrogens

Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

The prolactin receptor (PRLR) is a type I cytokine receptor encoded in humans by the PRLR gene on chromosome 5p13-14. It is the receptor for prolactin (PRL). The PRLR can also bind to and be activated by growth hormone (GH) and human placental lactogen (hPL). The PRLR is expressed in the mammary glands, pituitary gland, and other tissues. It plays an important role in lobuloalveolar development of the mammary glands during pregnancy and in lactation.

<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Transmembrane receptor found in humans

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR), is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

<span class="mw-page-title-main">Endoglin</span> Protein-coding gene in the species Homo sapiens

Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.

<span class="mw-page-title-main">RAR-related orphan receptor alpha</span> Protein-coding gene in the species Homo sapiens

RAR-related orphan receptor alpha (RORα), also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene. RORα participates in the transcriptional regulation of some genes involved in circadian rhythm. In mice, RORα is essential for development of cerebellum through direct regulation of genes expressed in Purkinje cells. It also plays an essential role in the development of type 2 innate lymphoid cells (ILC2) and mutant animals are ILC2 deficient. In addition, although present in normal numbers, the ILC3 and Th17 cells from RORα deficient mice are defective for cytokine production.

<span class="mw-page-title-main">GPRC6A</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor family C group 6 member A (GPRC6A) is a protein that in humans is encoded by the GPRC6A gene. This protein functions as a receptor of L-α-amino acids, cations, osteocalcin, and steroids. It is a membrane androgen receptor.

<span class="mw-page-title-main">Eukaryotic translation elongation factor 1 alpha 1</span> Constitutive promoter

Elongation factor 1-alpha 1 (eEF1a1) is a translation elongation protein, expressed across eukaryotes. In humans, it is encoded by the EEF1A1 gene.

<span class="mw-page-title-main">Neuropilin 1</span> Protein-coding gene in the species Homo sapiens

Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.

<span class="mw-page-title-main">GATA3</span> Protein-coding gene in the species Homo sapiens

GATA3 is a transcription factor that in humans is encoded by the GATA3 gene. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes.

<span class="mw-page-title-main">Zinc transporter SLC39A7</span> Protein found in humans

Zinc transporter SLC39A7 (ZIP7), also known as solute carrier family 39 member 7, is a transmembrane protein that in humans is encoded by the SLC39A7 gene. It belongs to the ZIP family, which consists of 14 proteins that transport zinc into the cytoplasm. Its primary role is to control the transport of zinc from the ER and Golgi apparatus to the cytoplasm. It also plays a role in glucose metabolism. Its structure consists of helices that bind to zinc in a binuclear metal center. Its fruit fly orthologue is Catsup.

<span class="mw-page-title-main">Sodium-coupled monocarboxylate transporter 1</span> Protein-coding gene in the species Homo sapiens

Sodium-coupled monocarboxylate transporter 1 (i.e., SMCT1) and sodium-coupled monocarboxylate transporter 2 (i.e., SMCT2) are plasma membrane transport proteins in the solute carrier family. They transport sodium cations in association with the anionic forms (see conjugated base) of certain short-chain fatty acids (i.e., SC-FAs) through the plasma membrane from the outside to the inside of cells. For example, propionic acid (i.e., CH
3CH
2CO
2H) in its anionic "propionate" form (i.e., CH
3CH
2CO−
2) along with sodium cations (i.e., Na+) are co-transported from the extracellular fluid into a SMCT1-epxressing cell's cytoplasm. Monocarboxylate transporters (MCTs) are also transport proteins in the solute carrier family. They co-transport the anionic forms of various compounds into cells in association with proton cations (i.e. H+). Four of the 14 MCTs, i.e. SLC16A1 (i.e., MCT1), SLC16A7 (i.e., MCT22), SLC16A8 (i.e., MCT3), and SLC16A3 (i.e., MCT4), transport some of the same SC-FAs anions that the SMCTs transport into cells. SC-FAs do diffuse into cells independently of transport proteins but at the levels normally occurring in tissues far greater amounts of the SC-FAs are brought into cells that express a SC-FA transporter.

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

<span class="mw-page-title-main">Proser2</span> Protein-coding gene in the species Homo sapiens

PROSER2, also known as proline and serine rich 2, is a protein that in humans is encoded by the PROSER2 gene. PROSER2, or c10orf47(Chromosome 10 open reading frame 47), is found in band 14 of the short arm of chromosome 10 (10p14) and contains a highly conserved SARG domain. It is a fast evolving gene with two paralogs, c1orf116 and specifically androgen-regulated gene protein isoform 1. The PROSER2 protein has a currently uncharacterized function however, in humans, it may play a role in cell cycle regulation, reproductive functioning, and is a potential biomarker of cancer.

Zinc transporter proteins (Zrt), or simply zinc transporters, are membrane transport proteins of the solute carrier family which control the membrane transport of zinc and regulate its intracellular and cytoplasmic concentrations. They include two major groups: (1) the zinc transporter (ZnT) or solute carrier 30 (SLC30) family, which controls the efflux of zinc from the cytoplasm out of the cell and from the cytoplasm into vesicles; and (2) the zinc importer, Zrt- and Irt-like protein (ZIP), or solute carrier 39A (SLC39A) family, which controls the influx of zinc into the cytoplasm from outside the cell and from vesicles.

<span class="mw-page-title-main">ZCCHC18</span> Protein-coding gene in the species Homo sapiens

Zinc finger CCHC-type containing 18 (ZCCHC18) is a protein that in humans is encoded by ZCCHC18 gene. It is also known as Smad-interacting zinc finger protein 2 (SIZN2), para-neoplastic Ma antigen family member 7b (PNMA7B), and LOC644353. Other names such as zinc finger, CCHC domain containing 12 pseudogene 1, P0CG32, ZCC18_HUMAN had been used to describe this protein.

MDA-MB-453 is a human breast cancer cell line.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048833 – Ensembl, May 2017
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  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  11. 1 2 Matsuura W, Yamazaki T, Yamaguchi-Iwai Y, Masuda S, Nagao M, Andrews GK, Kambe T (May 2009). "SLC39A9 (ZIP9) regulates zinc homeostasis in the secretory pathway: characterization of the ZIP subfamily I protein in vertebrate cells". Bioscience, Biotechnology, and Biochemistry. 73 (5): 1142–8. doi: 10.1271/bbb.80910 . PMID   19420709. S2CID   22746139.
  12. 1 2 Universal protein resource accession number Q9NUM3 at UniProt.
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  15. 1 2 Eide DJ (2005). "The Zip Family of Zinc Transporters". In Iuchi S, Kuldell N (eds.). Zinc Finger Proteins. Molecular Biology Intelligence Unit. Boston, MA: Molecular Biology Intelligence Unit. Springer. pp. 261–264. doi:10.1007/0-387-27421-9_35. ISBN   978-0-306-48229-8.
  16. ↑ Zhao L, Xia Z, Wang F (2014). "Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism". Frontiers in Pharmacology. 5: 33. doi: 10.3389/fphar.2014.00033 . PMC   3944790 . PMID   24639652.
  17. ↑ Bulldan A, Malviya VN, Upmanyu N, Konrad L, Scheiner-Bobis G (2017). "Testosterone/bicalutamide antagonism at the predicted extracellular androgen binding site of ZIP9". Biochim. Biophys. Acta. 1864 (12): 2402–2414. doi:10.1016/j.bbamcr.2017.09.012. PMID   28943399.
  18. 1 2 3 4 Taniguchi M, Fukunaka A, Hagihara M, Watanabe K, Kamino S, Kambe T, Enomoto S, Hiromura M (2013). "Essential role of the zinc transporter ZIP9/SLC39A9 in regulating the activations of Akt and Erk in B-cell receptor signaling pathway in DT40 cells". PLOS ONE. 8 (3): e58022. Bibcode:2013PLoSO...858022T. doi: 10.1371/journal.pone.0058022 . PMC   3591455 . PMID   23505453.
  19. 1 2 Li YV (March 2014). "Zinc and insulin in pancreatic beta-cells". Endocrine. 45 (2): 178–89. doi:10.1007/s12020-013-0032-x. PMID   23979673. S2CID   5153213.
  20. ↑ Pascal LE, Wang Z (November 2014). "Unzipping androgen action through ZIP9: a novel membrane androgen receptor". Endocrinology. 155 (11): 4120–3. doi: 10.1210/en.2014-1749 . PMID   25325426.
  21. ↑ Nagel I, Bug S, Tonnies H, Ammerpohl O, Richter J, Vater I, Callet-Bauchu E, Calasanz MJ, Martinez-Climent JA, Bastard C, Salido, M (August 2009). "Biallelic inactivation of TRAF3 in a subset of B-cell lymphomas with interstitial del (14)(q24. 1 q32. 33)". Leukemia. 23 (11): 2153–2156. doi: 10.1038/leu.2009.149 . PMID   19693093.
  22. ↑ "Biallelic inactivation of TRAF3 in a subset of B-cell lymphomas with interstitial del (14)(q24. 1 q32. 33)".{{cite web}}: Missing or empty |url= (help)
  23. 1 2 Rippey C, Walsh T, Gulsuner S, Brodsky M, Nord AS, Gasperini M, Pierce S, Spurrell C, Coe BP, Krumm N, Lee MK (October 2013). "Formation of chimeric genes by copy-number variation as a mutational mechanism in schizophrenia". The American Journal of Human Genetics. 93 (4): 697–710. doi:10.1016/j.ajhg.2013.09.004. PMC   3791253 . PMID   24094746.
  24. 1 2 "Formation of chimeric genes by copy-number variation as a mutational mechanism in schizophrenia".{{cite web}}: Missing or empty |url= (help)
  25. ↑ Kim J, Kim S, Ko S, In YH, Moon HG, Ahn SK, Kim MK, Lee M, Hwang JH, Ju YS, Kim JI (November 2015). "Recurrent fusion transcripts detected by whole‐transcriptome sequencing of 120 primary breast cancer samples". Genes, Chromosomes and Cancer. 54 (11): 681–691. doi:10.1002/gcc.22279. hdl: 10371/122075 . PMID   26227178. S2CID   22740643.
  26. ↑ "Recurrent fusion transcripts detected by whole‐transcriptome sequencing of 120 primary breast cancer samples".{{cite web}}: Missing or empty |url= (help)
  27. ↑ Münnich N, Wernhart S, Hogstrand C, Schlomann U, Nimsky C, Bartsch JW (December 2016). "Expression of the zinc importer protein ZIP9/SLC39A9 in glioblastoma cells affects phosphorylation states of p53 and GSK-3β and causes increased cell migration". Biometals. 29 (6): 995–1004. doi:10.1007/s10534-016-9971-z. PMID   27654922. S2CID   20068444.
  28. ↑ Huang L (2014). "Zinc and its transporters, pancreatic β-cells, and insulin metabolism". Vitamins and Hormones. 95: 365–90. doi:10.1016/b978-0-12-800174-5.00014-4. ISBN   9780128001745. PMID   24559925.
  29. 1 2 Lawson R, Maret W, Hogstrand C (September 2017). "Expression of the ZIP/SLC39A transporters in β-cells: a systematic review and integration of multiple datasets". BMC Genomics. 18 (1): 719. doi: 10.1186/s12864-017-4119-2 . PMC   5594519 . PMID   28893192.
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