The Novel Human HUEL (C4orf1) Gene Maps to Chromosome 4p12–p13 and Encodes a Nuclear Protein Containing the Nuclear Receptor Interaction Motif

Sim, Del L.C.; Chow, Vincent T.K.

doi:10.1006/geno.1999.5856

Cited by 53 publications

(41 citation statements)

References 48 publications

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“…However, ZnT9 is thought to have no zinc transport functions, because it lacks an essential histidine constituting the intramembranous zinc-binding site, and has not been shown to interact with other ZnT transporters, unlike ZnT6. Moreover, ZnT9 is predominantly localized in the cytoplasm, and its cell membrane localization was ruled out (376). ZnT9 acts as nuclear receptor coactivator and is renamed as GAC63 (GRIP1-associated coactivator 63) (51).…”

Section: Znt10mentioning

confidence: 99%

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Kambe

Tsuji

Hashimoto

et al. 2015

Physiological Reviews

803

729

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Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly important. In metazoan, two zinc transporter families, Zn transporters (ZnT) and Zrt-, Irt-related proteins (ZIP) function in zinc mobilization of influx, efflux, and compartmentalization/ sequestration across biological membranes. During the last two decades, significant progress has been made in understanding the molecular properties, expression, regulation, and cellular and physiological roles of ZnT and ZIP transporters, which underpin the multifarious functions of zinc. Moreover, growing evidence indicates that malfunctioning zinc homeostasis due to zinc transporter dysfunction results in the onset and progression of a variety of diseases. This review summarizes current progress in our understanding of each ZnT and ZIP transporter from the perspective of zinc physiology and pathogenesis, discussing challenging issues in their structure and zinc transport mechanisms.

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Section: Znt10mentioning

confidence: 99%

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Kambe

Tsuji

Hashimoto

et al. 2015

Physiological Reviews

803

729

View full text Add to dashboard Cite

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“…A gene named Huel was isolated from human embryonic lung cells (MRC-5) after a portion of its sequence was amplified with primers for the ligand-binding domain of the nuclear receptor c-erb Ab (94). The gene is located on human chromosome 4.…”

Section: Znt9mentioning

confidence: 99%

Mammalian Zinc Transporters

2004

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▪ Abstract New insights into mammalian zinc metabolism have been acquired through the identification and characterization of zinc transporters. These proteins all have transmembrane domains, and are encoded by two solute-linked carrier (SLC) gene families: ZnT (SLC30) and Zip (SLC39). There are at least 9 ZnT and 15 Zip transporters in human cells. They appear to have opposite roles in cellular zinc homeostasis. ZnT transporters reduce intracellular zinc availability by promoting zinc efflux from cells or into intracellular vesicles, while Zip transporters increase intracellular zinc availability by promoting extracellular zinc uptake and, perhaps, vesicular zinc release into the cytoplasm. Both the ZnT and Zip transporter families exhibit unique tissue-specific expression, differential responsiveness to dietary zinc deficiency and excess, and differential responsiveness to physiologic stimuli via hormones and cytokines.

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“…[8,12,13]). The expression of transcripts encoding all ZnT family members other than ZnT9 (which has been implicated in DNA excision-repair [15,16]) was examined by RT-PCR. As shown in Fig.…”

Section: Expression and Intracellular Distribution Of Znt Family Membmentioning

confidence: 99%

“…Ten genes encoding ZnT protein family members (ZnT1 through ZnT10, or SLC30A1 through SLC30A10) have been identified in the human genome [14]. ZnT9 (SLC30A9, also known as HUEL or C4orf1) is the most divergent member of the family and may not function in zinc transport but rather in DNA excision-repair [15,16]. The ZnT10 protein has not yet been characterized, thus its role in zinc transport remains hypothetical [14].…”

Section: Introductionmentioning

confidence: 99%

Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes

Falcón‐Pérez

Dell’Angelica

2007

Experimental Cell Research

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Zinc accumulation in the lumen of cytoplasmic vesicles is one of the mechanisms by which cells can store significant amounts of this essential but potentially toxic biometal. Previous studies had demonstrated reduced vesicular zinc levels in fibroblasts from mutant mice deficient in adaptor protein 3 (AP-3), a complex involved in protein trafficking to late endosomes and lysosomes. We have observed a similar phenotype in the human fibroblastoid cell line, M1, upon small interference RNA-mediated AP-3 knockdown. A survey of the expression and localization of zinc transporter (ZnT) family members identified ZnT2, ZnT3 and ZnT4 as likely mediators of vesicular zinc accumulation in M1 cells. Expression of green fluorescence protein (GFP)-tagged ZnT2 and ZnT3 promoted accumulation of vesicular zinc as visualized using the indicator zinquin. Moreover, GFPZnT2 overexpression elicited a significant accumulation of zinc within mature lysosomes, which in untransfected M1 cells contained little or no chelatable zinc, and restored the zinc storage capability of AP-3-deficient cells. These results suggest that ZnT2 can facilitate vesicular zinc accumulation independently of AP-3 function, and validate the M1 fibroblastoid line as a human cell culture system amenable to the study of vesicular zinc regulation using techniques compatible with functional genomic approaches.

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The Novel Human HUEL (C4orf1) Gene Maps to Chromosome 4p12–p13 and Encodes a Nuclear Protein Containing the Nuclear Receptor Interaction Motif

Cited by 53 publications

References 48 publications

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Mammalian Zinc Transporters

Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes

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