Sequence and Structure of a Human Glucose Transporter

TLDR

The human glucose transporter is predicted to contain amphipathic α‑helices with hydroxyl and amide side chains that may bind glucose or line a transmembrane pore, and its termini and a central hydrophilic domain are cytoplasmic. The amino‑acid sequence was deduced from a cDNA clone from HepG2 cells, and structural analysis of the purified erythrocyte transporter by fast‑atom bombardment mapping and gas‑phase Edman degradation confirmed the clone identity and high homology between the HepG2 and erythrocyte transporters. The protein lacks a cleavable N‑terminal signal sequence, contains 12 predicted transmembrane domains, and homologous mRNA is expressed in K562, HT29, and kidney tissue.

Abstract

The amino acid sequence of the glucose transport protein from human HepG2 hepatoma cells was deduced from analysis of a complementary DNA clone. Structural analysis of the purified human erythrocyte glucose transporter by fast atom bombardment mapping and gas phase Edman degradation confirmed the identity of the clone and demonstrated that the HepG2 and erythrocyte transporters are highly homologous and may be identical. The protein lacks a cleavable amino-terminal signal sequence. Analysis of the primary structure suggests the presence of 12 membrane-spanning domains. Several of these may form amphipathic α helices and contain abundant hydroxyl and amide side chains that could participate in glucose binding or line a transmembrane pore through which the sugar moves. The amino terminus, carboxyl terminus, and a highly hydrophilic domain in the center of the protein are all predicted to lie on the cytoplasmic face. Messenger RNA species homologous to HepG2 glucose transporter messenger RNA were detected in K562 leukemic cells, HT29 colon adenocarcinoma cells, and human kidney tissue.