We have carried out a detailed seque
nce a
nd fu
nctio
nal a
nalysis of a
novel huma
n facilitative glucose tra
nsporter, desig
nated GLUT10, located i
n the Type 2 diabetes-li
nked regio
n of huma
n chromosome 20q12&
ndash;13.1. The GLUT10 ge
ne is located betwee
n D20S888 a
nd D20S891 a
nd is e
ncoded by 5 exo
ns
spa
nni
ng 26.8 kb of ge
nomic DNA. The huma
n GLUT10 cDNA e
ncodes a 541 ami
no acid protei
n that shares betwee
n 31 a
nd 35 % ami
no acid ide
ntity with huma
n GLUT1&
ndash;8. The predicted ami
no acid seque
nce of GLUT10 is
nearly ide
ntical i
n le
ngth to the rece
ntly described GLUT9 homologue, but is lo
nger tha
n other k
now
n members of the GLUT family. I
n additio
n, we have clo
ned the mouse cDNA homologof GLUT10 that e
ncodes a 537 ami
no acid protei
n that shares 77.3 % ide
ntity with huma
n GLUT10. The ami
no acid seque
nce probably has 12 predictedtra
nsmembra
ne domai
ns a
nd shares characteristics of other mammalia
n glucose tra
nsporters. Huma
n a
nd mouse GLUT10 retai
n several seque
nce motifs characteristic of mammalia
n glucosetra
nsporters i
ncludi
ng VP
497ETKG i
n the cytoplasmic C-termi
nus, G
73R[K,R] betwee
n TMD2 a
nd TMD3 (PROSITE PS00216), VD
92RAGRR betwee
n TMD8 a
nd TMD9 (PROSITE PS00216), Q
242QLTG i
n TMD7, a
nd tryptopha
n residues W
430 (TMD10) a
nd W
454 (TMD11), that corre
spo
nd to trytopha
n residues previously implicated i
n GLUT1 cytochalasi
n B bi
ndi
ng a
nd hexose tra
nsport. Neither huma
n nor mouse GLUT10 retai
ns the full P[E,D,N]SPR motif after Loop6 but i
nstead is replaced with P
186AG[T,A]. A PROSITE search also shows that GLUT10 has lost the SUGAR
TRANSPORT2 pattern (PS00217), a result of the substitution G113S in TMD4, while all other known human GLUTs retain the glycine and the pattern match. The significance of this substitution is unknown. Sites for N-linked glycosylation are predicted at N334ATG between TMD8 and TMD9 and N526STG in the cytoplasmic C-terminus. Northern hybridization analysis identified a single 4.4-kb transcript for GLUT10 in human heart, lung, brain, liver, skeletal muscle, pancreas, placenta, and kidney. By RT-PCR analysis, GLUT10 mRNA was also detected in fetal brain and liver. When expressed in Xenopus oocytes, human GLUT10 exhibited 2-deoxy-d-glucose transport with an apparent Km of
n=center border=0 SRC=/images/glyphs/BQ1.GIF>0.3 mM. d-Glucose and d-galactose competed with 2-deoxy-d-glucose and transport was inhibited by phloretin. The gene localization and functional properties suggest a role for GLUT10 in glucose metabolism and Type 2 diabetes.