Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.
In mammalian small intestine, a H(+)-coupled peptide transporter is responsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotransporter has been isolated from a rabbit intestinal cDNA library (Fei, Y.J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F.H., Romero, M.F., Singh, S.K., Boron, W. F., and Hediger, M. A. (1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a probe derived from the rabbit H+/peptide cotransporter cDNA resulted in the identification of a cDNA which when expressed in HeLa cells or in Xenopus laevis oocytes induced H(+)-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-spanning domains and two putative sites for protein kinase C-dependent phosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino beta-lactam antibiotics but not free amino acids as substrates. The human H+/peptide cotransporter exhibits a high degree of homology (81% identity and 92% similarity) to the rabbit H+/peptide cotransporter. But surprisingly these transporters show only a weak homology to the H(+)-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell hybrid analysis and in situ hybridization have located the gene encoding the cloned human H+/peptide cotransporter to chromosome 13 q33-->q34.
Liang
R
R
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Fei
Y J
YJ
Prasad
P D
PD
Ramamoorthy
S
S
Han
H
H
Yang-Feng
T L
TL
Hediger
M A
MA
Ganapathy
V
V
Leibach
F H
FH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D007422:Intestines / Q000737:chemistry*; D008969:Molecular Sequence Data; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000032:analysis; D027981:Symporters; D014982:Xenopus laevis
D002352:Carrier Proteins; D018076:DNA, Complementary; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C082186:SLC15A1 protein, human; D027981:Symporters