NH2-terminal sequence of macrophage-expressed natural resistance-associated macrophage protein (Nramp) encodes a proline/serine-rich putative Src homology 3-binding domain.
The Lsh/Ity/Bcg locus on mouse chromosome 1 regulates macrophage (m phi) priming/activation for antimicrobial activity against intracellular pathogens. A candidate Bcg gene, designated natural resistance-associated m phi protein (Nramp), recently isolated from a pre-B cell cDNA library encodes a polytopic integral membrane protein with structural features common to prokaryotic and eukaryotic transporters. In the present study, an activated m phi cDNA library yielded new Nramp clones that differ in the 5' region from the published pre-B cell-derived clone sequence, resulting in addition of 64 amino acids at the NH2 terminus of the predicted protein. This new domain is rich in proline, serine, and basic amino acids, and includes three protein kinase C phosphorylation sites and a putative Src homology 3 binding domain. RNAs containing this domain are the only form found in the m phi. Hence, the protein encoded by this RNA is the candidate molecule mediating natural resistance to intra-m phi pathogens.
Barton
C H
CH
Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom.
White
J K
JK
Roach
T I
TI
Blackwell
J M
JM
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D004247:DNA; D033862:Iron-Binding Proteins; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D011392:Proline / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src); D017385:Sequence Homology; D012694:Serine / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004247:DNA; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D011392:Proline; D016392:Proto-Oncogene Proteins pp60(c-src); D012694:Serine; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2