The lamin B receptor of the nuclear envelope inner membrane: a polytopic protein with eight potential transmembrane domains.
The lamin B receptor is a previously identified integral membrane protein in the nuclear envelope of turkey erythrocytes that associates with the nuclear intermediate filament protein lamin B (Worman, H. J., J. Yuan, G. Blobel, and S. D. Georgatos. 1988. Proc. Natl. Acad. Sci. USA. 85:8531-8534). In the present report, we use cell fractionation and antibodies against the lamin B receptor to localize it to an 8-M urea-extracted membrane fraction of chicken liver nuclei, supporting an inner nuclear membrane localization. We deduced the amino acid sequence of the chicken lamin B receptor from overlapping clones obtained by screening cDNA libraries with a probe generated by the polymerase chain reaction with primers based on the partial protein sequence of the isolated protein. The mature lamin B receptor has a calculated molecular mass of 73,375 D and eight segments of hydrophobic amino acids that could function as transmembrane domains as determined by hydropathy analysis. Preceding the first putative transmembrane segment is a highly charged 204-residue-long amino terminal region that contains two consensus sites for phosphorylation by protein kinase A. Since the lamin B receptor has been shown to be phosphorylated by protein kinase A in vitro and in vivo and this phosphorylation affects lamin B binding (Applebaum, J., G. Blobel, and S. D. Georgatos. 1990. J. Biol. Chem. 265:4181-4185), it is likely that this amino terminal region faces the nucleoplasm. The amino terminal region also contains three DNA-binding motifs that are found in gene regulatory proteins and histones, suggesting that the lamin B receptor may additionally play a role in gene regulation and/or chromatin organization.
Worman
H J
HJ
Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York 10021.
Evans
C D
CD
Blobel
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D002645:Chickens; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D013329:Structure-Activity Relationship; D000097682:Lamin B Receptor
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor