MAN1, an Inner Nuclear Membrane Protein That Shares the LEM Domain with Lamina-associated Polypeptide 2 and Emerin

doi:10.1074/jbc.275.7.4840

MAN1, an Inner Nuclear Membrane Protein That Shares the LEM Domain with Lamina-associated Polypeptide 2 and Emerin*

From the ^‡Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, the ^§Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada,^¶Systèmes Moléculaires et Biologie Structurale, LMCP, CNRS UMR 7590, Universités Paris 6 and 7, 4 Place Jussieu, 75252 Paris Cedex 05, France, ^**Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada, and ^§§Ottawa Regional Cancer Centre and Department of Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada

Abstract

The “MAN antigens” are polypeptides recognized by autoantibodies from a patient with a collagen vascular disease and localized to the nuclear envelope. We now show that one of the human MAN antigens termed MAN1 is a 82.3-kDa protein with an amino-terminal domain followed by two hydrophobic segments and a carboxyl-terminal tail. The MAN1 gene contains seven protein-coding exons and is assigned to human chromosome 12q14. Its mRNA is approximately 5.5 kilobases and is detected in several different cell types that were examined. Cell extraction experiments show that MAN1 is an integral membrane protein. When expressed in transfected cells, MAN1 is exclusively targeted to the nuclear envelope, consistent with an inner nuclear membrane localization. Protein sequence analysis reveals that MAN1 shares a conserved globular domain of approximately 40 amino acids, which we term the LEM module, with inner nuclear membrane proteins lamina-associated polypeptide 2 and emerin. The LEM module is also present in two proteins ofCaenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization.

Footnotes

↵* This work was supported by National Institutes of Health (NIH) Grant RO1-CA66974 (to H. J. W.). The confocal microscopy facility was established by NIH Grant 1S10 RR10506 and supported by NIH Grant 5 P30 CA13696 as part of the Herbert Irving Cancer Center at Columbia University.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) , , and – .
↵‖ Supported in part by the Centre National de la Recherche Scientifique (CNRS) program “Physique et Chimie du Vivant.”
↵‡ Supported by a Medical Research Council of Canada scholarship (development grant).
↵¶¶ Supported by a grant from the Medical Research Council of Canada.
↵166 Supported in part as an Irma T. Hirschl Scholar and by a Greater New York Hepatology Primary Biliary Cirrhosis Seed Grant from the American Liver Foundation. To whom correspondence should be addressed: Dept. of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., 10th Floor, Rm. 508, New York, NY 10032. Tel.: 212-305-8156; Fax: 212-305-6443; E-mail: hjw14@ columbia.edu.
↵2 M. Paulin-Levasseur, unpublished observation.
Abbreviations:

LBR

lamin B receptor

LAP

lamin-associated polypeptide

GST

glutathioneS-transferase

HCA

hydrophobic cluster analysis
- Received August 24, 1999.
- Revision received October 26, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.