Characterization of MDGA1, a novel human glycosylphosphatidylinositol-anchored protein localized in lipid rafts.
We report the characterization of the novel human protein MDGA1 encoded by MDGA1 (MAM domain containing glycosylphosphatidylinositol anchor-1) gene, firstly termed as GPIM. MDGA1 has been mapped to 6p21 and it is expressed in human tissues and tumors. The deduced polypeptide consists of 955 amino acids and exhibits structural features found in different types of cell adhesion molecules (CAMs), such as the presence of both immunoglobulin domains and a MAM domain or the capacity to anchor to the cell membrane by a GPI (glycosylphosphatidylinositol) motif. Our results demonstrate that human MDGA1 (hMDGA1) is localized in the membrane of eukaryotic cells. The protein follows the secretion pathway and finally it is retained in the cell membrane by a GPI anchor, susceptible to be cleavaged by phospholipase C (PI-PLC). Moreover, our results reveal that hMDGA1 is localized specifically into membrane microdomains known as lipid rafts. Finally, as other proteins of the secretory pathway, hMDGA1 undergoes other post-translational modification consisting of N-glycosylation.
Díaz-López
A
A
Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Rivas
C
C
Iniesta
P
P
Morán
A
A
García-Aranda
C
C
Megías
D
D
Sánchez-Pernaute
A
A
Torres
A
A
Díaz-Rubio
E
E
Benito
M
M
De Juan
C
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D058851:GPI-Linked Proteins; D015870:Gene Expression; D005796:Genes; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; C460759:MDGA1 protein, human; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; D010738:Type C Phospholipases