VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved domain.
The MAGUKs (membrane-associated guanylate kinase homologues) constitute a family of peripheral membrane proteins that function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. Here, we report the characterization of the human vam-1 gene that encodes a novel member of the p55 subfamily of MAGUKs. The complete cDNA sequence of VAM-1, tissue distribution of its mRNA, genomic structure, chromosomal localization, and Veli-1 binding properties are presented. The vam-1 gene is composed of 12 exons and spans approx. 115 kb. By fluorescence in situ hybridization the vam-1 gene was localized to 7p15-21, a chromosome region frequently disrupted in some human cancers. VAM-1 mRNA was abundant in human testis, brain, and kidney with lower levels detectable in other tissues. The primary structure of VAM-1, predicted from cDNA sequencing, consists of 540 amino acids including a single PDZ domain near the N-terminus, a central SH3 domain, and a C-terminal GUK (guanylate kinase-like) domain. Sequence alignment, heterologous transfection, GST pull-down experiments, and blot overlay assays revealed a conserved domain in VAM-1 that binds to Veli-1, the human homologue of the LIN-7 adaptor protein in Caenorhabditis. LIN-7 is known to play an essential role in the basolateral localization of the LET-23 tyrosine kinase receptor, by linking the receptor to LIN-2 and LIN-10 proteins. Our results therefore suggest that VAM-1 may function by promoting the assembly of a Veli-1 containing protein complex in neuronal as well as epithelial cells.
Tseng
T C
TC
Section of Hematology-Oncology Research, Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, MA 02135, USA.
Marfatia
S M
SM
Bryant
P J
PJ
Pack
S
S
Zhuang
Z
Z
O'Brien
J E
JE
Lin
L
L
Hanada
T
T
Chishti
A H
AH
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D051528:Guanylate Kinases; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D014162:Transfection; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C114670:Lin7a protein, mouse; C496472:MPP6 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases