Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain.
CD97 is a monomeric glycoprotein of 75 to 85 kDa that is induced rapidly on the surface of most leukocytes upon activation. We herein report the isolation of a cDNA encoding human CD97 by expression cloning in COS cells. The 3-kb cDNA clone encodes a mature polypeptide chain of 722 amino acids with a predicted molecular mass of 79 kDa. Within the C-terminal part of the protein, a region with seven hydrophobic segments was identified, suggesting that CD97 is a seven-span transmembrane molecule. Sequence comparison indicates that CD97 is the first leukocyte Ag in a recently described superfamily that includes the receptors for secretin, calcitonin, and other mammalian and insect peptide hormones. Different from these receptors, CD97 has an extended extracellular region of 433 amino acids that possesses three N-terminal epidermal growth factor-like domains, two of them with a calcium-binding site, and a single Arg-Gly-Asp (RGD) motif. The existence of structural elements characteristic for extracellular matrix proteins in a seven-span transmembrane molecule makes CD97 a receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. The gene encoding CD97 is localized on chromosome 19 (19p13.12-13.2).
Hamann
J
J
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Eichler
W
W
Hamann
D
D
Kerstens
H M
HM
Poddighe
P J
PJ
Hoovers
J M
JM
Hartmann
E
E
Strauss
M
M
van Lier
R A
RA
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
C095004:ADGRE5 protein, human; D015703:Antigens, CD; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor