DNA contains 27.322 kb composed of 20 coding exons. Exons 1-2 encode the 5 untranslated region and the signal peptide, exons 3-7 the five EGF domains, exons 8-13 the extracellular stalk, exons 14-18 the seven-span transmembrane (TM7) domains and exons 19-20 the intracellular part and the 3 untranslated region.

3247 bp mRNA transcribed in telomeric to centromeric orientation; 2508 bp open reading frame. Human CD97 exists in three isoforms that result from alternative splicing of exons 5 and 6 and thus contain different numbers of EGF domains in the extracellular part of the molecule. The isoforms are designated as CD97(EGF1,2,5), CD97(EGF1,2,3,5) and CD97(EGF1-5) in human.

No pseudogenes reported.

CD97 belongs to the B family of G protein-coupled receptors (GCPRs). Subfamily B2 contains cell surface molecules with long extracellular N-termini (LNB-TM7) known also as adhesion class of heptahelical receptors.
CD97 is the founding member of a small subfamily within the adhesion class called EGF-TM7 family. All EGF-TM7 receptors (CD97, EMR1, EMR2, EMR3, EMR4) consist of extracellular tandemly arranged EGF domains, a stalk, the seven-span transmembrane (TM7) und a short intracellular part. They are expressed as heterodimers of a non-covalently bound alpha- and beta-chain resulting from intracellular autocatalytic cleavage at a conserved GCPR proteolytic site (GPS). The alpha-chain represents the extracellular region with the varying numbers of EGF domains and the main part of the stalk and the beta-chain consists of the stalk residue, the TM7 and intracellular part.
Three CD97 isoforms containing 3, 4 or 5 EGF domains are described. The mature full length proteins contain either 722, 766 or 815 amino acids (aa). After cleavage the (secretory) alpha-chains contain 420, 464, or 513 aa. The beta-chain theoretically contains 305 aa with a molecular weight of 34.3 kDa. However, immunoprecipitation of the beta-chain yielded a molecular weight of approximately 28 kDa. The discrepancy between the theoretical and actual molecular weight of the beta-chain is not yet clarified.
Depending on the cell type and transformation status of the cell, CD97 is completely or partly N-glycosylated or naked. In normal muscle cells CD97 is not or only slightly N-glycosylated. The molecular weight for the respective naked alpha-chain of the various CD97 isoforms are 45.6, 50.5 and 55.8 kDa. In hematopoetic cells CD97 is N-glycosylated at the EGF domains resulting in molecular weights of 74-78, 80-82, and 86-89 kDa for the alpha-chains of the respective isoform. During tumor transformation CD97 may get N-glycosylated. Although the CD97 stalk contains many Ser or Thr residues the molecule seems not to be O-glycosylated.

Broad, not cell-type specific.

Hematopoetic system: strong in peripheral blood myeloid cells and activated lymphocytes, moderately in subsets of tissue-derived leukocytes;

Strong in smooth muscle cells (except for arterial vascular smooth muscle cells), skeletal muscle cells (stronger in slow-twitch fibers), heart muscle cells;

Fat cells;

Low in normal intestinal, thyroidal epithelial cells, moderately in duct cells of the pancreas, parotis gland and in bile duct cells of the liver.

Usually at the cell membrane; soluble CD97 (sCD97) representing the CD97 alpha-chain in body fluids;
Skeletal muscle cells: at the sarcolemm and intracellularly in the sacroendoplasmatic reticulum (SR).

CD97 has the ability to bind cellular and extracellular matrix ligands. The first two EGF domains of CD97 bind CD55 (decay accelerating factor). The fourth EGF domain of CD97 and thus only the longest CD97 isoform interacts with the glycosaminoglycan chondroitin sulfate B. CD97 binds to alpha5beta1 and alphavbeta3 integrins through interaction with the CD97 stalk region.

Hematopoetic cells: Functional studies indicate a role of CD97 in leukocyte trafficking. CD97 antibodies block tissue localization of immune cells in vivo leading to impaired protection against bacteria and amelioration of autoimmune pathology.

Tumor cells: In vitro CD97 increases single cell random motility and directed migration and invasion of tumor cells in 2D and 3D matrices. CD97 enhances proteolytic activity of matrix metalloproteinases (MMPs) and secretion of chemokines in an isoform-specific manner. CD97 (EGF 1,2,5) overexpression promotes tumor growth in scid mice.
The alpha-chain of the longest CD97 (EGF1-5) isoform (sCD97) enhances angiogenesis in in vivo tumor models.

Muscle, fat, duct cells: function unknown.

H. sapiens: CD97
P. troglodytes: CD97
B. taurus: CD97
S. scrofa: CD97
C. lupus: CD97
M. musculus: CD97
R. norvegicus: CD97
Exists only in mammals.

unknown