CD97 

BL-KDD/F12

Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Carcinoma Cell
Muscle, Smooth
T Cell
B Cell
Granulocyte
Monocyte
Macrophage
Dendritic Cell
Gastrointestine
28 / 28
74 / 78
75 / 85
80 / 82
86 / 89

Expression
CD97 is expressed on activated T and B cells, monocytes, macrophages, dendritic cells, granulocytes but at low levels on resting T and B cells and lymphocytes.  Expression is predominately on cells of the immune system.  Expression is found on smooth muscle cells, a subset of thyroid and gastrointestinal tract carcinoma cells.

Structure
MOLECULAR FAMILY NAME:   Belongs to the G protein-coupled receptor subfamily.

CD97 is a multi-pass type-3, 7 span 722 aa glycoprotein.  CD97 is a single polypeptide that is then cleaved into two subunits (α and β) within the endoplasmic reticulum.  CD97α contains an large extracellular domain which contains 3-5 tandem EGF-like domains, two of which have Ca2+ binding sites, a RGD (arg-gly-asp) motif and 8 potential N-glycosylation sites.  CD97β is a 243 aa glycoprotein that is covalently linked to a 7-transmembrane moiety and contains a 46 aa intracellular cytoplasmic domain.  The 7-span transmembrane region also shows an ~25% sequence identity to members of the recently described glucagon/vasoactive intestinal peptide/calcitonin receptor family.  The first two EGF domains mediate interaction with CD55 (DAF), the third EGF domain is necessary for structural integrity of the binding region and binding to chondroitin sulfate is mediated by the fourth EGF domain.  CD97a has a reduced molecular weight of 75-85 kDa and an unreduced weight of 74-78 kDa, 80-82 kDa and 86-89 kDa while CD97b has a molcular weight of 28 kDa.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Activated peripheral blood mononuclear cell (PMBC) 74 kDa-78 kDa, 80 kDa-82 kDa, 86 kDa-89 kDa 75 kDa-85 kDa CD97a
Activated peripheral blood mononuclear cell (PMBC) 28 kDa 28 kDa CD97b

POST-TRANSCIPTIONAL MODIFICATION

Alternative splicing yields 3 isoforms different isoforms.  CD55 can bind all isoforms but with different affinity having the highest affinity for the 3 EGF domain-containing isoform and the lowest affinity for the 5 EGF domain-containing isoform.

POST-TRANSLATIONAL MODIFICATION

There is a cleavage of an approximate 20 aa leader sequence and 8 potential N-glycosylation sites.  CD97 is translated as a single polypeptide and cleaved in the endoplasmic reticulum (ER) into 2 subunits, a and b, which are non-covalently associated on the cell surface.  CD97a is the extracellular subunit and the CD97b is the transmembrane subunit.  The exact cleavage has not been determined but it is approximately at 530 aa in the isoform containing 4 EGF domains.


Ligands
CD97 binds CD55 an chondroitin sulphate.  COS cells expressing CD97 adhere to lymphocytes and erythrocytes.  This interaction is blocked by mAbs specific for CD55, a proposed cellular ligand for CD97. Immunoprecipitation studies have identified a 58 kDa protein non-covalently associated with CD97 on the cell surface.


LIGANDS AND MOLECULES ASSOCIATED WITH CD97
Molecule Comment
CD55 (DAF) The physiological role of this interaction is still unknown.  The CD55-binding site is formed by the EGF domain region.  3 tandemly arranged EGF domains are necessary for ligand binding.  The smallest isoform with 3 EGF domains binds CD55 with higher affinity compared to the larger isoforms possessing 4 and 5 EGF domains.  Remarkably, the interaction between CD97 and CD55 is phylogenetically restricted.


Function
CD97 functions as a receptor involved in adhesion and signaling processes early after leukocyte activation and there is some evidence that CD97 functions in neutrophil migration.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD97 IN INTACT ANIMAL

There is some evidence from in vivo studies that CD97 plays an important role in the migration of neutrophils as pre-incubation of neutrophils with anti-CD97 mAb delayed migration of these cells to sites of inflammation in experimental colitis.  Similarly, the presence of CD97 mAb impaired granulocyte recruitment to the lungs and reduced bacterial clearance in a model of pneumonia.  CD97 can coengage chondroitin sulfate (CS) and α5/β1 integrin to synergistically initiate endothelial cell invasion and may stimulate angiogenesis.  CD97 on activated T cells, dendritic cells and macrophages can bind CS expressed on B cells but this interaction has not been shown to stimulate B-cell oroliferation, Ig synthesis, or class switching.  CD97 has been implicated as having an importnat role in tumor cell migration and invasion as the level of CD97 is proportional to the aggressiveness and lymph node involvement in thyroid carcinomas.  Analysis of epithelial tumors revealed CD97 is a prognostic marker on the malignant cells in thyroid cancer and adenocarinomas of the gastrointestinal tracts.  In colorectal carcinoma, strong expression of CD97 in scattered tumor cells at the invasion front correlates with an increased likelihood of lymph node involvement and poor prognosis.  A high surface expression of CD97 has been found at sites of inflammatory conditions in central nervous system (CNS), multiple sclerosis, skin, lung and in the synovial tissue of patients with rhematoid arthritis.  Increased expression in the synovium is accompagnied by detectable levels of soluble CD97 in the synovial fluid.  

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD97: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD97: No information.

ADDITIONAL INSIGHTS

CD97 is a member of a superfamily of class II G-protein coupled receptors with highly related 7 TM sequences but diverse large extracellular regions.  The extracellular regions are generally unrelated in sequence but usually contain cell adhesion motifs.  The family is conserved in Drosophila and C. elegans.  For the receptors with N-terminal EGF domains, the designation EGF-TM7 family has been introduced.  Typically, isoforms with variable numbers of EGF domains exist.  So far, the EGF-TM7 family comprises CD97 and EMR1, the human homologue of F4/80.  Family members are preferentially expressed by cells of the immune system.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 976P48960
Antibodies
VIM3b.1   View Reactivity

Revised June 25, 2008


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