InterPro : IPR003056

Name  GPCR, family 2, CD97 antigen Short Name  GPCR_2_CD97
Type  Family Description  G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N terminus is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allow the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. CD97 is a member of the EGF-TM7 family of class II G-protein coupled receptors that can bind to CD55(DAF). CD97 has highly related 7TM sequences but diverse, large extracellular regions. The extracellular regions are generally unrelated in sequence but usually contain cell adhesion motifs. For receptors with N-terminal EGF domains the designation EGF-TM7 family has been introduced. Typically, isoforms with variable number of EGF domains exist.So far, the EGF-TM7 family consists of CD97 and EMR1, the human homologue of F4/80. Family members are preferentially expressed by cells of the immunesystem []. High surface expression of CD97 has been found at sites of inflammation in skin and lung and in rheumatoid arthritis. At the same sites, elevated levels of soluble CD97 are detectable. Analysis of epithelial tumors revealed CD97 expression on the malignant cells in thyroid cancer and adenocarcinomas of the gastro-intestinal tract [].

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



0 Child Features

6 Contains

Id Name Short Name Type
IPR001881 EGF-like calcium-binding domain EGF-like_Ca-bd_dom Domain
IPR000742 Epidermal growth factor-like domain EG-like_dom Domain
IPR000203 GPS motif GPS Domain
IPR017981 GPCR, family 2-like GPCR_2-like Domain
IPR000152 EGF-type aspartate/asparagine hydroxylation site EGF-type_Asp/Asn_hydroxyl_site PTM
IPR018097 EGF-like calcium-binding, conserved site EGF_Ca-bd_CS Conserved_site

0 Found In

1 Parent Features

Id Name Short Name Type
IPR000832 GPCR, family 2, secretin-like GPCR_2_secretin-like Family

12 Publications

First Author Title Year Journal Volume Pages
Attwood TK Fingerprinting G-protein-coupled receptors. 1994 Protein Eng 7 195-203
Vassilatis DK The G protein-coupled receptor repertoires of human and mouse. 2003 Proc Natl Acad Sci U S A 100 4903-8
Kolakowski LF Jr GCRDb: a G-protein-coupled receptor database. 1994 Receptors Channels 2 1-7
Foord SM International Union of Pharmacology. XLVI. G protein-coupled receptor list. 2005 Pharmacol Rev 57 279-88
Harmar AJ IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. 2009 Nucleic Acids Res 37 D680-5
Bjarnadóttir TK Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. 2006 Genomics 88 263-73
Civelli O G protein-coupled receptor deorphanizations. 2013 Annu Rev Pharmacol Toxicol 53 127-46
Ishihara T Molecular cloning and expression of a cDNA encoding the secretin receptor. 1991 EMBO J 10 1635-41
Ishihara T Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. 1992 Neuron 8 811-9
Lin HY Expression cloning of an adenylate cyclase-coupled calcitonin receptor. 1991 Science 254 1022-4
Jüppner H A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. 1991 Science 254 1024-6
Hamann J 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. 1995 J Immunol 155 1942-50

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Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)