PR01694

BAIPRECURSOR

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameBAIPRECURSOR

Description
Imported from IPR008077

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
[9]
. 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
[3]
. 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)
[3, 12, 11, 10, 8]
. 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
[9]
. 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
[5]
.

The secretin-like GPCRs include secretin
[4]
, calcitonin
[1]
, parathyroid hormone/parathyroid hormone-related peptides
[2]
and vasoactive intestinal peptide
[7]
, 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-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows 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.

Three human secretin-like GPCRs that are expressed specifically in the brain, and appear to have a role in the inhibition of angiogenesis, have been identified and named BAI (brain-specific angiogenesis inhibitor) 1-3
[6]
. In addition to the characteristic 7 TM domains, the BAIs also have a large extracellular domain containing a number of thrombospondin type 1 repeats - these have been shown to inhibit in vivo angiogenesis induced by bFGF in rat cornea. BAI1 has been found to be transcriptionally regulated by p53 and is absent in many glioblastoma cell lines, suggesting that it may play an important role in suppression of the disease.

BAI is also known as adhesion G protein-coupled receptor B (ADGRB). Disregulation of these GPCRs (aGPCRs) has been observed in cancer
[13]
.

References
Imported from IPR008077

1.Expression cloning of an adenylate cyclase-coupled calcitonin receptor. Lin HY, Harris TL, Flannery MS, Aruffo A, Kaji EH, Gorn A, Kolakowski LF Jr, Lodish HF, Goldring SR. Science 254, 1022-4, (1991). View articlePMID: 1658940

2.A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Juppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J, Kolakowski LF Jr, Hock J, Potts JT Jr, Kronenberg HM. Science 254, 1024-6, (1991). View articlePMID: 1658941

3.Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

4.Molecular cloning and expression of a cDNA encoding the secretin receptor. Ishihara T, Nakamura S, Kaziro Y, Takahashi T, Takahashi K, Nagata S. EMBO J. 10, 1635-41, (1991). View articlePMID: 1646711

5.G protein-coupled receptor deorphanizations. Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schioth HB. Annu. Rev. Pharmacol. Toxicol. 53, 127-46, (2013). PMID: 23020293

6.A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y, Tokino T. Oncogene 15, 2145-50, (1997). View articlePMID: 9393972

7.Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S. Neuron 8, 811-9, (1992). View articlePMID: 1314625

8.Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Bjarnadottir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schioth HB. Genomics 88, 263-73, (2006). View articlePMID: 16753280

9.The G protein-coupled receptor repertoires of human and mouse. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA. Proc. Natl. Acad. Sci. U.S.A. 100, 4903-8, (2003). View articlePMID: 12679517

10.IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Harmar AJ, Hills RA, Rosser EM, Jones M, Buneman OP, Dunbar DR, Greenhill SD, Hale VA, Sharman JL, Bonner TI, Catterall WA, Davenport AP, Delagrange P, Dollery CT, Foord SM, Gutman GA, Laudet V, Neubig RR, Ohlstein EH, Olsen RW, Peters J, Pin JP, Ruffolo RR, Searls DB, Wright MW, Spedding M. Nucleic Acids Res. 37, D680-5, (2009). View articlePMID: 18948278

11.International Union of Pharmacology. XLVI. G protein-coupled receptor list. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. Pharmacol. Rev. 57, 279-88, (2005). View articlePMID: 15914470

12.GCRDb: a G-protein-coupled receptor database. Kolakowski LF Jr. Recept. Channels 2, 1-7, (1994). PMID: 8081729

13.Adhesion GPCRs in Tumorigenesis. Aust G, Zhu D, Van Meir EG, Xu L. Handb Exp Pharmacol 234, 369-396, (2016). PMID: 27832497

Supplementary References

1. Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1). Shiratsuchi T, Nishimori H, Ichise H, Nakamura Y, Tokino T. Cytogenet. Cell Genet. 79, 103-8, (1997). PMID: 9533023

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