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ADGRB2

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Target id: 175

Nomenclature: ADGRB2

Family: Adhesion Class GPCRs

Contents:

Gene and Protein Information Click here for help
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1585 1p35.2 ADGRB2 adhesion G protein-coupled receptor B2 10
Mouse 7 1561 4 D2.2 Adgrb2 adhesion G protein-coupled receptor B2 5
Rat 7 1548 5q36 Adgrb2 adhesion G protein-coupled receptor B2
Previous and Unofficial Names Click here for help
BAI2 | brain-specific angiogenesis inhibitor 2
Database Links Click here for help
Specialist databases
GPCRdb agrb2_human (Hs), agrb2_mouse (Mm)
Other databases
Alphafold O60241 (Hs), Q8CGM1 (Mm)
CATH/Gene3D 2.20.100.10
Ensembl Gene ENSG00000121753 (Hs), ENSMUSG00000028782 (Mm), ENSRNOG00000014375 (Rn)
Entrez Gene 576 (Hs), 230775 (Mm), 313058 (Rn)
Human Protein Atlas ENSG00000121753 (Hs)
KEGG Gene hsa:576 (Hs), mmu:230775 (Mm), rno:313058 (Rn)
OMIM 602683 (Hs)
Pharos O60241 (Hs)
RefSeq Nucleotide NM_001294335 (Hs), NM_173071 (Mm), NM_001107914 (Rn)
RefSeq Protein NP_001281264 (Hs), NP_775094 (Mm), NP_001101384 (Rn)
UniProtKB O60241 (Hs), Q8CGM1 (Mm)
Wikipedia ADGRB2 (Hs)
Agonist Comments
GA-binding protein gamma (GABPγ) associates with the cytoplasmic domain of ADGRB2, and GABPα/γ or GABPα/β works as a transcriptional repressor of VEGF in SHSY5Y cells [3]. The cytoplasmic region of ADGRB2 binds to glutaminase interacting protein (GIP) [11].
Primary Transduction Mechanisms Click here for help
Comments:  Principal transduction via Gαz [8].
Signaling to NFAT (nuclear factor of activated T cells) and stimulation of IP3, binding to Gα16 suggested. NFAT reporter assay of HEK293 overexpressing ADGRB2 or BAI2-CTF, signaling enhanced by co-expression of Gα16 [6]. A R1465W receptor mutation confers increased coupling to Gαi [8].
References: 
Tissue Distribution Click here for help
Brain but not gut, heart, kidney, liver, lung, skeletal muscle, spleen, thymus in adult and newborn.
Brain and possible weak signals in other tissues in embryo.
Species:  Mouse
Technique:  Northern blotting.
References:  10
Brain-specific expression, absent from gut, heart, kidney, liver, lung, muscle, spleen, aorta, testis, thymus
Species:  Mouse
Technique:  RT-PCR
References:  5,9
Preferential expression in muscle-myenteric nerve layer of gastrointestinal tract, absent from mucosal nerve layer
Species:  Mouse
Technique:  RT-PCR
References:  2
Expressed in many different brain regions, appears to be neuron specific
Species:  Rat
Technique:  in situ hybridisation
References:  5
Expression in most neurons of the cerebral cortex but highest in layers II to III (as was ADGRB1). High levels also in pyramidal neurons of all fields of the hippocampus, in the granule cell and polymorphic layers of dentate gyrus, medial and lateral, and medial and lateral habenular nucleus.
Species:  Rat
Technique:  in situ hybridisation.
References:  10
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Signaling to NFAT (nuclear factor of activated T cells) and stimulation IP3, binding to Gα16 suggested. NFAT reporter assay of HEK293 overexpressing ADGRB2 or BAI2-CTF, signaling enhanced by co-expression of Gα16
Species:  Human
Tissue:  Transfected cells
Response measured:  NFAT signaling and IP3 accumulation
References:  6
Physiological Consequences of Altering Gene Expression Click here for help
ADGRB2 expression decreased after hypoxia. ADGRB2 expression decreased after hypoxia and preceded the increased expression of vascular endothelial growth factor (VEGF).
Species:  Rat
Tissue: 
Technique:  Focal cerebral ischemia model
References:  5
ADGRB2-deficient mice showed significant antidepressant-like behavior in the social defeat test and in the tail suspension test compared with wild-type mice.
Species:  Mouse
Tissue:  Full-body
Technique:  Gene knockouts
References:  7
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Bai2tm1Dgen Bai2tm1Dgen/Bai2tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:2451244  MP:0003063 increased coping response
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Role:  Mutations in ADGRB2 are associated with HER2+, HR+ and triple-negative forms of breast cancer
References:  4
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human M615I Mutation associated with HER2+ breast cancer 4
Missense Human D707N Mutation associated with HR+ breast cancer 4
Missense Human S714R Mutation associated with triple-negative breast cancer 4
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Role:  Mutations in ADGRB2 are associated with squamous cell carcinoma of the lung and other forms of lung cancer
References:  4
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L25P 4
Missense Human S358L Mutation associated with squamous cell carcinoma 4
Missense Human G397S Mutation associated with squamous cell carcinoma 4
Clinically-Relevant Mutations and Pathophysiology Comments
All mutations listed are correlations of human mutation and disease from the same reference.
General Comments
ADGRB2 (adhesion G protein-coupled receptor B2, formerly known as BAI2: brain angiogenesis inhibitor 2) is an orphan receptor belonging to Family VII Adhesion-GPCRs together with ADGRB1 and ADGRB3 [1]. The gene is localized on human chromosome 1 and mouse chromosome 4.

References

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1. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun, 301 (3): 725-34. [PMID:12565841]

2. Ito J, Ito M, Nambu H, Fujikawa T, Tanaka K, Iwaasa H, Tokita S. (2009) Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice. Cell Tissue Res, 338 (2): 257-69. [PMID:19763624]

3. Jeong BC, Kim MY, Lee JH, Kee HJ, Kho DH, Han KE, Qian YR, Kim JK, Kim KK. (2006) Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor. FEBS Lett, 580 (2): 669-76. [PMID:16412436]

4. Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM, Yue P, Haverty PM, Bourgon R, Zheng J, Moorhead M, Chaudhuri S, Tomsho LP, Peters BA, Pujara K, Cordes S, Davis DP, Carlton VE, Yuan W, Li L, Wang W, Eigenbrot C, Kaminker JS, Eberhard DA, Waring P, Schuster SC, Modrusan Z, Zhang Z, Stokoe D, de Sauvage FJ, Faham M, Seshagiri S. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature, 466 (7308): 869-73. [PMID:20668451]

5. Kee HJ, Koh JT, Kim MY, Ahn KY, Kim JK, Bae CS, Park SS, Kim KK. (2002) Expression of brain-specific angiogenesis inhibitor 2 (BAI2) in normal and ischemic brain: involvement of BAI2 in the ischemia-induced brain angiogenesis. J Cereb Blood Flow Metab, 22 (9): 1054-67. [PMID:12218411]

6. Okajima D, Kudo G, Yokota H. (2010) Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. J Recept Signal Transduct Res, 30 (3): 143-53. [PMID:20367554]

7. Okajima D, Kudo G, Yokota H. (2011) Antidepressant-like behavior in brain-specific angiogenesis inhibitor 2-deficient mice. J Physiol Sci, 61 (1): 47-54. [PMID:21110148]

8. Purcell RH, Toro C, Gahl WA, Hall RA. (2017) A disease-associated mutation in the adhesion GPCR BAI2 (ADGRB2) increases receptor signaling activity. Hum Mutat, 38 (12): 1751-1760. [PMID:28891236]

9. Regard JB, Sato IT, Coughlin SR. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell, 135 (3): 561-71. [PMID:18984166]

10. Shiratsuchi T, Nishimori H, Ichise H, Nakamura Y, Tokino T. (1997) Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1). Cytogenet Cell Genet, 79 (1-2): 103-8. [PMID:9533023]

11. Zencir S, Ovee M, Dobson MJ, Banerjee M, Topcu Z, Mohanty S. (2011) Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein. Biochem Biophys Res Commun, 411 (4): 792-7. [PMID:21787750]

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