Nomenclature: BAI2

Family: Adhesion Class GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1572 1p35 BAI2 brain-specific angiogenesis inhibitor 2 9
Mouse 7 1561 4D2.2 Bai2 brain-specific angiogenesis inhibitor 2 5
Rat 7 1548 5q36 Bai2 brain-specific angiogenesis inhibitor 2
Previous and Unofficial Names
brain-specific angiogenesis inhibitor 2
BAI2
Bai2_predicted
LOC313058
brain-specific angiogenesis inhibitor 2 (predicted)
brain angiogenesis inhibitor 2
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Agonist Comments
GA-binding protein gamma (GABPγ) associates with the cytoplasmic domain of BAI2, and GABPα/γ or GABPα/β works as a transcriptional repressor of VEGF in SHSY5Y cells [3]. The cytoplasmic region of BAI2 binds to glutaminase interacting protein (GIP) [10].
Primary Transduction Mechanisms
Comments:  Signaling to NFAT (nuclear factor of activated T cells) and stimulation of IP3, binding to Gα16 suggested. NFAT reporter assay of HEK293 overexpressing BAI2 or BAI2-CTF, signaling enhanced by co-expression of Gα16 [6].
References: 
Tissue Distribution
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:  9
Brain-specific expression, absent from gut, heart, kidney, liver, lung, muscle, spleen, aorta, testis, thymus
Species:  Mouse
Technique:  RT-PCR
References:  5,8
Preferential expression in muscle-myenteric nerve layer of gastrointestinal tract, absent from mucosal nerve layer
Species:  Mouse
Technique:  RT-PCR
References:  2
Expression in most neurons of the cerebral cortex but highest in layers II to III (as was BAI1). 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:  9
Expressed in many different brain regions, appears to be neuron specific
Species:  Rat
Technique:  in situ hybridisation
References:  5
Expression Datasets

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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
Signaling to NFAT (nuclear factor of activated T cells) and stimulation IP3, binding to Gα16 suggested. NFAT reporter assay of HEK293 overexpressing BAI2 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
BAI2-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
BAI2 expression decreased after hypoxia. BAI2 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
Phenotypes, Alleles and Disease Models 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
Disease:  Breast cancer (triple neg)
References:  4
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Type Species Molecular location Description Reference
Missense Human 714S>R 4
Disease:  Breast cancer (HR+)
References:  4
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Type Species Molecular location Description Reference
Missense Human 707D>N 4
Disease:  Breast cancer (HER2+)
References:  4
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Type Species Molecular location Description Reference
Missense Human 615M>I 4
Disease:  Lung cancer (carcinoma squamous cell)
References:  4
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Type Species Molecular location Description Reference
Missense Human 397G>S 4
Missense Human 358S>L 4
Disease:  Lung cancer (others)
References:  4
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Type Species Molecular location Description Reference
Missense Human 25L>P 4
Clinically-Relevant Mutations and Pathophysiology Comments
All mutations listed are correlations of human mutation and disease from the same reference.
General Comments
BAI2 (brain angiogenesis inhibitor 2) is an orphan receptor belonging to Family VII Adhesion-GPCRs together with BAI1 and BAI3 [1]. The gene is localized on human chromosome 1 and mouse chromosome 4.
Available Assays
DiscoveRx PathHunter® CHO-K1 BAI2 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0546C2)
PathHunter® eXpress BAI2 CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0546E2CP1M)
more info

REFERENCES

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. Nature466 (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 Metab22: 1054-1067. [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 Sci61 (1): 47-54. [PMID:21110148]

8. Regard JB, Sato IT, Coughlin SR. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell135: 561-571. [PMID:18984166]

9. 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 Genet79: 103-108. [PMID:9533023]

10. 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]

To cite this database page, please use the following:

Demet Arac-Ozkan, David C. Martinelli, Tom I. Bonner.
Adhesion Class GPCRs: BAI2. Last modified on 23/07/2013. Accessed on 01/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=175.

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