Nomenclature: BAI1

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 1584 8q24 BAI1 brain-specific angiogenesis inhibitor 1 14
Mouse 7 1582 15 D3 Bai1 brain-specific angiogenesis inhibitor 1 11
Rat 7 1585 7q34 Bai1 brain-specific angiogenesis inhibitor 1
Previous and Unofficial Names
brain-specific angiogenesis inhibitor 1
FLJ41988
BAI1
GDAIF
Bai1_predicted
LOC362931
brain-specific angiogenesis inhibitor 1 (predicted)
B830018M07Rik
R75078
brain angiogenesis inhibitor 1
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
Natural/Endogenous Ligands
phosphatidylserine
Agonist Comments
The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. It is suggested that the cytoplasmic region of BAI1 directly binds to ELMO and coopertaes with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells [17]. The following proteins bind to the intracellular region of BAI1: BAI1-associated protein 1 (BAIAP1) [19], BAI1-associated protein 2 (BAIAP2) [15], BAI1-associated protein 3 (BAIAP3) [20], BAI1-associated protein 4 (BAIAP4) [11].
Tissue Distribution
Brain-specific expression, absent from placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, intestines, leukocytes
Species:  Human
Technique:  Northern blot
References:  14
Expressed in neuronal cells of the cerebral cortex but not in astrocytes
Species:  Human
Technique:  Immunohistochemistry
References:  13
Expressed in brain, absent from gut, heart, kidney, liver, lung, muscle, spleen, thymus, aorta, testis
Species:  Mouse
Technique:  Northern blot and RT-PCR
References:  11,18
Preferential expression in muscle-myenteric nerve layer of gastrointestinal tract, reduced in mucosal nerve layer
Species:  Mouse
Technique:  RT-PCR
References:  6
Strongly expressed in growing blood vessels of cerebral cortex and hippocampus, partially expressed in the lateral regions of striatum, but mostly absent on the thalamus
Species:  Mouse
Technique:  Immunohistochemistry
References:  16
Expressed in many different brain regions, appears to be neuron specific
Species:  Rat
Technique:  in situ hybridisation
References:  11
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
Over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice.
Species:  Human
Tissue:  Panc1 cells
Response measured:  Delayed tumor growth
References:  3
Functional Assay Comments
Binding of surface lipopolysaccharides on bacteria to CHO cells overexpressing BAI1 causes Rac activation in bacterial engulfment [2]. The following papers have reported antiangiogenesis effects mediated by the cleaved and secreted extracellular region of BAI1 (called vasculostatin): [1,5,8-10,12,21].
Physiological Consequences of Altering Gene Expression
Overexpression of BAI1 in the human pancreatic adenomcarcinoma cell line Panc-1 by means of adenoviral vector infection suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice.
Species:  Human
Tissue: 
Technique:  Transgenesis.
References:  3
Clinically-Relevant Mutations and Pathophysiology
Disease:  Lung cancer (carcinoma squamous cell)
References:  7
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human 113T>N 7
Missense Human 1311R>S 7
Missense Human 833R>M 7
Disease:  Ovarian cancer
References:  7
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human 1008K>R 7
Clinically-Relevant Mutations and Pathophysiology Comments
All mutations listed are correlations of human mutation and disease from the same reference.
General Comments
BAI1 (brain angiogenesis inhibitor 1) is a receptor belonging to Family VII Adhesion-GPCRs together with BAI2 and BAI3 [4]. The gene is localized on human chromosome 8 and mouse chromosome 15.
Available Assays
DiscoveRx PathHunter® CHO-K1 BAI1 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0545C2) more info

REFERENCES

1. Cork SM, Kaur B, Devi NS, Cooper L, Saltz JH, Sandberg EM, Kaluz S, Van Meir EG. (2012) A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1. Oncogene31 (50): 5144-52. [PMID:22330140]

2. Das S, Owen KA, Ly KT, Park D, Black SG, Wilson JM, Sifri CD, Ravichandran KS, Ernst PB, Casanova JE. (2011) Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc. Natl. Acad. Sci. U.S.A.108 (5): 2136-41. [PMID:21245295]

3. Duda DG, Sunamura M, Lozonschi L, Yokoyama T, Yatsuoka T, Motoi F, Horii A, Tani K, Asano S, Nakamura Y, Matsuno S. (2002) Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. Br J Cancer86: 490-496. [PMID:11875720]

4. 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]

5. Hardcastle J, Kurozumi K, Dmitrieva N, Sayers MP, Ahmad S, Waterman P, Weissleder R, Chiocca EA, Kaur B. (2010) Enhanced antitumor efficacy of vasculostatin (Vstat120) expressing oncolytic HSV-1. Mol. Ther.18 (2): 285-94. [PMID:19844198]

6. 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]

7. 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]

8. Kang X, Xiao X, Harata M, Bai Y, Nakazaki Y, Soda Y, Kurita R, Tanaka T, Komine F, Izawa K, Kunisaki R, Setoyama M, Nishimori H, Natsume A, Sunamura M, Lozonshi L, Saitoh I, Tokino T, Asano S, Nakamura Y, Tani K. (2006) Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas. Cancer Gene Ther.13 (4): 385-92. [PMID:16244591]

9. Kaur B, Cork SM, Sandberg EM, Devi NS, Zhang Z, Klenotic PA, Febbraio M, Shim H, Mao H, Tucker-Burden C, Silverstein RL, Brat DJ, Olson JJ, Van Meir EG. (2009) Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res.69 (3): 1212-20. [PMID:19176395]

10. Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC, Lee JH, Kim MY, Yoon KC, Jung S, Kim KK. (2004) Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin. Exp. Cell Res.294 (1): 172-84. [PMID:14980512]

11. Koh JT, Lee ZH, Ahn KY, Kim JK, Bae CS, Kim HH, Kee HJ, Kim KK. (2001) Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding protein. Brain Res Mol Brain Res87: 223-237. [PMID:11245925]

12. Kudo S, Konda R, Obara W, Kudo D, Tani K, Nakamura Y, Fujioka T. (2007) Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma. Oncol. Rep.18 (4): 785-91. [PMID:17786337]

13. Mori K, Kanemura Y, Fujikawa H, Nakano A, Ikemoto H, Ozaki I, Matsumoto T, Tamura K, Yokota M, Arita N. (2002) Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells. Neurosci. Res.43 (1): 69-74. [PMID:12074842]

14. Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y, Tokino T. (1997) A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene15: 2145-2150. [PMID:9393972]

15. Oda K, Shiratsuchi T, Nishimori H, Inazawa J, Yoshikawa H, Taketani Y, Nakamura Y, Tokino T. (1999) Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. Cytogenet. Cell Genet.84 (1-2): 75-82. [PMID:10343108]

16. Ozkan A, Biçer A, Avşar T, Seker A, Toktaş ZO, Bozkurt SU, Başak AN, Kılıç T. (2012) Temporal expression analysis of angiogenesis-related genes in brain development. Vasc Cell4 (1): 16. [PMID:23020941]

17. Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL, Mandell JW, Ravichandran KS. (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature450 (7168): 430-4. [PMID:17960134]

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

19. Shiratsuchi T, Futamura M, Oda K, Nishimori H, Nakamura Y, Tokino T. (1998) Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing protein that interacts with BAI1. Biochem. Biophys. Res. Commun.247 (3): 597-604. [PMID:9647739]

20. Shiratsuchi T, Oda K, Nishimori H, Suzuki M, Takahashi E, Tokino T, Nakamura Y. (1998) Cloning and characterization of BAP3 (BAI-associated protein 3), a C2 domain-containing protein that interacts with BAI1. Biochem. Biophys. Res. Commun.251 (1): 158-65. [PMID:9790924]

21. Zhu D, Hunter SB, Vertino PM, Van Meir EG. (2011) Overexpression of MBD2 in glioblastoma maintains epigenetic silencing and inhibits the antiangiogenic function of the tumor suppressor gene BAI1. Cancer Res.71 (17): 5859-70. [PMID:21724586]

To cite this database page, please use the following:

Demet Arac-Ozkan, David C. Martinelli, Tom I. Bonner.
Adhesion Class GPCRs: BAI1. Last modified on 02/05/2014. Accessed on 01/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=174.

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