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ADGRB1

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Target not currently curated in GtoImmuPdb

Target id: 174

Nomenclature: ADGRB1

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 1584 8q24.3 ADGRB1 adhesion G protein-coupled receptor B1 16
Mouse 7 1582 15 D3 Adgrb1 adhesion G protein-coupled receptor B1 13
Rat 7 1585 7q34 Adgrb1 adhesion G protein-coupled receptor B1
Previous and Unofficial Names Click here for help
BAI1 | brain-specific angiogenesis inhibitor 1
Database Links Click here for help
Specialist databases
GPCRdb bai1_human (Hs), bai1_mouse (Mm)
Other databases
Alphafold O14514 (Hs), Q3UHD1 (Mm)
CATH/Gene3D 2.20.100.10
Ensembl Gene ENSG00000181790 (Hs), ENSMUSG00000034730 (Mm), ENSRNOG00000029450 (Rn)
Entrez Gene 575 (Hs), 107831 (Mm), 362931 (Rn)
Human Protein Atlas ENSG00000181790 (Hs)
KEGG Gene hsa:575 (Hs), mmu:107831 (Mm), rno:362931 (Rn)
OMIM 602682 (Hs)
Pharos O14514 (Hs)
RefSeq Nucleotide NM_001702 (Hs), NM_174991 (Mm), NM_001170597 (Rn)
RefSeq Protein NP_001693 (Hs), NP_778156 (Mm), NP_001164068 (Rn)
UniProtKB O14514 (Hs), Q3UHD1 (Mm)
Wikipedia ADGRB1 (Hs)
Natural/Endogenous Ligands Click here for help
phosphatidylserine
Agonist Comments
The thrombospondin type 1 repeats within the extracellular region of ADGRB1 mediate direct binding to phosphatidylserine. It is suggested that the cytoplasmic region of ADGRB1 directly binds to ELMO and coopertaes with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells [19]. The following proteins bind to the intracellular region of ADGRB1: BAI1-associated protein 1 (BAIAP1) [21], BAI1-associated protein 2 (BAIAP2) [17], BAI1-associated protein 3 (BAIAP3) [22], BAI1-associated protein 4 (BAIAP4) [13].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Cellular signalling
Tissue Distribution Click here for help
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:  16
Expressed in neuronal cells of the cerebral cortex but not in astrocytes
Species:  Human
Technique:  Immunohistochemistry
References:  15
Expressed in brain, absent from gut, heart, kidney, liver, lung, muscle, spleen, thymus, aorta, testis
Species:  Mouse
Technique:  Northern blot and RT-PCR
References:  13,20
Preferential expression in muscle-myenteric nerve layer of gastrointestinal tract, reduced in mucosal nerve layer
Species:  Mouse
Technique:  RT-PCR
References:  8
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:  18
Expressed in many different brain regions, appears to be neuron specific
Species:  Rat
Technique:  in situ hybridisation
References:  13
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
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 ADGRB1 causes Rac activation in bacterial engulfment [2]. The following papers have reported antiangiogenesis effects mediated by the cleaved and secreted extracellular region of ADGRB1 (called vasculostatin): [1,6,10-12,14,23].
Physiological Consequences of Altering Gene Expression Click here for help
Overexpression of ADGRB1 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
ADGRB1 suppresses medulloblastoma formation. Knockout of Adgrb1 in mice leads to accelerated tumour growth in the Ptch1+/- transgenic MB mouse model.
Species:  Mouse
Tissue:  Brain
Technique: 
References:  24
ADGRB1 mediates a key transition in dendrite development. BAI1 loss from mouse or rat hippocampal neurons causes dendritic hypertrophy. BAI1 overexpression precipitates dendrite retraction.
Species:  Mouse
Tissue:  mouse or rat hippocampal neurons.
Technique: 
References:  4
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Role:  Mutations in ADGRB1 are associated with squamous cell carcinoma of the lung
References:  9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human T113N Mutation associated with squamous cell carcimoma 9
Missense Human R833M Mutation associated with squamous cell carcimoma 9
Missense Human R1311S Mutation associated with squamous cell carcimoma 9
Disease:  Ovarian cancer
Disease Ontology: DOID:2394
OMIM: 167000
References:  9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human K1008R 9
Clinically-Relevant Mutations and Pathophysiology Comments
All mutations listed are correlations of human mutation and disease from the same reference.
General Comments
ADGRB1 (adhesion G protein-coupled receptor B1, formerly known as BAI1: brain angiogenesis inhibitor 1) is a receptor belonging to Family VII Adhesion-GPCRs together with ADGRB2 (formerly BAI2) and ADGRB3 (formerly BAI3) [5]. The gene is localized on human chromosome 8 and mouse chromosome 15. A recent study disputes the previously reported expression of ADGRB1 by macrophages [7].

References

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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. Oncogene, 31 (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 USA, 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 et al.. (2002) Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. Br J Cancer, 86 (3): 490-6. [PMID:11875720]

4. Duman JG, Mulherkar S, Tu YK, Erikson KC, Tzeng CP, Mavratsas VC, Ho TS, Tolias KF. (2019) The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest. Elife, 8. [PMID:31461398]

5. 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]

6. 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]

7. Hsiao CC, van der Poel M, van Ham TJ, Hamann J. (2019) Macrophages Do Not Express the Phagocytic Receptor BAI1/ADGRB1. Front Immunol, 10: 962. [PMID:31130954]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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 Res, 87 (2): 223-37. [PMID:11245925]

14. 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]

15. 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]

16. 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. Oncogene, 15: 2145-2150. [PMID:9393972]

17. 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]

18. 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 Cell, 4 (1): 16. [PMID:23020941]

19. 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. Nature, 450 (7168): 430-4. [PMID:17960134]

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

21. 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]

22. 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]

23. 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]

24. Zhu D, Osuka S, Zhang Z, Reichert ZR, Yang L, Kanemura Y, Jiang Y, You S, Zhang H, Devi NS et al.. (2018) BAI1 Suppresses Medulloblastoma Formation by Protecting p53 from Mdm2-Mediated Degradation. Cancer Cell, 33 (6): 1004-1016.e5. [PMID:29894688]

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