ADGRL4 | Adhesion Class GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

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ADGRL4

Target not currently curated in GtoImmuPdb

Target id: 181

Nomenclature: ADGRL4

Family: Adhesion Class GPCRs

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

Gene and Protein Information
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 832 1p31.1 ADGRL4 adhesion G protein-coupled receptor L4
Mouse 7 739 3 H3-H4 Adgrl4 adhesion G protein-coupled receptor L4
Rat 7 738 2q45 Adgrl4 adhesion G protein-coupled receptor L4 7
Previous and Unofficial Names
ETL | EGF-TM7-latrophilin-related protein | ELTD1 | EGF, latrophilin seven transmembrane domain containing 1
Database Links
Specialist databases
GPCRDB agrl4_human (Hs), agrl4_mouse (Mm), agrl4_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Agonist Comments
No ligands identified: orphan receptor.
Tissue Distribution
Cardiac myocytes, ventricles
Species:  Human
Technique:  Northern blot and Western blot
References:  7
(Brain) vessels, perhaps endothelial cells
Species:  Human
Technique:  Immunohistochemistry and Western blot, microarray analysis
References:  2,6,9-10
Ventricles
Species:  Mouse
Technique:  Western blot
References:  11
Hematopoietic stem cells
Species:  Mouse
Technique:  Microarray analysis
References:  8
Expression in rat cardiomyocytes and abundant expression in vascular and bronchiolar smooth muscle cells.
Species:  Rat
Technique:  in situ hybridisation.
References:  7
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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Physiological Consequences of Altering Gene Expression
Mice with null allele have augmented cardiac hypertrophy in response to pressure overload
Species:  Mouse
Tissue:  Heart
Technique:  Gene knockouts
References:  11
Biologically Significant Variants
Type:  Single nucleotide polymorphisms
Species:  Human
Description:  Associated with subcutaneous fat thickness in human and pig
References:  4
Type:  Microsatellite locus
Species:  Human
Description:  Associated with susceptibility for moderate to severe graft-versus-host disease (GVHD)
References:  3
General Comments
ADGRL4 (adhesion G protein-coupled receptor L4, formerly known as ELTD1 :EGF, latrophilin and seven transmembrane domain containing 1) is an orphan receptor that belongs to Family I Adhesion-GPCRs together with latrophilins 1-3 [1].

Full coding sequence human cDNA is publicly available, IMAGE:5229055 [5] in the mammalian expression vector pCMV-SPORT6. Clone differs from genomic at rs12754818, having the more common allele. Clone represents the more common alternative transcription start site encoding a protein of 690 amino acids.

ADGRL4 as a drug target: A 2017 publication validates ADGRL4 as an anti-angiogenic target for glioma [12]. In this study a mAb tageting ADGRL4 exhibited effective anti-tumour effects in preclinical glioma xenograft models, and this approach was shown to be as efficacious as anti-vascular endothelial growth factor (VEGF) and anti-MET antibody therapies.

References

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1. Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB. (2004) The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics, 84: 23-33. [PMID:15203201]

2. Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomäki H, Teichert M, Huang H, Edqvist PH, Kraus T et al.. (2012) Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization. J. Pathol., 228 (3): 378-90. [PMID:22786655]

3. Harkensee C, Oka A, Onizuka M, Middleton PG, Inoko H, Nakaoka H, Gennery AR, Ando K, Morishima Y, Japan Marrow Donor Programme (JMDP). (2013) Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. Immunogenetics, 65 (6): 417-27. [PMID:23474535]

4. Lee KT, Byun MJ, Kang KS, Park EW, Lee SH, Cho S, Kim H, Kim KW, Lee T, Park JE et al.. (2011) Neuronal genes for subcutaneous fat thickness in human and pig are identified by local genomic sequencing and combined SNP association study. PLoS ONE, 6 (2): e16356. [PMID:21311593]

5. Lennon G, Auffray C, Polymeropoulos M, Soares MB. (1996) The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics, 33: 151-152. [PMID:8617505]

6. Martínez-Poveda B, García-Vilas JA, Cárdenas C, Melgarejo E, Quesada AR, Medina MA. (2013) The brominated compound aeroplysinin-1 inhibits proliferation and the expression of key pro- inflammatory molecules in human endothelial and monocyte cells. PLoS ONE, 8 (1): e55203. [PMID:23383109]

7. Nechiporuk T, Urness LD, Keating MT. (2001) ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily. J Biol Chem, 276: 4150-4157. [PMID:11050079]

8. Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL. (2001) From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc. Natl. Acad. Sci. U.S.A., 98 (14): 7934-9. [PMID:11438738]

9. Towner RA, Jensen RL, Colman H, Vaillant B, Smith N, Casteel R, Saunders D, Gillespie DL, Silasi-Mansat R, Lupu F et al.. (2013) ELTD1, a potential new biomarker for gliomas. Neurosurgery, 72 (1): 77-90; discussion 91. [PMID:23096411]

10. Wallgard E, Larsson E, He L, Hellström M, Armulik A, Nisancioglu MH, Genove G, Lindahl P, Betsholtz C. (2008) Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature. Arterioscler. Thromb. Vasc. Biol., 28 (8): 1469-76. [PMID:18483404]

11. Xiao J, Jiang H, Zhang R, Fan G, Zhang Y, Jiang D, Li H. (2012) Augmented cardiac hypertrophy in response to pressure overload in mice lacking ELTD1. PLoS ONE, 7 (5): e35779. [PMID:22606234]

12. Ziegler J, Pody R, Coutinho de Souza P, Evans B, Saunders D, Smith N, Mallory S, Njoku C, Dong Y, Chen H et al.. (2017) ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models. Neuro-oncology, 19 (2): 175-185. [PMID:27416955]

Contributors

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How to cite this page

Gabriela Aust, Tom I. Bonner.
Adhesion Class GPCRs: ADGRL4. Last modified on 25/07/2017. Accessed on 20/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=181.