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ADGRL3

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Target not currently curated in GtoImmuPdb

Target id: 208

Nomenclature: ADGRL3

Family: Adhesion Class GPCRs

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 1447 4q13.1 ADGRL3 adhesion G protein-coupled receptor L3
Mouse 7 1537 5 D-E1 Adgrl3 adhesion G protein-coupled receptor L3
Rat 7 1550 14p21 Adgrl3 adhesion G protein-coupled receptor L3
Previous and Unofficial Names Click here for help
LPHN3 (latrophilin 3) | CIRL3 (calcium-independent receptor of alpha-latrotoxin 3) | LEC3 (Lectomedin-3) | CL3 (CIRL/latrophilin 3)
Database Links Click here for help
Specialist databases
GPCRDB lphn3_human (Hs), agrl3_mouse (Mm), agrl3_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Protein Comments
Extracellular and transmembrane interactors: teneurin-3 [11], FLRT-1, -3 [11], UNC5A [5].
Natural/Endogenous Ligands Click here for help
FLRT3 {Sp: Rat}

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
FLRT3 {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 7.8 pKd 11
pKd 7.8 (Kd 1.47x10-8 M) [11]
Agonist Comments
The interaction between ADGRL3 and FLRT3 is important for the in vivo formation and strength of glutamatergic synaptic inputs in dentate girus granule neurons, but not in CA1 pyramidal neurons.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
G12/G13 family
References:  8
Tissue Distribution Click here for help
Highest expression in brain. Detectable in most tissues, notably placenta and heart
Species:  Human
Technique:  Northern blot
References:  4,14
High expression in brain (all regions) and olfactory gland. Detectable in ovary and testis. Conflicting data regarding expression in lung
Species:  Mouse
Technique:  RT-PCR
References:  3,12
Highest expression in brain (all regions) and lung. Detectable in uterus and spleen. Hardly detectable in olfactory bulb
Species:  Rat
Technique:  Northern blot and RT-PCR
References:  3,9
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
shRNA knockdown of FLRT3 expression
Species:  Rat
Tissue:  Hippocampal culture
Response measured:  Decrease in the number of glutamatergic synapses
References:  11
In vivo knockdown of FLRT3 expression by shRNA
Species:  Mouse
Tissue:  Dentate gyrus
Response measured:  Decrease in the number of glutamatergic synapses
References:  11
Competitive inhibition of ADGRL3-FLRT3 complex by soluble FLRT3-Ig
Species:  Rat
Tissue:  Hippocampal culture
Response measured:  Decrease in the number of glutamatergic synapses
References:  11
Physiological Functions Click here for help
Positive regulation of the number of glutamatergic synapses forming on the dentrites of the dentate gyrus granule cells
Species:  Mouse
Tissue:  Dentate gyrus
References:  11
Xenobiotics Influencing Gene Expression Click here for help
17α-ethynyl estradiol results in increased expression of ADGRL3 mRNA
Species:  Rat
Tissue:  Testis and epididymis
Technique:  Microarray
References:  10
Methylselenic acid increases expression of ADGRL3 mRNA
Species:  Human
Tissue:  Prostate
Technique:  Microarray
References:  15
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  43 intronic SNPs in ADGRL3 are associated with attention deficit/hyperactivity disorder
References:  7
Type:  Single nucleotide polymorphism
Species:  Human
Description:  5 missense (Ala247 -> Ser, Arg465 -> Gln, Asp615 -> Asn, Thr783 -> Met, Leu928 -> Val), 8 synonymous and 8 intronic SNPs in ADGRL3 are associated with attention deficit/hyperactivity disorder
References:  1,13
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNPs rs1947274, rs2345039, rd6551655, and rs6858066 in ADGRL3 are associated with response to methylphenidate treatment in ADHD children
SNP accession: 
References:  6
General Comments
ADGRL3 (formerly LPHN3; latrophilin 3) is a receptor that belongs to Family I Adhesion-GPCRs along with ADGRL1 (latrophilin 1), ADGRL2 (latrophilin 2) and ADGRL4 (ELTD1) [2]. Family I Adhesion-GPCRs have orthologs in vertebrate and invertebrate species.

References

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1. Arcos-Burgos M, Jain M, Acosta MT, Shively S, Stanescu H, Wallis D, Domené S, Vélez JI, Karkera JD, Balog J et al.. (2010) A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol. Psychiatry, 15 (11): 1053-66. [PMID:20157310]

2. 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 (1): 23-33. [PMID:15203201]

3. Haitina T, Olsson F, Stephansson O, Alsiö J, Roman E, Ebendal T, Schiöth HB, Fredriksson R. (2008) Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat. BMC Neurosci, 9: 43. [PMID:18445277]

4. Ichtchenko K, Bittner MA, Krasnoperov V, Little AR, Chepurny O, Holz RW, Petrenko AG. (1999) A novel ubiquitously expressed alpha-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors. J. Biol. Chem., 274 (9): 5491-8. [PMID:10026162]

5. Jackson VA, Mehmood S, Chavent M, Roversi P, Carrasquero M, Del Toro D, Seyit-Bremer G, Ranaivoson FM, Comoletti D, Sansom MS et al.. (2016) Super-complexes of adhesion GPCRs and neural guidance receptors. Nat Commun, 7: 11184. [PMID:27091502]

6. Labbe A, Liu A, Atherton J, Gizenko N, Fortier MÈ, Sengupta SM, Ridha J. (2012) Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD. Am. J. Med. Genet. B Neuropsychiatr. Genet., 159B (7): 776-85. [PMID:22851411]

7. Martinez AF, Muenke M, Arcos-Burgos M. (2011) From the black widow spider to human behavior: Latrophilins, a relatively unknown class of G protein-coupled receptors, are implicated in psychiatric disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet., 156B (1): 1-10. [PMID:21184579]

8. Mathiasen S, Palmisano T, Perry NA, Stoveken HM, Vizurraga A, McEwen DP, Okashah N, Langenhan T, Inoue A, Lambert NA et al.. (2020) G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nat Chem Biol, [Epub ahead of print]. [PMID:32778842]

9. Matsushita H, Lelianova VG, Ushkaryov YA. (1999) The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution. FEBS Lett., 443 (3): 348-52. [PMID:10025961]

10. Naciff JM, Hess KA, Overmann GJ, Torontali SM, Carr GJ, Tiesman JP, Foertsch LM, Richardson BD, Martinez JE, Daston GP. (2005) Gene expression changes induced in the testis by transplacental exposure to high and low doses of 17{alpha}-ethynyl estradiol, genistein, or bisphenol A. Toxicol. Sci., 86 (2): 396-416. [PMID:15901920]

11. O'Sullivan ML, de Wit J, Savas JN, Comoletti D, Otto-Hitt S, Yates 3rd JR, Ghosh A. (2012) FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron, 73 (5): 903-10. [PMID:22405201]

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

13. Ribasés M, Ramos-Quiroga JA, Sánchez-Mora C, Bosch R, Richarte V, Palomar G, Gastaminza X, Bielsa A, Arcos-Burgos M, Muenke M et al.. (2011) Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes Brain Behav., 10 (2): 149-57. [PMID:21040458]

14. Sugita S, Ichtchenko K, Khvotchev M, Südhof TC. (1998) alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis. J. Biol. Chem., 273 (49): 32715-24. [PMID:9830014]

15. Zhang H, Dong Y, Zhao H, Brooks JD, Hawthorn L, Nowak N, Marshall JR, Gao AC, Ip C. (2005) Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer. Cancer Genomics Proteomics, 2 (2): 97-114. [PMID:18548127]

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