Nomenclature: LPHN3

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 1447 4q13.1 LPHN3 latrophilin 3
Mouse 7 1537 5 D-E1 Lphn3 latrophilin 3
Rat 7 1550 14p21 Lphn3 latrophilin 3
Previous and Unofficial Names
KIAA0768
latrophilin 3
Lectomedin-3
CIRL3
calcium-independent alpha-latrotoxin receptor homolog 3
LEC3
lectomedin-3
Latrophilin-3
calcium-independent α-latrotoxin receptor 3
CIRL-3
lectomedin 3
5430402I23Rik
D130075K09Rik
calcium-independent of α-latrotoxin 3
CIRL/latrophilin 3
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
FLRT3 {Sp: Rat} Rn Full agonist 7.8 pKd 9
pKd 7.8 (Kd 1.47x10-8 M) [9]
Agonist Comments
The interaction between latrophilin-3 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.
Tissue Distribution
Highest expression in brain. Detectable in most tissues, notably placenta and heart
Species:  Human
Technique:  Northern blot
References:  4,12
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:  3,10
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:  3,7
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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Functional Assays
Competitive inhibition of LPH3-FLRT3 complex by soluble FLRT3-Ig
Species:  Rat
Tissue:  Hippocampal culture
Response measured:  Decrease in the number of glutamatergic synapses
References:  9
shRNA knockdown of FLRT3 expression
Species:  Rat
Tissue:  Hippocampal culture
Response measured:  Decrease in the number of glutamatergic synapses
References:  9
In vivo knockdown of FLRT3 expression by shRNA
Species:  Mouse
Tissue:  Dentate gyrus
Response measured:  Decrease in the number of glutamatergic synapses
References:  9
Physiological Functions
Positive regulation of the number of glutamatergic synapses forming on the dentrites of the dentate gyrus granule cells
Species:  Mouse
Tissue:  Dentate gyrus
References:  9
Xenobiotics Influencing Gene Expression
17α-ethynyl estradiol results in increased expression of LPHN3 mRNA
Species:  Rat
Tissue:  Testis and epididymis
Technique:  Microarray
References:  8
Methylselenic acid increases expression of LPHN3 mRNA
Species:  Human
Tissue:  Prostate
Technique:  Microarray
References:  13
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  43 intronic SNPs in LPHN3 are associated with attention deficit/hyperactivity disorder
References:  6
Type:  Single nucletide polymorphism
Species:  Human
Description:  SNPs rs1947274, rs2345039, rd6551655, and rs6858066 in LPHN3 are associated with response to methylphenidate treatment in ADHD children
SNP accession: 
References:  5
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 LPHN3 are associated with attention deficit/hyperactivity disorder
References:  1,11
General Comments
LPHN3 (latrophilin 3) is a receptor that belongs to Family I Adhesion-GPCRs along with latrophilin 1, latrophilin 2 and ELTD1 [2]. Family I Adhesion-GPCRs have orthologs in vertebrate and invertebrate species.

REFERENCES

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. Psychiatry15 (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. Genomics84: 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 Neurosci9: 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. 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]

6. 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]

7. 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]

8. 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]

9. 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. Neuron73 (5): 903-10. [PMID:22405201]

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

11. 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]

12. 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]

13. 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 Proteomics2 (2): 97-114. [PMID:18548127]

To cite this database page, please use the following:

Yuri Ushkaryov, Tobias Langenhan, Tom I. Bonner.
Adhesion Class GPCRs: LPHN3. Last modified on 23/07/2013. Accessed on 25/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=208.

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