ADGRL3 Membrane Protein Introduction

Introduction of ADGRL3

ADGRL3, also known as Calcium-independent alpha-latrotoxin receptor 3 or Latrophilin-3 (LPHN3), is a protein that in human encoded by the ADGRL3 gene. As a member of the latrophilin subfamily of G-protein-coupled receptors (GPCRs), ADGRL3 has seven transmembrane regions as well as large extracellular and intracellular domains.

Basic Information of ADGRL3
Protein Name	Adhesion G protein-coupled receptor L3
Gene Name	ADGRL3
Aliases	Calcium-independent alpha-latrotoxin receptor 3, CIRL-3, Latrophilin-3, Lectomedin-3
Organism	Homo sapiens (Human)
UniProt ID	Q9HAR2
Transmembrane Times	7
Length (aa)	1469
Sequence	MWPSQLLIFMMLLAPIIHAFSRAPIPMAVVRRELSCESYPIELRCPGTDVIMIESANYGRTDDKICDSDP AQMENIRCYLPDAYKIMSQRCNNRTQCAVVAGPDVFPDPCPGTYKYLEVQYECVPYKVEQKVFLCPGLLK GVYQSEHLFESDHQSGAWCKDPLQASDKIYYMPWTPYRTDTLTEYSSKDDFIAGRPTTTYKLPHRVDGTG FVVYDGALFFNKERTRNIVKFDLRTRIKSGEAIIANANYHDTSPYRWGGKSDIDLAVDENGLWVIYATEQ NNGKIVISQLNPYTLRIEGTWDTAYDKRSASNAFMICGILYVVKSVYEDDDNEATGNKIDYIYNTDQSKD SLVDVPFPNSYQYIAAVDYNPRDNLLYVWNNYHVVKYSLDFGPLDSRSGQAHHGQVSYISPPIHLDSELE RPSVKDISTTGPLGMGSTTTSTTLRTTTLSPGRSTTPSVSGRRNRSTSTPSPAVEVLDDMTTHLPSASSQ IPALEESCEAVEAREIMWFKTRQGQIAKQPCPAGTIGVSTYLCLAPDGIWDPQGPDLSNCSSPWVNHITQ KLKSGETAANIARELAEQTRNHLNAGDITYSVRAMDQLVGLLDVQLRNLTPGGKDSAARSLNKLQKRERS CRAYVQAMVETVNNLLQPQALNAWRDLTTSDQLRAATMLLHTVEESAFVLADNLLKTDIVRENTDNIKLE VARLSTEGNLEDLKFPENMGHGSTIQLSANTLKQNGRNGEIRVAFVLYNNLGPYLSTENASMKLGTEALS TNHSVIVNSPVITAAINKEFSNKVYLADPVVFTVKHIKQSEENFNPNCSFWSYSKRTMTGYWSTQGCRLL TTNKTHTTCSCNHLTNFAVLMAHVEVKHSDAVHDLLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDRN TIHKNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFESEHSRR KYFYLVGYGMPALIVAVSAAVDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIMLNVIFLGIALYKMFHHT AILKPESGCLDNINYEDNRPFIKSWVIGAIALLCLLGLTWAFGLMYINESTVIMAYLFTIFNSLQGMFIF IFHCVLQKKVRKEYGKCLRTHCCSGKSTESSIGSGKTSGSRTPGRYSTGSQSRIRRMWNDTVRKQSESSF ITGDINSSASLNREGLLNNARDTSVMDTLPLNGNHGNSYSIASGEYLSNCVQIIDRGYNHNETALEKKIL KELTSNYIPSYLNNHERSSEQNRNLMNKLVNNLGSGREDDAIVLDDATSFNHEESLGLELIHEESDAPLL PPRVYSTENHQPHHYTRRRIPQDHSESFFPLLTNEHTEDLQSPHRDSLYTSMPTLAGVAATESVTTSTQT EPPPAKCGDAEDVYYKSMPNLGSRNHVHQLHTYYQLGRGSSDGFIVPPNKDGTPPEGSSKGPAHLVTSL

Function of ADGRL3 Membrane Protein

As a member of the latrophilin subfamily of G-protein-coupled receptors (GPCRs) which contains very large N-terminal, ADGRL3 is only expressed almost exclusively in the brain and mostly is highly expressed in regions neurophysiologically associated with the pathology of attention-deficit/hyperactivity disorder (ADHD). It has been reported that ADGRL3 could act as a chimera between cell surface receptors and intracellular signaling molecules. Recently, studies have shown that the ADGRL3 and its ligand-FLRT3 partnership play an important role in glutamatergic synapse development. What’s more, gene ontology pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse, are overrepresented when ADGRL3 variants associated with ADHD are tested. It indicates that there is an association between ADGRL3 and ADHD pathophysiology.

Fig.1 Diagram of LPHN3/FLRT3/UNC5D/Ten2 at a cellular junction. (Lu, et.al. 2015)

Application of ADGRL3 Membrane Protein in Literature

1. Martinez AF., et.al. An ultraconserved brain-specific enhancer within ADGRL3 (LPHN3) underpins attention-deficit/hyperactivity disorder susceptibility. Biological psychiatry. 2016, 80(12): 943-54. PubMed ID: 27692237

This article suggests that there is an association between rs2271338 and reduced ADGRL3 expression in the thalamus. It provides the first functional evidence of common noncoding variants with potential implications for the pathology of attention-deficit/hyperactivity disorder.

2. Acosta MT., et.al. ADGRL 3 (LPHN 3) variants are associated with a refined phenotype of ADHD in the MTA study. Molecular genetics & genomic medicine. 2016, 4(5): 540-7. PubMed ID: 5023939

This article provides evidence that there is an association between ADGRL3 and attention-deficit/hyperactivity disorder. Exploring genetic effects in longitudinal cohorts, in which refined, age-dependent phenotypes are documented, is crucial to understand the natural history of attention-deficit/hyperactivity disorder.

3. Ribases Á., et.al. Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes, Brain ,and Behavior. 2011, 10(2): 149-57. PubMed ID: 21040458

This article suggests that the LPHN3 could contribute to combined type attention-deficit/hyperactivity disorder (ADHD), and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan.

ADGRL3 Preparation Options

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Reference

Lu, et al. (2015). Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion. Structure, 23(9), 1678-1691.

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