ADGRL2 (adhesion G protein-coupled receptor L2 )

2003-11-01   Jim Heighway 

Roy Castle International Centre for Lung Cancer Research, Liverpool, UK

Identity

HGNC
LOCATION
1p31.1
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CIRL2,CL2,LEC1,LPHH1,LPHN2
FUSION GENES

DNA/RNA

Atlas Image
Representation of the genomic structure of LPHH1. Black blocks represent core exons which are present in the majority of gene transcripts. The yellow blocks represent alternatively spliced coding exons which may be incorporated variably in transcripts derived from different cell types/tissues or as a consequence of differing cellular states. The red boxes represent the presence of multiple, in some cases tissue-specific, leader exons that have been identified for this gene, an observation consistent with the existence of multiple dispersed promoter elements. The most variably spliced region of the coding sequence was the carboxy-terminal domain D.

Description

LPHH1 consists of 19 commonly used coding exons. A further seven exons have been identified which may be alternatively spliced into the core backbone with variable frequencies and tissue specificities. At least a number of these additional exons are highly conserved in mammalian species. The core exons (ATG, exon 1 to stop, exon 19) span a region of about 154kb. However, the 5end of the gene is not precisely defined with transcripts in different tissues apparently initiating from specific locations over an extensive region. The most distant leader exon identified (foetal lung) lies approximately 390kb from exon 1 which makes the total size of the gene at least 550kb.

Transcription

Expression has been observed by RT-PCR in all normal tissues and lines tested with the clear exception of lymphocytes and lymphoblastoid cells. Strongest expression was observed in foetal lung, normal adult lung and thyroid. Alternative splicing to some degree in at least one domain (minimally the carboxy-terminal domain D) was seen in each tissue and line examined with human brain showing a characteristic pattern and additional variability in the other three coding sequence domains.

Pseudogene

No known pseudogene.

Proteins

Atlas Image
Alternative splicing in domain D dramatically alters the structure of the carboxy-terminus of the encoded protein, latrophilin 2. Variable splicing in this region occurs in all tissues and cell lines tested.

Description

LPHH1 encodes a putative seven-span transmembrane receptor with atypically large extra membrane N (predicted to be extra-cellular) and C termini. In addition to the seven hydrophobic membrane spanning domains, a putative lectin-like region is present near the N-terminus.

Expression

Protein likely to be ubiquitously expressed in adherent cells but that has not so far been confirmed. Human brain-specific alternative splices alter the structure of the extra-membrane, intra-cellular loop between TM domains 5 and 6, a region thought to be critical for G-protein/receptor interactions.

Localisation

Likely to be plasma membrane.

Function

Likely role in coupling cell adhesion to cell signalling.

Homology

Latrophilin 2 is part of a small sub-family of 7TMs which includes latrophilins 1 and 3. Latrophilin 1 is the receptor for Black Widow spider toxin: -latrotoxin.

Mutations

Note

None reported.

Implicated in

Entity name
Breast carcinoma
Note
Analysis of breast cancer cell lines has demonstrated dramatic differences in transcript levels between certain lines. In one case, strong expression was allelically imbalanced.
Entity name
Lung carcinoma
Note
strong expression in normal lung was reduced in 55% (35/64) of matched primary non-small cell lung carcinomas (NSCLC). Over-representation was not scored in any tumour, nor in any lung cancer cell line tested and transcript was undetectable by RT-PCR in one line (1/15) and very low in a further two. Loss of heterozygosity was scored in 8/16 informative NSCLC lesions. Primary and SCLC lines showed a characteristic pattern of alternative splicing.

Bibliography

Pubmed IDLast YearTitleAuthors
109946492000A family of heptahelical receptors with adhesion-like domains: a marriage between two super families.Hayflick JS et al
107605722000Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines.White GR et al

Other Information

Locus ID:

NCBI: 23266
MIM: 607018
HGNC: 18582
Ensembl: ENSG00000117114

Variants:

dbSNP: 23266
ClinVar: 23266
TCGA: ENSG00000117114
COSMIC: ADGRL2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000117114ENST00000319517O95490
ENSG00000117114ENST00000359929O95490
ENSG00000117114ENST00000370713O95490
ENSG00000117114ENST00000370715O95490
ENSG00000117114ENST00000370717O95490
ENSG00000117114ENST00000370721B1ALU1
ENSG00000117114ENST00000370723O95490
ENSG00000117114ENST00000370725O95490
ENSG00000117114ENST00000370727B1ALU3
ENSG00000117114ENST00000370728O95490
ENSG00000117114ENST00000370730O95490
ENSG00000117114ENST00000402328H0Y3V3
ENSG00000117114ENST00000449420H0Y5C0
ENSG00000117114ENST00000627151B1ALU3

Expression (GTEx)

0
10
20
30
40
50
60
70
80

References

Pubmed IDYearTitleCitations
303405422018A de novo variant in ADGRL2 suggests a novel mechanism underlying the previously undescribed association of extreme microcephaly with severely reduced sulcation and rhombencephalosynapsis.2

Citation

Jim Heighway

ADGRL2 (adhesion G protein-coupled receptor L2 )

Atlas Genet Cytogenet Oncol Haematol. 2003-11-01

Online version: http://atlasgeneticsoncology.org/gene/313/adgrl2