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ADGRF1

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Target id: 190

Nomenclature: ADGRF1

Family: Adhesion Class GPCRs

Contents:

Gene and Protein Information Click here for help
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 910 6p12.3 ADGRF1 adhesion G protein-coupled receptor F1 3
Mouse 7 908 17 B3 Adgrf1 adhesion G protein-coupled receptor F1
Rat 7 909 9q12 Adgrf1 adhesion G protein-coupled receptor F1
Previous and Unofficial Names Click here for help
GPR110 (G protein-coupled receptor 110) | PGR19
Database Links Click here for help
Specialist databases
GPCRdb agrf1_human (Hs), agrf1_mouse (Mm)
Other databases
Alphafold Q5T601 (Hs), Q8VEC3 (Mm)
CATH/Gene3D 3.30.70.960
ChEMBL Target CHEMBL4523872 (Hs)
Ensembl Gene ENSG00000153292 (Hs), ENSMUSG00000041293 (Mm), ENSRNOG00000062544 (Rn)
Entrez Gene 266977 (Hs), 77596 (Mm), 301266 (Rn)
Human Protein Atlas ENSG00000153292 (Hs)
KEGG Gene hsa:266977 (Hs), mmu:77596 (Mm), rno:301266 (Rn)
Pharos Q5T601 (Hs)
RefSeq Nucleotide NM_153840 (Hs), NM_133776 (Mm)
RefSeq Protein NP_722582 (Hs), NP_598537 (Mm)
UniProtKB Q5T601 (Hs), Q8VEC3 (Mm)
Wikipedia ADGRF1 (Hs)
Endogenous agonists
Peptides derived from the Stachel sequence TSFSILMSPFVPSTIFPVVKWIT  [1,8]
Agonist Comments
N-docosahexaenoylethanolamine (synaptamide) is an ADGRF1 agonist [5], as are peptides derived from the Stachel sequence TSFSILMSPFVPSTIFPVVKWIT [1,8].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
References:  1,5
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
References:  1,8
Tissue Distribution Click here for help
Unigene expression profile: high frequency in trachea, mouth, kidney, lung, prostate.
Species:  Human
Technique: 
References: 
Kidney and prostate, overexpressed in lung and prostate tumors, present in lung cancer cell lines (A549, H460, H23) and the prostate cell line PC-3
Species:  Human
Technique:  RT-PCR and immunohistochemistry
References:  6
Peripheral blood cells/bone marrow of pediatric B-precursor acute lymphoblastic leukemia patients
Species:  Human
Technique:  Microarray analysis
References:  4
Spleen, T lymphomas
Species:  Mouse
Technique:  RT-PCR
References:  6
Liver, kidney (renal pelvis), adrenal gland
Species:  Mouse
Technique:  RT-PCR and LacZ insertion
References:  7
Unigene expression profile: high frequency in the eye.
Species:  Rat
Technique: 
References: 
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
ADGRF1 couples to Gs proteins in COS-7 cells and neural stem cells, as determined by Alpha screen assay, cAMP measurement and GTPγS binding.
Species:  None
Tissue:  COS-7 cells, neural stem cells.
Response measured: 
References:  1,5
ADGRF1 couples to Gq proteins as determined by GTPγS binding assay and IP1 assay.
Species:  None
Tissue: 
Response measured: 
References:  1,8
General Comments
ADGRF1 (formerly GPR110) is an orphan receptor that belongs to Family VI Adhesion-GPCRs together with ADGRF2-5 (formerly GPR111, GPR113, GPR115 and GPR116 respectively) [2]. The genes of Family VI Adhesion-GPCRs except ADGRF3 are syntenically clustered on human chromosome 6 and mouse chromosome 17 suggesting the evolution from an ancestral gene through gene duplication and exon shuffling [7]. The N terminus of ADGRF1 contains a GPCR proteolysis site (GPS) and a SEA (Sperm protein, Enterokinase and Agrin) domain. ADGRF1 is a receptor for N-docosahexaenoylethanolamine (synaptamide), an endogenous metabolite of docosahexaenoic acid, that potently promotes neurogenesis, neuritogenesis and synaptogenesis. ADGRF1 knockout mice show significant deficits in object recognition and spatial memory [5].

References

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1. Demberg LM, Winkler J, Wilde C, Simon KU, Schön J, Rothemund S, Schöneberg T, Prömel S, Liebscher I. (2017) Activation of Adhesion G Protein-coupled Receptors: AGONIST SPECIFICITY OF STACHEL SEQUENCE-DERIVED PEPTIDES. J Biol Chem, 292 (11): 4383-4394. [PMID:28154189]

2. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun, 301 (3): 725-34. [PMID:12565841]

3. Fredriksson R, Lagerström MC, Höglund PJ, Schiöth HB. (2002) Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions. FEBS Lett, 531 (3): 407-14. [PMID:12435584]

4. Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, Chen IM, Atlas SR, Kang H, Ar K et al.. (2010) Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood, 116 (23): 4874-84. [PMID:20699438]

5. Lee JW, Huang BX, Kwon H, Rashid MA, Kharebava G, Desai A, Patnaik S, Marugan J, Kim HY. (2016) Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function. Nat Commun, 7: 13123. [PMID:27759003]

6. Lum AM, Wang BB, Beck-Engeser GB, Li L, Channa N, Wabl M. (2010) Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer. BMC Cancer, 10: 40. [PMID:20149256]

7. Prömel S, Waller-Evans H, Dixon J, Zahn D, Colledge WH, Doran J, Carlton MB, Grosse J, Schöneberg T, Russ AP et al.. (2012) Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev Dyn, 241 (10): 1591-602. [PMID:22837050]

8. Stoveken HM, Hajduczok AG, Xu L, Tall GG. (2015) Adhesion G protein-coupled receptors are activated by exposure of a cryptic tethered agonist. Proc Natl Acad Sci USA, 112 (19): 6194-9. [PMID:25918380]

Contributors

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