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ADGRF5

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Target not currently curated in GtoImmuPdb

Target id: 196

Nomenclature: ADGRF5

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 1346 6p12.3 ADGRF5 adhesion G protein-coupled receptor F5 11
Mouse 7 1348 17 B3 Adgrf5 adhesion G protein-coupled receptor F5 13
Rat 7 1349 9q13 Adgrf5 adhesion G protein-coupled receptor F5 1
Previous and Unofficial Names Click here for help
GPR116 (G protein-coupled receptor 116) | Ig-Hepta | KIAA0758
Database Links Click here for help
Specialist databases
GPCRDB agrf5_human (Hs), agrf5_rat (Rn)
Other databases
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Endogenous agonists
Peptides derived from the Stachel sequence: TSFSILMSPDSPD  [5]
Agonist Comments
Peptides derived from the Stachel sequence: TSFSILMSPDSPD has agonist activity [5].
Immuno Process Associations
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0048821 erythrocyte development IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0043031 negative regulation of macrophage activation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes, IEA only
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GO:0043031 negative regulation of macrophage activation IEA
GO:0048821 erythrocyte development IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0043031 negative regulation of macrophage activation IEA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
References:  3,5,9,15
Tissue Distribution Click here for help
Unigene expression profile gives high normalized expression and multiple ESTs in thyroid, placenta, uterus, spleen, stomach, lung, kidney, brain, connective tissue, heart, eye, liver, muscle, pancreas, pharynx, testis.
Species:  Human
Technique: 
References: 
KIAA0758 highest in lung and kidney, then heart ovary, brain and skeletal muscle
Species:  Human
Technique:  RT-PCR.
References:  11
Endothelium, lung epithelium and lung adenocarcinoma cells
Species:  Human
Technique:  RT-PCR
References:  4,16
Embryonic kidney (glomeruli) and E18.5 brain microvessels
Species:  Mouse
Technique:  in situ hydridisation and RT-PCR
References:  8,16
Lung, liver, heart, kidney, testis, spleen, bonemarrow, skin, ovaries, thymus, adrenal gland
Species:  Mouse
Technique:  RT-PCR
References:  14
Mature adipocytes, stromal vascular cells
Species:  Mouse
Technique:  RT-PCR
References:  12
Very high expression in lung (alveolar walls); weak but detectable expression in kidney (cortex) and heart
Species:  Rat
Technique:  Northern blot and immunohistochemistry
References:  1
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
ADGRF5 couples to Gq proteins in COS-7 cells.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in IP1.
References:  5
Physiological Functions Click here for help
Skin barrier assay
Species:  Mouse
Tissue:  Skin
References:  14
Physiological Consequences of Altering Gene Expression Click here for help
Adipose-specific knockout mice showed a phenotype of exacerbated glucose intolerance and insulin resistance, hyperlipidemia, ectopic lipid accumulation, reduced adipocyte size, disregulated adipokine expression in adipocytes.
Species:  Mouse
Tissue:  Tissue/cell-type specific expression (Fabp4 promotor-driven)
Technique:  Gene knockouts
References:  12
ADGRF5 deficiency leads to dysregulation of the lung surfactant homeostasis.
Species:  None
Tissue: 
Technique: 
References:  2,7,17
General Comments
ADGRF5 (formerly GPR116) is an orphan receptor that belongs to Family VI Adhesion-GPCRs together with ADGRF1-4 and 6 [6]. 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 [14].

Full coding sequence human cDNA is publicly available, IMAGE:5298732 [10] in pBluescript vector. This clone has two known amino acid changing polymorphisms, rs586024 and rs547499. The Met604 and Thr856 alleles in this clone are both the more common allele in Europeans and Asians but the less common allele in sub-Saharan Africans. The N terminus of ADGRF5 contains a GPCR proteolysis site (GPS), up to three immunoglobuline-like (Ig) domains and a SEA (Sperm protein, Enterokinase and Agrin) domain. There are numerous transcript variants and the domain architecture and C terminus structure can vary between transcript variants [9].

References

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1. Abe J, Suzuki H, Notoya M, Yamamoto T, Hirose S. (1999) Ig-hepta, a novel member of the G protein-coupled hepta-helical receptor (GPCR) family that has immunoglobulin-like repeats in a long N-terminal extracellular domain and defines a new subfamily of GPCRs. J Biol Chem, 274 (28): 19957-64. [PMID:10391944]

2. Bridges JP, Ludwig MG, Mueller M, Kinzel B, Sato A, Xu Y, Whitsett JA, Ikegami M. (2013) Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. Am J Respir Cell Mol Biol, 49 (3): 348-57. [PMID:23590306]

3. Brown K, Filuta A, Ludwig MG, Seuwen K, Jaros J, Vidal S, Arora K, Naren AP, Kandasamy K, Parthasarathi K et al.. (2017) Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling. JCI Insight, 2 (11). [PMID:28570277]

4. Davidson B, Stavnes HT, Risberg B, Nesland JM, Wohlschlaeger J, Yang Y, Shih IeM, Wang TL. (2012) Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions. Hum Pathol, 43 (5): 684-94. [PMID:21937081]

5. 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]

6. 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]

7. Fukuzawa T, Ishida J, Kato A, Ichinose T, Ariestanti DM, Takahashi T, Ito K, Abe J, Suzuki T, Wakana S et al.. (2013) Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PLoS ONE, 8 (7): e69451. [PMID:23922714]

8. He L, Sun Y, Patrakka J, Mostad P, Norlin J, Xiao Z, Andrae J, Tryggvason K, Samuelsson T, Betsholtz C et al.. (2007) Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis. Kidney Int, 71 (9): 889-900. [PMID:17332733]

9. Knierim AB, Röthe J, Çakir MV, Lede V, Wilde C, Liebscher I, Thor D, Schöneberg T. (2019) Genetic basis of functional variability in adhesion G protein-coupled receptors. Sci Rep, 9 (1): 11036. [PMID:31363148]

10. Lennon G, Auffray C, Polymeropoulos M, Soares MB. (1996) The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics, 33 (1): 151-2. [PMID:8617505]

11. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O. (1998) Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res, 5: 277-286. [PMID:9872452]

12. Nie T, Hui X, Gao X, Li K, Lin W, Xiang X, Ding M, Kuang Y, Xu A, Fei J et al.. (2012) Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function. FEBS Lett, 586 (20): 3618-25. [PMID:22971422]

13. Okazaki N, F-Kikuno R, Ohara R, Inamoto S, Koseki H, Hiraoka S, Saga Y, Seino S, Nishimura M, Kaisho T et al.. (2004) Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. DNA Res, 11 (3): 205-18. [PMID:15368895]

14. 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]

15. Tang X, Jin R, Qu G, Wang X, Li Z, Yuan Z, Zhao C, Siwko S, Shi T, Wang P et al.. (2013) GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway. Cancer Res, 73 (20): 6206-18. [PMID:24008316]

16. Wallgard E, Larsson E, He L, Hellström M, Armulik A, Nisancioglu MH, Genove G, Lindahl P, Betsholtz C. (2008) Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature. Arterioscler Thromb Vasc Biol, 28 (8): 1469-76. [PMID:18483404]

17. Yang MY, Hilton MB, Seaman S, Haines DC, Nagashima K, Burks CM, Tessarollo L, Ivanova PT, Brown HA, Umstead TM et al.. (2013) Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell Rep, 3 (5): 1457-64. [PMID:23684610]

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