Protein-coding gene in the species Homo sapiens
| HCAR1 |
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| Identifiers |
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| Aliases | HCAR1, GPR104, GPR81, HCA1, LACR1, TA-GPCR, TAGPCR, FKSG80, hydroxycarboxylic acid receptor 1 |
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| External IDs | OMIM: 606923 MGI: 2441671 HomoloGene: 13060 GeneCards: HCAR1 |
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| Gene location (Human) |
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 | | Chr. | Chromosome 12 (human)[1] |
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| | Band | 12q24.31 | Start | 122,726,076 bp[1] |
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| End | 122,730,844 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | Chromosome 5 (mouse)[2] |
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| | Band | 5|5 F | Start | 124,014,799 bp[2] |
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| End | 124,018,083 bp[2] |
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| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - spleen
- minor salivary glands
- body of stomach
- subcutaneous adipose tissue
- stromal cell of endometrium
- right lobe of thyroid gland
- left lobe of thyroid gland
- ganglionic eminence
- kidney
- canal of the cervix
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| | Top expressed in | - brown adipose tissue
- white adipose tissue
- mammary gland
- subcutaneous adipose tissue
- esophagus
- lacrimal gland
- aorta
- stomach
- visual cortex
- dermis
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| | More reference expression data |
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| BioGPS |  | | More reference expression data |
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| Gene ontology |
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| Molecular function | - G protein-coupled receptor activity
- signal transducer activity
| | Cellular component | - integral component of membrane
- plasma membrane
- membrane
| | Biological process | - signal transduction
- G protein-coupled receptor signaling pathway
| | Sources:Amigo / QuickGO |
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| Orthologs |
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| Species | Human | Mouse |
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| Entrez | | |
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| Ensembl | | |
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| UniProt | | |
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| RefSeq (mRNA) | | |
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| RefSeq (protein) | | |
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| Location (UCSC) | Chr 12: 122.73 – 122.73 Mb | Chr 5: 124.01 – 124.02 Mb |
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| PubMed search | [3] | [4] |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
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Hydroxycarboxylic acid receptor 1 (HCA1), formerly known as G protein-coupled receptor 81 (GPR81), is a protein that in humans is encoded by the HCAR1 gene.[5][6] HCA1, like the other hydroxycarboxylic acid receptors HCA2 and HCA3, is a Gi/o-coupled G protein-coupled receptor (GPCR).[7][8] The primary endogenous agonist of HCA1 is lactic acid (and its conjugate base, lactate).[7][8] More recently, 3,5-dihydroxybenzoic acid has been reported to activate HCA1.[9]
Lactate was initially found to activate HCA1 on fat cells and thereby to inhibit these cells lipolysis i.e., break-down of their fats into free fatty acids and glycerol.[10][11] Subsequent studies have found that in addition to fat cells, HCA1 is expressed on cells in the brain, skeletal muscle, lymphoid tissue, uterus, kidney, liver, and pancreas as well as on immune cells such as macrophages and antigen-presenting cells. In the brain, HCA1 acts to dampen neuron excitation and may also function to promote neurogenesis (i.e., production of neurons from neural stem cells) and angiogenesis, i.e., formation of new blood vessels from pre-existing blood vessels). The functions of HCA1 in non-fat and non-neural tissues have not been fully defined but in many cases appear to involve promoting the survival of cells, including various types of cancer cells.[12]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000196917 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049241 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: GPR81 G protein-coupled receptor 81".
- ^ Lee DK, Nguyen T, Lynch KR, Cheng R, Vanti WB, Arkhitko O, Lewis T, Evans JF, George SR, O'Dowd BF (September 2001). "Discovery and mapping of ten novel G protein-coupled receptor genes". Gene. 275 (1): 83–91. doi:10.1016/S0378-1119(01)00651-5. PMID 11574155.
- ^ a b Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP (June 2011). "International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)". Pharmacological Reviews. 63 (2): 269–90. doi:10.1124/pr.110.003301. PMID 21454438.
- ^ a b S Offermanns, SL Colletti, AP IJzerman, TW Lovenberg, G Semple, A Wise, MG Waters. "Hydroxycarboxylic acid receptors". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018.
{{cite web}}: CS1 maint: multiple names: authors list (link) - ^ Wagner W, Sobierajska K, Pułaski Ł, Stasiak A, Ciszewski WM (April 2023). "Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations". Critical Reviews in Food Science and Nutrition: 1–19. doi:10.1080/10408398.2023.2203762. PMID 37096487. S2CID 258310985.
- ^ Liu C, Wu J, Zhu J, Kuei C, Yu J, Shelton J, Sutton SW, Li X, Yun SJ, Mirzadegan T, Mazur C, Kamme F, Lovenberg TW (January 2009). "Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81". The Journal of Biological Chemistry. 284 (5): 2811–22. doi:10.1074/jbc.M806409200. PMID 19047060.
- ^ Cai TQ, Ren N, Jin L, Cheng K, Kash S, Chen R, Wright SD, Taggart AK, Waters MG (December 2008). "Role of GPR81 in lactate-mediated reduction of adipose lipolysis". Biochemical and Biophysical Research Communications. 377 (3): 987–91. doi:10.1016/j.bbrc.2008.10.088. PMID 18952058.
- ^ Colucci AC, Tassinari ID, Loss ED, de Fraga LS (June 2023). "History and Function of the Lactate Receptor GPR81/HCAR1 in the Brain: A Putative Therapeutic Target for the Treatment of Cerebral Ischemia". Neuroscience. 526: 144–163. doi:10.1016/j.neuroscience.2023.06.022. PMID 37391123. S2CID 259279124.
Further reading
- Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters. 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878. S2CID 7116392.
- Mao M, Biery MC, Kobayashi SV, Ward T, Schimmack G, Burchard J, Schelter JM, Dai H, He YD, Linsley PS (June 2004). "T lymphocyte activation gene identification by coregulated expression on DNA microarrays". Genomics. 83 (6): 989–99. doi:10.1016/j.ygeno.2003.12.019. PMID 15177553.
- Madaan A, Nadeau-Vallée M, Rivera JC, Obari D, Hou X, Sierra EM, Girard S, Olson DM, Chemtob S (September 2016). "Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1)". American Journal of Obstetrics and Gynecology. 216 (1): 60.e1–60.e17. doi:10.1016/j.ajog.2016.09.072. PMID 27615440.
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