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Urocortin

From Wikipedia, the free encyclopedia
UCN
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesUCN,UI, UROC, urocortin
External IDsOMIM:600945;MGI:1276123;HomoloGene:2515;GeneCards:UCN;OMA:UCN - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7349

22226

Ensembl

ENSG00000163794

ENSMUSG00000038676

UniProt

P55089

P81615

RefSeq (mRNA)

NM_003353

NM_021290
NM_001346010

RefSeq (protein)

NP_003344

NP_001332939
NP_067265

Location (UCSC)Chr 2: 27.31 – 27.31 MbChr 5: 31.3 – 31.3 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Urocortinis aproteinthat in humans is encoded by theUCNgene.Urocortin belongs to thecorticotropin-releasing factor(CRF) family of proteins which includesCRF,urotensin I,sauvagine,urocortin IIandurocortin III.Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response.[5][6][7]

Structure, localization, and interactions

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Urocortin is apeptidecomposed of 40amino acids.Urocortin is composed of a singlealpha helixstructure. The humanUCNgene contains two exons, and the entirety of the coding region is contained within the second exon.[5]Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF.[8]Areas of similarity between urocortin and CRF expression include thesupraoptic nucleusand thehippocampus.[9][10]Urocortin is also expressed in areas distinct from CRF expression; these areas notably include themedian eminence,theEdinger-Westphal nucleus,and the sphenoid nucleus.[10]Additionally, Urocortin is expressed in peripheral tissues such as the heart.[11]

Urocortin is known to interact both with theCRF type 1andCRF type 2receptors.[12][13][14]Furthermore, Urocortin is thought to be the primary ligand for the CRF type 2 receptor, as it has higher binding affinity for the CRF type 2 receptor than CRF.[12]Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain.[15]

Stress response and social behavior

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Urocortin is closely related to CRF, which mediates the mammalian stress response. Urocortin is consequently implicated in a number of stress responses, primarily relating to appetite and food intake. Administration of urocortin to the central nervous system of mice and rats has been shown to decrease appetite.[16]Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats.[16]These general anxiety-linked behaviors are likely induced through the CRF type 1 receptor, and the appetite behaviors are likely induced through the CRF type 2 receptor. The reduction in appetite from urocortin treatment could be a result of suppression of gastric emptying and/or hypoglycemia, which have been shown to result from urocortin treatment.[17]Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in thesupraoptic nucleus.[18]

Montane VolesandMeadow Volesare closely related species of voles which are regularly studied as a model for social and mating behavior. The distribution of urocortin-expressing neurons differs in meadow voles compared to montane voles, suggesting urocortin may also play a role in modulating social behavior in some species.[19]

Cardiovascular effects

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Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally.[11]These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in thecardiac atriaand ventricles.[20]Urocortin also functions to protect cardiovascular tissue fromischemicinjury.[21]Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.

In non-mammals

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Urocortin is not present in all non-mammals; the closet analogue inteleostfish is urotensin I.[22]However, in amphibian species such asXenopus laevis,urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin inXenopushas been shown to increasecAMPaccumulation and inhibit appetite[22]

References

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  1. ^abcGRCh38: Ensembl release 89: ENSG00000163794–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000038676–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^abZhao L, Donaldson CJ, Smith GW, Vale WW (May 1998). "The structures of the mouse and human urocortin genes (Ucn and UCN)".Genomics.50(1): 23–33.doi:10.1006/geno.1998.5292.PMID9628819.
  6. ^Tsarev OB (July 1977). "[Dynamics of matrix synthesis in molecular biophysics. II. Principle of insertability and the single-valued solution of feedback tasks]".Biofizika.22(2): 197–200.PMID861256.
  7. ^"Entrez Gene: UCN urocortin".
  8. ^Furman BL (2007-01-01). "Urocortin".XPharm: The Comprehensive Pharmacology Reference.New York: Elsevier. pp. 1–2.doi:10.1016/B978-008055232-3.62835-1.ISBN978-0-08-055232-3.
  9. ^Smagin GN, Heinrichs SC, Dunn AJ (2001). "The role of CRH in behavioral responses to stress".Peptides.22(5): 713–24.CiteSeerX10.1.1.337.3880.doi:10.1016/S0196-9781(01)00384-9.PMID11337084.S2CID15756279.
  10. ^abMorin SM, Ling N, Liu XJ, Kahl SD, Gehlert DR (1999). "Differential distribution of urocortin- and corticotropin-releasing factor-like immunoreactivities in the rat brain".Neuroscience.92(1): 281–91.doi:10.1016/S0306-4522(98)00732-5.PMID10392850.S2CID33000632.
  11. ^abLatchman DS (August 2002). "Urocortin".The International Journal of Biochemistry & Cell Biology.34(8): 907–10.doi:10.1016/S1357-2725(02)00011-0.PMID12007627.
  12. ^abVaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C (November 1995). "Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor".Nature.378(6554): 287–92.Bibcode:1995Natur.378..287V.doi:10.1038/378287a0.PMID7477349.S2CID4373077.
  13. ^Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin".Neuropharmacology.36(10): 1439–46.doi:10.1016/S0028-3908(97)00098-1.PMID9423932.S2CID6235036.
  14. ^Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (May 1996)."Cloning and characterization of human urocortin".Endocrinology.137(5): 2167–70.doi:10.1210/endo.137.5.8612563.PMID8612563.
  15. ^Baigent SM, Lowry PJ (2000)."Urocortin is the principal ligand for the corticotrophin-releasing factor binding protein in the ovine brain with no evidence for a sauvagine-like peptide".Journal of Molecular Endocrinology.24(1): 53–63.doi:10.1677/jme.0.0240053.PMID10656997.
  16. ^abSkelton KH, Owens MJ, Nemeroff CB (2000). "The neurobiology of urocortin".Regulatory Peptides.93(1–3): 85–92.doi:10.1016/S0167-0115(00)00180-4.PMID11033056.S2CID34797789.
  17. ^Stengel A, Taché Y (2014-01-01)."CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress".Frontiers in Neuroscience.8:52.doi:10.3389/fnins.2014.00052.PMC3957495.PMID24672423.
  18. ^Hara Y, Ueta Y, Isse T, Kabashima N, Shibuya I, Hattori Y, Yamashita H (1997). "Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation".Neuroscience Letters.229(1): 65–8.doi:10.1016/S0304-3940(97)00419-9.PMID9224803.S2CID6006767.
  19. ^Lim MM, Tsivkovskaia NO, Bai Y, Young LJ, Ryabinin AE (2006-01-01)."Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain".Brain, Behavior and Evolution.68(4): 229–40.doi:10.1159/000094360.PMC1828133.PMID16816534.
  20. ^Kishimoto T, Pearse RV, Lin CR, Rosenfeld MG (February 1995)."A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle".Proceedings of the National Academy of Sciences of the United States of America.92(4): 1108–12.Bibcode:1995PNAS...92.1108K.doi:10.1073/pnas.92.4.1108.PMC42647.PMID7755719.
  21. ^Brar BK, Jonassen AK, Stephanou A, Santilli G, Railson J, Knight RA, Yellon DM, Latchman DS (March 2000)."Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway".The Journal of Biological Chemistry.275(12): 8508–14.doi:10.1074/jbc.275.12.8508.PMID10722688.
  22. ^abBoorse GC, Crespi EJ, Dautzenberg FM, Denver RJ (November 2005)."Urocortins of the South African clawed frog, Xenopus laevis: conservation of structure and function in tetrapod evolution".Endocrinology.146(11): 4851–60.doi:10.1210/en.2005-0497.PMID16037378.

Further reading

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