PTHR1
(Preusmjereno sa PTH1R)
Paratiroidnom hormonu srodni peptidni receptor paratiroidnog hormona, znan i kao receptor 1 paratiroidnog hormona (PTH1R), jest protein koji je kod ljudi kodiran genom PTH1R sa hromosoma 3. PTH1R funkcionira kao receptor za paratiroidni hormon (PTH) i za proteine povezane s paratiroidnim hormonom (protein povezan s paratiroidnim hormonom (PTHrP), koji se također naziva paratiroidnohormonoliki hormon (PTHLH).
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 593 aminokiseline, а molekulska težina 66.361 Da.[5]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGTARIAPGL | ALLLCCPVLS | SAYALVDADD | VMTKEEQIFL | LHRAQAQCEK | ||||
| RLKEVLQRPA | SIMESDKGWT | SASTSGKPRK | DKASGKLYPE | SEEDKEAPTG | ||||
| SRYRGRPCLP | EWDHILCWPL | GAPGEVVAVP | CPDYIYDFNH | KGHAYRRCDR | ||||
| NGSWELVPGH | NRTWANYSEC | VKFLTNETRE | REVFDRLGMI | YTVGYSVSLA | ||||
| SLTVAVLILA | YFRRLHCTRN | YIHMHLFLSF | MLRAVSIFVK | DAVLYSGATL | ||||
| DEAERLTEEE | LRAIAQAPPP | PATAAAGYAG | CRVAVTFFLY | FLATNYYWIL | ||||
| VEGLYLHSLI | FMAFFSEKKY | LWGFTVFGWG | LPAVFVAVWV | SVRATLANTG | ||||
| CWDLSSGNKK | WIIQVPILAS | IVLNFILFIN | IVRVLATKLR | ETNAGRCDTR | ||||
| QQYRKLLKST | LVLMPLFGVH | YIVFMATPYT | EVSGTLWQVQ | MHYEMLFNSF | ||||
| QGFFVAIIYC | FCNGEVQAEI | KKSWSRWTLA | LDFKRKARSG | SSSYSYGPMV | ||||
| SHTSVTNVGP | RVGLGLPLSP | RLLPTATTNG | HPQLPGHAKP | GTPALETLET | ||||
| TPPAMAAPKD | DGFLNGSCSG | LDEEASGPER | PPALLQEEWE | TVM |
Funkcija[uredi | uredi izvor]
Ovaj "klasični" PTH-receptor eksprimiran je u visokim nivoima u kostima i bubrezima i regulira homeostazu kalcijskih iona, putem aktivacije adenilat-ciklaze i fosfolipaze C.[6][7] U kostima eksprimira se na površini osteoblasta. Kada se receptor aktivira preko PTH vezivanja, osteoblasti eksprimiraju RANKL (receptor aktivator kB liganda jedarnog faktora), koji se vezuje za RANK (receptor aktivator jedarnog faktora kB) na osteoklastima. Ovo uključuje osteoklaste, kako bi se na kraju povećala stopa resorpcije.
Mehanizam[uredi | uredi izvor]
PTH1R je član porodice sekretina G-protein spregnutih receptora. Aktivnost ovog receptora je posredovana Gs G-proteinia, koji aktiviraju adenilil-ciklazu. Osim toga, također aktiviraju sistem fosfatidilinozitol-kalcijskog drugog glasnika.
Klinički značaj[uredi | uredi izvor]
Poznato je da su defekti ovog receptora uzrok Jansenove metafizne hondrodisplazije (JMC) i Blomstrandove hondrodisplazije tipa (BOCD), kao i endohromatoze[8] i primarnog nedostatka nicanja zuba.[9]
Interakcije[uredi | uredi izvor]
Pokazalo se da receptor paratiroidnog hormona 1 ima interakcije sa regulatornim kofaktorom izmjene natrijum-vodik 2[10] i regulatorom 1 natrij-vodik antiportera 3.[10]
Modelni organizmi[uredi | uredi izvor]
U proučavanju funkcije PTH1R korišteni su i modelni organizam. Uslovna linija nokaut-miševa pod nazivom Pth1r tm1a(EUCOMM)Hmgu generirana je i Institut Wellcome Trust Sanger.[11] Mužjaci i ženke uključeni su u standardno fenotipsko snimanje[12] za otkrivanje efekata delecija.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping[17]
| Svojstvo | Fenotip |
|---|---|
| Svi podaci raspoloživi su na liinku. | |
| Leukociti periferne krvi, šest sedmica | Normalan |
| Insulin | Normalan |
| Hematologija šest sedmica | Normalan |
| Vijabilnost homozigota na P14 | Nenormalanan |
| Studija recesivne letalnosti | Nenormalan |
| Tjelesna težina | Normalan |
| Neurološka procjena | Normalan |
| Jačina stiska | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Normalan |
| Radiografija | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Normalan |
| Hematologija 16 sedmica | Normalan |
| Leukociti periferne krvi 16 sedmica | Normalan |
| Težina srca | Normalan |
| Salmonella infekcija | Normalan |
| Funkcija citotoksičnih ćelija | Normalan |
| Imunofenotipizacija slezene | Normalan |
| Imunofenotipizacija mezenternog limfnog čvora | Normalan |
| Imunofenotipizacija koštane srži | Normalan |
| Kompozicija epidermnw imunosti | Normalan |
| Izazov gripe | Normalan |
Također pogledajte[uredi | uredi izvor]
Reference[uredi | uredi izvor]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000160801 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032492 - Ensembl, maj 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.
- ^ "UniProt, Q03431" (jezik: engleski). Pristupljeno 4. 11. 2021.
- ^ Mannstadt M, Jüppner H, Gardella TJ (Nov 1999). "Receptors for PTH and PTHrP: their biological importance and functional properties". The American Journal of Physiology. 277 (5 Pt 2): F665-75. doi:10.1152/ajprenal.1999.277.5.F665. PMID 10564229. Arhivirano s originala, 13. 2. 2009. Pristupljeno 17. 12. 2007.
- ^ Offermanns S, Iida-Klein A, Segre GV, Simon MI (maj 1996). "G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells". Molecular Endocrinology. 10 (5): 566–74. doi:10.1210/me.10.5.566. PMID 8732687.
- ^ "Entrez Gene: PTH1R parathyroid hormone 1 receptor".
- ^ Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I (Jul 2011). "Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese". Journal of Bone and Mineral Research. 26 (7): 1655–61. doi:10.1002/jbmr.385. PMID 21404329. S2CID 23855913.
- ^ a b Mahon MJ, Donowitz M, Yun CC, Segre GV (Jun 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. 417 (6891): 858–61. doi:10.1038/nature00816. PMID 12075354. S2CID 4379134.
- ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
- ^ "International Mouse Phenotyping Consortium".
- ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
- ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
- ^ "Infection and Immunity Immunophenotyping (3i) Consortium".[mrtav link]
Dopunska literatura[uredi | uredi izvor]
- Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE (Apr 2010). "Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation". The Journal of Biological Chemistry. 285 (16): 12435–44. doi:10.1074/jbc.M109.093138. PMC 2852981. PMID 20172855.
- Bonaventure J, Silve C (Nov 2005). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]" (PDF). Médecine/Sciences. 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID 16274647.
- Dawson SJ, White LA (maj 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- Schipani E, Kruse K, Jüppner H (Apr 1995). "A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia". Science. 268 (5207): 98–100. Bibcode:1995Sci...268...98S. doi:10.1126/science.7701349. PMID 7701349.
- Schipani E, Weinstein LS, Bergwitz C, Iida-Klein A, Kong XF, Stuhrmann M, Kruse K, Whyte MP, Murray T, Schmidtke J (maj 1995). "Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene". The Journal of Clinical Endocrinology and Metabolism. 80 (5): 1611–21. doi:10.1210/jc.80.5.1611. PMID 7745008.
- Pausova Z, Bourdon J, Clayton D, Mattei MG, Seldin MF, Janicic N, Rivière M, Szpirer J, Levan G, Szpirer C (Mar 1994). "Cloning of a parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma (UMR 106) cell line: chromosomal assignment of the gene in the human, mouse, and rat genomes". Genomics. 20 (1): 20–6. doi:10.1006/geno.1994.1122. PMID 8020952.
- McCuaig KA, Clarke JC, White JH (maj 1994). "Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 5051–5. Bibcode:1994PNAS...91.5051M. doi:10.1073/pnas.91.11.5051. PMC 43929. PMID 8197183.
- Schipani E, Karga H, Karaplis AC, Potts JT, Kronenberg HM, Segre GV, Abou-Samra AB, Jüppner H (maj 1993). "Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor". Endocrinology. 132 (5): 2157–65. doi:10.1210/en.132.5.2157. PMID 8386612.
- Schneider H, Feyen JH, Seuwen K, Movva NR (Jul 1993). "Cloning and functional expression of a human parathyroid hormone receptor". European Journal of Pharmacology. 246 (2): 149–55. doi:10.1016/0922-4106(93)90092-N. PMID 8397094.
- Schipani E, Langman CB, Parfitt AM, Jensen GS, Kikuchi S, Kooh SW, Cole WG, Jüppner H (Sep 1996). "Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia". The New England Journal of Medicine. 335 (10): 708–14. doi:10.1056/NEJM199609053351004. PMID 8703170.
- Zhou AT, Bessalle R, Bisello A, Nakamoto C, Rosenblatt M, Suva LJ, Chorev M (Apr 1997). "Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3644–9. Bibcode:1997PNAS...94.3644Z. doi:10.1073/pnas.94.8.3644. PMC 20494. PMID 9108031.
- Schipani E, Jensen GS, Pincus J, Nissenson RA, Gardella TJ, Jüppner H (Jun 1997). "Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia". Molecular Endocrinology. 11 (7): 851–8. doi:10.1210/me.11.7.851. PMID 9178745.
- Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C (Jul 1998). "Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia". The Journal of Clinical Investigation. 102 (1): 34–40. doi:10.1172/JCI2918. PMC 509062. PMID 9649554.
- Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF (Sep 1998). "Binding domain of human parathyroid hormone receptor: from conformation to function". Biochemistry. 37 (37): 12737–43. doi:10.1021/bi981265h. PMID 9737850.
- Zhang P, Jobert AS, Couvineau A, Silve C (Sep 1998). "A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 83 (9): 3365–8. doi:10.1210/jc.83.9.3373. PMID 9745456.
- Adams AE, Bisello A, Chorev M, Rosenblatt M, Suva LJ (Nov 1998). "Arginine 186 in the extracellular N-terminal region of the human parathyroid hormone 1 receptor is essential for contact with position 13 of the hormone". Molecular Endocrinology. 12 (11): 1673–83. doi:10.1210/me.12.11.1673. PMID 9817594.
- Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, Nishinakamura R, Toyama Y, Yabe Y, Hori M, Takahashi N, Suda T (Feb 1999). "Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene". Endocrinology. 140 (2): 925–32. doi:10.1210/en.140.2.925. PMID 9927325.
- Schipani E, Langman C, Hunzelman J, Le Merrer M, Loke KY, Dillon MJ, Silve C, Jüppner H (Sep 1999). "A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 84 (9): 3052–7. doi:10.1210/jc.84.9.3052. PMID 10487664.
- Karperien M, van der Harten HJ, van Schooten R, Farih-Sips H, den Hollander NS, Kneppers SL, Nijweide P, Papapoulos SE, Löwik CW (Oct 1999). "A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 84 (10): 3713–20. doi:10.1210/jc.84.10.3713. PMID 10523019.
- Watson PH, Fraher LJ, Natale BV, Kisiel M, Hendy GN, Hodsman AB (Mar 2000). "Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation". Bone. 26 (3): 221–5. doi:10.1016/S8756-3282(99)00264-1. PMID 10709993.
- Truneh A, Sharma S, Silverman C, Khandekar S, Reddy MP, Deen KC, McLaughlin MM, Srinivasula SM, Livi GP, Marshall LA, Alnemri ES, Williams WV, Doyle ML (Jul 2000). "Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor". The Journal of Biological Chemistry. 275 (30): 23319–25. doi:10.1074/jbc.M910438199. PMID 10770955.
Vanjski linkovi[uredi | uredi izvor]
- "Parathyroid Hormone Receptors: PTH1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano s originala, 16. 5. 2011. Pristupljeno 4. 11. 2021.
- Receptor, Parathyroid Hormone, Type 1 na US National Library of Medicine Medical Subject Headings (MeSH)
Šablon:G-protein spregnuti receptori Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.