PTHR1
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
urediDužina 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
urediOvaj "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
urediPTH1R 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
urediPoznato 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
urediPokazalo 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
urediU 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
urediReference
uredi- ^ 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.
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- ^ 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.
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- ^ 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
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- 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.
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- 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.
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Vanjski linkovi
uredi- "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)
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.