Receptor paratiroidnog hormona 1

Receptor paratiroidnog hormona 1
Prikaz baziran na 1BL1​
Dostupne strukture
1BL1​, 3C4M​, 3H3G​, 3L2J​
Identifikatori
Simboli PTH1R; PFE; PTHR; PTHR1
Vanjski ID OMIM: 168468 MGI: 97801 HomoloGene: 267 IUPHAR: PTH1 GeneCards: PTH1R Gene
Ontologija gena
Molekularna funkcija • aktivnost receptora paratiroidnog hormona
• vezivanje peptidnog hormona
• proteinska samoasocijacija
Celularna komponenta • jedro
• citoplazma
• ćelijska membrana
• integralno sa ćelijskom membranom
• bazolateralna ćelijska membrana
Biološki proces • razvoj skeletalnog sistema
• hondrocitna diferencijacija
• razvoj osteoblasta
• signalni put G-protein spregnutog receptora
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 5745 19228
Ensembl ENSG00000160801 ENSMUSG00000032492
UniProt Q03431 P41593
RefSeq (mRNA) NM_000316.2 NM_001083935.1
RefSeq (protein) NP_000307.1 NP_001077404.1
Lokacija (UCSC) Chr 3:
46.92 - 46.95 Mb		 Chr 9:
110.62 - 110.65 Mb
PubMed pretraga [1] [2]

Receptor paratiroidnog hormona 1 je protein koji je kod ljudi kodiran PTH1R genom. PTH1R deluje kao receptor za paratiroidni hormon (PTH) i za paratiroidnom hormonu srodan protein (PTHrP, ili PTHLH).

Funkcija

Ovaj „klasični“ PTH receptor je izražen u visokim nivoima u kostima i bubrezima. On reguliše homeostazu jona kalcijuma putem aktivacije adenilat ciklaze i fosfolipaze C.[1][2] U kostima, on je izražen na površini osteoblasta. Kad je receptor aktiviran putem vezivanja PTH, osteoblasti izražavaju RANKL (receptorski aktivator za nuklearni faktor κB ligand), koji se vezuje za RANK (Receptorski aktivator za nuklearni faktor kB) na osteoklastima. Time se osteoklasti aktiviraju da povećaju brzinu resorpcije.

Mehanizam

On je član sekretinske familije G protein spregnutih receptora. Aktivnost ovog receptora je poredovana Gs tipom G proteina koji aktiviraju adenilil ciklazu. Osim toga, oni mogu da aktiviraju fosfatidilinozitol-kalcijumski sistem sekundarnih glasnika.

Interakcije

Receptor paratiroidnog hormona 1 formira interakcije sa regulatornim kofaktorom 2 natrijum-vodonične razmene[3] i regulatorom 1 natrijum-vodoničnog antiportera 3.[3]

Reference

  1. ^ Mannstadt M, Jüppner H, Gardella TJ (1999). „Receptors for PTH and PTHrP: their biological importance and functional properties”. Am. J. Physiol. 277 (5 Pt 2): F665—75. PMID 10564229. Архивирано из оригинала 13. 02. 2009. г. Приступљено 04. 08. 2012. 
  2. ^ Offermanns S, Iida-Klein A, Segre GV, Simon MI (1996). „G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells”. Mol. Endocrinol. 10 (5): 566—74. PMID 8732687. doi:10.1210/me.10.5.566. 
  3. ^ а б Mahon, Matthew J; Donowitz Mark; et al. (2002). „Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling”. Nature. England. 417 (6891): 858—61. ISSN 0028-0836. PMID 12075354. doi:10.1038/nature00816. 

Literatura

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  • Schipani E, Kruse K, Jüppner H (1995). „A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia.”. Science. 268 (5207): 98—100. PMID 7701349. doi:10.1126/science.7701349. 
  • Schipani E; Weinstein LS; Bergwitz C; et al. (1995). „Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene.”. J. Clin. Endocrinol. Metab. 80 (5): 1611—21. PMID 7745008. doi:10.1210/jc.80.5.1611. 
  • Pausova Z; Bourdon J; Clayton D; et al. (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. PMID 8020952. doi:10.1006/geno.1994.1122. 
  • McCuaig KA, Clarke JC, White JH (1994). „Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor.”. Proc. Natl. Acad. Sci. U.S.A. 91 (11): 5051—5. PMID 8197183. doi:10.1073/pnas.91.11.5051. 
  • Schipani E; Karga H; Karaplis AC; et al. (1993). „Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor.”. Endocrinology. 132 (5): 2157—65. PMID 8386612. doi:10.1210/en.132.5.2157. 
  • Schneider H, Feyen JH, Seuwen K, Movva NR (1993). „Cloning and functional expression of a human parathyroid hormone receptor.”. Eur. J. Pharmacol. 246 (2): 149—55. PMID 8397094. doi:10.1016/0922-4106(93)90092-N. 
  • Schipani E; Langman CB; Parfitt AM; et al. (1996). „Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia.”. N. Engl. J. Med. 335 (10): 708—14. PMID 8703170. doi:10.1056/NEJM199609053351004. 
  • Zhou AT; Bessalle R; Bisello A; et al. (1997). „Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking.”. Proc. Natl. Acad. Sci. U.S.A. 94 (8): 3644—9. PMID 9108031. doi:10.1073/pnas.94.8.3644. 
  • Schipani E; Jensen GS; Pincus J; et al. (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.”. Mol. Endocrinol. 11 (7): 851—8. PMID 9178745. doi:10.1210/me.11.7.851. 
  • Jobert AS; Zhang P; Couvineau A; et al. (1998). „Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia.”. J. Clin. Invest. 102 (1): 34—40. PMID 9649554. doi:10.1172/JCI2918. 
  • Pellegrini M; Bisello A; Rosenblatt M; et al. (1998). „Binding domain of human parathyroid hormone receptor: from conformation to function.”. Biochemistry. 37 (37): 12737—43. PMID 9737850. doi:10.1021/bi981265h. 
  • Zhang P, Jobert AS, Couvineau A, Silve C (1998). „A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia.”. J. Clin. Endocrinol. Metab. 83 (9): 3365—8. PMID 9745456. doi:10.1210/jc.83.9.3373. 
  • Adams AE; Bisello A; Chorev M; et al. (1999). „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.”. Mol. Endocrinol. 12 (11): 1673—83. PMID 9817594. doi:10.1210/me.12.11.1673. 
  • Matsuzaki K; Katayama K; Takahashi Y; et al. (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. PMID 9927325. doi:10.1210/en.140.2.925. 
  • Schipani E; Langman C; Hunzelman J; et al. (1999). „A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia.”. J. Clin. Endocrinol. Metab. 84 (9): 3052—7. PMID 10487664. doi:10.1210/jc.84.9.3052. 
  • Karperien M; van der Harten HJ; van Schooten R; et al. (1999). „A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia.”. J. Clin. Endocrinol. Metab. 84 (10): 3713—20. PMID 10523019. doi:10.1210/jc.84.10.3713. 
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Vidi još

Spoljašnje veze

  • „Parathyroid Hormone Receptors: PTH1”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 16. 05. 2011. г. 
  • Receptor,+Parathyroid+Hormone,+Type+1 на US National Library of Medicine Medical Subject Headings (MeSH)
  • п
  • р
  • у
Klasa A: Rodopsinu slični
Neurotransmiter
Adrenergički
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Purinski
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
Serotoninski
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
Eikozanoidni
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6) • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
Neuropeptidni
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
Orfan
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
Orfan
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
Ukus
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4) • VNR (1, 2, 3, 5)
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni