parathyroid hormone-related protein

副甲状腺ホルモン関連ペプチド PTHrP

WordNet

1. have or establish a relationship to; "She relates well to her peers"
2. be in a relationship with; "How are these two observations related?" (同)interrelate
3. give an account of; "The witness related the events"
4. connected by kinship, common origin, or marriage
5. being connected either logically or causally or by shared characteristics ; "painting and the related arts"; "school-related activities"; "related to micelle formation is the...ability of detergent actives to congregate at oil-water interfaces" (同)related to
6. any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
7. the secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has a specific effect (同)endocrine, internal_secretion

PrepTutorEJDIC

1. (…に)〈事件・事情など〉‘を'『物語る』《+『名』+『to』+『名』》 / (…と)…‘を'『関係させる』,結びつける《+『名』+『to(with)』+『名』》 / 〈物・事が〉(…に)関係がある,かかわる《+『to(with)』+『名(wh・節・句)』》 / (…に)〈人が〉なじむ,順応する《+『to』+『名』》
2. 関係のある
3. 蛋白(たんばく)質
4. ホルモン
5. 副甲状腺の,上皮小体の

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/27 15:18:26」(JST)

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Parathyroid hormone-like hormone
PDB rendering based on 1bzg.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BZG, 1ET3, 1M5N, 3FFD, 3H3G
Identifiers
Symbols	PTHLH ; BDE2; HHM; PLP; PTHR; PTHRP
External IDs	OMIM: 168470 MGI: 97800 HomoloGene: 2113 GeneCards: PTHLH Gene
Gene ontology Molecular function • hormone activity • peptide hormone receptor binding Cellular component • extracellular region • extracellular space • nucleoplasm • cytoplasm • Golgi apparatus Biological process • skeletal system development • endochondral ossification • osteoblast development • adenylate cyclase-activating G-protein coupled receptor signaling pathway • cell-cell signaling • endoderm development • female pregnancy • positive regulation of cell proliferation • negative regulation of cell proliferation • epidermis development • regulation of gene expression • protein processing • positive regulation of cAMP biosynthetic process • epithelial cell differentiation • negative regulation of chondrocyte differentiation • surfactant homeostasis • negative regulation of sequence-specific DNA binding transcription factor activity • cAMP metabolic process • lung alveolus development • mammary gland bud elongation • nipple sheath formation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5744	19227
Ensembl	ENSG00000087494	ENSMUSG00000048776
UniProt	P12272	n/a
RefSeq (mRNA)	NM_002820	NM_008970
RefSeq (protein)	NP_002811	NP_032996
Location (UCSC)	Chr 12: 27.96 – 27.97 Mb	Chr 6: 147.25 – 147.26 Mb
PubMed search	[1]	[2]

Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell lung carcinoma). However, it also has normal functions.

Function

PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width. It also regulates epithelial-mesenchymal interactions during the formation of the mammary glands.

Tooth eruption

PTHrP is critical in intraosseous phase of tooth eruption where it acts as a signalling molecule to stimulate local bone resorption. Without PTHrP, the bony crypt surrounding the tooth follicle will not resorb, and therefore the tooth will not erupt. In the context of tooth eruption, PTHrP is secreted by the cells of the Reduced Enamel Epithelium.

Mammary glands

It aids in normal mammary gland development. It is necessary for maintenance of the mammary bud. Loss of PTHrP or its receptor causes the mammary bud cell fate to change back into epidermis. In lactation, it may regulate in conjunction with the calcium sensing receptor the mobilization and transfer of calcium to the milk, as well as placental transfer of calcium.

Humoral hypercalcemia of malignancy

PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia. As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy.

PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and inhibition of proximal tubular phosphate transport.

However, PTHrP is less likely than PTH to stimulate 1,25-dihydroxyvitamin D production. Therefore, PTHrP does not increase intestinal calcium absorption.

Genetics

Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone.

Discovery

The protein was first isolated in 1987 by T.J. Martin's team at the University of Melbourne. Miao et al. showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function.

Interactions

Parathyroid hormone-related protein has been shown to interact with KPNB1 and Arrestin beta 1.

References

Further reading

• Miao D, Li J, Xue Y, Su H, Karaplis AC, Goltzman D (August 2004). "Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice". Endocrinology 145 (8): 3554–62. doi:10.1210/en.2003-1695. PMID 15090463. 
• Casey ML, MacDonald PC (1997). "The endothelin-parathyroid hormone-related protein vasoactive peptide system in human endometrium: modulation by transforming growth factor-beta". Hum. Reprod. 11 Suppl 2: 62–82. doi:10.1093/humrep/11.suppl_2.62. PMID 8982748. 
• Lam MH, Thomas RJ, Martin TJ et al. (2000). "Nuclear and nucleolar localization of parathyroid hormone-related protein". Immunol. Cell Biol. 78 (4): 395–402. doi:10.1046/j.1440-1711.2000.00919.x. PMID 10947864. 
• Fiaschi-Taesch NM, Stewart AF (2003). "Minireview: parathyroid hormone-related protein as an intracrine factor--trafficking mechanisms and functional consequences". Endocrinology 144 (2): 407–11. doi:10.1210/en.2002-220818. PMID 12538599. 
• Jans DA, Thomas RJ, Gillespie MT (2003). "Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles". Vitam. Horm. Vitamins & Hormones 66: 345–84. doi:10.1016/S0083-6729(03)01010-0. ISBN 978-0-12-709866-1. PMID 12852260. 
• Maioli E, Fortino V, Pacini A (2005). "Parathyroid hormone-related protein in preeclampsia: a linkage between maternal and fetal failures". Biol. Reprod. 71 (6): 1779–84. doi:10.1095/biolreprod.104.030932. PMID 15286039. 
• Fenton AJ, Kemp BE, Kent GN et al. (1991). "A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts". Endocrinology 129 (4): 1762–8. doi:10.1210/endo-129-4-1762. PMID 1915066. 
• Fenton AJ, Kemp BE, Hammonds RG et al. (1991). "A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related protein; PTHrP[107-111]". Endocrinology 129 (6): 3424–6. doi:10.1210/endo-129-6-3424. PMID 1954916. 
• Moniz C, Burton PB, Malik AN et al. (1991). "Parathyroid hormone-related peptide in normal human fetal development". J. Mol. Endocrinol. 5 (3): 259–66. doi:10.1677/jme.0.0050259. PMID 2288637. 
• Hammonds RG, McKay P, Winslow GA et al. (1989). "Purification and characterization of recombinant human parathyroid hormone-related protein". J. Biol. Chem. 264 (25): 14806–11. PMID 2549037. 
• Yasuda T, Banville D, Hendy GN, Goltzman D (1989). "Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects". J. Biol. Chem. 264 (13): 7720–5. PMID 2708388. 
• Suva LJ, Mather KA, Gillespie MT et al. (1989). "Structure of the 5' flanking region of the gene encoding human parathyroid-hormone-related protein (PTHrP)". Gene 77 (1): 95–105. doi:10.1016/0378-1119(89)90363-6. PMID 2744490. 
• Mangin M, Webb AC, Dreyer BE et al. (1988). "Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 597–601. doi:10.1073/pnas.85.2.597. PMC 279598. PMID 2829195. 
• Moseley JM, Kubota M, Diefenbach-Jagger H et al. (1987). "Parathyroid hormone-related protein purified from a human lung cancer cell line". Proc. Natl. Acad. Sci. U.S.A. 84 (14): 5048–52. doi:10.1073/pnas.84.14.5048. PMC 305244. PMID 2885845. 
• Mangin M, Ikeda K, Dreyer BE, Broadus AE (1989). "Isolation and characterization of the human parathyroid hormone-like peptide gene". Proc. Natl. Acad. Sci. U.S.A. 86 (7): 2408–12. doi:10.1073/pnas.86.7.2408. PMC 286922. PMID 2928340. 
• Thiede MA, Strewler GJ, Nissenson RA et al. (1988). "Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene". Proc. Natl. Acad. Sci. U.S.A. 85 (13): 4605–9. doi:10.1073/pnas.85.13.4605. PMC 280483. PMID 3290897. 
• Suva LJ, Winslow GA, Wettenhall RE et al. (1987). "A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression". Science 237 (4817): 893–6. doi:10.1126/science.3616618. PMID 3616618. 
• Campos RV, Zhang L, Drucker DJ (1995). "Differential expression of RNA transcripts encoding unique carboxy-terminal sequences of human parathyroid hormone-related peptide". Mol. Endocrinol. 8 (12): 1656–66. doi:10.1210/me.8.12.1656. PMID 7708054. 
• Holick MF, Ray S, Chen TC et al. (1994). "A parathyroid hormone antagonist stimulates epidermal proliferation and hair growth in mice". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 8014–6. doi:10.1073/pnas.91.17.8014. PMC 44535. PMID 8058749. 
• Seitz PK, Cooper KM, Ives KL et al. (1993). "Parathyroid hormone-related peptide production and action in a myoepithelial cell line derived from normal human breast". Endocrinology 133 (3): 1116–24. doi:10.1210/en.133.3.1116. PMID 8396010. 
• Li H, Seitz PK, Selvanayagam P et al. (1996). "Effect of endogenously produced parathyroid hormone-related peptide on growth of a human hepatoma cell line (Hep G2)". Endocrinology 137 (6): 2367–74. doi:10.1210/en.137.6.2367. PMID 8641188. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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• 1. 高カルシウム血症への診断的アプローチ diagnostic approach to hypercalcemia
• 2. 悪性腫瘍の高カルシウム血症 hypercalcemia of malignancy
• 3. 副甲状腺ホルモンの分泌および作用 parathyroid hormone secretion and action
• 4. 肉芽腫性疾患における高カルシウム血症 hypercalcemia in granulomatous diseases
• 5. 高カルシウム血症の原因 etiology of hypercalcemia

English Journal

• Matrix rigidity regulates the transition of tumor cells to a bone-destructive phenotype through integrin β3 and TGF-β receptor type II.

• Page JM1, Merkel AR2, Ruppender NS1, Guo R1, Dadwal UC3, Cannonier SA4, Basu S5, Guelcher SA6, Sterling JA7.
• Biomaterials.Biomaterials.2015 Sep;64:33-44. doi: 10.1016/j.biomaterials.2015.06.026. Epub 2015 Jun 16.
• Cancer patients frequently develop skeletal metastases that significantly impact quality of life. Since bone metastases remain incurable, a clearer understanding of molecular mechanisms regulating skeletal metastases is required to develop new therapeutics that block establishment of tumors in bone.
• PMID 26115412

• PTHrP-Induced Refractory Malignant Hypercalcemia in a Patient With Chronic Lymphocytic Leukemia Responding to Denosumab.

• Salahudeen AA1, Gupta A1, Jones JC1, Cowan RW2, Vusirikala M3, Kwong C4, Naina HV5.
• Clinical lymphoma, myeloma & leukemia.Clin Lymphoma Myeloma Leuk.2015 Sep;15(9):e137-40. doi: 10.1016/j.clml.2015.06.007. Epub 2015 Jun 19.
• PMID 26187654

• Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth.

• Page JM1, Merkel AR2, Ruppender NS1, Guo R1, Dadwal UC3, Cannonier S4, Basu S5, Guelcher SA6, Sterling JA7.
• Data in brief.Data Brief.2015 Jul 13;4:440-6. doi: 10.1016/j.dib.2015.07.003. eCollection 2015.
• The contents of this data in brief are related to the article titled "Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II". In this DIB we will present our supplemental data investigating Integrin expression, attach
• PMID 26306316

Japanese Journal

• 高Ca血症を呈し急激な転帰をとった肺多形癌胃転移の1例

• 中澤 俊之,廣野 靖夫,小練 研可,永野 秀樹,村上 真,五井 孝憲,飯田 敦,片山 寛次,伊藤 浩史,山口 明夫
• 日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 109(7), 1204-1212, 2012-07-05
• 69歳男性．全身倦怠感，咳嗽，食欲不振の精査で行った&#x518 …
• NAID 10030803085

• 症例報告 PTHrPの産生を認めた卵巣明細胞腺癌の1例

• 関川 佳奈,雨宮 貴子,齊藤 和毅 [他]
• 東京産科婦人科学会会誌 61(2), 276-280, 2012-07
• NAID 40019407626

• 亜鉛トランスポーターSLC39A14/ZIP14による全身成長の制御

• 北條 慎太郎,深田 俊幸
• Biomedical research on trace elements 23(1), 6-13, 2012-04-27
• NAID 10030756017

Related Links

• Parathyroid Hormone-Related Protein

Parathyroid hormone-related protein (PTHrP) is actually a family of protein hormones produced by most if not all tissues in the body. A segment of PHRH is closely related to parathyroid hormone, and hence its name, but PHRH ...

• Update: Parathyroid Hormone-Related Protein: An Update

Parathyroid hormone-related protein enhances human ss-cell proliferation and function with associated induction of cyclin-dependent kinase 2 and cyclin E expression. Diabetes 59:3131–3138. [PMC free article] [PubMed] 93. . [] ...

Related Pictures

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★リンクテーブル★

リンク元	「副甲状腺ホルモン関連ペプチド」「PTHrP」「副甲状腺ホルモン関連タンパク」
関連記事	「relate」「related protein」「parathyroid」「parathyroid hormone」

「副甲状腺ホルモン関連ペプチド」

　　[★]

英

parathyroid hormone-related peptide, PTHrP

同

副甲状腺ホルモン関連タンパク質、副甲状腺ホルモン関連蛋白、副甲状腺ホルモン関連蛋白質、parathyroid hormone-related protein

関

副甲状腺、高カルシウム血症、副甲状腺ホルモン

[show details]

副甲状腺ホルモン関連ペプチド : 約 28,600 件
副甲状腺ホルモン関連タンパク : 55 件
副甲状腺ホルモン関連タンパク質 : 55 件
副甲状腺ホルモン関連蛋白 : 約 24,500 件
副甲状腺ホルモン関連蛋白質 : 44 件

• 悪性腫瘍による高カルシウム血症を引き起こしうる。扁平上皮癌(頭頚部癌、肺癌、皮膚癌)、乳癌、泌尿器系の癌、消化器癌(HIM.618)
• 成人T細胞白血病おける高カルシウム血症はPTHrPによる

臨床検査

PTHrP

• 異常高値：悪性腫瘍に伴う高カルシウム血症(HHM)、褐色細胞腫

「PTHrP」

　　[★]

• 副甲状腺ホルモン関連ペプチド parathyroid hormone-related peptide = 副甲状腺ホルモン関連タンパク質 parathyroid hormone-related protein

「副甲状腺ホルモン関連タンパク」

　　[★]

英

parathyroid hormone-related protein

関

副甲状腺ホルモン関連タンパク質、副甲状腺ホルモン関連蛋白

「relate」

　　[★]

• v.

• 関連する、関係する

関

associate、association、attach、bearing、concern、connect、connection、correlate、correlation、germane、implicate、implication、interplay、link、pertain、pertinent、referable、reference、relation、relationship、relative、relevance、relevant、respect

　 　 　 　

「related protein」

　　[★]

• 関連タンパク質、関連タンパク

関

associated protein

「parathyroid」

　　[★]

• adj.

• 副甲状腺の、上皮小体の

関

parathyroid gland

「parathyroid hormone」

　　[★] 副甲状腺ホルモン PTH