PTH

Parathyroid hormone

• SMART accession number: SM00087
• Interpro abstract (IPR001415):

  Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Parathyroid hormone-related protein (PTH-rP) is structurally related to PTH [(PUBMED:2682846)] and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and endochondral bone formation [(PUBMED:11760831)].

  PTH and PTH-rP bind to the same G-protein coupled receptor.

  This entry represents parathyroid hormone and parathyroid hormone-related protein.
• GO component: extracellular region (GO:0005576)
• GO function: hormone activity (GO:0005179)

There are 37 PTH domains in 37 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Martin TJ et al.
• Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action.
• Recent Prog Horm Res. 1989; 45: 467-502

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
100.00	map04080	Neuroactive ligand-receptor interaction

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PTH domain which could be assigned to a KEGG orthologous group, and not all proteins containing PTH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PTH domains in PDB

PDB code	Title
1bwx	The solution structure of human parathyroid hormone fragment 1-39, nmr, 10 structures
1bzg	The solution structure of human parathyroid hormone-related protein (1-34) in near-physiological solution, nmr, 30 structures
1et1	Crystal structure of human parathyroid hormone 1-34 at 0.9 a resolution
1fvy	Solution structure of the osteogenic 1-31 fragment of the human parathyroid hormone
1hph	Structure of human parathyroid hormone 1-37 in solution
1hpy	The solution structure of human parathyroid hormone fragment 1-34 in 20% trifluorethanol, nmr, 10 structures
1hth	The solution structure of cyclic human parathyroid hormone fragment 1-34, nmr, 10 structures
1zwa	Structure of human parathyroid hormone fragment 1-34, nmr, structures
1zwb	Structure of human parathyroid hormone fragment 2-37, nmr, structures
1zwc	Structure of bovine parathyroid hormone fragment 1-37, nmr, structures
1zwd	Structure of human parathyroid hormone fragment 3-37, nmr, structures
1zwe	Structure of human parathyroid hormone fragment 4-37, nmr, structures
1zwf	Structure of n-terminal acetylated human parathyroid hormone, nmr, 10 structures
1zwg	Succinyl human parathyroid hormone 4-37, nmr, 10 structures
3c4m	Structure of human parathyroid hormone in complex with the extracellular domain of its g-protein-coupled receptor (pth1r)
3ffd	Structure of parathyroid hormone-related protein complexed to a neutralizing monoclonal antibody
3h3g	Crystal structure of the extracellular domain of the human parathyroid hormone receptor (pth1r) in complex with parathyroid hormone-related protein (pthrp)

Links (links to other resources describing this domain)

• INTERPRO: IPR001415