Description: Homo sapiens parathyroid hormone-like hormone (PTHLH), transcript variant 1, mRNA. RefSeq Summary (NM_198965): The protein encoded by this gene is a member of the parathyroid hormone family. This hormone, via its receptor, PTHR1, regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. It is responsible for most cases of humoral hypercalcemia of malignancy, and mutations in this gene are associated with brachydactyly type E2 (BDE2). Alternatively spliced transcript variants have been found for this gene. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, downstream of the initiator AUG codon, resulting in nuclear forms of this hormone. [provided by RefSeq, Nov 2013]. Transcript (Including UTRs) Position: hg19 chr12:28,111,017-28,124,916 Size: 13,900 Total Exon Count: 5 Strand: - Coding Region Position: hg19 chr12:28,111,492-28,122,427 Size: 10,936 Coding Exon Count: 3
ID:PTHR_HUMAN DESCRIPTION: RecName: Full=Parathyroid hormone-related protein; Short=PTH-rP; Short=PTHrP; AltName: Full=Parathyroid hormone-like protein; Short=PLP; Contains: RecName: Full=PTHrP[1-36]; Contains: RecName: Full=PTHrP[38-94]; Contains: RecName: Full=Osteostatin; AltName: Full=PTHrP[107-139]; Flags: Precursor; FUNCTION: Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity). Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1- dependent manner through activation of Rac1. FUNCTION: Osteostatin is a potent inhibitor of osteoclastic bone resorption. SUBUNIT: PTHrP interacts with PTH1R (via N-terminal extracellular domain). SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Secreted. TISSUE SPECIFICITY: Ubiquitous. Also expressed in the mammary gland. PTM: There are 3 principal secretory forms, called PTHrP[1-36], PTHrP[38-94], and osteostatin (PTHrP[107-139]) arising from endoproteolytic cleavage of the initial translation product. Each of these secretory forms is believed to have one or more of its own receptors that mediates the normal paracrine, autocrine and endocrine actions. DISEASE: Defects in PTHLH are the cause of brachydactyly type E2 (BDE2) [MIM:613382]. BDE2 is a form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. In brachydactyly type E2 variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges. SIMILARITY: Belongs to the parathyroid hormone family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PTHLHID41897ch12p11.html";
Adiponectin James B Meigs et al. BMC medical genetics 2007, Genome-wide association with diabetes-related traits in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903298]
Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. Framingham 100K data replicate the TCF7L2 association with diabetes.
Aspartate Aminotransferases Emelia J Benjamin et al. BMC medical genetics 2007, Genome-wide association with select biomarker traits in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903293]
The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.
Attention Deficit Disorder with Hyperactivity Jessica Lasky-Su et al. American journal of medical genetics. Part B, Neuropsychiatric genetics 2008, Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations., American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetic.
[PubMed 18821565]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12272
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
