PTHLH

The protein encoded by this gene is a member of the parathyroid hormone family. This hormone regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. This hormone is involved in lactation possibly by regulating the mobilization and transfer of calcium to the milk. The receptor of this hormone, PTHR1, is responsible for most cases of humoral hypercalcemia of malignancy. 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. [provided by RefSeq]

Full Name

PTHLH

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. Up-regulates 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 Rac1B.
Osteostatin is a potent inhibitor of osteoclastic bone resorption.

Biological Process

Adenylate cyclase-activating G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentIDA:MGI
Bone mineralizationIEA:InterPro
cAMP metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Cell-cell signalingManual Assertion Based On ExperimentTAS:ProtInc
Epidermis developmentManual Assertion Based On ExperimentTAS:ProtInc
Female pregnancyManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of cell population proliferationManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of chondrocyte developmentManual Assertion Based On ExperimentIDA:MGI
Negative regulation of chondrocyte differentiationManual Assertion Based On ExperimentIDA:MGI
Osteoblast developmentManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cell population proliferationManual Assertion Based On ExperimentTAS:ProtInc
Regulation of chondrocyte differentiationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of gene expressionManual Assertion Based On ExperimentIDA:MGI
Skeletal system developmentManual Assertion Based On ExperimentIDA:MGI

Cellular Location

Cytoplasm
Nucleus
Secreted

Involvement in disease

Brachydactyly E2 (BDE2):
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.

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.