PTPRD

Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.{{cite journal | vauthors = Pulido R, Krueger NX, Serra-Pagès C, Saito H, Streuli M | title = Molecular characterization of the human transmembrane protein-tyrosine phosphatase delta. Evidence for tissue-specific expression of alternative human transmembrane protein-tyrosine phosphatase delta isoforms | journal = The Journal of Biological Chemistry | volume = 270 | issue = 12 | pages = 6722–6728 | date = March 1995 | pmid = 7896816 | doi = 10.1074/jbc.270.12.6722 | doi-access = free }}{{cite journal | vauthors = Mizuno K, Hasegawa K, Katagiri T, Ogimoto M, Ichikawa T, Yakura H | title = MPTP delta, a putative murine homolog of HPTP delta, is expressed in specialized regions of the brain and in the B-cell lineage | journal = Molecular and Cellular Biology | volume = 13 | issue = 9 | pages = 5513–5523 | date = September 1993 | pmid = 8355697 | pmc = 360267 | doi = 10.1128/MCB.13.9.5513 }}{{cite web | title = Entrez Gene: PTPRD protein tyrosine phosphatase, receptor type, D| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5789}}

Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chick and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple tissue specific alternatively spliced transcript variants of this gene have been reported.

Ligand binding

PTPRD is the orexigenic receptor of asprosin, a hormone that is produced by the C-terminal cleavage of profibrillin from the FBN1 gene.{{cite journal | vauthors = Mishra I, Xie WR, Bournat JC, He Y, Wang C, Silva ES, Liu H, Ku Z, Chen Y, Erokwu BO, Jia P, Zhao Z, An Z, Flask CA, He Y, Xu Y, Chopra AR | display-authors = 6 | title = Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor | journal = Cell Metabolism | volume = 34 | issue = 4 | pages = 549–563.e8 | date = April 2022 | pmid = 35298903 | pmc = 8986618 | doi = 10.1016/j.cmet.2022.02.012 }} In mice, asprosin acts on an olfactory receptor, Olfr734 in the liver to regulate its gluconeogenic effects.{{cite journal | vauthors = Li E, Shan H, Chen L, Long A, Zhang Y, Liu Y, Jia L, Wei F, Han J, Li T, Liu X, Deng H, Wang Y | display-authors = 6 | title = OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin | journal = Cell Metabolism | volume = 30 | issue = 2 | pages = 319–328.e8 | date = August 2019 | pmid = 31230984 | doi = 10.1016/j.cmet.2019.05.022 | s2cid = 195327523 | doi-access = free }} However, PTPRD has been identified as the neural receptor for asprosin. Genetic ablation of PTPRD results in extreme leanness and loss of appetite. More specifically, resistance to diet-induced obesity can occur through the loss of PTPRD in AgRP neurons. When asprosin binds to PTPRD, this leads to the de-phosphorylation and de-activation of Stat3.

Clinical significance

PTPRD is highly expressed throughout the entire brain, especially in the cerebellum and cerebellar hemisphere. PTPRD is also highly expressed in the coronary arteries, the aorta, and the ovaries. Mutations in the PTPRD gene are also associated with autism,{{cite web | url = http://www.abstracts2view.com/pas/view.php?nu=PAS10L1_120&terms | title = Autism Is Associated with Inherited Deletions in PTPRD and NCAM2 | vauthors = Lei N, etal | year = 2010 | work = PAS 2010; Abstract 2320.1 | publisher = Pediatric Academic Societies | access-date = 2010-05-09 | archive-date = 2010-05-07 | archive-url = https://web.archive.org/web/20100507000650/http://www.abstracts2view.com/pas/view.php?nu=PAS10L1_120&terms | url-status = dead }} obsessive–compulsive disorder,{{Cite web|title = OCD: New Genetic Marker Reported|url = http://guardianlv.com/2014/06/ocd-new-genetic-marker-reported/|access-date = 2015-08-16|date = 2014-06-07}} and breast cancer.{{cite journal | vauthors = Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, etal | collaboration = Cancer Genome Atlas Network | title = Comprehensive molecular portraits of human breast tumours | journal = Nature | volume = 490 | issue = 7418 | pages = 61–70 | date = October 2012 | pmid = 23000897 | pmc = 3465532 | doi = 10.1038/nature11412 | bibcode = 2012Natur.490...61T }}

Interactions

PTPRD has been shown to interact with PTPRS{{cite journal | vauthors = Wallace MJ, Fladd C, Batt J, Rotin D | title = The second catalytic domain of protein tyrosine phosphatase delta (PTP delta) binds to and inhibits the first catalytic domain of PTP sigma | journal = Molecular and Cellular Biology | volume = 18 | issue = 5 | pages = 2608–2616 | date = May 1998 | pmid = 9566880 | pmc = 110640 | doi = 10.1128/MCB.18.5.2608 }} and liprin-alpha-1.{{cite journal | vauthors = Pulido R, Serra-Pagès C, Tang M, Streuli M | title = The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 25 | pages = 11686–11690 | date = December 1995 | pmid = 8524829 | pmc = 40467 | doi = 10.1073/pnas.92.25.11686 | doi-access = free | bibcode = 1995PNAS...9211686P }}

PTPRD

Function

Ligand binding

Clinical significance

Interactions

References

Further reading