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PTPRD

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PTPRD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTPRD, HPTP, HPTPD, HPTPDELTA, PTPD, RPTPDELTA, protein tyrosine phosphatase, receptor type D, protein tyrosine phosphatase receptor type D, R-PTP-delta
External IDsOMIM: 601598; MGI: 97812; HomoloGene: 88669; GeneCards: PTPRD; OMA:PTPRD - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5789

19266

Ensembl

ENSG00000153707
ENSG00000282932

ENSMUSG00000028399

UniProt

P23468
Q3KPI9

Q64487

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 9: 8.31 – 10.61 MbChr 4: 75.94 – 78.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.[5][6][7]

Function

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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.[7]

Ligand binding

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PTPRD is the orexigenic receptor of asprosin, a hormone that is produced by the C-terminal cleavage of profibrillin from the FBN1 gene.[8] In mice, asprosin acts on an olfactory receptor, Olfr734 in the liver to regulate its gluconeogenic effects.[9] 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.[8]

Clinical significance

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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,[10] obsessive–compulsive disorder,[11] and breast cancer.[12]

Interactions

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PTPRD has been shown to interact with PTPRS[13] and liprin-alpha-1.[14]

References

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  1. ^ a b c ENSG00000282932 GRCh38: Ensembl release 89: ENSG00000153707, ENSG00000282932 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028399 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Pulido R, Krueger NX, Serra-Pagès C, Saito H, Streuli M (March 1995). "Molecular characterization of the human transmembrane protein-tyrosine phosphatase delta. Evidence for tissue-specific expression of alternative human transmembrane protein-tyrosine phosphatase delta isoforms". The Journal of Biological Chemistry. 270 (12): 6722–6728. doi:10.1074/jbc.270.12.6722. PMID 7896816.
  6. ^ Mizuno K, Hasegawa K, Katagiri T, Ogimoto M, Ichikawa T, Yakura H (September 1993). "MPTP delta, a putative murine homolog of HPTP delta, is expressed in specialized regions of the brain and in the B-cell lineage". Molecular and Cellular Biology. 13 (9): 5513–5523. doi:10.1128/MCB.13.9.5513. PMC 360267. PMID 8355697.
  7. ^ a b "Entrez Gene: PTPRD protein tyrosine phosphatase, receptor type, D".
  8. ^ a b Mishra I, Xie WR, Bournat JC, He Y, Wang C, Silva ES, et al. (April 2022). "Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor". Cell Metabolism. 34 (4): 549–563.e8. doi:10.1016/j.cmet.2022.02.012. PMC 8986618. PMID 35298903.
  9. ^ Li E, Shan H, Chen L, Long A, Zhang Y, Liu Y, et al. (August 2019). "OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin". Cell Metabolism. 30 (2): 319–328.e8. doi:10.1016/j.cmet.2019.05.022. PMID 31230984. S2CID 195327523.
  10. ^ Lei N, et al. (2010). "Autism Is Associated with Inherited Deletions in PTPRD and NCAM2". PAS 2010; Abstract 2320.1. Pediatric Academic Societies. Archived from the original on 2010-05-07. Retrieved 2010-05-09.
  11. ^ "OCD: New Genetic Marker Reported". 2014-06-07. Retrieved 2015-08-16.
  12. ^ Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, et al. (Cancer Genome Atlas Network) (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. Bibcode:2012Natur.490...61T. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.
  13. ^ Wallace MJ, Fladd C, Batt J, Rotin D (May 1998). "The second catalytic domain of protein tyrosine phosphatase delta (PTP delta) binds to and inhibits the first catalytic domain of PTP sigma". Molecular and Cellular Biology. 18 (5): 2608–2616. doi:10.1128/MCB.18.5.2608. PMC 110640. PMID 9566880.
  14. ^ Pulido R, Serra-Pagès C, Tang M, Streuli M (December 1995). "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". Proceedings of the National Academy of Sciences of the United States of America. 92 (25): 11686–11690. Bibcode:1995PNAS...9211686P. doi:10.1073/pnas.92.25.11686. PMC 40467. PMID 8524829.

Further reading

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