Phosphatase Subfamily PTPRD

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Phosphatase Classification: Fold CC1: Superfamily CC1: Family PTP: Subfamily PTPRD


PTPRC (CD45) is a vertebrate-specific receptor PTP involved in immune signaling.

Evolution

PTPRD subfamily is found in holozoan (metazoan plus it closest relative choanoflagellate). PTPRD subfamily has three gene members in most vertebrates: PTPRD, PTPRF and PTPRS. It has single member in most invertebrate metazoan. Interestingly, it greatly expanded in sponge.

Domain Structure

All three members of PTPRD subfamily in human has twin intracellular PTP phosphatase domains, and extracellular Ig domains and FN3 domains. Each of them have multiple alternative splicing isoforms.

Functions

Human PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers [1]. PTPRD loss can cause of aberrant STAT3 activation in gliomas [2]. Human PTPRD is also associated with restless legs syndrome, but the underlying mechanism is unclear. PTPRD interacts with MIM-B, a putative metastasis suppressor protein binding to actin [3]. It is not clear whether MIM-B is its substrate. The 2nd phosphatase domain of PTPRD can bind to inhibit the 1st phosphatase domain of PTPRS [4].

References

  1. Furlan G, Minowa T, Hanagata N, Kataoka-Hamai C, and Kaizuka Y. Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters. J Biol Chem. 2014 Oct 10;289(41):28514-25. DOI:10.1074/jbc.M114.574319 | PubMed ID:25128530 | HubMed [furlan14]