Phosphatase Subfamily PTPRD
Phosphatase Classification: Fold CC1: Superfamily CC1: Family PTP: Subfamily PTPRD
PTPRD (LAR) subfamily consists of three members in human.
Evolution
PTPRD subfamily is found in holozoan (metazoan plus it closest relative choanoflagellate). PTPRD subfamily has three gene members in human and most vertebrates: PTPRD, PTPRF and PTPRS. It has single member in most invertebrate metazoan and is under intensive studies in frtui fly. 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 (for example, [1]).
Functions
The best characterized member of the three human genes in the subfamily is PTPRF, aka LAR.
Human PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers [2]. PTPRD loss can cause of aberrant STAT3 activation in gliomas [3]. Human PTPRD is also associated with restless legs syndrome [4], but the underlying mechanism is unclear. PTPRD interacts with MIM-B, a putative metastasis suppressor protein binding to actin [5]. 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 [6].
References
- Veeriah S, Brennan C, Meng S, Singh B, Fagin JA, Solit DB, Paty PB, Rohle D, Vivanco I, Chmielecki J, Pao W, Ladanyi M, Gerald WL, Liau L, Cloughesy TC, Mischel PS, Sander C, Taylor B, Schultz N, Major J, Heguy A, Fang F, Mellinghoff IK, and Chan TA. The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9435-40. DOI:10.1073/pnas.0900571106 |
- Ortiz B, Fabius AW, Wu WH, Pedraza A, Brennan CW, Schultz N, Pitter KL, Bromberg JF, Huse JT, Holland EC, and Chan TA. Loss of the tyrosine phosphatase PTPRD leads to aberrant STAT3 activation and promotes gliomagenesis. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8149-54. DOI:10.1073/pnas.1401952111 |
- Schormair B, Kemlink D, Roeske D, Eckstein G, Xiong L, Lichtner P, Ripke S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Högl B, Frauscher B, Gschliesser V, Poewe W, Peglau I, Vodicka P, Vávrová J, Sonka K, Nevsimalova S, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T, and Winkelmann J. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet. 2008 Aug;40(8):946-8. DOI:10.1038/ng.190 |
- Woodings JA, Sharp SJ, and Machesky LM. MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. Biochem J. 2003 Apr 15;371(Pt 2):463-71. DOI:10.1042/BJ20021962 |
- Wallace MJ, Fladd C, Batt J, and Rotin D. The second catalytic domain of protein tyrosine phosphatase delta (PTP delta) binds to and inhibits the first catalytic domain of PTP sigma. Mol Cell Biol. 1998 May;18(5):2608-16. DOI:10.1128/MCB.18.5.2608 |
- 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 |
