Phosphatase Subfamily PTPN1
Phosphatase Classification: Fold CC1:Superfamily CC1: Family PTP: Subfamily PTPN1
The PTPN1 subfamily dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).
Evolution
PTPN1 subfamily emerged in animals, as it is found in most if not all eumetazoa, Porifera (e.g. sponge) and Placozoa (e.g. Trichoplax), but absent from Choanoflagellata (e.g. Monosiga) (for the phylogeny of animal at here). In human, there are two copies: PTPN1 (PTP1B) and PTPN2 (TCPTP). The two copies can be traced back to the time when vertebrates emerged. The orthologs for each of them are found in most vertebrates from fish to primates, and there is a single copy in non-vertebrate metazoa.
Domain
The PTPN1 subfamily has a single structural domain, phosphatase domain.
Functions
The PTPN1 subfamily has various functions [1, 2, 3, 4]. It dephoshorylates kinases of various families, such as Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).
PTPN1 (PTP1B) inhibited BRK, a member of SRM subfamily, SRC family, by directly dephosphorylating the Tyr-342 autophosphorylation site [5].
PTPN1 is regulated via glutathionylation of cysteine at the catalytic motif Cx5R [6].
References
- Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim YB, Elmquist JK, Tartaglia LA, Kahn BB, and Neel BG. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002 Apr;2(4):489-95. DOI:10.1016/s1534-5807(02)00148-x |
- Tonks NK. PTP1B: from the sidelines to the front lines!. FEBS Lett. 2003 Jul 3;546(1):140-8. DOI:10.1016/s0014-5793(03)00603-3 |
- Zhang S and Zhang ZY. PTP1B as a drug target: recent developments in PTP1B inhibitor discovery. Drug Discov Today. 2007 May;12(9-10):373-81. DOI:10.1016/j.drudis.2007.03.011 |
- Tiganis T. PTP1B and TCPTP--nonredundant phosphatases in insulin signaling and glucose homeostasis. FEBS J. 2013 Jan;280(2):445-58. DOI:10.1111/j.1742-4658.2012.08563.x |
- Fan G, Aleem S, Yang M, Miller WT, and Tonks NK. Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase. J Biol Chem. 2015 Jun 26;290(26):15934-47. DOI:10.1074/jbc.M115.651703 |
- Barrett WC, DeGnore JP, König S, Fales HM, Keng YF, Zhang ZY, Yim MB, and Chock PB. Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry. 1999 May 18;38(20):6699-705. DOI:10.1021/bi990240v |
