Phosphatase Subfamily DSP14

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Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP14

Eumetazoan-specific subfamily of MAPK phosphatases.


DSP14 emerged in eumetazoa and duplicated in vertebrates, giving rise to four human members: DUSP14 (MKP6), DUSP18, DUSP21, and DUSP28 (VHP) [1].


DSP14 consist of a single phosphatase domain.


DUSP14 (MKP6) dephosphorylates TGF-beta-activated kinase 1 (TAK1), a member of MAPKKK, at Thr-187 within its activation loop. Thus, DUSP14 negatively regulates TNF- or IL-1-induced NF-kappaB activation [2]. DUSP14 is widely expressed in different tissues with highest expression in skin (see GTEx).

DUSP18 interacts with and dephosphorylates JNK in vitro and in vivo. It does not dephosphorylate p38 or ERK1 [3]. DUSP18 was widely expressed in different tissues [4]. RNA-seq from GTEx shows expression predominantly in testis and pituitary.

DUSP21 is almost exclusively expressed in testis, but has been reported as a cancer-testis (CT) antigen and required for survival in a hepatocellular carcinoma cell line by RNAi [5].

DUSP28 (VHP) is widely expressed in different tissues according to RNA-seq data from GTEx, but its function is unknown.

The single Drosophila member, CG15528, and the 4 C. elegans members have not been characterized.


  1. Chen MJ, Dixon JE, and Manning G. Genomics and evolution of protein phosphatases. Sci Signal. 2017 Apr 11;10(474). DOI:10.1126/scisignal.aag1796 | PubMed ID:28400531 | HubMed [Chen]
  2. Zheng H, Li Q, Chen R, Zhang J, Ran Y, He X, Li S, and Shu HB. The dual-specificity phosphatase DUSP14 negatively regulates tumor necrosis factor- and interleukin-1-induced nuclear factor-κB activation by dephosphorylating the protein kinase TAK1. J Biol Chem. 2013 Jan 11;288(2):819-25. DOI:10.1074/jbc.M112.412643 | PubMed ID:23229544 | HubMed [Zheng13]
  3. Wu Q, Huang S, Sun Y, Gu S, Lu F, Dai J, Yin G, Sun L, Zheng D, Dou C, Feng C, Ji C, Xie Y, and Mao Y. Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo. Front Biosci. 2006 Sep 1;11:2714-24. PubMed ID:16720344 | HubMed [Wu06]
  4. Wu Q, Gu S, Dai J, Dai J, Wang L, Li Y, Zeng L, Xu J, Ye X, Zhao W, Ji C, Xie Y, and Mao Y. Molecular cloning and characterization of a novel dual-specificity phosphatase18 gene from human fetal brain. Biochim Biophys Acta. 2003 Feb 20;1625(3):296-304. DOI:10.1016/s0167-4781(02)00629-2 | PubMed ID:12591617 | HubMed [Wu03]
  5. Deng Q, Li KY, Chen H, Dai JH, Zhai YY, Wang Q, Li N, Wang YP, and Han ZG. RNA interference against cancer/testis genes identifies dual specificity phosphatase 21 as a potential therapeutic target in human hepatocellular carcinoma. Hepatology. 2014 Feb;59(2):518-30. DOI:10.1002/hep.26665 | PubMed ID:23929653 | HubMed [Deng14]
All Medline abstracts: PubMed | HubMed