Phosphatase Subfamily DSP14

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

Eumetazoan-specific subfamily acting on the MAPK cascade.

Evolution

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

Domain

DSP14 consist of a single phosphatase domain.

Function

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 [1]. 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 [2]. DUSP18 was widely expressed in different tissues [3]. 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 [4].

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

References

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