Alternative titles; symbols
HGNC Approved Gene Symbol: DUSP12
Cytogenetic location: 1q23.3 Genomic coordinates (GRCh38): 1:161,749,786-161,757,238 (from NCBI)
Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to dephosphorylate both tyrosine and serine/threonine residues. They have been implicated as major modulators of critical signaling pathways. DUSP12 contains the consensus DUSP C-terminal catalytic domain but lacks the N-terminal CH2 domain found in the MKP (mitogen-activated protein kinase phosphatase) class of DUSPs (see 600714) (summary by Patterson et al., 2009).
By searching a human EST database for sequences that are similar to S. cerevisiae YVH1, Muda et al. (1999) identified DUSP12. The full-length DUSP12 coding sequence encodes a deduced 340-amino acid protein that shares 31% sequence identity with S. cerevisiae YVH1. Both proteins contain an N-terminal phosphatase domain within the first 200 amino acids, followed by a conserved cysteine-rich C-terminal domain of approximately 100 amino acids. The C-terminal domain of DUSP12 can coordinate 2 moles of zinc per mole of protein, defining it as a novel zinc finger domain. Western blot analysis showed that DUSP12 is an approximately 38-kD protein that is expressed in a variety of cell lines. Subcellular localization studies indicated that DUSP12 localizes predominantly to the nucleus. Northern blot analysis detected a 1.4-kb DUSP12 transcript in most of the tissues tested, with highest expression in spleen, testis, ovary, and peripheral blood leukocytes and lower expression in liver and lung.
Muda et al. (1999) noted that, in S. cerevisiae, inactivation of the YVH1 gene results in strikingly slow growth. They demonstrated that recombinant DUSP12 can complement the growth defect caused by disruption of the S. cerevisiae YVH1 gene. The noncatalytic C-terminal domain of DUSP12 was essential for this complementation. However, it was largely dispensable for in vitro phosphatase activity.
By radiation hybrid mapping, Muda et al. (1999) mapped the DUSP12 gene to 1q21-q22.
Muda, M., Manning, E. R., Orth, K., Dixon, J. E. Identification of the human YVH1 protein-tyrosine phosphatase orthologue reveals a novel zinc binding domain essential for in vivo function. J. Biol. Chem. 274: 23991-23995, 1999. [PubMed: 10446167] [Full Text: https://doi.org/10.1074/jbc.274.34.23991]
Patterson, K. I., Brummer, T., O'Brien, P. M., Daly, R. J. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem. J. 418: 475-489, 2009. [PubMed: 19228121] [Full Text: https://doi.org/10.1042/bj20082234]