title: The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ.
abstract: The smallest active protein-tyrosine phosphatase yet (only 16 kDa) is described here and given the name VHZ for VH1-like member Z because it belongs to the group of small Vaccinia virus VH1-related dual specific phosphatases exemplified by VHR, VHX, and VHY. Human VHZ is remarkably well conserved through evolution as it has species orthologs in frogs, fish, fly, and Archaea. The gene for VHZ, which we designate as DUSP25, is located on human chromosome 1q23.1 and consists of only two coding exons. VHZ is broadly expressed in tissues and cells, including resting blood lymphocytes, Jurkat T cells, HL-60, and RAMOS. In transfected cells, VHZ was located in the cytosol and in other cells also in the nucleoli. Endogenous VHZ showed a similar but more granular distribution. We show that VHZ is an active phosphatase and analyze its structure by computer modeling, which shows that in comparison with the 185-amino acid residue VHR, the 150-residue VHZ is a shortened version of VHR and contains the minimal set of secondary structure elements conserved in all known phosphatases from this class. The surface charge distribution of VHZ differs from that of VHR and is therefore unlikely to dephosphorylate mitogen-activated protein kinases. The remarkably high degree of conservation of VHZ through evolution may indicate a role in some ancient and fundamental physiological process.
authors.affiliation: Program of Signal Transduction, The Burnham Institute, La Jolla, California 92037, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Alonso
authors.forename: Stephen
authors.initials: S
authors.lastname: Burkhalter
authors.forename: Joanna
authors.initials: J
authors.lastname: Sasin
authors.forename: Lutz
authors.initials: L
authors.lastname: Tautz
authors.forename: Jori
authors.initials: J
authors.lastname: Bogetz
authors.forename: Huong
authors.initials: H
authors.lastname: Huynh
authors.forename: Meire C D
authors.initials: MC
authors.lastname: Bremer
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Holsinger
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002878:Chromosomes, Human, Pair 1; D054637:Dual-Specificity Phosphatases; D019143:Evolution, Molecular; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014616:Vaccinia virus / Q000201:enzymology / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins; C497817:DUSP23 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases