The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ.
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.
Alonso
Andres
A
Program of Signal Transduction, The Burnham Institute, La Jolla, California 92037, USA.
Burkhalter
Stephen
S
Sasin
Joanna
J
Tautz
Lutz
L
Bogetz
Jori
J
Huynh
Huong
H
Bremer
Meire C D
MC
Holsinger
Leslie J
LJ
Godzik
Adam
A
Mustelin
Tomas
T
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
D014764:Viral Proteins; C497817:DUSP23 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases