A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases.
Protein-tyrosine-phosphatases (PTPases, EC 3.1.3.48) play a crucial role in the regulation of protein tyrosine phosphorylation. Recently, it was found that the PTPase gene family exhibits a large variety of different functional domains associated with the PTPase catalytic domains. In this paper, we report the complete cDNA sequence of a human transmembrane PTPase, PTP zeta, isolated from fetal brain cDNA libraries. The deduced amino acid sequence of human PTP zeta is composed of a putative signal peptide of 19 amino acids, a very large extracellular domain of 1616 amino acids, a transmembrane peptide of 26 amino acids, and a cytoplasmic domain of 653 amino acids. The extracellular portion of human PTP zeta contains two striking structural features: the N-terminal 280-amino acid sequence that is homologous to carbonic anhydrases (carbonate hydro-lyase, EC 4.2.1.1), and a sequence of 1048 amino acids without a cysteine residue. While it is unlikely that the carbonic anhydrase-like domain of PTP zeta has any carbonic anhydrase activity, its three-dimensional structure may be quite similar to that of carbonic anhydrases, a structure that appears ideal for binding a small soluble ligand. The cytoplasmic portion of human PTP zeta contains two repeated PTPase-like domains, which, when expressed in Escherichia coli, had PTPase activity in vitro. Mutational analyses indicate that only the membrane-proximal PTPase domain is catalytically active. Reverse transcription-polymerase chain reaction analyses indicate that human PTP zeta is highly expressed in a glioblastoma cell line.
Krueger
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Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Saito
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H
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002256:Carbonic Anhydrases / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005333:Fetus; D015723:Gene Library; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D007527:Isoenzymes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004247:DNA; D017027:Protein Tyrosine Phosphatases; D002256:Carbonic Anhydrases