The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases

Int J Mol Sci. 2021 Apr 10;22(8):3925. doi: 10.3390/ijms22083925.

Abstract

Here, we review the haloacid dehalogenase (HAD) class of protein phosphatases, with a particular emphasis on an unusual group of enzymes, the eyes absent (EYA) family. EYA proteins have the unique distinction of being structurally and mechanistically classified as HAD enzymes, yet, unlike other HAD phosphatases, they are protein tyrosine phosphatases (PTPs). Further, the EYA proteins are unique among the 107 classical PTPs in the human genome because they do not use a Cysteine residue as a nucleophile in the dephosphorylation reaction. We will provide an overview of HAD phosphatase structure-function, describe unique features of the EYA family and their tyrosine phosphatase activity, provide a brief summary of the known substrates and cellular functions of the EYA proteins, and speculate about the evolutionary origins of the EYA family of proteins.

Keywords: EYA; EYA1; EYA2; EYA3; EYA4; HAD; PTP; eyes absent; tyrosine phosphatase.

Publication types

  • Review

MeSH terms

  • Cysteine / metabolism
  • Evolution, Molecular*
  • Genome, Human / genetics*
  • Humans
  • Hydrolases / genetics*
  • Hydrolases / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Structure-Activity Relationship

Substances

  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Hydrolases
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases
  • 2-haloacid dehalogenase
  • Cysteine