Phosphatase Family HP2

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Phosphatase Classification: Fold HP: Superfamily HP: Family HP, branch 2 (HP2)

The histidine phosphatase, branch 2 (HP2) family is found throughout eukaryotes. It has subfamilies that are protein phosphatases, non-protein phosphatases, and pseudophosphatases. See also Pfam PF00328. All subfamilies other than PPIP5K encode an N-terminal signal peptide or signal anchor, and many have a C-terminal transmembrane domain. One of its subfamily ACP2 can function as tyrosine protein phosphatase.


ACP2: pTyr and small molecule phosphatase

The ACP2 subfamily is a protein phosphatase subfamily that usually has multiple copies per genome. Human has three copies with different tissue specificity. It is found in holozoa, ameobozoa, and some protists.

ACP6: lysophosphatidic acid-specific phosphatase
MINPP1: Ins5P and Ins6P phosphatase

A non-protein phosphatase found in a broad of eukaryotes, including most metazoa and amoebozoa. Known substrates include InsP6 and 2,3-BPG.

PXYLP1 (ACPL2): xylose phosphatase

The PXYLP1 (ACPL2) subfamily dephosphorylates xylose, a sugar, in the glycosaminoglycan-protein linkage region of proteoglycans [1]. It is widely found in bilateria.

PPIP5K: pseudophosphatase domain binding to PtdIns(3,4,5)P3

The PPIP5K subfamily has two domains: a pseudophosphatase domain which binds PtdIns(3,4,5)P3, and a kinase domain of the RimK superfamily, which converts InsP6 and 5-InsP7 to 1-InsP7 and InsP8. PPIP5K is found throughout eukaryotes; vertebrates usually have two copies per genome.

Cf60: Pseudophosphatase

Cf60 is a pseudophosphatase found in many amoebozoa. The Dictyostelium discoideum cf60 encodes a secreted 450-kDa complex of proteins called counting factor (CF), through which Dictyostelium discoideum cells sense and regulate the size of groups and fruiting bodies.


  1. Koike T, Izumikawa T, Sato B, and Kitagawa H. Identification of phosphatase that dephosphorylates xylose in the glycosaminoglycan-protein linkage region of proteoglycans. J Biol Chem. 2014 Mar 7;289(10):6695-708. DOI:10.1074/jbc.M113.520536 | PubMed ID:24425863 | HubMed [koike14]
  2. Zhang XQ, Lee MS, Zelivianski S, and Lin MF. Characterization of a prostate-specific tyrosine phosphatase by mutagenesis and expression in human prostate cancer cells. J Biol Chem. 2001 Jan 26;276(4):2544-50. DOI:10.1074/jbc.M006661200 | PubMed ID:11067847 | HubMed [ACPP_1]
  3. Meng TC and Lin MF. Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells. J Biol Chem. 1998 Aug 21;273(34):22096-104. PubMed ID:9705354 | HubMed [ACPP_2]
All Medline abstracts: PubMed | HubMed