Difference between revisions of "Phosphatase Subfamily PPIP5K"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP2|Family HP, branch 2]]: [[Phosphatase_Subfamily_PPIP5K|PPIP5K]]
 
[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP2|Family HP, branch 2]]: [[Phosphatase_Subfamily_PPIP5K|PPIP5K]]
  
PPIP5K has a pseudophosphatase domain which bind to PtdIns(3,4,5)P3 and a kinase domain of RimK superfamily. The proteins therefore show kinase activity which convert InsP6 and 5-InsP7 to 1-InsP7 and InsP8.
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PPIP5K is a phosphoinositol kinase that also has a pseudophosphatase domain which bind to PtdIns(3,4,5)P3. PPIP5K converts InsP6 and 5-InsP7 to 1-InsP7 and InsP8.
  
 
=== Evolution ===
 
=== Evolution ===
PPIP5K is conserved broadly in eukaryotes, including animals, fungi and plants. Most vertebrates have at least two copies. Non-vertebrate metazoan and fungi usually have one copy per genome.
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PPIP5K is found in most eukaryotes. Most vertebrates have at least two copies, while invertebrates usually have one.
  
 
=== Domain ===
 
=== Domain ===
PPIP5K has two domains: N-terminal RimK/ATP-grasp domain, and C-terminal HP2 domain <cite>fridy07</cite>. The same domain combination is also found in plants.
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PPIP5K has two domains: N-terminal RimK/ATP-grasp domain, and C-terminal HP2 domain <cite>fridy07</cite>. The RimK is the active kinase domain <cite>fridy07, choi07</cite>.
 
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RimK/ATP-grasp domain confer PPIP5K's kinase activity that converts InsP6 and 5-InsP7 to 1-InsP7 and InsP8 <cite>fridy07, choi07</cite>.
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Unlike other members of HP2 family which are protein or non-protein phosphatases, the HP2 domain of PPIP5K is not catalytically active. Instead, this HP2 domain is specialized for binding PtdIns(3,4,5)P3, as a partial PH (pleckstrin homology) consensus sequence is spliced into this HP2 domain <cite>gokhale13</cite>.
 
Unlike other members of HP2 family which are protein or non-protein phosphatases, the HP2 domain of PPIP5K is not catalytically active. Instead, this HP2 domain is specialized for binding PtdIns(3,4,5)P3, as a partial PH (pleckstrin homology) consensus sequence is spliced into this HP2 domain <cite>gokhale13</cite>.
  
 
=== Catalytic activity and functions ===
 
=== Catalytic activity and functions ===
As mentioned above, the phosphatase domain of PPIP5K, HP2 domain, is catalytically inactive <cite>gokhale13</cite>. Because the kinase domain is active, the proteins show kinase activity in general. In particular, human PPIP5K1 and PPIP5K2 mediates phosphorylation of InsP6 and 5-InsP7 to 1-InsP7 and InsP8. InsP7 and InsP8 are multifunctional signaling molecules that regulate diverse cellular activities <cite>fridy07, choi07</cite>.
 
  
 
=== References ===
 
=== References ===

Revision as of 22:16, 6 January 2015

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): Family HP, branch 2: PPIP5K

PPIP5K is a phosphoinositol kinase that also has a pseudophosphatase domain which bind to PtdIns(3,4,5)P3. PPIP5K converts InsP6 and 5-InsP7 to 1-InsP7 and InsP8.

Evolution

PPIP5K is found in most eukaryotes. Most vertebrates have at least two copies, while invertebrates usually have one.

Domain

PPIP5K has two domains: N-terminal RimK/ATP-grasp domain, and C-terminal HP2 domain [1]. The RimK is the active kinase domain [1, 2].

Unlike other members of HP2 family which are protein or non-protein phosphatases, the HP2 domain of PPIP5K is not catalytically active. Instead, this HP2 domain is specialized for binding PtdIns(3,4,5)P3, as a partial PH (pleckstrin homology) consensus sequence is spliced into this HP2 domain [3].

Catalytic activity and functions

References

  1. Fridy PC, Otto JC, Dollins DE, and York JD. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J Biol Chem. 2007 Oct 19;282(42):30754-62. DOI:10.1074/jbc.M704656200 | PubMed ID:17690096 | HubMed [fridy07]
  2. Choi JH, Williams J, Cho J, Falck JR, and Shears SB. Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress. J Biol Chem. 2007 Oct 19;282(42):30763-75. DOI:10.1074/jbc.M704655200 | PubMed ID:17702752 | HubMed [choi07]
  3. Gokhale NA, Zaremba A, Janoshazi AK, Weaver JD, and Shears SB. PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains. Biochem J. 2013 Aug 1;453(3):413-26. DOI:10.1042/BJ20121528 | PubMed ID:23682967 | HubMed [gokhale13]
All Medline abstracts: PubMed | HubMed