Difference between revisions of "Phosphatase Family HP1"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]  
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__NOTOC__
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]]:  [[Phosphatase_Family_HP1|HP, branch1 family]]  
  
=== Subfamilies ===
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HP1 is one of two major families within the Histidine Phosphatase fold, that uses a pHis intermediate during catalysis. HP1 includes several non-protein phosphatases, and two protein phosphatase subfamilies: PGAM5 is a serine phosphatase and STS (TULA or UBASH3) is a tyrosine phosphatase.
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=== Subfamilies found in human ===
  
 
======[[Phosphatase_Subfamily_PGAM|PGAM]]======
 
======[[Phosphatase_Subfamily_PGAM|PGAM]]======
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PGAMs mainly function as glycolytic enzymes regulating intracellular levels of their substrate [[Phosphatase_Glossary#3-phosphoglycerate|3-phosphoglycerate]] and product [[Phosphatase_Glossary#2-phosphoglycerate|2-phosphoglycerate]]. Human BPGM is a 2,3-bisphosphoglycerate mutase. They are found throughout most eukaryotes.
  
======[[Phosphatase_Subfamily_PGAM5|PGAM5]]======
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======[[Phosphatase_Subfamily_PGAM5|PGAM5]]: serine phosphatase at inner mitochondria membrane ======
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PGAM5 is a protein serine phosphatase conserved in metazoa. It localized to inner mitochondria membrane. It has distinct substrates, such as ASK1, Drp1, FUNDC1. PGAM5 is involved in mitophagy regulation.
  
======[[Phosphatase_Subfamily_TIGAR|TIGAR]]======
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======[[Phosphatase_Subfamily_TIGAR|TIGAR]]: TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase======
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TIGAR inhibits glycolysis and negatively modulates the level of intracellular reactive oxygen species (ROS), therefore regulating autophagy and apoptosis. TIGAR is found in chordates some basal [[Phosphatase_Glossary#Eumetazoa|eumetazoa]], but is absent from nematodes and arthropods.
  
======[[Phosphatase_Subfamily_STS|STS]]======
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======[[Phosphatase_Subfamily_STS|STS]] (TULA or UBASH3): tyrosine phosphatase ======
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STS is a protein tyrosine phosphatase involved in T-cell receptor signaling. In particular, STS dephosphorylates the Syk subfamily kinases Syk and ZAP-70. STS is conserved in metazoa, but ''C. elegans'' lost the signature domains, SH3 and H2 domain, which are common among STSs.
  
 
======[[Phosphatase_Subfamily_PFKFB|PFKFB]]======
 
======[[Phosphatase_Subfamily_PFKFB|PFKFB]]======
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PFKFB is a bifunctional enzyme responsible for the synthesis (as kinase) and degradation (as phosphatase) of [[Phosphatase_Glossary#Fructose-2.2C6-bisphosphatase|fructose-2,6-bisphosphate]] a glycolytic regulator.
  
======[[Phosphatase_Subfamily_Cele-STS-like|Cele-STS-like]]======
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=== Other subfamilies ===
  
 
======[[Phosphatase_Subfamily_TFC7|TFC7]]======
 
======[[Phosphatase_Subfamily_TFC7|TFC7]]======
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TFC7 is a RNA pol III transcription initiation factor complex (TFIIIC) subunit found in fungi and Dictyostelium.
  
 
======[[Phosphatase_Subfamily_HP1LE|HP1LE]]======
 
======[[Phosphatase_Subfamily_HP1LE|HP1LE]]======
 
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HP1LE  subfamily is found in choanoflagellates and sponge, but is absent from eumetazoa. Its function is unclear.
======[[Phosphatase_Subfamily_Dicty-HP1-sf1|Dicty-HP1-sf1]]======
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======STSs/TULAs======
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There are two TULAs in human, UBASH3A (STS-2 or TULA-1) and UBASH3B (STS-1 or TULA-2). Both TULAs negatively regulate the endocytosis of receptor tyrosine kinases. The UBA domain of TULA-1 and SH3-dependent Cbl-binding are required for this function. TULA-1 (STS-2) is a lymphoid protein, whereas TULA-2 (STS-1) is expressed ubiquitously. It has been shown that TULA-2 can dephosphorylate phospho-tyrosines on EGFR and Syk. The histidine phosphatase domain of TULA-2, but not of TULA-1, dephosphorylates the EGFR at multiple tyrosines, and thereby terminating its signalling and endocytosis <cite>STS_1</cite>. TULA-2 decreases tyrosine phosphorylation of Syk in vivo and in vitro. Inactivated TULA-2 increases tyrosine phosphorylation of Syk in cells co-transfected to overexpress these proteins, thus acting as a dominant-negative form that suppresses dephosphorylation of Syk caused by endogenous TULA-2. However, the same assay on TULA-1 shows the phosphatase activity of TULA-1 is negligible compared to TULA-2 <cite>STS_2</cite>. TULA-1 is present in lobe-finned fish, birds and mammals, but not other bony fishes. TULA-2 emerged earlier than TULA-1, which is found in most metazoan, from sponge to nematodes, insects, fishes, birds, and mammals.
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Latest revision as of 21:54, 25 October 2016

Phosphatase Classification: Fold HP: Superfamily HP: HP, branch1 family


HP1 is one of two major families within the Histidine Phosphatase fold, that uses a pHis intermediate during catalysis. HP1 includes several non-protein phosphatases, and two protein phosphatase subfamilies: PGAM5 is a serine phosphatase and STS (TULA or UBASH3) is a tyrosine phosphatase.

Subfamilies found in human

PGAM

PGAMs mainly function as glycolytic enzymes regulating intracellular levels of their substrate 3-phosphoglycerate and product 2-phosphoglycerate. Human BPGM is a 2,3-bisphosphoglycerate mutase. They are found throughout most eukaryotes.

PGAM5: serine phosphatase at inner mitochondria membrane

PGAM5 is a protein serine phosphatase conserved in metazoa. It localized to inner mitochondria membrane. It has distinct substrates, such as ASK1, Drp1, FUNDC1. PGAM5 is involved in mitophagy regulation.

TIGAR: TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase

TIGAR inhibits glycolysis and negatively modulates the level of intracellular reactive oxygen species (ROS), therefore regulating autophagy and apoptosis. TIGAR is found in chordates some basal eumetazoa, but is absent from nematodes and arthropods.

STS (TULA or UBASH3): tyrosine phosphatase

STS is a protein tyrosine phosphatase involved in T-cell receptor signaling. In particular, STS dephosphorylates the Syk subfamily kinases Syk and ZAP-70. STS is conserved in metazoa, but C. elegans lost the signature domains, SH3 and H2 domain, which are common among STSs.

PFKFB

PFKFB is a bifunctional enzyme responsible for the synthesis (as kinase) and degradation (as phosphatase) of fructose-2,6-bisphosphate a glycolytic regulator.

Other subfamilies

TFC7

TFC7 is a RNA pol III transcription initiation factor complex (TFIIIC) subunit found in fungi and Dictyostelium.

HP1LE

HP1LE subfamily is found in choanoflagellates and sponge, but is absent from eumetazoa. Its function is unclear.