Difference between revisions of "Phosphatase Subfamily PPM1A"

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=== Evolution ===
 
=== Evolution ===
The PPM1A subfamily is found across [[Phosphatase_Glossary#holozoa|holozoan]].
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The PPM1A subfamily is found across [[Phosphatase_Glossary#holozoa|holozoan]].
 +
 
 +
PPM1A and PPM1B probably arose by gene duplication in vertebrates, but not through whole-genome duplication, since they do not locate in double-conserved synteny.
  
 
PPM1N probably emerged in placentals and lost by independent evolutionary events in different lineages, as implied by [http://resdev.gene.com/gOrtholog/view/cluster/MC0033446/overview internal orthology database] and BLAST NR database. For BLAST, human PPM1N was defined as the hits that have a better (lower) E-values than human PPM1A and PPM1B.
 
PPM1N probably emerged in placentals and lost by independent evolutionary events in different lineages, as implied by [http://resdev.gene.com/gOrtholog/view/cluster/MC0033446/overview internal orthology database] and BLAST NR database. For BLAST, human PPM1N was defined as the hits that have a better (lower) E-values than human PPM1A and PPM1B.
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===== Human PPM1A =====
 
===== Human PPM1A =====
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Human PPM1A or PPM1B results in dephosphorylation of IKKβ at Ser-177 and Ser-181 and termination of IKKβ-induced NF-κB activation <cite>Sun09</cite>.
  
 
===== Human PPM1B =====
 
===== Human PPM1B =====
PPM1B is expressed in a broad types of tissues, most abundantly in skeletal muscle (see RNA-seq data from [http://www.gtexportal.org/home/gene/PPM1B  GTEx]). It dephosphorylates Ser-172 of kinase TBK1 and negatively regulates antiviral response <cite>Zhao12</cite>.
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PPM1B is expressed in a broad types of tissues, most abundantly in skeletal muscle as shown by RNA-seq data from [http://www.gtexportal.org/home/gene/PPM1B  GTEx] and northern blot <cite>Marley98</cite>. The substrates of PPM1B include:
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* TAK1.
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* TBK1 at Ser-172. TBK1 is a kinase activates antiviral response. The dephosphorylation therefore results in negatively regulates antiviral response <cite>Zhao12</cite>.
 +
 
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PPM1B is phosphorylated by PKA at Ser-195 <cite>Choi12</cite>. The Ser-195 is a signature of PPM1A subfamily, because 1) all PPM1A members have serine at the position, 2) PPMs of other subfamilies only have serine, occasionally.
  
PKA phosphorylates PPM1B at Ser-195 <cite>Choi12</cite>. The Ser-195 and PKA regulation on its phosphorylation state is a signature of PPM1A subfamily, because 1) all PPM1A members have serine at the position, 2) PPMs of other subfamilies only have serine, occasionally.  
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PPM1B is modified with ISG15 at least through Lys-12 and Lys-142 <cite>Takeuchi06</cite>. ISG15 is an interferon-upregulated ubiquitin-like protein, which is covalently conjugated to various cellular proteins (ISGylation). ISG15 is found mainly in marsupials and placentals. In comparison, Lys-12 is found in all vertebrate PPM1Bs and PPM1As. Lys-142 is only found in primate and eutheria PPM1Bs, and was replaced by Thr in rodent PPM1B, by Asp or Glu even Ser in marsupial, reptile and fish PPM1Bs, by Gln and Ser even His in PPM1A.
  
 
===== Human PPM1N =====
 
===== Human PPM1N =====
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#Baril06 pmid=19064708
 
#Baril06 pmid=19064708
 
#Choi12 pmid=23756813
 
#Choi12 pmid=23756813
 +
#Maryley98 pmid=9684878
 +
#Sun09 pmid=18930133
 +
#Takeuchi06 pmid=16872604
 
#Zhao12 pmid=22750291
 
#Zhao12 pmid=22750291
 
</biblio>
 
</biblio>

Revision as of 18:53, 4 June 2015

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1A

Evolution

The PPM1A subfamily is found across holozoan.

PPM1A and PPM1B probably arose by gene duplication in vertebrates, but not through whole-genome duplication, since they do not locate in double-conserved synteny.

PPM1N probably emerged in placentals and lost by independent evolutionary events in different lineages, as implied by internal orthology database and BLAST NR database. For BLAST, human PPM1N was defined as the hits that have a better (lower) E-values than human PPM1A and PPM1B.

Functions

Human PPM1A

Human PPM1A or PPM1B results in dephosphorylation of IKKβ at Ser-177 and Ser-181 and termination of IKKβ-induced NF-κB activation [1].

Human PPM1B

PPM1B is expressed in a broad types of tissues, most abundantly in skeletal muscle as shown by RNA-seq data from GTEx and northern blot [2]. The substrates of PPM1B include:

  • TAK1.
  • TBK1 at Ser-172. TBK1 is a kinase activates antiviral response. The dephosphorylation therefore results in negatively regulates antiviral response [3].

PPM1B is phosphorylated by PKA at Ser-195 [4]. The Ser-195 is a signature of PPM1A subfamily, because 1) all PPM1A members have serine at the position, 2) PPMs of other subfamilies only have serine, occasionally.

PPM1B is modified with ISG15 at least through Lys-12 and Lys-142 [5]. ISG15 is an interferon-upregulated ubiquitin-like protein, which is covalently conjugated to various cellular proteins (ISGylation). ISG15 is found mainly in marsupials and placentals. In comparison, Lys-12 is found in all vertebrate PPM1Bs and PPM1As. Lys-142 is only found in primate and eutheria PPM1Bs, and was replaced by Thr in rodent PPM1B, by Asp or Glu even Ser in marsupial, reptile and fish PPM1Bs, by Gln and Ser even His in PPM1A.

Human PPM1N

PPM1N's function is unknown. It is generally expressed at low level across tissues except spleen (see RNA-seq data from GTEx).

Fruit fly alph (alphabet): negatively regulates RAS/MAPK and SAPK

Alphabet, the PPM1A in fruit fly, negatively regulates RAS/MAPK signaling in Drosophila [6] and stress-activated protein kinase (SAPK) [7]. However, its substrates in these signaling pathways are unclear.

References

Error fetching PMID 16600208:
Error fetching PMID 19064708:
Error fetching PMID 23756813:
Error fetching PMID 9684878:
Error fetching PMID 18930133:
Error fetching PMID 16872604:
Error fetching PMID 22750291:
  1. Error fetching PMID 18930133: [Sun09]
  2. Error fetching PMID 22750291: [Zhao12]
  3. Error fetching PMID 23756813: [Choi12]
  4. Error fetching PMID 16872604: [Takeuchi06]
  5. Error fetching PMID 16600208: [Baril06]
  6. Error fetching PMID 19064708: [Baril06]
  7. Error fetching PMID 9684878: [Maryley98]
All Medline abstracts: PubMed | HubMed