Difference between revisions of "Phosphatase Subfamily PPM1H"
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| + | __NOTOC__ | ||
[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_PPM|Fold PPM (PP2C)]]: [[Phosphatase_Superfamily_PPM|Superfamily PPM (PP2C)]]: [[Phosphatase_Family_PPM|Family PPM (PP2C)]]: [[Phosphatase_Subfamily_PPM1H|Subfamily PPM1H]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_PPM|Fold PPM (PP2C)]]: [[Phosphatase_Superfamily_PPM|Superfamily PPM (PP2C)]]: [[Phosphatase_Family_PPM|Family PPM (PP2C)]]: [[Phosphatase_Subfamily_PPM1H|Subfamily PPM1H]] | ||
=== Evolution === | === Evolution === | ||
| + | The PPM1H subfamily are found throughout animals from sponge to human. In invertebrates, it usually has a single copy per genome. Human has three copies, arose by two independent duplication events. The genes PPM1H and PPM1J emerged by duplication in early vertebrates or chordates; the gene PPM1M emerged later in [http://en.wikipedia.org/wiki/Sarcopterygii sarcopterygii] (lobe-finned fish + terrestrial vertebrates). Neither of the duplication events were whole-genome duplication, as evidenced by no obvious [[Phosphatase_Glossary#Double-conserved_synteny|double-conserved synteny]] were detected. | ||
=== Domain === | === Domain === | ||
| + | The PPM1H subfamily has a single structural domain, phosphatase domain. No obvious target peptide has been found so far, so PPM1Hs probably functions mainly in cytoplasm. | ||
=== Functions === | === Functions === | ||
| − | The three human members have distinct expression pattern across tissues, according the RNA-seq data from GTEx. They are expressed in a broad types of tissues, but most abundantly in different tissues: [http://www.gtexportal.org/home/gene/PPM1H PPM1H] in brain, [http://www.gtexportal.org/home/gene/PPM1J PPM1J] in testis | + | |
| + | ===== Tissue-specific expression and subcellular localization ===== | ||
| + | The three human members have distinct expression pattern across tissues, according the RNA-seq data from GTEx and studies on individual phosphatases by northern blot analysis or similar assays. They are expressed in a broad types of tissues, but most abundantly in different tissues: | ||
| + | * [http://www.gtexportal.org/home/gene/PPM1H PPM1H] in brain, localized in [http://en.wikipedia.org/wiki/Neurite neurites], [http://en.wikipedia.org/wiki/Growth_cone growth cones] and nucleus of neurons <cite>Labes98</cite>. | ||
| + | * [http://www.gtexportal.org/home/gene/PPM1J PPM1J] in testis <cite>Kashiwaba03</cite>. | ||
| + | * [http://www.gtexportal.org/home/gene/PPM1M PPM1M] in white cell and spleen, localized mainly in cell nuclei <cite>Komaki03</cite>. | ||
| + | |||
| + | In addition, PPM1H is over-expressed in colon cancer cell lines, where PPM1H is localized in cytoplasm <cite>Sugiura08</cite>. | ||
| + | |||
| + | ===== Substrates and interacting parterns ===== | ||
| + | PPM1H directly interacted with Smad1/5/8 through its Smad-binding domain, and dephosphorylates phospho-Smad1/5/8 (P-Smad1/5/8) in the cytoplasm <cite>Shen14</cite>. The Smad1/2/8 are critical players in bone morphogenetic protein (BMP) signaling, which are also phosphorylated by PPM1A <cite>Duan06</cite>. | ||
| + | |||
| + | PPM1H was found to dephosphorylate the [http://en.wikipedia.org/wiki/CDKN1B tumor suppressor p27] at Thr-187, in a search for [http://en.wikipedia.org/wiki/Trastuzumab trastuzumab (Herceptin)] resistance mechanism(s) by RNAi screening <cite>LeeHoeflich11</cite>. The dephosphorylation remove a signal for proteasomal degradation from p27. | ||
| + | |||
| + | PPM1H also associatesd with and probably dephosphorylates CSE1L, a proliferation and apoptosis-related protein <cite>Sugiura08</cite>. | ||
| + | |||
| + | PPM1J associated with ubiquitin conjugating enzyme 9 (UBC9) <cite>Kashiwaba03</cite>. | ||
| + | |||
| + | PPM1M dephosphorylated IKKβ in vitro <cite>Henmi09</cite>. | ||
=== References === | === References === | ||
| + | <biblio> | ||
| + | #Duan06 pmid=16931515 | ||
| + | #Henmi09 pmid=19594441 | ||
| + | #Labes98 pmid=9770338 | ||
| + | #LeeHoeflich11 pmid=22586611 | ||
| + | #Kashiwaba03 pmid=12633878 | ||
| + | #Komaki03 pmid=14654243 | ||
| + | #Shen14 pmid=24732009 | ||
| + | #Sugiura08 pmid=18059182 | ||
| + | </biblio> | ||
Revision as of 17:10, 5 June 2015
Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1H
Evolution
The PPM1H subfamily are found throughout animals from sponge to human. In invertebrates, it usually has a single copy per genome. Human has three copies, arose by two independent duplication events. The genes PPM1H and PPM1J emerged by duplication in early vertebrates or chordates; the gene PPM1M emerged later in sarcopterygii (lobe-finned fish + terrestrial vertebrates). Neither of the duplication events were whole-genome duplication, as evidenced by no obvious double-conserved synteny were detected.
Domain
The PPM1H subfamily has a single structural domain, phosphatase domain. No obvious target peptide has been found so far, so PPM1Hs probably functions mainly in cytoplasm.
Functions
Tissue-specific expression and subcellular localization
The three human members have distinct expression pattern across tissues, according the RNA-seq data from GTEx and studies on individual phosphatases by northern blot analysis or similar assays. They are expressed in a broad types of tissues, but most abundantly in different tissues:
- PPM1H in brain, localized in neurites, growth cones and nucleus of neurons [1].
- PPM1J in testis [2].
- PPM1M in white cell and spleen, localized mainly in cell nuclei [3].
In addition, PPM1H is over-expressed in colon cancer cell lines, where PPM1H is localized in cytoplasm [4].
Substrates and interacting parterns
PPM1H directly interacted with Smad1/5/8 through its Smad-binding domain, and dephosphorylates phospho-Smad1/5/8 (P-Smad1/5/8) in the cytoplasm [5]. The Smad1/2/8 are critical players in bone morphogenetic protein (BMP) signaling, which are also phosphorylated by PPM1A [6].
PPM1H was found to dephosphorylate the tumor suppressor p27 at Thr-187, in a search for trastuzumab (Herceptin) resistance mechanism(s) by RNAi screening [7]. The dephosphorylation remove a signal for proteasomal degradation from p27.
PPM1H also associatesd with and probably dephosphorylates CSE1L, a proliferation and apoptosis-related protein [4].
PPM1J associated with ubiquitin conjugating enzyme 9 (UBC9) [2].
PPM1M dephosphorylated IKKβ in vitro [8].
References
Error fetching PMID 19594441:
Error fetching PMID 9770338:
Error fetching PMID 22586611:
Error fetching PMID 12633878:
Error fetching PMID 14654243:
Error fetching PMID 24732009:
Error fetching PMID 18059182:
- Error fetching PMID 9770338:
- Error fetching PMID 12633878:
- Error fetching PMID 14654243:
- Error fetching PMID 18059182:
- Error fetching PMID 24732009:
- Error fetching PMID 16931515:
- Error fetching PMID 22586611:
- Error fetching PMID 19594441:
