Difference between revisions of "Phosphatase Subfamily PPM1H"
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=== 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. | + | The PPM1H subfamily has a single structural domain, phosphatase domain. The phosphatase domain has a signature insertion (316-379 of human PPM1H), which is only found in PPM1H, but not other PPMs, even not other proteins. |
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| + | No obvious target peptide has been found so far, so PPM1Hs probably functions mainly in cytoplasm. | ||
=== Functions === | === Functions === | ||
Revision as of 21:23, 18 June 2015
Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1H
Contents
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. The phosphatase domain has a signature insertion (316-379 of human PPM1H), which is only found in PPM1H, but not other PPMs, even not other proteins.
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
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- 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:
