Summary: Inositol hexakisphosphate
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Protein tyrosine phosphatase Edit Wikipedia article
| Protein-tyrosine-phosphatase | |||||||||
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Protein tyrosine phosphatase 1, trimer, Human
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| Identifiers | |||||||||
| EC number | 3.1.3.48 | ||||||||
| CAS number | 79747-53-8 | ||||||||
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| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; EC 3.1.3.48) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation, transformation, and synaptic plasticity.[1][2][3][4]
Contents
Functions
Together with tyrosine kinases, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family. PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinases.
PTPs have been implicated in regulation of many cellular processes, including, but not limited to:
- Cell growth
- Cellular differentiation
- Mitotic cycles
- Oncogenic transformation
- Receptor endocytosis[5]
Classification
By mechanism
PTP activity can be found in four protein families.[6][7]
Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.
Class I
The class I PTPs, are the largest group of PTPs with 99 members, which can be further subdivided into
- 38 classical PTPs
- 21 receptor tyrosine phosphatase
- 17 nonreceptor-type PTPs
- 61 VH-1-like or dual-specific phosphatases (DSPs)
- 11 MAPK phosphatases (MPKs)
- 3 Slingshots
- 3 PRLs
- 4 CDC14s
- 19 atypical DSPs
- 5 Phosphatase and tensin homologs (PTENs)
- 16 Myotubularins
Dual-specificity phosphatases (dTyr and dSer/dThr) dual-specificity protein-tyrosine phosphatases. Ser/Thr and Tyr dual-specificity phosphatases are a group of enzymes with both Ser/Thr (EC 3.1.3.16) and tyrosine-specific protein phosphatase (EC 3.1.3.48) activity able to remove the serine/threonine or the tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase. Dual-specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle.
LEOPARD syndrome, Noonan syndrome, and Metachondromatosis are associated with PTPN11.
Elevated levels of activated PTPN5 negatively affects synaptic stability and plays a role in Alzheimer’s disease,[3] Fragile X Syndrome[4] schizophrenia,[8] and Parkinson’s disease.[9] Decreased levels of PTPN5 has been implicated in Huntington's disease,[10][11] cerebral ischemia[12] alcohol abuse,[13][14] and stress disorders.[15][16] Together these findings indicate that only at optimal levels of PTPN5 is synaptic function unimpaired.
Class II
LMW (low-molecular-weight) phosphatases, or acid phosphatases, act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[17][18]
The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP).
Class III
Cdc25 phosphatases (dTyr and/or dThr)
The Class III PTPs contains three members, CDC25 A, B, and C
Class IV
These are members of the HAD fold and superfamily, and include phosphatases specific to pTyr and pSer/Thr as well as small molecule phosphatases and other enzymes.[19] The subfamily EYA (eyes absent) is believed to be pTyr-specific, and has four members in human, EYA1, EYA2, EYA3, and EYA4. This class has a distinct catalytic mechanism from the other three classes.[20]
By location
Based on their cellular localization, PTPases are also classified as:
- Receptor-like, which are transmembrane receptors that contain PTPase domains.[21] In terms of structure, all known receptor PTPases are made up of a variable-length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains, or carbonic anhydrase-like domains in their extracellular region. In general, the cytoplasmic region contains two copies of the PTPase domain. The first seems to have enzymatic activity, whereas the second is inactive.
- Non-receptor (intracellular) PTPases[22]
Common elements
All PTPases, other than those of the eya family, carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and possess a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif.[23] Functional diversity between PTPases is endowed by regulatory domains and subunits.
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Expression pattern
Individual PTPs may be expressed by all cell types, or their expression may be strictly tissue-specific. Most cells express 30% to 60% of all the PTPs, however hematopoietic and neuronal cells express a higher number of PTPs in comparison to other cell types. T cells and B cells of hematopoietic origin express around 60 to 70 different PTPs. The expression of several PTPS is restricted to hematopoietic cells, for example, LYP, SHP1, CD45, and HePTP.[28] The expression of PTPN5 is restricted to the brain. Differential expression of PTPN5 is found in many brain regions, with no expression in the cerebellum.[29][30][31]
References
- ^ Dixon JE, Denu JM (1998). "Protein tyrosine phosphatases: mechanisms of catalysis and regulation". Curr Opin Chem Biol. 2 (5): 633–41. PMID 9818190.
- ^ Paul S, Lombroso PJ (2003). "Receptor and nonreceptor protein tyrosine phosphatases in the nervous system". Cell. Mol. Life Sci. 60 (11): 2465–82. doi:10.1007/s00018-003-3123-7. PMID 14625689.
- ^ a b Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ (Nov 2010). "Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model". Proceedings of the National Academy of Sciences of the United States of America. 107 (44): 19014–9. doi:10.1073/pnas.1013543107. PMC 2973892
. PMID 20956308. - ^ a b Goebel-Goody SM, Wilson-Wallis ED, Royston S, Tagliatela SM, Naegele JR, Lombroso PJ (Jul 2012). "Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model". Genes, Brain, and Behavior. 11 (5): 586–600. doi:10.1111/j.1601-183X.2012.00781.x. PMC 3922131 . PMID 22405502.
- ^ Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ (Apr 2010). "Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61". The Journal of Neuroscience. 30 (17): 5948–57. doi:10.1523/JNEUROSCI.0157-10.2010. PMC 2868326 . PMID 20427654.
- ^ Sun JP, Zhang ZY, Wang WQ (2003). "An overview of the protein tyrosine phosphatase superfamily". Curr Top Med Chem. 3 (7): 739–48. doi:10.2174/1568026033452302. PMID 12678841.
- ^ Alonso A, Sasin J, et al. (2004). "Protein tyrosine phosphatases in the human genome". Cell. 117 (6): 699–711. doi:10.1016/j.cell.2004.05.018. PMID 15186772.
- ^ Carty NC, Xu J, Kurup P, Brouillette J, Goebel-Goody SM, Austin DR, Yuan P, Chen G, Correa PR, Haroutunian V, Pittenger C, Lombroso PJ (2012). "The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications". Translational Psychiatry. 2 (7): e137. doi:10.1038/tp.2012.63. PMC 3410627 . PMID 22781170.
- ^ Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC (Jan 2015). "STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's disease". Proceedings of the National Academy of Sciences of the United States of America. 112 (4): 1202–7. doi:10.1073/pnas.1417423112. PMC 4313846 . PMID 25583483.
- ^ Saavedra A, Giralt A, Rué L, Xifró X, Xu J, Ortega Z, Lucas JJ, Lombroso PJ, Alberch J, Pérez-Navarro E (Jun 2011). "Striatal-enriched protein tyrosine phosphatase expression and activity in Huntington's disease: a STEP in the resistance to excitotoxicity". The Journal of Neuroscience. 31 (22): 8150–62. doi:10.1523/JNEUROSCI.3446-10.2011. PMC 3472648 . PMID 21632937.
- ^ Gladding CM, Sepers MD, Xu J, Zhang LY, Milnerwood AJ, Lombroso PJ, Raymond LA (Sep 2012). "Calpain and STriatal-Enriched protein tyrosine phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model". Human Molecular Genetics. 21 (17): 3739–52. doi:10.1093/hmg/dds154. PMC 3412376 . PMID 22523092.
- ^ Deb I, Manhas N, Poddar R, Rajagopal S, Allan AM, Lombroso PJ, Rosenberg GA, Candelario-Jalil E, Paul S (Nov 2013). "Neuroprotective role of a brain-enriched tyrosine phosphatase, STEP, in focal cerebral ischemia". The Journal of Neuroscience. 33 (45): 17814–26. doi:10.1523/JNEUROSCI.2346-12.2013. PMC 3818554 . PMID 24198371.
- ^ Hicklin TR, Wu PH, Radcliffe RA, Freund RK, Goebel-Goody SM, Correa PR, Proctor WR, Lombroso PJ, Browning MD (Apr 2011). "Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase". Proceedings of the National Academy of Sciences of the United States of America. 108 (16): 6650–5. doi:10.1073/pnas.1017856108. PMC 3081035 . PMID 21464302.
- ^ Darcq E, Hamida SB, Wu S, Phamluong K, Kharazia V, Xu J, Lombroso P, Ron D (Jun 2014). "Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption". Journal of Neurochemistry. 129 (6): 1024–34. doi:10.1111/jnc.12701. PMC 4055745 . PMID 24588427.
- ^ Yang CH, Huang CC, Hsu KS (May 2012). "A critical role for protein tyrosine phosphatase nonreceptor type 5 in determining individual susceptibility to develop stress-related cognitive and morphological changes". The Journal of Neuroscience. 32 (22): 7550–62. doi:10.1523/JNEUROSCI.5902-11.2012. PMID 22649233.
- ^ Dabrowska J, Hazra R, Guo JD, Li C, Dewitt S, Xu J, Lombroso PJ, Rainnie DG (Dec 2013). "Striatal-enriched protein tyrosine phosphatase-STEPs toward understanding chronic stress-induced activation of corticotrophin releasing factor neurons in the rat bed nucleus of the stria terminalis". Biological Psychiatry. 74 (11): 817–26. doi:10.1016/j.biopsych.2013.07.032. PMC 3818357 . PMID 24012328.
- ^ Wo YY, Shabanowitz J, Hunt DF, Davis JP, Mitchell GL, Van Etten RL, McCormack AL (1992). "Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase". J. Biol. Chem. 267 (15): 10856–10865. PMID 1587862.
- ^ Shekels LL, Smith AJ, Bernlohr DA, Van Etten RL (1992). "Identification of the adipocyte acid phosphatase as a PAO-sensitive tyrosyl phosphatase". Protein Sci. 1 (6): 710–721. doi:10.1002/pro.5560010603. PMC 2142247 . PMID 1304913.
- ^ Mark J. Chen, Jack E. Dixon & Gerard Manning (2017). "Genomics and evolution of protein phosphatases". Science signaling. 10 (474). doi:10.1126/scisignal.aag1796. PMID 28400531.
- ^ William C. Plaxton; Michael T. McManus (2006). Control of primary metabolism in plants. Wiley-Blackwell. pp. 130–. ISBN 978-1-4051-3096-7. Retrieved 12 December 2010.
- ^ Knapp S, Longman E, Debreczeni JE, Eswaran J, Barr AJ (2006). "The crystal structure of human receptor protein tyrosine phosphatase kappa phosphatase domain 1". Protein Sci. 15 (6): 1500–1505. doi:10.1110/ps.062128706. PMC 2242534 . PMID 16672235.
- ^ Perrimon N, Johnson MR, Perkins LA, Melnick MB (1996). "The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila". Dev. Biol. 180 (1): 63–81. doi:10.1006/dbio.1996.0285. PMID 8948575.
- ^ Barford D, Das AK, Egloff MP (1998). "The structure and mechanism of protein phosphatase s: insights into catalysis and regulation". Annu. Rev. Biophys. Biomol. Struct. 27 (1): 133–64. doi:10.1146/annurev.biophys.27.1.133. PMID 9646865.
- ^ Su XD, Taddei N, Stefani M, Ramponi G, Nordlund P (August 1994). "The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase". Nature. 370 (6490): 575–8. doi:10.1038/370575a0. PMID 8052313.
- ^ Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, Saper MA (August 1994). "Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate". Nature. 370 (6490): 571–5. doi:10.1038/370571a0. PMID 8052312.
- ^ Yuvaniyama J, Denu JM, Dixon JE, Saper MA (May 1996). "Crystal structure of the dual specificity protein phosphatase VHR". Science. 272 (5266): 1328–31. doi:10.1126/science.272.5266.1328. PMID 8650541.
- ^ Aceti DJ, Bitto E, Yakunin AF, et al. (October 2008). "Structural and functional characterization of a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000". Proteins. 73 (1): 241–53. doi:10.1002/prot.22041. PMC 4437517 . PMID 18433060.
- ^ Mustelin T, Vang T, Bottini N (2005). "Protein tyrosine phosphatases and the immune response". Nat. Rev. Immunol. 5 (1): 43–57. doi:10.1038/nri1530. PMID 15630428.
- ^ Lombroso PJ, Murdoch G, Lerner M (Aug 1991). "Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum". Proceedings of the National Academy of Sciences of the United States of America. 88 (16): 7242–6. doi:10.1073/pnas.88.16.7242. PMC 52270 . PMID 1714595.
- ^ Bult A, Zhao F, Dirkx R, Sharma E, Lukacsi E, Solimena M, Naegele JR, Lombroso PJ (Dec 1996). "STEP61: a member of a family of brain-enriched PTPs is localized to the endoplasmic reticulum". The Journal of Neuroscience. 16 (24): 7821–31. PMID 8987810.
- ^ Lombroso PJ, Naegele JR, Sharma E, Lerner M (Jul 1993). "A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures". The Journal of Neuroscience. 13 (7): 3064–74. PMID 8331384.
Sources
- This article incorporates text from the public domain Pfam and InterPro IPR000106
External links
- PTP Summary and Relevant Publications at Monash University
- Protein-Tyrosine-Phosphatase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.1.3.48
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Inositol hexakisphosphate Provide feedback
Inositol hexakisphosphate, often called phytate, is found in abundance in seeds and acting as an inorganic phosphate reservoir. Phytases are phosphatases that hydrolyze phytate to less-phosphorylated myo-inositol derivatives and inorganic phosphate. The active-site sequence (HCXXGXGR) of the phytase identified from the gut micro-organism Selenomonas ruminantium forms a loop (P loop) at the base of a substrate binding pocket that is characteristic of protein tyrosine phosphatases (PTPs). The depth of this pocket is an important determinant of the substrate specificity of PTPs. In humans this enzyme is thought to aid bone mineralization and salvage the inositol moiety prior to apoptosis [3].
Literature references
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Chu HM, Guo RT, Lin TW, Chou CC, Shr HL, Lai HL, Tang TY, Cheng KJ, Selinger BL, Wang AH;, Structure. 2004;12:2015-2024.: Structures of the Selenomonas ruminantium phytase in complex with persulfated phytate: DSP phytase fold and mechanism for sequential substrate hydrolysis. PUBMED:15530366 EPMC:15530366
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Gruninger RJ, Selinger LB, Mosimann SC;, FEBS J. 2008;275:3783-3792.: Effect of ionic strength and oxidation on the P-loop conformation of the protein tyrosine phosphatase-like phytase, PhyAsr. PUBMED:18573100 EPMC:18573100
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Caffrey JJ, Hidaka K, Matsuda M, Hirata M, Shears SB;, FEBS Lett. 1999;442:99-104.: The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossification. PUBMED:9923613 EPMC:9923613
Internal database links
| SCOOP: | CDKN3 DSPc DUF442 Init_tRNA_PT Y_phosphatase Y_phosphatase2 Y_phosphatase3 |
| Similarity to PfamA using HHSearch: | Y_phosphatase DSPc |
This tab holds annotation information from the InterPro database.
No InterPro data for this Pfam family.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Phosphatase (CL0031), which has the following description:
This family includes tyrosine and dual specificity phosphatase enzymes.
The clan contains the following 16 members:
CDKN3 DSPc DSPn DUF442 Init_tRNA_PT LMWPc Myotub-related NleF_casp_inhib PTPlike_phytase PTS_IIB Rhodanese Ssu72 Syja_N Y_phosphatase Y_phosphatase2 Y_phosphatase3Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (45) |
Full (1493) |
Representative proteomes | UniProt (2465) |
NCBI (5404) |
Meta (17) |
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| RP15 (459) |
RP35 (918) |
RP55 (1220) |
RP75 (1478) |
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| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (45) |
Full (1493) |
Representative proteomes | UniProt (2465) |
NCBI (5404) |
Meta (17) |
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| RP15 (459) |
RP35 (918) |
RP55 (1220) |
RP75 (1478) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_194 (release 26.0) |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Coggill P 
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| Number in seed: | 45 |
| Number in full: | 1493 |
| Average length of the domain: | 151.00 aa |
| Average identity of full alignment: | 30 % |
| Average coverage of the sequence by the domain: | 34.56 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 156 | ||||||||||||
| Family (HMM) version: | 6 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
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Interactions
There is 1 interaction for this family. More...
PTPlike_phytaseStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PTPlike_phytase domain has been found. There are 51 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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