G5EC24
SS
Gene name |
ptp-2 (F59G1.5) |
Protein name |
Tyrosine-protein phosphatase non-receptor type ptp-2 |
Names |
EC 3.1.3.48 , Protein-tyrosine phosphatase 2 |
Species |
Caenorhabditis elegans |
KEGG Pathway |
cel:CELE_F59G1.5 |
EC number |
3.1.3.48: Phosphoric monoester hydrolases |
Protein Class |
|
Descriptions
SHPTP2 is a widely-expressed Src homology 2 (SH2) domain-containing protein tyrosine phosphatase (PTP) that is important for normal cell development. It plays a critical role in a variety of signal transduction pathways, including growth factor-mediated cell proliferation. Regulation of SHPTP2 activity is, in part, achieved by an intramolecular interaction between the PTP domain containing the catalytic site and the SH2 1 domain, which leads to closed protein conformation and autoinhibition. Accordingly, opening of the SH2 1 and PTP domains is required for the protein to become active. The binding of phosphopeptides to the SH2 1 domain is known to induce the opening event.
Autoinhibitory domains (AIDs)
Target domain |
263-582 (PTP domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Tartaglia M et al. (2010) "Noonan syndrome: clinical aspects and molecular pathogenesis", Molecular syndromology, 1, 2-26
- Darian E et al. (2011) "Structural mechanism associated with domain opening in gain-of-function mutations in SHP2 phosphatase", Proteins, 79, 1573-88
- Garcia Fortanet J et al. (2016) "Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor", Journal of medicinal chemistry, 59, 7773-82
- LaRochelle JR et al. (2018) "Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition", Nature communications, 9, 4508
- Hou Y et al. (2023) "How a single mutation alters the protein structure: a simulation investigation on protein tyrosine phosphatase SHP2", RSC advances, 13, 4263-4274
- Wu X et al. (2019) "Small Molecule Inhibitor that Stabilizes the Autoinhibited Conformation of the Oncogenic Tyrosine Phosphatase SHP2", Journal of medicinal chemistry, 62, 1125-1137
- Shen D et al. (2020) "Therapeutic potential of targeting SHP2 in human developmental disorders and cancers", European journal of medicinal chemistry, 190, 112117
- LaRochelle JR et al. (2016) "Structural and Functional Consequences of Three Cancer-Associated Mutations of the Oncogenic Phosphatase SHP2", Biochemistry, 55, 2269-77
- Pei D et al. (1994) "Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains", Biochemistry, 33, 15483-93
- Wang W et al. (2011) "Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation", Journal of cellular biochemistry, 112, 2062-71
Autoinhibited structure
Activated structure
1 structures for G5EC24
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-G5EC24-F1 | Predicted | AlphaFoldDB |
No variants for G5EC24
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for G5EC24 | |||||
No associated diseases with G5EC24
6 regional properties for G5EC24
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Peptidase C19, ubiquitin carboxyl-terminal hydrolase | 169 - 654 | IPR001394 |
| conserved_site | Ubiquitin interacting motif | 97 - 116 | IPR003903-1 |
| conserved_site | Ubiquitin interacting motif | 124 - 140 | IPR003903-2 |
| conserved_site | Ubiquitin specific protease, conserved site | 170 - 185 | IPR018200-1 |
| conserved_site | Ubiquitin specific protease, conserved site | 591 - 608 | IPR018200-2 |
| domain | Ubiquitin specific protease domain | 169 - 657 | IPR028889 |
Functions
| Description | ||
|---|---|---|
| EC Number | 3.1.3.48 | Phosphoric monoester hydrolases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoplasmic vesicle | A vesicle found in the cytoplasm of a cell. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| non-membrane spanning protein tyrosine phosphatase activity | Catalysis of the reaction |
| phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
11 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| dephosphorylation | The process of removing one or more phosphoric (ester or anhydride) residues from a molecule. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| mitotic cell cycle | Progression through the phases of the mitotic cell cycle, the most common eukaryotic cell cycle, which canonically comprises four successive phases called G1, S, G2, and M and includes replication of the genome and the subsequent segregation of chromosomes into daughter cells. In some variant cell cycles nuclear replication or nuclear division may not be followed by cell division, or G1 and G2 phases may be absent. |
| muscle organ development | The process whose specific outcome is the progression of the muscle over time, from its formation to the mature structure. The muscle is an organ consisting of a tissue made up of various elongated cells that are specialized to contract and thus to produce movement and mechanical work. |
| nematode larval development | The process whose specific outcome is the progression of the nematode larva over time, from its formation to the mature structure. Nematode larval development begins with the newly hatched first-stage larva (L1) and ends with the end of the last larval stage (for example the fourth larval stage (L4) in C. elegans). Each stage of nematode larval development is characterized by proliferation of specific cell lineages and an increase in body size without alteration of the basic body plan. Nematode larval stages are separated by molts in which each stage-specific exoskeleton, or cuticle, is shed and replaced anew. |
| oogenesis | The complete process of formation and maturation of an ovum or female gamete from a primordial female germ cell. Examples of this process are found in Mus musculus and Drosophila melanogaster. |
| positive regulation of epidermal growth factor receptor signaling pathway | Any process that activates or increases the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity. |
| positive regulation of Ras protein signal transduction | Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction. |
| positive regulation of vulval development | Any process that activates or increases the frequency, rate or extent of development of the vulva. Vulval development is the process whose specific outcome is the progression of the egg-laying organ of female and hermaphrodite nematodes over time, from its formation to the mature structure. In nematodes, the vulva is formed from ventral epidermal cells during larval stages to give rise to a fully formed vulva in the adult. |
| regulation of cell projection organization | Any process that modulates the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of cell projections. |
7 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q90687 | PTPN11 | Tyrosine-protein phosphatase non-receptor type 11 | Gallus gallus (Chicken) | SS |
| Q06124 | PTPN11 | Tyrosine-protein phosphatase non-receptor type 11 | Homo sapiens (Human) | EV |
| P29350 | PTPN6 | Tyrosine-protein phosphatase non-receptor type 6 | Homo sapiens (Human) | EV |
| P35235 | Ptpn11 | Tyrosine-protein phosphatase non-receptor type 11 | Mus musculus (Mouse) | SS |
| P29351 | Ptpn6 | Tyrosine-protein phosphatase non-receptor type 6 | Mus musculus (Mouse) | SS |
| P41499 | Ptpn11 | Tyrosine-protein phosphatase non-receptor type 11 | Rattus norvegicus (Rat) | SS |
| P81718 | Ptpn6 | Tyrosine-protein phosphatase non-receptor type 6 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPRLALRQYN | FYYRVNGEKA | EELLKEYGED | GDFLLRYSES | NPQNFSISVR | VAEDKILHIK |
| 70 | 80 | 90 | 100 | 110 | 120 |
| VTKYESDMLS | IFEDERTTPN | QFGSITELAE | FYMEFPEKLR | EKNGLFLELK | KPVYVPYHLE |
| 130 | 140 | 150 | 160 | 170 | 180 |
| ACAEEQRRTQ | LYRWWHGNLP | ASSANKLLQT | EKNGTYLLRA | SQHIPGALVI | SAKTEGQVVH |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LTIYQDPSTG | RFNIDGDRTK | FQSAWLLIDS | YSKNPIVEKG | EASRVLYLEE | PLFNTFIEAD |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LFVDRFEIIR | RPINPRESME | KTGISEEFDR | LSQEALPAEQ | YLSKREGRRP | VNAEKNRYKN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| IVPFDHTRVI | LTDRPNTPGS | DYINASYVRF | ENSQRTKNVT | FACEKSFIAT | QGCLETTISD |
| 370 | 380 | 390 | 400 | 410 | 420 |
| FWSMVWQENS | RVIVMPTMEN | ERKEKCARYW | PAEVNKPEVH | GDISLTCTIE | RKVQRAVSDE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| VKAELEQEKT | NRIAKGLVPE | AELNGDGISY | ILRTLVMKKG | KDTREIRQLQ | YLTWPDHGCP |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LHPYAVLNFL | EDVDREYDYF | NAQPIAASLP | QGPIVVHCSA | GIGRTGTVLV | LDALLNQVKK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| VGLLCPMDVY | KMVKYVRTYR | SGLVQTEQQY | QFLYKALAFY | LKNNNPYPVK | SFIDGDTDAF |
| 610 | 620 | 630 | 640 | 650 | 660 |
| DFPRRLRPTP | NASRPSSARQ | VTSSRPSSSA | SSRTSHSRPR | TGPQAEPIFE | RSTSSTSSSS |
| TLLKSTKK |