P81718
Gene name |
Ptpn6 (Ptph6) |
Protein name |
Tyrosine-protein phosphatase non-receptor type 6 |
Names |
EC 3.1.3.48 , Protein-tyrosine phosphatase SHP-1 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:116689 |
EC number |
3.1.3.48: Phosphoric monoester hydrolases |
Protein Class |
|

Descriptions
Autoinhibitory domains (AIDs)
Target domain |
245-519 (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 P81718
Entry ID | Method | Resolution | Chain | Position | Source |
---|---|---|---|---|---|
AF-P81718-F1 | Predicted | AlphaFoldDB |
No variants for P81718
Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
---|---|---|---|---|---|
No variants for P81718 |
No associated diseases with P81718
6 regional properties for P81718
Type | Name | Position | InterPro Accession |
---|---|---|---|
domain | Tyrosine-specific protein phosphatase, PTPase domain | 245 - 519 | IPR000242 |
domain | Tyrosine-specific protein phosphatases domain | 432 - 508 | IPR000387 |
domain | SH2 domain | 4 - 102 | IPR000980-1 |
domain | SH2 domain | 110 - 215 | IPR000980-2 |
domain | Protein-tyrosine phosphatase, catalytic | 410 - 516 | IPR003595 |
active_site | Protein-tyrosine phosphatase, active site | 453 - 463 | IPR016130 |
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 |
6 GO annotations of cellular component
Name | Definition |
---|---|
alpha-beta T cell receptor complex | A T cell receptor complex in which the TCR heterodimer comprises alpha and beta chains, associated with the CD3 complex; recognizes a complex consisting of an antigen-derived peptide bound to a class I or class II MHC protein. |
apical dendrite | A dendrite that emerges near the apical pole of a neuron. In bipolar neurons, apical dendrites are located on the opposite side of the soma from the axon. |
cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
11 GO annotations of molecular function
Name | Definition |
---|---|
cell adhesion molecule binding | Binding to a cell adhesion molecule. |
cytokine receptor binding | Binding to a cytokine receptor. |
natural killer cell lectin-like receptor binding | Binding to a lectin-like natural killer cell receptor. |
non-membrane spanning protein tyrosine phosphatase activity | Catalysis of the reaction |
phosphorylation-dependent protein binding | Binding to a protein upon phosphorylation of the target protein. |
phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
protein tyrosine phosphatase activity | Catalysis of the reaction |
SH2 domain binding | Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class. |
SH3 domain binding | Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins. |
transmembrane receptor protein tyrosine phosphatase activity | Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction |
32 GO annotations of biological process
Name | Definition |
---|---|
B cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell. |
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. |
cellular response to macrophage colony-stimulating factor stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a macrophage colony-stimulating factor stimulus. |
epididymis development | The process whose specific outcome is the progression of an epididymis over time, from its formation to the mature structure. |
hematopoietic progenitor cell differentiation | The process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a class of cell types including myeloid progenitor cells and lymphoid progenitor cells. |
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. |
MAPK cascade | An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers |
megakaryocyte development | The process whose specific outcome is the progression of a megakaryocyte cell over time, from its formation to the mature structure. Megakaryocyte development does not include the steps involved in committing a cell to a megakaryocyte fate. A megakaryocyte is a giant cell 50 to 100 micron in diameter, with a greatly lobulated nucleus, found in the bone marrow. |
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. |
natural killer cell mediated cytotoxicity | The directed killing of a target cell by a natural killer cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors. |
negative regulation of humoral immune response mediated by circulating immunoglobulin | Any process that stops, prevents, or reduces the frequency, rate, or extent of a humoral immune response mediated by circulating immunoglobulin. |
negative regulation of inflammatory response to wounding | Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response to wounding. |
negative regulation of interleukin-6 production | Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-6 production. |
negative regulation of MAPK cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the MAPKKK cascade. |
negative regulation of mast cell activation involved in immune response | Any process that stops, prevents, or reduces the frequency, rate, or extent of mast cell activation as part of an immune response. |
negative regulation of peptidyl-tyrosine phosphorylation | Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. |
negative regulation of T cell proliferation | Any process that stops, prevents or reduces the rate or extent of T cell proliferation. |
negative regulation of T cell receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell. |
negative regulation of tumor necrosis factor production | Any process that stops, prevents, or reduces the frequency, rate, or extent of tumor necrosis factor production. |
platelet aggregation | The adhesion of one platelet to one or more other platelets via adhesion molecules. |
platelet formation | The process in which platelets bud from long processes extended by megakaryocytes. |
positive regulation of cell adhesion mediated by integrin | Any process that activates or increases the frequency, rate, or extent of cell adhesion mediated by integrin. |
positive regulation of cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | Any process that activates or increases the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. |
protein dephosphorylation | The process of removing one or more phosphoric residues from a protein. |
regulation of B cell differentiation | Any process that modulates the frequency, rate or extent of B cell differentiation. |
regulation of ERK1 and ERK2 cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
regulation of G1/S transition of mitotic cell cycle | Any signalling pathway that modulates the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle. |
regulation of release of sequestered calcium ion into cytosol | Any process that modulates the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria. |
response to axon injury | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus. |
T cell proliferation | The expansion of a T cell population by cell division. Follows T cell activation. |
T cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. |
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 |
G5EC24 | ptp-2 | Tyrosine-protein phosphatase non-receptor type ptp-2 | Caenorhabditis elegans | SS |
10 | 20 | 30 | 40 | 50 | 60 |
MLSRGWFHRD | LSGPDAETLL | KGRGVPGSFL | ARPSRKNQGD | FSLSVRVDDQ | VTHIRIQNSG |
70 | 80 | 90 | 100 | 110 | 120 |
DFYDLYGGEK | FATSTELVEY | YTQQQGILQD | RDGTIIHLKY | PLNCSDPTSE | RWYHGHMSGG |
130 | 140 | 150 | 160 | 170 | 180 |
QAESLLQAKG | EPWTFLVRES | LSQPGDFVLS | VLNDQPKAAP | GSPLRVTHIK | VMCEGGRYTV |
190 | 200 | 210 | 220 | 230 | 240 |
GGSETFDSLT | DLVEHFKKTG | IEEASGAFVY | LRQPYYATRV | NAADIENRVL | ELNKKQESED |
250 | 260 | 270 | 280 | 290 | 300 |
TAKAGFWEEF | ESLQKQEAKN | LHQRLEGQRP | ENKSKNRYKN | ILPFDHSRVI | LQGRDSNIPG |
310 | 320 | 330 | 340 | 350 | 360 |
SDYINANYVK | NQLLGPDENS | KTYIASQGCL | DATVNDFWQM | AWQENTRVIV | MTTREVEKGR |
370 | 380 | 390 | 400 | 410 | 420 |
NKCVPYWPEV | GTQRVYGLYS | VTNCKEHDTA | EYKLRTLQIS | PLDNGDLVRE | IWHYQYLSWP |
430 | 440 | 450 | 460 | 470 | 480 |
DHGVPSEPGG | VLSFLDQINQ | RQESLPHAGP | IIVHCSAGIG | RTGTIIVIDM | LMESVSTKGL |
490 | 500 | 510 | 520 | 530 | 540 |
DCDIDIQKTI | QMVRAQRSGM | VQTEAQYKFI | YVAIAQFIET | TKKKLEIIQS | QRGQESEYGN |
550 | 560 | 570 | 580 | 590 | 600 |
ITYPPALRSA | HAKASRTSSK | HKEEVYENVH | SKNKKEEKVK | KQRSADKEKN | KGSLKRNISL |
610 | |||||
TPCRGLRWAD | RDL |