P29351

SS
Gene name
Ptpn6 (Hcp, Hcph, Ptp1C)
Protein name
Tyrosine-protein phosphatase non-receptor type 6
Names
EC 3.1.3.48 , 70Z-SHP , Hematopoietic cell protein-tyrosine phosphatase , PTPTY-42 , Protein-tyrosine phosphatase 1C , PTP-1C , SH-PTP1 , SHP-1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:15170
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)

2-100 (SH2-1 domain) SS

Target domain

243-517 (PTP domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P29351

Entry ID Method Resolution Chain Position Source
AF-P29351-F1 Predicted AlphaFoldDB

39 variants for P29351

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388857085 14 A>V No EVA
rs3397369793 16 T>A No EVA
rs3397244313 19 K>R No EVA
rs3388861822 22 G>E No EVA
rs3388844772 35 N>Y No EVA
rs3388860914 59 D>N No EVA
rs3388853763 66 G>W No EVA
77 E>VPRPHIWRAGGVTAAGQGRALD motheaten (me) [UniProt] No
100 L>del motheaten (me) [UniProt] No
rs3388850414 122 S>* No EVA
rs3388860915 123 L>V No EVA
rs3388852890 124 L>M No EVA
rs3388857206 125 Q>E No EVA
rs3388857191 130 P>H No EVA
rs3388853736 133 F>C No EVA
rs3388858285 184 F>Y No EVA
rs3388852879 185 D>V No EVA
rs3388860894 189 D>Y No EVA
rs3388861844 211 Q>* No EVA
rs3388862263 232 K>M No EVA
rs3388852849 280 L>F No EVA
rs3388858299 302 I>M No EVA
rs3388853798 320 T>S No EVA
rs3397369785 331 T>Y No EVA
rs3388853749 357 G>S No EVA
rs13473439 383 R>W No EVA
rs3388853752 421 G>V No EVA
rs3388840303 435 Q>K No EVA
rs3388850460 472 S>N No EVA
rs3388857234 472 S>R No EVA
rs3388823637 476 K>N No EVA
rs3388865544 484 I>L No EVA
rs3388850419 492 R>Q No EVA
rs3412920116 497 G>D No EVA
rs3388862240 542 P>T No EVA
rs3388861885 570 K>N No EVA
rs3388861842 581 R>Q No EVA
rs3388862286 586 E>D No EVA
rs229904953 592 L>V No EVA

1 associated diseases with P29351

Without disease ID

6 regional properties for P29351

Type Name Position InterPro Accession
domain Tyrosine-specific protein phosphatase, PTPase domain 243 - 517 IPR000242
domain Tyrosine-specific protein phosphatases domain 430 - 506 IPR000387
domain SH2 domain 2 - 100 IPR000980-1
domain SH2 domain 108 - 213 IPR000980-2
domain Protein-tyrosine phosphatase, catalytic 408 - 514 IPR003595
active_site Protein-tyrosine phosphatase, active site 451 - 461 IPR016130

Functions

Description
EC Number 3.1.3.48 Phosphoric monoester hydrolases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • In neurons, translocates into the nucleus after treatment with angiotensin II
  • Shuttles between the cytoplasm and nucleus via its association with PDPK1 (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 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.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleolus A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.

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

31 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.
cytokine-mediated signaling pathway The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
dephosphorylation The process of removing one or more phosphoric (ester or anhydride) residues from a molecule.
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.
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.
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
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
G5EC24 ptp-2 Tyrosine-protein phosphatase non-receptor type ptp-2 Caenorhabditis elegans SS
10 20 30 40 50 60
MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT HIRIQNSGDF
70 80 90 100 110 120
YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL NCSDPTSERW YHGHISGGQA
130 140 150 160 170 180
ESLLQAKGEP WTFLVRESLS QPGDFVLSVL NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG
190 200 210 220 230 240
SETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA
250 260 270 280 290 300
KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD
310 320 330 340 350 360
YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT TREVEKGRNK
370 380 390 400 410 420
CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL DNGDLVREIW HYQYLSWPDH
430 440 450 460 470 480
GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ESISTKGLDC
490 500 510 520 530 540
DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT
550 560 570 580 590
YPPAVRSAHA KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK