Search results for PTPN6

Showing 14 results out of 21

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Species

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Protein (3 results from a total of 5)

Identifier: R-HSA-197938
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PTPN6: P29350
Identifier: R-HSA-9008911
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PTPN6: P29350
Identifier: R-HSA-6799641
Species: Homo sapiens
Compartment: specific granule lumen
Primary external reference: UniProt: PTPN6: P29350

Interactor (1 results from a total of 1)

Identifier: P29350-3
Species: Homo sapiens
Primary external reference: UniProt: P29350-3

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9008901
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000111679

Reaction (3 results from a total of 8)

Identifier: R-HSA-9701507
Species: Homo sapiens
Compartment: cytosol
PTPN6, also known as SHP1, dephosphorylates JAK3 downstream of ALK signaling, leading to the inactivation and increased proteolytic degradation of JAK3 (Han et al, 2006 a, b; reviewed in Palmer et al, 2009; Chiarle et al, 2008). PTPN6 gene expression is lost in some cases of anaplastic large cell lymphoma (ALCL) due to changes in promoter methylation, resulting in increased JAK3 activity in these cancers (Khoury et al, 2004; reviewed in Chiarle et al, 2008; Palmer et al, 2009).
Identifier: R-HSA-1169188
Species: Homo sapiens
Compartment: cytosol, plasma membrane
SHP1 (PTPN6) dephosphorylates GH-activated JAK2, limiting the duration of signaling (Hackett et al. 1999).
Identifier: R-HSA-5684169
Species: Homo sapiens
Compartment: cytosol, plasma membrane
G6B is a member of the immunoglobulin superfamily. The G6B-B variant is the only variant to contain both a transmembrane region and two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that support binding to the SH2 domain-containing protein tyrosine phosphatases PTPN6 (SHP1) and PTPN11 (SHP2) (de Vet et al. 2001, Senis et al. 2007). ITIMs are defined by the consensus sequence (L/I/V/S)-X-Y-X-X-(L/V) and are commonly present in pairs separated by 15 to 30 amino acid residues. ITIM-containing receptors were originally identified by their ability to inhibit signaling by ITAM receptors (Bijsterbosch & Klaus 1985). Expression of the GPVI-FcR gamma-chain complex orC-type lectin domain family 1 member B (CLEC1B, CLEC2) in DT40 (chicken) B cells leads to the generation of both constitutive and agonist-induced signals that are inhibited by G6B. This effect is dependent on the two ITIMs in the cytosolic tail of G6B, but is reported to be independent of the two SH2 domain-containing tyrosine phosphatases PTPN6 and PTPN11, and the inositol lipid 5”²-phosphatase SHIP1 (Mori et al. 2008). A more recent study (Coxon et al. 2011) found that other SH2 domain-containing proteins including SYK and PLCgamma2 also recognize G6B phosphomotifs, which may explain why G6B remains inhibitory in the absence of both PTPN6 and PTPN11.

The tandem SH2 domains of PTPN11 have a 100-fold higher binding affinity for G6B than that of PTPN6. PTPN6 has an absolute binding requirement for phosphorylation at both ITAM motifs, while PTPN11 can associate with G6B when only one motif is phosphorylated. The presence of dual phosphorylated G6B in washed human platelets reduced the EC(50) for both CRP and collagen-induced aggregation (Coxon et al. 2011). G6B is proposed to inhibit sustained constitutive signaling from GPVI-FcRgamma and CLEC1B (Mori et al. 2008).

Set (1 results from a total of 1)

Identifier: R-HSA-389744
Species: Homo sapiens
Compartment: cytosol

Complex (3 results from a total of 3)

Identifier: R-HSA-205181
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5690677
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-389749
Species: Homo sapiens
Compartment: plasma membrane

Pathway (1 results from a total of 1)

Identifier: R-HSA-391160
Species: Homo sapiens
Compartment: plasma membrane
Signal regulatory protein alpha (SIRPA, SHPS1, CD172a) is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a ligand for SIRP alpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRPA with CD47 is important for the regulation of migration and phagocytosis. SIRPA functions as a docking protein to recruit and activate PTPN6 (SHP-1) or PTPN11 (SHP-2) at the cell membrane in response to extracellular stimuli. SIRPA also binds other intracellular proteins including the adaptor molecules Src kinase-associated protein (SKAP2 SKAP55hom/R), Fyn-binding protein/SLP-76-associated phosphoprotein (FYB/SLAP-130) and the tyrosine kinase PYK2. SIRPA also binds the extracellular proteins, surfactant-A (SP-A) and surfactant-D (SP-D).
The SIRP family members SIRPB and SIRPG show high sequence similarity and similar extracellular structural topology, including three Ig domains, but their ligand binding topology might differ. SIRPB is expressed on myeloid cells, including monocytes, granulocytes and DCs. It has no known natural ligand. SIRPG can bind CD47 but with lower affinity than SIRPA.

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Steve Jupe
Designer: Cristoffer Sevilla
PTPN6 icon
Tyrosine-protein phosphatase non-receptor type 6
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