Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | no autoinhibition | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
plasma membrane | - |
Saccharomyces cerevisiae | 5886 | - |
plasma membrane | - |
Homo sapiens | 5886 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
[FYN kinase]-tyrosine phosphate + H2O | Homo sapiens | - |
[FYN kinase]-tyrosine + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9H3S7 | - |
- |
Saccharomyces cerevisiae | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
[FYN kinase]-tyrosine phosphate + H2O | - |
Homo sapiens | [FYN kinase]-tyrosine + phosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
HD-PTP | - |
Saccharomyces cerevisiae |
HD-PTP | - |
Homo sapiens |
His domain protein tyrosine phosphatase | - |
Saccharomyces cerevisiae |
His domain protein tyrosine phosphatase | - |
Homo sapiens |
PTPN23 | - |
Saccharomyces cerevisiae |
PTPN23 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | enzyme HD-PTP depletion causes a striking accumulation of tubulo-vesicular endosomal compartments that contain a build-up of ubiquitin-protein conjugates and reduces sorting of EGFR to the endosomal lumen | Homo sapiens |
metabolism | analysis of multivesicular body (MVB) sorting, involving the enzyme, of internalised membrane proteins that have entered the early endosome, overview. The multivesicular body is an intermediate compartment en route to the degradative milieu of the lysosome | Saccharomyces cerevisiae |
metabolism | analysis of multivesicular body (MVB) sorting, involving the enzyme, of internalised membrane proteins that have entered the early endosome, overview. The multivesicular body is an intermediate compartment en route to the degradative milieu of the lysosome | Homo sapiens |
additional information | in HD-PTP, the PRR is particularly extensive and is followed by a PTP domain and a PEST region. The PTP domain has no readily observable catalytic activity towards model PTPase substrates, but displays PTPase activity towards FYN kinase | Homo sapiens |
physiological function | role of His domain protein tyrosine phosphatase/PTPN23 (HD-PTP) and ESCRTs (endosomal sorting complexes required for transport) in sorting activated epidermal growth factor receptor to the multivesicular body, interactions involving HD-PTP and ESCRTs. HD-PTP acts selectively at the endosome and is essential for the forward movement of epidermal growth factor receptor (EGFR) from the early endosome towards the lysosome. HD-PTP binds the EGFR adaptor Grb2, via the proline-rich region (PRR). The importance of HD-PTP for MVB sorting is highlighted by its necessity for the down-regulation of platelet-derived growth factor receptor and alpha5beta1 integrin, as well as MHC (major histocompatibility complex) class I targeted by the K3 ubiquitin ligase of Karposi's sarcoma-associated herpes virus. Consistent with a role in receptor downregulation, HD-PTP is a tumour suppressor and HD-PTP haploinsufficiency is linked to a poor clinical prognosis. HD-PTP works closely with ESCRT-0, and indeed is essential for releasing EGFR from ESCRT-0 and allowing it to engage ESCRT-III. The ESCRT-0 subunit STAM2 binds directly to HD-PTP at two sites. HD-PTP forms an open console on which ESCRTs can shuffle via competitive interactions. STAM2, SARA and endofin can potentially modulate the multivesicular body (MVB) sorting of multiple receptors by preventing HD-PTP from binding to CHMP4B. Meanwhile, their regulated release can conceivably leave an opened binding pocket into which the CHMP4B C-terminal peptide is then accepted. This binding switch may explain how HD-PTP moves EGFR from ESCRT-0 towards ESCRT-III. Potential mechanism for EGFR sorting to the MVB, overview | Homo sapiens |
physiological function | role of His domain protein tyrosine phosphatase/PTPN23 (HD-PTP) and ESCRTs (endosomal sorting complexes required for transport) in sorting activated epidermal growth factor receptor to the multivesicular body, interactions involving HD-PTP and ESCRTs. Potential mechanism for EGFR sorting to the MVB, comparisons to Homo sapiens, overview | Saccharomyces cerevisiae |