Phosphatase Subfamily PTPN23 - Revision history

Gerard: /* Interacting partners */

2017-07-24T07:59:43Z

‎Interacting partners

Gerard: /* Domain Structure */

2017-04-13T23:47:23Z

‎Domain Structure

Gerard at 23:45, 13 April 2017

2017-04-13T23:45:59Z

Gerard at 23:44, 13 April 2017

2017-04-13T23:44:43Z

Gerard: /* Is PTPN23 catalytically inactive? */

2016-09-07T22:23:29Z

‎Is PTPN23 catalytically inactive?

Gerard: /* Is PTPN23 catalytically inactive? */

2016-09-07T22:22:22Z

‎Is PTPN23 catalytically inactive?

Gerard: /* Is PTPN23 catalytically inactive? */

2016-09-07T22:07:16Z

‎Is PTPN23 catalytically inactive?

Gerard at 22:06, 7 September 2016

2016-09-07T22:06:15Z

Gerard: /* Functions */

2016-09-07T22:05:33Z

‎Functions

Gerard: /* Is PTPN23 catalytically inactive? */

2016-09-07T22:04:07Z

‎Is PTPN23 catalytically inactive?

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 ====== Interacting partners ======
-PTPN23 has below interacting partners, which functions in endosomal protein sorting and trafficking, apoptosis, and cell adhesion. Thus, PTPN23 is probably involved in these processes, too. In fact, PTPN23 is a key regulator of endocytic trafficking in which ESCRT-III binding is important but not strictly essential <cite>Doyotte08</cite>. PTPN23 also acts as a central coordinator of the ESCRT pathway for EGFR, where concerted recruitment of CHMP4B and UBPY to PTPN23 and the engagement of UBPY/USP8 by STAM2 displaces ESCRT-0 from PTPN23, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III <cite>Ali13</cite>.
+PTPN23 has several interacting partners, which function in endosomal protein sorting and trafficking, apoptosis, and cell adhesion. PTPN23 is a known regulator of endocytic trafficking in which ESCRT-III binding is important but not strictly essential <cite>Doyotte08</cite>. PTPN23 also acts as a central coordinator of the ESCRT pathway for EGFR, where concerted recruitment of CHMP4B and UBPY to PTPN23 and the engagement of UBPY/USP8 by STAM2 displaces ESCRT-0 from PTPN23, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III <cite>Ali13</cite>.
 * [http://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&dopt=default&rn=1&list_uids=128866 CHMP4B], charged multivesicular body protein 4B, a component of the endosomal sorting complex required for transport (ESCRT) complex III (ESCRT-III), which functions in the sorting of endocytosed cell-surface receptors into multivesicular endosomes. The interaction is mediated by BRO1 domain of PTPN23 <cite>Ichioka07, Ali13</cite>.
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 * Rab4. PTPN23 interacts with Rab4 and regulates the spatial distribution of Rab4 and integrin trafficking in human and fruit fly, therefore modulating cell adhesion and migration <cite>Chen12</cite>.
 * FAK, Focal Adhesion Kinase, a crucial regulator of cell migration. PTPN23 is a negative regulator of FAK phosphorylation, but it is unclear whether it dephosphorylates FAK in vivo <cite>Castiglioni07</cite>.
 ====== PTPN23 and cancer ======

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 ===Domain Structure ===
-PTPN23 has an N-terminal BRO1 domain not seen in other protein phosphatases. The BRO1 domain of fungal and mammalian proteins binds with multivesicular body components (ESCRT-III proteins) such as yeast Snf7 and mammalian CHMP4b, and can function to target BRO1 domain-containing proteins to endosomes (see [http://www.ebi.ac.uk/interpro/entry/IPR004328 InterPro]).
+PTPN23 has an N-terminal BRO1 domain not seen in other protein phosphatases. Fungal and mammalian BRO1 domains bind multivesicular body components (ESCRT-III proteins) such as yeast Snf7 and mammalian CHMP4b, and can target BRO1 domain-containing proteins to endosomes (see [http://www.ebi.ac.uk/interpro/entry/IPR004328 InterPro]).
-PTPN23 has five other main regions: an ALIX_LYPXL_bnd domain immediately after the BRO1 domain, a central proline-rich domain with numerous dispersed His residues (HD), a phosphatase domain (PTP) and a second proline-rich domain towards the C-terminal end. Both the central and the C-terminal proline-rich domains have PEST motifs and appear to have disordered secondary structures <cite>Tanase10</cite> and Figure 2 <cite>Ali13</cite>. The accessory domains mediates the interactions with different protein (see below).
+PTPN23 has five other main regions: an ALIX_LYPXL_bnd domain immediately after the BRO1 domain, a central proline-rich domain with numerous dispersed His residues (HD), a phosphatase domain (PTP) and a second proline-rich domain towards the C-terminal end. Both the central and the C-terminal proline-rich domains have PEST motifs and appear to have disordered secondary structures <cite>Tanase10</cite> and Figure 2 <cite>Ali13</cite>. The accessory domains mediates the interactions with different proteins (see below).
 ===Functions===

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 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_PTP|Family PTP]]: [[Phosphatase_Subfamily_PTPN23|Subfamily PTPN23]] (HD-PTP)
-PTPN23 subfamily functions in endosomal protein sorting. It has a signature BRO1 domain that distinguishes it from other protein phosphatases. It is under debate whether PTPN23 is catalytically inactive. PTPN23 emerged in holozoan but absent from some individual lineages, such as sponge and nematode.
+PTPN23 functions in endosomal protein sorting. It has a signature BRO1 domain that distinguishes it from other protein phosphatases. It is unclear whether PTPN23 is catalytically inactive. PTPN23 emerged in holozoa but absent from some lineages, such as sponge and nematodes.
 ===Evolution===
@@ Line 56: / Line 56: @@
 #Castiglioni12 pmid=22510412
 #Chen12 pmid=22825871
-#Chen pmid= 8400531
+#Chen pmid=28400531
 #Doyotte08 pmid=18434552
 #Ichioka07 pmid=17174262

@@ Line 5: / Line 5: @@
 ===Evolution===
-PTPN23 is found across [[holozoa]]. Nematodes have a protein (ego-2/Y53H1C in C. elegans) that retains the BRO1 and ALIX_LYPXL_bnd domains but has lost the phosphatase domain. Fungi also have a BRO1-ALIX_LYPXL_bnd protein (e.g. S. cerevisiae Bro1)
+PTPN23 is found across [[holozoa]]. <cite>Chen</cite>. A nematode ortholog (ego-2/Y53H1C in C. elegans) retains the BRO1 and ALIX_LYPXL_bnd domains but has lost the phosphatase domain. Fungi also have a likely ortholog (Bro1 in S. cerevisiae) that lacks a phosphatase domain, but retains the BRO1 and ALIX_LYPXL_bnd domains.
 ===Domain Structure ===
@@ Line 56: / Line 56: @@
 #Castiglioni12 pmid=22510412
 #Chen12 pmid=22825871
 #Doyotte08 pmid=18434552
 #Ichioka07 pmid=17174262

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 ====== Is PTPN23 catalytically inactive? ======
-PTPN23 was reported to be catalytically inactive, with no phosphatase activity toward tyrosine or lipids <cite>Gingras09</cite>. It was proposed that serine at position 1452 within Cx5R catalytic motif caused the inactivity. Replacing serine with alanine, which is found in catalytically active PTPs, induced tyrosine phosphatase activity <cite>Gingras09</cite>. The serine is conserved in all vertebrate PTPN23; some invertebrate PTPN23 have alanine in this position, and others have other residues that may or may not be catalytically active.
+PTPN23 was reported to be catalytically inactive, with no phosphatase activity toward tyrosine or lipids <cite>Gingras09</cite>. It was proposed that serine at position 1452 within Cx5R catalytic motif caused the inactivity. Replacing serine with alanine, which is found in catalytically active PTPs, induced tyrosine phosphatase activity <cite>Gingras09</cite>. The serine is conserved in all vertebrate PTPN23; some invertebrate PTPN23 have alanine in this position (e.g. Monosiga, Nematostella and sea urchin), and others have other residues that may or may not be catalytically active.
 Other studies have disagreed on catalytic activity: one claimed that Src, E-cadherin, and beta-catenin are direct substrates of PTPN23 <cite>Lin11</cite>, while another showed that PTPN23 did not modulate the levels of Src phosphorylation either in vitro and in vivo <cite>Mariotti09</cite>.

@@ Line 59: / Line 59: @@
 #Ichioka07 pmid=17174262
 #Gingras09 pmid=19340315
 #Lin11 pmid=21724833
 #Mariotti06 pmid=16720300

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 ===Functions===
-PTPN23 is widely expressed in different tissues (see [http://www.gtexportal.org/home/gene/PTPN23 GTEx]). Fibroblast Growth Factor-2 induces PTPN23 degradation via the proteasome, while Vascular Endothelial Growth Factor does not affect protein levels <cite>Mariotti06</cite>.
+PTPN23 is widely expressed in different tissues (see [http://www.gtexportal.org/home/gene/PTPN23 GTEx]). Fibroblast Growth Factor-2 induces PTPN23 degradation via the proteasome, while VEGF did not <cite>Mariotti06</cite>.
 ====== Is PTPN23 catalytically inactive? ======

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 ====== Is PTPN23 catalytically inactive? ======
-PTPN23 was reported to be catalytically inactive, - no phosphatase activity toward tyrosine or lipid. It was proposed that serine at position 1452 within Cx5R catalytic motif caused the inactivity. Replacing serine with alanine, which is found in catalytically active PTPs, can restore the phosphatase activity <cite>Gingras09</cite>.
+PTPN23 was reported to be catalytically inactive, with no phosphatase activity toward tyrosine or lipids <cite>Gingras09</cite>. It was proposed that serine at position 1452 within Cx5R catalytic motif caused the inactivity. Replacing serine with alanine, which is found in catalytically active PTPs, restored the phosphatase activity <cite>Gingras09</cite>.
 However, another study found SRC, E-cadherin, and beta-catenin are direct substrates of PTPN23 <cite>Lin11</cite>. But, yet another study showed that PTPN23 did not modulate the levels of Src phosphorylation both in vitro and in vivo <cite>Mariotti09</cite>.