Phosphatase Subfamily PTPRN - Revision history

Gerard: /* Domain Structure */

2017-04-02T17:24:15Z

‎Domain Structure

Gerard: /* Evolution */

2016-03-07T06:57:49Z

‎Evolution

Gerard at 20:59, 6 March 2016

2016-03-06T20:59:46Z

Gerard: /* Domain Structure */

2016-03-06T20:53:32Z

‎Domain Structure

Gerard: /* Evolution */

2016-03-06T20:52:27Z

‎Evolution

Gerard: /* Drosophila IA-2 */

2016-01-04T06:01:45Z

‎Drosophila IA-2

Gerard at 06:01, 4 January 2016

2016-01-04T06:01:23Z

Gerard: /* C. elegans ida-1 */

2016-01-04T02:02:20Z

‎C. elegans ida-1

Gerard: /* Drosophila IA-2 */

2016-01-04T02:02:09Z

‎Drosophila IA-2

Gerard: /* Functions */

2016-01-04T02:01:35Z

‎Functions

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 ===Domain Structure===
-PTPRN has a extracellular region containning an N-terminal RESP18 domain and a membrane-proximal a ferredoxin-like fold domain (also known as [http://pfam.xfam.org/family/PF11548.3 Receptor_IA-2])  <cite>Primo08, Primo11, Noguera15</cite>. One of two C. elegans homologs lacks the signal peptide and extracellular domain homology, which may phenocopy the proteolytic cleavage of the cytoplasmic region seen in mammalian PTPRNs.
+Human PTPRNs have a extracellular region containning an N-terminal RESP18 domain and a membrane-proximal a ferredoxin-like domain (also known as [http://pfam.xfam.org/family/PF11548.3 Receptor_IA-2])  <cite>Primo08, Primo11, Noguera15</cite>.  The RESP18 is vertebrate specific, and the ferredoxin-like domain is also lost in nematodes. Drosophila and some other insects lack a clear signal peptide. This may phenocopy the proteolytic cleavage of the cytoplasmic region seen in mammalian PTPRNs.
 The cytoplasmic region has a putative PEST motif, followed by a phosphatase domain flanked by two short regions required to bind the β2‐syntrophin PDZ domain <cite>Ort01</cite>.

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 ===Evolution===
-PTPRN subfamily is found across metazoans, with no obvious losses. Human has two members, PTPRN (IA-2/ICA521) and PTPRN2 (phogrin/IA-2b).
+PTPRN is found across metazoans, with no obvious losses. Human has two members, PTPRN (IA-2/ICA521) and PTPRN2 (phogrin/IA-2b).
 ===Domain Structure===

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 Human PTPRN and PTPRN2 are expressed in pancreatic beta cells and were first characterized as [http://en.wikipedia.org/wiki/Antigen#Autoantigens autoantigens] leading to type I diabetes. They are also abundantly expressed in brain. They cycle between secretory vesicles and the plasma membrane and are believed to be involved in both endocrine and neuronal exocytosis <cite>Cai11</cite>.
-Both proteins have alterations to key residues in the phosphatase domain and lack phosphatase activity against PNPP or protein substrates.  Back mutation of D936A within the Cx5R motif of rat PTPRN2 restored some catalytic function against PNPP <cite>Fitzgerald</cite>, and additional mutations to restore the Y of the KNRY motif, and the P and D of the WPD motif further increased PNPP activity in mouse PTPRN (H740Y/A877D/D911A) or PTPRN2 (S762Y/Y898P/D933A) <cite>Drake</cite>. Rat PTPRN2 has been reported to act as a phosphatidylinositol phosphatase <cite>Caromile10</cite>, so these alterations to conserved motifs may play a role in substrate specificity rather than catalytic activity.
+Both proteins have alterations to key residues in the phosphatase domain and lack phosphatase activity against PNPP or protein substrates.  Back mutation of D936A within the Cx5R motif of rat PTPRN2 restored some catalytic function against PNPP <cite>Fitzgerald</cite>, and additional mutations to restore the Y of the KNRY motif, and the P and D of the WPD motif further increased PNPP activity in mouse PTPRN (H740Y/A877D/D911A) or PTPRN2 (S762Y/Y898P/D933A) <cite>Drake</cite>. Rat PTPRN2 has been reported to act as a phosphatidylinositol phosphatase <cite>Caromile10</cite>, so these alterations to conserved motifs may play a role in substrate specificity rather than catalytic activity, and suggest that all family members may be phosphatidylinositol rather than protein phosphatases.
-−
 ====== PTPRN (IA-2/ICA512) ======

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 ===Domain Structure===
-PTPRN has a extracellular region, a transmembrane domain and a cytoplasmic region. The extracellular region contains an N-terminal RESP18 domain and a membrane-proximal a ferredoxin-like fold domain also known as [http://pfam.xfam.org/family/PF11548.3 Receptor_IA-2]  <cite>Primo08, Primo11, Noguera15</cite>. One of two C. elegans homologs lacks the signal peptide and extracellular domain homology, which may phenocopy the proteolytic cleavage of the cytoplasmic region seen in mammalian PTPRNs.
+PTPRN has a extracellular region containning an N-terminal RESP18 domain and a membrane-proximal a ferredoxin-like fold domain (also known as [http://pfam.xfam.org/family/PF11548.3 Receptor_IA-2])  <cite>Primo08, Primo11, Noguera15</cite>. One of two C. elegans homologs lacks the signal peptide and extracellular domain homology, which may phenocopy the proteolytic cleavage of the cytoplasmic region seen in mammalian PTPRNs.
-The cytoplasmic region of PTPRN has a putative PEST motif, followed by a phosphatase domain flanked by two short regions required to bind the β2‐syntrophin PDZ domain <cite>Ort01</cite>.
+The cytoplasmic region has a putative PEST motif, followed by a phosphatase domain flanked by two short regions required to bind the β2‐syntrophin PDZ domain <cite>Ort01</cite>.
 ===Functions===

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 ===Evolution===
-PTPRN subfamily emerged in metazoa and duplicated in jawed vertebrates. Human has two members, PTPRN (IA-2/ICA521) and PTPRN2 (phogrin/IA-2b).
+PTPRN subfamily is found across metazoans, with no obvious losses. Human has two members, PTPRN (IA-2/ICA521) and PTPRN2 (phogrin/IA-2b).
 ===Domain Structure===

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 ======Drosophila  IA-2 ======
-IA-2 modulates insulin-like peptide expression expression and is expressed in the central nervous system and midgut <cite>Kim</cite>. The neuronal expression pattern was very similar to that mammalian PTPRN
+IA-2 modulates insulin-like peptide expression expression and is expressed in the central nervous system and midgut <cite>Kim</cite>. The neuronal expression pattern was very similar to that mammalian PTPRN.
 ====== ''C. elegans'' ida-1======

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 ====== ''C. elegans'' ida-1======
-C. elegans ida-1 is involved in dense-core vesicle cargo release with parallels to insulin signaling in mammals <cite>Zahn01, Cai04</cite>.
+ida-1 is involved in dense-core vesicle cargo release with parallels to insulin signaling in mammals <cite>Zahn01, Cai04</cite>.
 === [[Phosphatase_Subfamily_PTPRN_Tech_Note|Technical notes]] ===

← Older revision		Revision as of 02:01, 4 January 2016
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	Both proteins have alterations to key residues in the phosphatase domain and lack phosphatase activity against PNPP or protein substrates. Back mutation of D936A within the Cx5R motif of rat PTPRN2 restored some catalytic function against PNPP <cite>Fitzgerald</cite>, and additional mutations to restore the Y of the KNRY motif, and the P and D of the WPD motif further increased PNPP activity in mouse PTPRN (H740Y/A877D/D911A) or PTPRN2 (S762Y/Y898P/D933A) <cite>Drake</cite>. Rat PTPRN2 has been reported to act as a phosphatidylinositol phosphatase <cite>Caromile10</cite>, so these alterations to conserved motifs may play a role in substrate specificity rather than catalytic activity.		Both proteins have alterations to key residues in the phosphatase domain and lack phosphatase activity against PNPP or protein substrates. Back mutation of D936A within the Cx5R motif of rat PTPRN2 restored some catalytic function against PNPP <cite>Fitzgerald</cite>, and additional mutations to restore the Y of the KNRY motif, and the P and D of the WPD motif further increased PNPP activity in mouse PTPRN (H740Y/A877D/D911A) or PTPRN2 (S762Y/Y898P/D933A) <cite>Drake</cite>. Rat PTPRN2 has been reported to act as a phosphatidylinositol phosphatase <cite>Caromile10</cite>, so these alterations to conserved motifs may play a role in substrate specificity rather than catalytic activity.

−
−
−	~~Human PTPRN and PTPRN2 have been proposed to be enzymatically inactive due to mutations at catalytic Cx5R motif and WPD motif <cite>Kharitidi13</cite>.~~

	====== PTPRN (IA-2/ICA512) ======		====== PTPRN (IA-2/ICA512) ======