Difference between revisions of "Phosphatase Subfamily PTPN1"

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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_PTPN1|Subfamily PTPN1]]
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__NOTOC__
  
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PTPN1 subfamily dephoshorylate kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2). The phosphatase emerged later than the related kinases. The phosphatase first emerged in Trichoplax. EGFR is conserved from sponge to human but lost in Trichoplax, and InsR is conserved from Trichoplax to human.
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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_PTPN1|Subfamily PTPN1]]
  
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=== Evolution ===
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The PTPN1 subfamily dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).  
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PTPN1 subfamily emerged in animals, as it is found in most if not all eumetazoa, Porifera (e.g. sponge) and Placozoa (e.g. Trichoplax), but absent from Choanoflagellata (e.g. Monosiga) (for the phylogeny of animal at [http://en.wikipedia.org/wiki/Animal#Ctenophora.2C_Porifera.2C_Placozoa.2C_Cnidaria_and_Bilateria here]). In human, there are two copies:  [[Phosphatase_Gene_PTPN1|PTPN1 (PTP1B)]] and [[Phosphatase_Gene_PTPN2|PTPN2]]. The two copies can be traced back to the time when vertebrates emerged. The orthologs for each of them are found in most vertebrates from fish to primates, and there is a single copy in non-vertebrate metazoa.
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It substrate EGFR is conserved from sponge to human but lost in Trichoplax, and InsR is conserved from Trichoplax to human.
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===Evolution===
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PTPN1 subfamily emerged in animals, as it is found in most if not all eumetazoa, Porifera (e.g. sponge) and Placozoa (e.g. Trichoplax), but absent from Choanoflagellata (e.g. Monosiga) (for the phylogeny of animal at [http://en.wikipedia.org/wiki/Animal#Ctenophora.2C_Porifera.2C_Placozoa.2C_Cnidaria_and_Bilateria here]). In human, there are two copies:  [[Phosphatase_Gene_PTPN1|PTPN1 (PTP1B)]] and [[Phosphatase_Gene_PTPN2|PTPN2 (TCPTP)]]. The two copies can be traced back to the time when vertebrates emerged. The orthologs for each of them are found in most vertebrates from fish to primates, and there is a single copy in non-vertebrate metazoa.
  
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(PS: Why PTPN1 and PTPN2 have different functions?)
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===Domain ===
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The PTPN1 subfamily has a single structural domain, phosphatase domain.
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===Functions===
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The PTPN1 subfamily has various functions <cite>Zabolotny02, Tonks03, Zhang07, Tiganis13</cite>. It dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).
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PTPN1 is regulated via glutathionylation of cysteine at the catalytic motif Cx5R <cite>Barrett99</cite>.
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===References===
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<biblio>
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#Barrett99 pmid=10350489
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#Tiganis13 pmid=22404968
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#Tonks03 pmid=12829250
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#Zabolotny02 pmid=11970898
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#Zhang07 pmid=17467573
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</biblio>

Revision as of 23:49, 24 March 2015


Phosphatase Classification: Fold CC1:Superfamily CC1: Family PTP: Subfamily PTPN1

The PTPN1 subfamily dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).

Evolution

PTPN1 subfamily emerged in animals, as it is found in most if not all eumetazoa, Porifera (e.g. sponge) and Placozoa (e.g. Trichoplax), but absent from Choanoflagellata (e.g. Monosiga) (for the phylogeny of animal at here). In human, there are two copies: PTPN1 (PTP1B) and PTPN2 (TCPTP). The two copies can be traced back to the time when vertebrates emerged. The orthologs for each of them are found in most vertebrates from fish to primates, and there is a single copy in non-vertebrate metazoa.

Domain

The PTPN1 subfamily has a single structural domain, phosphatase domain.

Functions

The PTPN1 subfamily has various functions [1, 2, 3, 4]. It dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).

PTPN1 is regulated via glutathionylation of cysteine at the catalytic motif Cx5R [5].

References

  1. Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim YB, Elmquist JK, Tartaglia LA, Kahn BB, and Neel BG. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002 Apr;2(4):489-95. DOI:10.1016/s1534-5807(02)00148-x | PubMed ID:11970898 | HubMed [Zabolotny02]
  2. Tonks NK. PTP1B: from the sidelines to the front lines!. FEBS Lett. 2003 Jul 3;546(1):140-8. DOI:10.1016/s0014-5793(03)00603-3 | PubMed ID:12829250 | HubMed [Tonks03]
  3. Zhang S and Zhang ZY. PTP1B as a drug target: recent developments in PTP1B inhibitor discovery. Drug Discov Today. 2007 May;12(9-10):373-81. DOI:10.1016/j.drudis.2007.03.011 | PubMed ID:17467573 | HubMed [Zhang07]
  4. Tiganis T. PTP1B and TCPTP--nonredundant phosphatases in insulin signaling and glucose homeostasis. FEBS J. 2013 Jan;280(2):445-58. DOI:10.1111/j.1742-4658.2012.08563.x | PubMed ID:22404968 | HubMed [Tiganis13]
  5. Barrett WC, DeGnore JP, König S, Fales HM, Keng YF, Zhang ZY, Yim MB, and Chock PB. Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry. 1999 May 18;38(20):6699-705. DOI:10.1021/bi990240v | PubMed ID:10350489 | HubMed [Barrett99]
All Medline abstracts: PubMed | HubMed
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