protein tyrosine phosphatase non-receptor type 1 | Protein tyrosine phosphatases non-receptor type (PTPN) | IUPHAR/BPS Guide to PHARMACOLOGY

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protein tyrosine phosphatase non-receptor type 1

Target not currently curated in GtoImmuPdb

Target id: 2976

Nomenclature: protein tyrosine phosphatase non-receptor type 1

Abbreviated Name: PTP1B

Family: Protein tyrosine phosphatases non-receptor type (PTPN)

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 435 20q13.13 PTPN1 protein tyrosine phosphatase non-receptor type 1 1
Mouse - 432 2 H3 Ptpn1 protein tyrosine phosphatase, non-receptor type 1
Rat - 432 3q42 Ptpn1 protein tyrosine phosphatase, non-receptor type 1
Gene and Protein Information Comments
A second isoform from the human gene with a shorter N-terminus has been detected (RefSeq NP_001265547).
Previous and Unofficial Names
protein tyrosine phosphatase | protein tyrosine phosphatase, non-receptor type 1 | PTP1B
Database Links
BRENDA 3.1.3.48
ChEMBL Target CHEMBL335 (Hs), CHEMBL3336 (Mm), CHEMBL2371 (Rn)
Ensembl Gene ENSG00000196396 (Hs), ENSMUSG00000027540 (Mm), ENSRNOG00000010574 (Rn)
Entrez Gene 5770 (Hs), 19246 (Mm), 24697 (Rn)
Human Protein Atlas ENSG00000196396 (Hs)
KEGG Enzyme 3.1.3.48
KEGG Gene hsa:5770 (Hs), mmu:19246 (Mm), rno:24697 (Rn)
OMIM 176885 (Hs)
RefSeq Nucleotide NM_002827 (Hs), NM_011201 (Mm), NM_012637 (Rn)
RefSeq Protein NP_002818 (Hs), NP_035331 (Mm), NP_036769 (Rn)
UniProtKB P18031 (Hs), P35821 (Mm), P20417 (Rn)
Wikipedia PTPN1 (Hs)
Enzyme Reaction
EC Number: 3.1.3.48
Description Reaction Reference
Dephosphorylates O-phosphotyrosine groups in phosphoproteins. Protein tyrosine phosphate + H2O <=> protein tyrosine + phosphate

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NC1 Hs Inhibition 5.1 pKi 4
⤷ pKi 5.1 (Ki 8x10-6 M) [4]
HPN Hs Inhibition 6.2 pIC50 7
⤷ pIC50 6.2 (IC50 6.3x10-7 M) [7]
Description: In a surface plasmon resonance (SPR) assay using immobilised recombinant enzyme PTP1B1–321.
trodusquemine Hs Inhibition 6.0 pIC50 3
⤷ pIC50 6.0 (IC50 1x10-6 M) [3]
Description: In a cell-free assay using recombinant enzyme.
compound 7b [Haftchenary et al., 2013] Hs Inhibition 5.3 pIC50 2
⤷ pIC50 5.3 (IC50 4.9x10-6 M) [2]
I-C11 Hs Inhibition 4.9 pIC50 9
⤷ pIC50 4.9 (IC50 1.18x10-5 M) [9]
General Comments
PTPN1 (a.k.a. PTP1B) is a non-receptor protein tyrosine phosphatase. It negatively regulates insulin signalling by dephosphorylating the phosphotryosine residues on the insulin receptor. It is a potential drug target for the treatment of type 2 diabetes (insulin resistance) [5]. PTPN1 inhibitors have been reported to have hypoglycaemic and other anti-diabetic effects [6,8].

References

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1. Brown-Shimer S, Johnson KA, Lawrence JB, Johnson C, Bruskin A, Green NR, Hill DE. (1990) Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B. Proc. Natl. Acad. Sci. U.S.A., 87 (13): 5148-52. [PMID:2164224]

2. Haftchenary S, Ball DP, Aubry I, Landry M, Shahani VM, Fletcher S, Page BDG, Jouk AO, Tremblay ML, Gunning PT. (2013) Identification of a potent salicylic acid-based inhibitor of tyrosine phosphatase PTP1B. MedChemComm., (4): 987-992.

3. Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, McLane MP. (2010) Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring), 18 (8): 1516-23. [PMID:20075852]

4. Li K, Hou X, Li R, Bi W, Yang F, Chen X, Xiao P, Liu T, Lu T, Zhou Y et al.. (2019) Identification and structure-function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22. J. Biol. Chem., 294 (21): 8653-8663. [PMID:30979725]

5. Liu G, Trevillyan JM. (2002) Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr Opin Investig Drugs, 3 (11): 1608-16. [PMID:12476961]

6. Luo J, Xu Q, Jiang B, Zhang R, Jia X, Li X, Wang L, Guo C, Wu N, Shi D. (2018) Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor. Br. J. Pharmacol., 175 (1): 140-153. [PMID:29059712]

7. Shi D, Guo S, Jiang B, Guo C, Wang T, Zhang L, Li J. (2013) HPN, a synthetic analogue of bromophenol from red alga Rhodomela confervoides: synthesis and anti-diabetic effects in C57BL/KsJ-db/db mice. Mar Drugs, 11 (2): 350-62. [PMID:23364683]

8. Taylor SD, Hill B. (2004) Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs, 13 (3): 199-214. [PMID:15013940]

9. Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. (2007) Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc. Natl. Acad. Sci. U.S.A., 104 (50): 19767-72. [PMID:18056643]

How to cite this page

Protein tyrosine phosphatases non-receptor type (PTPN): protein tyrosine phosphatase non-receptor type 1. Last modified on 06/05/2019. Accessed on 19/02/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2976.