PTPN1

Protein tyrosine phosphatase, non-receptor type 1
	; PDB rendering based on 1a5y.
Available structures
PDB	1A5Y, 1AAX, 1BZC, 1BZH, 1BZJ, 1C83, 1C84, 1C85, 1C86, 1C87, 1C88, 1ECV, 1EEN, 1EEO, 1G1F, 1G1G, 1G1H, 1G7F, 1G7G, 1GFY, 1I57, 1JF7, 1KAK, 1KAV, 1L8G, 1LQF, 1NL9, 1NNY, 1NO6, 1NWE, 1NWL, 1NZ7, 1OEM, 1OEO, 1OES, 1OET, 1OEU, 1OEV, 1ONY, 1ONZ, 1PA1, 1PH0, 1PTT, 1PTU, 1PTV, 1PTY, 1PXH, 1PYN, 1Q1M, 1Q6J, 1Q6M, 1Q6N, 1Q6P, 1Q6S, 1Q6T, 1QXK, 1SUG, 1T48, 1T49, 1T4J, 1WAX, 1XBO, 2AZR, 2B07, 2B4S, 2BGD, 2BGE, 2CM2, 2CM3, 2CM7, 2CM8, 2CMA, 2CMB, 2CMC, 2CNE, 2CNF, 2CNG, 2CNH, 2CNI, 2F6F, 2F6T, 2F6V, 2F6W, 2F6Y, 2F6Z, 2F70, 2F71, 2FJM, 2FJN, 2H4G, 2H4K, 2HB1, 2HNP, 2HNQ, 2NT7, 2NTA, 2QBP, 2QBQ, 2QBR, 2QBS, 2VEU, 2VEV, 2VEW, 2VEX, 2VEY, 2ZMM, 2ZN7, 3A5J, 3A5K, 3CWE, 3D9C, 3EAX, 3EB1, 3EU0, 3I7Z, 3I80
Identifiers
Symbols	PTPN1; PTP1B
External IDs	OMIM: 176885 MGI: 97805 HomoloGene: 2119 GeneCards: PTPN1 Gene
EC number	3.1.3.48
Gene Ontology
Molecular function	• protein tyrosine phosphatase activity; • protein tyrosine phosphatase activity; • protein tyrosine phosphatase activity; • insulin receptor binding; • protein binding; • zinc ion binding; • hydrolase activity;
Cellular component	• insoluble fraction; • endoplasmic reticulum; • endoplasmic reticulum membrane; • cytosol; • cytosol; • membrane; • cytoplasmic vesicle;
Biological process	• signal transduction; • blood coagulation; • cytokine-mediated signaling pathway; • peptidyl-tyrosine dephosphorylation; • peptidyl-tyrosine dephosphorylation; • peptidyl-tyrosine dephosphorylation; • negative regulation of insulin receptor signaling pathway; • interferon-gamma-mediated signaling pathway; • regulation of interferon-gamma-mediated signaling pathway; • type I interferon-mediated signaling pathway; • regulation of type I interferon-mediated signaling pathway;
	Sources: Amigo / QuickGO
Orthologs

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Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene.^[1] PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes.^[2]

[edit] Function

PTP1B was first isolated from a human placental protein extract,^[3]^[4] but it is expressed in many tissues.^[5] PTP1B is localized to the cytoplasmic face of the endoplasmic reticulum.^[6] PTP1B can dephosphorylate the phosphotyrosine residues of the activated insulin receptor kinase.^[4]^[7]^[8] In mice, genetic ablation of PTPN1 results in enhanced insulin sensitivity.^[9]^[10] Several other tyrosine kinases, including epidermal growth factor receptor,^[11] insulin-like growth factor 1 receptor,^[12] colony stimulating factor 1 receptor,^[13] c-Src,^[14] Janus kinase 2,^[15] TYK2,^[15] and focal adhesion kinase^[16] as well as other tyrosine-phosphorylated proteins, including STAT5,^[17] BCAR1,^[18] DOK1,^[19] beta-catenin^[20] and cortactin^[21] have also been described as PTP1B substrates.

[edit] Interactions

PTPN1 has been shown to interact with BCAR1,^[18] epidermal growth factor receptor,^[22]^[23] Grb2^[18]^[24] and IRS1.^[24]^[25]

[edit] See also

Protein tyrosine phosphatase

[edit] References

^ Brown-Shimer S, Johnson KA, Lawrence JB, Johnson C, Bruskin A, Green NR, Hill DE (Aug 1990). "Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B". Proc Natl Acad Sci USA 87 (13): 5148–52. doi:10.1073/pnas.87.13.5148. PMC 54279. PMID 2164224. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54279.
^ Combs AP (March 2010). "Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer". J. Med. Chem. 53 (6): 2333–44. doi:10.1021/jm901090b. PMID 20000419.
^ Tonks NK, Diltz CD, Fischer EH (May 1988). "Purification of the major protein-tyrosine-phosphatases of human placenta". J. Biol. Chem. 263 (14): 6722–30. PMID 2834386. http://www.jbc.org/content/263/14/6722.full.pdf.
^ ^a ^b Tonks NK, Diltz CD, Fischer EH (May 1988). "Characterization of the major protein-tyrosine-phosphatases of human placenta". J. Biol. Chem. 263 (14): 6731–7. PMID 2834387. http://www.jbc.org/content/263/14/6731.full.pdf.
^ Chernoff J, Schievella AR, Jost CA, Erikson RL, Neel BG (April 1990). "Cloning of a cDNA for a major human protein-tyrosine-phosphatase". Proc. Natl. Acad. Sci. U.S.A. 87 (7): 2735–9. doi:10.1073/pnas.87.7.2735. PMC 53765. PMID 2157211. http://www.pnas.org/content/87/7/2735.abstract.
^ Frangioni JV, Beahm PH, Shifrin V, Jost CA, Neel BG (February 1992). "The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence". Cell 68 (3): 545–60. doi:10.1016/0092-8674(92)90190-N. PMID 1739967.
^ Cicirelli MF, Tonks NK, Diltz CD, Weiel JE, Fischer EH, Krebs EG (July 1990). "Microinjection of a protein-tyrosine-phosphatase inhibits insulin action in Xenopus oocytes". Proc. Natl. Acad. Sci. U.S.A. 87 (14): 5514–8. doi:10.1073/pnas.87.14.5514. PMC 54355. PMID 2164686. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54355.
^ Seely BL, Staubs PA, Reichart DR, Berhanu P, Milarski KL, Saltiel AR, Kusari J, Olefsky JM (October 1996). "Protein tyrosine phosphatase 1B interacts with the activated insulin receptor". Diabetes 45 (10): 1379–85. doi:10.2337/diabetes.45.10.1379. PMID 8826975.
^ Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP (March 1999). "Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene". Science 283 (5407): 1544–8. doi:10.1126/science.283.5407.1544. PMID 10066179.
^ Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM, Moghal N, Lubkin M, Kim YB, Sharpe AH, Stricker-Krongrad A, Shulman GI, Neel BG, Kahn BB (August 2000). "Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice". Mol. Cell. Biol. 20 (15): 5479–89. doi:10.1128/MCB.20.15.5479-5489.2000. PMC 85999. PMID 10891488. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85999.
^ Flint AJ, Tiganis T, Barford D, Tonks NK (March 1997). "Development of "substrate-trapping" mutants to identify physiological substrates of protein tyrosine phosphatases". Proc. Natl. Acad. Sci. U.S.A. 94 (5): 1680–5. doi:10.1073/pnas.94.5.1680. PMC 19976. PMID 9050838. http://www.pnas.org/content/94/5/1680.long.
^ Buckley DA, Cheng A, Kiely PA, Tremblay ML, O'Connor R (April 2002). "Regulation of Insulin-Like Growth Factor Type I (IGF-I) Receptor Kinase Activity by Protein Tyrosine Phosphatase 1B (PTP-1B) and Enhanced IGF-I-Mediated Suppression of Apoptosis and Motility in PTP-1B-Deficient Fibroblasts". Mol. Cell. Biol. 22 (7): 1998–2010. doi:10.1128/MCB.22.7.1998-2010.2002. PMC 133665. PMID 11884589. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133665.
^ Heinonen KM, Dubé N, Bourdeau A, Lapp WS, Tremblay ML (February 2006). "Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling". Proc. Natl. Acad. Sci. U.S.A. 103 (8): 2776–81. doi:10.1073/pnas.0508563103. PMC 1413784. PMID 16477024. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1413784.
^ Zhu S, Bjorge JD, Fujita DJ (November 2007). "PTP1B contributes to the oncogenic properties of colon cancer cells through Src activation". Cancer Res. 67 (21): 10129–37. doi:10.1158/0008-5472.CAN-06-4338. PMID 17974954.
^ ^a ^b Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, Parisien JP, Salmeen A, Barford D, Tonks NK (December 2001). "TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B". J. Biol. Chem. 276 (51): 47771–4. doi:10.1074/jbc.C100583200 (inactive 2010-09-10). PMID 11694501.
^ Zhang Z, Lin SY, Neel BG, Haimovich B (January 2006). "Phosphorylated alpha-actinin and protein-tyrosine phosphatase 1B coregulate the disassembly of the focal adhesion kinase x Src complex and promote cell migration". J. Biol. Chem. 281 (3): 1746–54. doi:10.1074/jbc.M509590200. PMID 16291744.
^ Aoki N, Matsuda T (December 2000). "A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b". J. Biol. Chem. 275 (50): 39718–26. doi:10.1074/jbc.M005615200. PMID 10993888.
^ ^a ^b ^c Liu F, Hill DE, Chernoff J (December 1996). "Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas)". J. Biol. Chem. 271 (49): 31290–5. doi:10.1074/jbc.271.49.31290. PMID 8940134.
^ Dubé N, Cheng A, Tremblay ML (February 2004). "The role of protein tyrosine phosphatase 1B in Ras signaling". Proc. Natl. Acad. Sci. U.S.A. 101 (7): 1834–9. doi:10.1073/pnas.0304242101. PMC 357013. PMID 14766979. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=357013.
^ Balsamo J, Arregui C, Leung T, Lilien J (October 1998). "The Nonreceptor Protein Tyrosine Phosphatase PTP1B Binds to the Cytoplasmic Domain of N-Cadherin and Regulates the Cadherin–Actin Linkage". J. Cell Biol. 143 (2): 523–32. doi:10.1083/jcb.143.2.523. PMC 2132848. PMID 9786960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132848.
^ Stuible M, Dubé N, Tremblay ML (June 2008). "PTP1B regulates cortactin tyrosine phosphorylation by targeting Tyr446". J. Biol. Chem. 283 (23): 15740–6. doi:10.1074/jbc.M710534200. PMID 18387954.
^ Sarmiento M, Puius YA, Vetter SW, Keng YF, Wu L, Zhao Y, Lawrence DS, Almo SC, Zhang ZY (July 2000). "Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition". Biochemistry 39 (28): 8171–9. doi:10.1021/bi000319w. PMID 10889023.
^ Zhang ZY, Walsh AB, Wu L, McNamara DJ, Dobrusin EM, Miller WT (March 1996). "Determinants of substrate recognition in the protein-tyrosine phosphatase, PTP1". J. Biol. Chem. 271 (10): 5386–92. doi:10.1074/jbc.271.10.5386. PMID 8621392.
^ ^a ^b Goldstein BJ, Bittner-Kowalczyk A, White MF, Harbeck M (February 2000). "Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein". J. Biol. Chem. 275 (6): 4283–9. doi:10.1074/jbc.275.6.4283. PMID 10660596.
^ Ravichandran LV, Chen H, Li Y, Quon MJ (October 2001). "Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor". Mol. Endocrinol. 15 (10): 1768–80. doi:10.1210/me.15.10.1768. PMID 11579209.