PTPN1

Protein tyrosine phosphatase, non-receptor type 1
PDB rendering based on 1a5y.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 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, 3SME, 3ZV2
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 • insulin receptor binding • protein binding • zinc ion binding • hydrolase activity • ephrin receptor binding Cellular component • insoluble fraction • early endosome • endoplasmic reticulum • endoplasmic reticulum membrane • cytosol • plasma membrane • cytoplasmic vesicle Biological process • blood coagulation • regulation of signal transduction • cytokine-mediated signaling pathway • regulation of endocytosis • platelet activation • actin cytoskeleton reorganization • 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 • JAK-STAT cascade involved in growth hormone signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5770	19246
Ensembl	ENSG00000196396	ENSMUSG00000027540
UniProt	P18031	P35821
RefSeq (mRNA)	NM_002827.2	NM_011201.3
RefSeq (protein)	NP_002818.1	NP_035331.3
Location (UCSC)	Chr 20: 49.13 – 49.2 Mb	Chr 2: 167.76 – 167.8 Mb
PubMed search	[1]	[2]
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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]

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.

Interactions

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

See also

• Protein tyrosine phosphatase

References

v t e PDB gallery 1a5y: PROTEIN TYROSINE PHOSPHATASE 1B CYSTEINYL-PHOSPHATE INTERMEDIATE   1aax: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO BIS(PARA-PHOSPHOPHENYL)METHANE (BPPM) MOLECULES   1bzc: HUMAN PTP1B CATALYTIC DOMAIN COMPLEXED WITH TPI   1bzh: CYCLIC PEPTIDE INHIBITOR OF HUMAN PTP1B   1bzj: Human ptp1b complexed with tpicooh   1c83: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 6-(OXALYL-AMINO)-1H-INDOLE-5-CARBOXYLIC ACID   1c84: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 3-(OXALYL-AMINO)-NAPHTHALENE-2-CARBOXLIC ACID   1c85: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 2-(OXALYL-AMINO)-BENZOIC ACID   1c86: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (R47V,D48N) COMPLEXED WITH 2-(OXALYL-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID   1c87: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 2-(OXALYL-AMINO-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC ACID   1c88: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 2-(OXALYL-AMINO)-4,5,6,7-TETRAHYDRO-THIENO[2,3-C]PYRIDINE-3-CARBOXYLIC ACID   1ecv: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID   1een: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH ACETYL-D-A-D-BPA-PTYR-L-I-P-Q-Q-G   1eeo: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH ACETYL-E-L-E-F-PTYR-M-D-Y-E-NH2   1g1f: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A TRI-PHOSPHORYLATED PEPTIDE (RDI(PTR)ETD(PTR)(PTR)RK) FROM THE INSULIN RECEPTOR KINASE   1g1g: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A MONO-PHOSPHORYLATED PEPTIDE (ETDY(PTR)RKGGKGLL) FROM THE INSULIN RECEPTOR KINASE   1g1h: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH A BIS-PHOSPHORYLATED PEPTIDE (ETD(PTR)(PTR)RKGGKGLL) FROM THE INSULIN RECEPTOR KINASE   1g7f: HUMAN PTP1B CATALYTIC DOMAIN COMPLEXED WITH PNU177496   1g7g: HUMAN PTP1B CATALYTIC DOMAIN COMPLEXES WITH PNU179326   1gfy: RESIDUE 259 IS A KEY DETERMINANT OF SUBSTRATE SPECIFICITY OF PROTEIN-TYROSINE PHOSPHATASE 1B AND ALPHA   1i57: CRYSTAL STRUCTURE OF APO HUMAN PTP1B (C215S) MUTANT   1jf7: HUMAN PTP1B CATALYTIC DOMAIN COMPLEXED WITH PNU177836   1kak: Human Tyrosine Phosphatase 1B Complexed with an Inhibitor   1kav: Human Tyrosine Phosphatase 1B Complexed with an Inhibitor   1l8g: Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid   1lqf: Structure of PTP1b in Complex with a Peptidic Bisphosphonate Inhibitor   1nl9: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 12 Using a Linked-Fragment Strategy   1nny: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 23 Using a Linked-Fragment Strategy   1no6: Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy   1nwe: Ptp1B R47C Modified at C47 with N-[4-(2-{2-[3-(2-Bromo-acetylamino)-propionylamino]-3-hydroxy-propionylamino}-ethyl)-phenyl]-oxalamic acid   1nwl: Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic   1nz7: POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.   1oem: PTP1B WITH THE CATALYTIC CYSTEINE OXIDIZED TO A SULFENYL-AMIDE BOND   1oeo: PTP1B WITH THE CATALYTIC CYSTEINE OXIDIZED TO SULFONIC ACID   1oes: OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B   1oet: OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B   1oeu: OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B   1oev: OXIDATION STATE OF PROTEIN TYROSINE PHOSPHATASE 1B   1ony: Oxalyl-Aryl-Amino Benzoic Acid inhibitors of PTP1B, compound 17   1onz: Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b   1pa1: Crystal structure of the C215D mutant of protein tyrosine phosphatase 1B   1ph0: Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site   1ptt: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH PHOSPHOTYROSINE-CONTAINING TETRA-PEPTIDE (AC-DEPYL-NH2)   1ptu: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH PHOSPHOTYROSINE-CONTAINING HEXA-PEPTIDE (DADEPYL-NH2)   1ptv: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH PHOSPHOTYROSINE   1pty: CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO PHOSPHOTYROSINE MOLECULES   1pxh: Crystal structure of protein tyrosine phosphatase 1B with potent and selective bidentate inhibitor compound 2   1pyn: DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITE   1q1m: A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors   1q6j: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 2   1q6m: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 3   1q6n: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 4   1q6p: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 6   1q6s: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 9   1q6t: THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11   1qxk: Monoacid-Based, Cell Permeable, Selective Inhibitors of Protein Tyrosine Phosphatase 1B   1sug: 1.95 A structure of apo protein tyrosine phosphatase 1B   1t48: Allosteric Inhibition of Protein Tyrosine Phosphatase 1B   1t49: Allosteric Inhibition of Protein Tyrosine Phosphatase 1B   1t4j: Allosteric Inhibition of Protein Tyrosine Phosphatase 1B   1wax: PROTEIN TYROSINE PHOSPHATASE 1B WITH ACTIVE SITE INHIBITOR   1xbo: PTP1B complexed with Isoxazole Carboxylic Acid   2azr: Crystal structure of PTP1B with Bicyclic Thiophene inhibitor   2b07: Crystal structure of PTP1B with Tricyclic Thiophene inhibitor.   2b4s: Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase   2bgd: STRUCTURE-BASED DESIGN OF PROTEIN TYROSINE PHOSPHATASE-1B INHIBITORS   2bge: STRUCTURE-BASED DESIGN OF PROTEIN TYROSINE PHOSPHATASE-1B INHIBITORS   2cm2: STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (P212121)   2cm3: STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B (C2)   2cm7: STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS   2cm8: STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS   2cma: STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS   2cmb: STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS   2cmc: STRUCTURAL BASIS FOR INHIBITION OF PROTEIN TYROSINE PHOSPHATASE 1B BY ISOTHIAZOLIDINONE HETEROCYCLIC PHOSPHONATE MIMETICS   2cne: STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B   2cnf: STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B   2cng: STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B   2cnh: STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B   2cni: STRUCTURAL INSIGHTS INTO THE DESIGN OF NONPEPTIDIC ISOTHIAZOLIDINONE-CONTAINING INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B   2f6f: The structure of the S295F mutant of human PTP1B   2f6t: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f6v: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f6w: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f6y: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f6z: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f70: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2f71: Protein tyrosine phosphatase 1B with sulfamic acid inhibitors   2fjm: The structure of phosphotyrosine phosphatase 1B in complex with compound 2   2fjn: The structure of phosphotyrosine phosphatase 1B in complex with compound 2   2h4g: Crystal structure of PTP1B with monocyclic thiophene inhibitor   2h4k: Crystal structure of PTP1B with a monocyclic thiophene inhibitor   2hb1: Crystal Structure of PTP1B with Monocyclic Thiophene Inhibitor   2hnp: CRYSTAL STRUCTURE OF HUMAN PROTEIN TYROSINE PHOSPHATASE 1B   2hnq: CRYSTAL STRUCTURE OF HUMAN PROTEIN TYROSINE PHOSPHATASE 1B   2nt7: Crystal structure of PTP1B-inhibitor complex   2nta: Crystal Structure of PTP1B-inhibitor Complex

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