SMART: PTPc_DSPc domain annotation

PTPc_DSPc Protein tyrosine phosphatase, catalytic domain, undefined specificity

SMART accession number:	SM00012
Description:	Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.
Family alignment:	View or

There are 23 PTPc_DSPc domains in 22 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PTPc_DSPc domain is also avaliable.

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Go to specific node: Mus musculus, Rattus norvegicus
Cellular role (predicted cellular role)
Cellular role: signalling
Binding / catalysis: protein tyrosine phosphatase
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- VanVactor D
- Protein tyrosine phosphatases in the developing nervous system.
- Curr Opin Cell Biol. 1998; 10: 174-81
- Display abstract
- Protein tyrosine phosphatases (PTPs) constitute a diverse family of intracellular and transmembrane proteins. Expression data and recent genetic analyses indicate that many PTPs play important roles in different aspects of nervous system development. Although PTP mechanisms are still poorly understood, current data suggest considerable complexity in these signaling pathways.
- Zhang ZY
- Protein-tyrosine phosphatases: biological function, structural characteristics, and mechanism of catalysis.
- Crit Rev Biochem Mol Biol. 1998; 33: 1-52
- Display abstract
- The protein-tyrosine phosphatases (PTPases) superfamily consists of tyrosine-specific phosphatases, dual specificity phosphatases, and the low-molecular-weight phosphatases. They are modulators of signal transduction pathways that regulate numerous cell functions. Malfunction of PTPases have been linked to a number of oncogenic and metabolic disease states, and PTPases are also employed by microbes and viruses for pathogenicity. There is little sequence similarity among the three subfamilies of phosphatases. Yet, three-dimensional structural data show that they share similar conserved structural elements, namely, the phosphate-binding loop encompassing the PTPase signature motif (H/V)C(X)5R(S/T) and an essential general acid/base Asp residue on a surface loop. Biochemical experiments demonstrate that phosphatases in the PTPase superfamily utilize a common mechanism for catalysis going through a covalent thiophosphate intermediate that involves the nucleophilic Cys residue in the PTPase signature motif. The transition states for phosphoenzyme intermediate formation and hydrolysis are dissociative in nature and are similar to those of the solution phosphate monoester reactions. One strategy used by these phosphatases for transition state stabilization is to neutralize the developing negative charge in the leaving group. A conformational change that is restricted to the movement of a flexible loop occurs during the catalytic cycle of the PTPases. However, the relationship between loop dynamics and enzyme catalysis remains to be established. The nature and identity of the rate-limiting step in the PTPase catalyzed reaction requires further investigation and may be dependent on the specific experimental conditions such as temperature, pH, buffer, and substrate used. In-depth kinetic and structural analysis of a representative number of phosphatases from each group of the PTPase superfamily will most likely continue to yield insightful mechanistic information that may be applicable to the rest of the family members.
- Neel BG, Tonks NK
- Protein tyrosine phosphatases in signal transduction.
- Curr Opin Cell Biol. 1997; 9: 193-204
- Display abstract
- Protein-tyrosyl phosphorylation, regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs), is a key cellular control mechanism. Until recently, little was known about PTPs. However, the past two years have witnessed an explosion of information about PTP structure, regulation and function. Crystal structures of several PTPs have provided insights into enzymatic mechanisms and regulation and suggested the design of 'substrate-trapping' mutants. Candidate homophilic and heterophilic ligands for transmembrane PTPs have been identified, and roles for transmembrane PTPs in regulating cell-cell interactions have been suggested. Finally, progress has been made in understanding signaling by Src homology 2 domain containing PTPs and PTPs controlling yeast osmoregulatory pathways.
- Takagi T, Moore CR, Diehn F, Buratowski S
- An RNA 5'-triphosphatase related to the protein tyrosine phosphatases.
- Cell. 1997; 89: 867-73
- Display abstract
- mRNA capping requires the sequential action of three enzymatic activities: RNA triphosphatase, guanylyl-transferase, and methyltransferase. Here we characterize a gene (CEL-1) believed to encode the C. elegans capping enzyme. CEL-1 has a C-terminal domain containing motifs found in yeast and vaccinia virus capping enzyme guanylyltransferases. The N-terminal domain of CEL-1 has RNA triphosphatase activity. Surprisingly, this domain does not resemble the vaccinia virus capping enzyme but does have significant sequence similarity to the protein tyrosine phosphatase (PTP) enzyme family. However, CEL-1 has no detectable PTP activity. The mechanism of the RNA triphosphatase is similar to that of PTPs: the active site contains a conserved nucleophilic cysteine required for activity. These results broaden the superfamily of PTP-like phosphatases to include enzymes with RNA substrates.
- Zhang ZY
- Structure, mechanism, and specificity of protein-tyrosine phosphatases.
- Curr Top Cell Regul. 1997; 35: 21-68
- Fauman EB, Saper MA
- Structure and function of the protein tyrosine phosphatases.
- Trends Biochem Sci. 1996; 21: 413-7
- Display abstract
- The tyrosine and dual-specificity phosphatases are involved in signaling, cell growth and differentiation, and the cell cycle. The enzymes share a common catalytic mechanism mediated by an active site cysteine, arginine and aspartic acid. Supplementary domains assist in targeting and substrate specificity.
- Tonks NK, Neel BG
- From form to function: signaling by protein tyrosine phosphatases.
- Cell. 1996; 87: 365-8
- Yuvaniyama J, Denu JM, Dixon JE, Saper MA
- Crystal structure of the dual specificity protein phosphatase VHR.
- Science. 1996; 272: 1328-31
- Display abstract
- Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Here, the crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), was determined at 2.1 angstrom resolution. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A "recognition region," connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs.
- Barford D, Jia Z, Tonks NK
- Protein tyrosine phosphatases take off.
- Nat Struct Biol. 1995; 2: 1043-53
- Display abstract
- Protein tyrosine phosphatases (PTPs) are a family of signal transduction enzymes that dephosphorylate phosphotyrosine containing proteins. Structural and kinetic studies provide a molecular understanding of how these enzymes regulate a wide range of intracellular processes.
- Egloff MP, Cohen PT, Reinemer P, Barford D
- Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate.
- J Mol Biol. 1995; 254: 942-59
- Display abstract
- Protein phosphatase 1 (PP1) is a serine/threonine protein phosphatase that is essential in regulating diverse cellular processes. Here we report the crystal structure of the catalytic subunit of human PP1 gamma 1 and its complex with tungstate at 2.5 A resolution. The anomalous scattering from tungstate was used in a multiple wavelength anomalous dispersion experiment to derive crystallographic phase information. The protein adopts a single domain with a novel fold, distinct from that of the protein tyrosine phosphatases. A di-nuclear ion centre consisting of Mn2+ and Fe2+ is situated at the catalytic site that binds the phosphate moiety of the substrate. Proton-induced X-ray emission spectroscopy was used to identify the nature of the ions bound to the enzyme. The structural data indicate that dephosphorylation is catalysed in a single step by a metal-activated water molecule. This contrasts with other phosphatases, including protein tyrosine phosphatases, acid and alkaline phosphatases which form phosphoryl-enzyme intermediates. The structure of PP1 provides insight into the molecular mechanism for substrate recognition, enzyme regulation and inhibition of this enzyme by toxins and tumour promoters and a basis for understanding the expanding family of related phosphatases which include PP2A and PP2B (calcineurin).
- Jia Z, Barford D, Flint AJ, Tonks NK
- Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.
- Science. 1995; 268: 1754-8
- Display abstract
- The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the period and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.
- Barford D, Flint AJ, Tonks NK
- Crystal structure of human protein tyrosine phosphatase 1B.
- Science. 1994; 263: 1397-404
- Display abstract
- Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of phosphotyrosine residues and are characterized by homologous catalytic domains. The crystal structure of a representative member of this family, the 37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 A resolution. The enzyme consists of a single domain with the catalytic site located at the base of a shallow cleft. The phosphate recognition site is created from a loop that is located at the amino-terminus of an alpha helix. This site is formed from an 11-residue sequence motif that is diagnostic of PTPs and the dual specificity phosphatases, and that contains the catalytically essential cysteine and arginine residues. The position of the invariant cysteine residue within the phosphate binding site is consistent with its role as a nucleophile in the catalytic reaction. The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.
- Stuckey JA, Schubert HL, Fauman EB, Zhang ZY, Dixon JE, Saper MA
- Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate.
- Nature. 1994; 370: 571-5
- Display abstract
- Protein tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation. Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase, Yop51, that enters and suppresses host immune cells. Though the catalytic domain is only approximately 20% identical to human PTP1B, the Yersinia PTPase contains all of the invariant residues present in eukaryotic PTPases, including the nucleophilic Cys 403 which forms a phosphocysteine intermediate during catalysis. We present here structures of the unliganded (2.5 A resolution) and tungstate-bound (2.6 A) crystal forms which reveal that Cys 403 is positioned at the centre of a distinctive phosphate-binding loop. This loop is at the hub of several hydrogen-bond arrays that not only stabilize a bound oxyanion, but may activate Cys 403 as a reactive thiolate. Binding of tungstate triggers a conformational change that traps the oxyanion and swings Asp 356, an important catalytic residue, by approximately 6 A into the active site. The same anion-binding loop in PTPases is also found in the enzyme rhodanese.
- Rohan PJ et al.
- PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase.
- Science. 1993; 259: 1763-6
- Display abstract
- Tyrosine phosphorylation of proteins is required for signal transduction in cells and for growth regulation. A mitogen-induced gene (PAC-1) has been cloned from human T cells and encodes a 32-kilodalton protein that contains a sequence that defines the enzymatic site of known protein phosphotyrosine phosphatases (PTPases). Other than this sequence, PAC-1 is different from several other known related PTPases exemplified by PTP-1b. PAC-1 is similar to a phosphatase induced by mitogens or heat shock in fibroblasts, a yeast gene, and a vaccinia virus-encoded serine-tyrosine phosphatase (VH1). PAC-1 was predominantly expressed in hematopoietic tissues and localized to the nucleus in transfected COS-7 cells and in mitogen-stimulated T cells.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of PTPc_DSPc domains in PDB

PDB code	Main view	Title
1bzj		Human ptp1b complexed with tpicooh
1d5r		Crystal structure of the pten tumor suppressor
1fpz		Crystal structure analysis of kinase associated phosphatase (kap) with a substitution of the catalytic site cysteine (cys140) to a serine
1fq1		Crystal structure of kinase associated phosphatase (kap) in complex with phospho-cdk2
1g7f		Human ptp1b catalytic domain complexed with pnu177496
1g7g		Human ptp1b catalytic domain complexes with pnu179326
1i9s		Crystal structure of the rna triphosphatase domain of mouse mrna capping enzyme
1i9t		Crystal structure of the oxidized rna triphosphatase domain of mouse mrna capping enzyme
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
1lqf		Structure of ptp1b in complex with a peptidic bisphosphonate inhibitor
1lw3		Crystal structure of myotubularin-related protein 2 complexed with phosphate
1m7r		Crystal structure of myotubularin-related protein-2 (mtmr2) complexed with phosphate
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
1ohc		Structure of the proline directed phosphatase cdc14
1ohd		Structure of cdc14 in complex with tungstate
1ohe		Structure of cdc14b phosphatase with a peptide ligand
1ony		Oxalyl-aryl-amino benzoic acid inhibitors of ptp1b, compound 17
1onz		Oxalyl-aryl-amino benzoic acid inhibitors of ptp1b, compound 8b
1ph0		Non-carboxylic acid-containing inhibitor of ptp1b targeting the second phosphotyrosine site
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
1r6h		Solution structure of human prl-3
1rxd		Crystal structure of human protein tyrosine phosphatase 4a1
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
1v3a		Structure of human prl-3, the phosphatase associated with cancer metastasis
1wax		Protein tyrosine phosphatase 1b with active site inhibitor
1x24		Prl-1 (ptp4a)
1xbo		Ptp1b complexed with isoxazole carboxylic acid
1xm2		Crystal structure of human prl-1
1yn9		Crystal structure of baculovirus rna 5'-phosphatase complexed with phosphate
1ywf		Crystal structure of mycobacterium tuberculosis protein tyrosine phosphatase ptpb
1zck		Native structure prl-1 (ptp4a1)
1zcl		Prl-1 c104s mutant in complex with sulfate
1zsq		Crystal structure of mtmr2 in complex with phosphatidylinositol 3-phosphate
1zvr		Crystal structure of mtmr2 in complex with phosphatidylinositol 3,5-bisphosphate
2azr		Crystal structure of ptp1b with bicyclic thiophene inhibitor
2b07		Crystal structure of ptp1b with tricyclic thiophene inhibitor.
2bgd		Structure-based design of protein tyrosine phosphatase-1b inhibitors
2bge		Structure-based design of protein tyrosine phosphatase-1b inhibitors
2c46		Crystal structure of the human rna guanylyltransferase and 5'-phosphatase
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
2dxp		Crystal structure of the complex of the archaeal sulfolobus ptp-fold phosphatase with phosphopeptides a-(p)y-r
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
2i6i		Crystal structures of the archaeal sulfolobus ptp-fold phosphatase
2i6j		Crystal structure of the complex of the archaeal sulfolobus ptp-fold phosphatase with phosphate ion
2i6m		Crystal structure of the complexes of the archaeal sulfolobus ptp-fold phosphatase with tungstate
2i6o		Crystal structure of the complex of the archaeal sulfolobus ptp-fold phosphatase with phosphopeptides n-g-(p)y-k-n
2i6p		Crystal structure of the complex of the archaeal sulfolobus ptp-fold phosphatase with pnpp
2img		Crystal structure of dual specificity protein phosphatase from homo sapiens in complex with ligand malate ion
2nt7		Crystal structure of ptp1b-inhibitor complex
2nta		Crystal structure of ptp1b-inhibitor complex
2oz5		Crystal structure of mycobacterium tuberculosis protein tyrosine phosphatase ptpb in complex with the specific inhibitor omts
2qbp		Crystal structure of ptp1b-inhibitor complex
2qbq		Crystal structure of ptp1b-inhibitor complex
2qbr		Crystal structure of ptp1b-inhibitor complex
2qbs		Crystal structure of ptp1b-inhibitor complex
2veu		Crystal structure of protein tyrosine phosphatase 1b in complex with an isothiazolidinone-containing inhibitor
2vev		Crystal strucutre of protein tyrosine phosphatase 1b in complex with an isothiazolidinone-containing inhibitor
2vew		Crystal strucutre of protein tyrosine phosphatase 1b in complex with an isothiazolidinone-containing inhibitor
2vex		Crystal strucutre of protein tyrosine phosphatase 1b in complex with an isothiazolidinone-containing inhibitor
2vey		Crystal strucutre of protein tyrosine phosphatase 1b in complex with an isothiazolidinone-containing inhibitor
2zmm		Crystal structure of ptp1b-inhibitor complex
2zn7		Crystal structures of ptp1b-inhibitor complexes
3cwe		Ptp1b in complex with a phosphonic acid inhibitor
3d9c		Crystal structure ptp1b complex with aryl seleninic acid
3eax		Crystal structure ptp1b complex with small molecule compound lzp-6
3eb1		Crystal structure ptp1b complex with small molecule inhibitor lzp-25
3emu		Crystal structure of a leucine rich repeat and phosphatase domain containing protein from entamoeba histolytica
3eu0		Crystal structure of the s-nitrosylated cys215 of ptp1b
3f41		Structure of the tandemly repeated protein tyrosine phosphatase like phytase from mitsuokella multacida
3gxg		Crystal structure of putative phosphatase (duf442) (yp_001181608.1) from shewanella putrefaciens cn-32 at 1.60 a resolution
3gxh		Crystal structure of putative phosphatase (duf442) (yp_001181608.1) from shewanella putrefaciens cn-32 at 1.40 a resolution