cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   5 NRPAPVEVSYRHMRFLITHNPSNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535   1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543527  85 LSLLKAKFYNDPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535  81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

protein tyrosine phosphatase type IVA 3; Protein tyrosine phosphatase type IVA 3 (PTP-IVa3), also known as protein-tyrosine phosphatase of regenerating liver 3 (PRL-3), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It exerts its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1. PRL-3 is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   5 NRPAPVEVSYRHMRFLITHNPSNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535   1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543527  85 LSLLKAKFYNDPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535  81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  31 STFIEDLKKYGATTVVRVC-EVTYDKTPLEKDGITVVDWPFDDGAPPPgkvVEDWLSLLK-AKFYNDPGSCVAVHCVAGL 108
Cdd:COG2453  15 GGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGI 91

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 31543527 109 GRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 153
Cdd:COG2453  92 GRTGTVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 137

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527    38 KKYGATTVVRVCEVTYDKTPLEKdgiTV-----VDWPfDDGAPppgkvvEDWLSLLKA-----KFYNDPGSC-VAVHCVA 106
Cdd:pfam00102 109 KEDEKDYTVRTLEVSNGGSEETR---TVkhfhyTGWP-DHGVP------ESPNSLLDLlrkvrKSSLDGRSGpIVVHCSA 178

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 31543527   107 GLGRAPVLVALALIESGMKYE------DAIQFIRQKRRGAINSK-QLTYL 149
Cdd:pfam00102 179 GIGRTGTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVQTLeQYIFL 228

protein tyrosine phosphatase type IVA 3; Protein tyrosine phosphatase type IVA 3 (PTP-IVa3), also known as protein-tyrosine phosphatase of regenerating liver 3 (PRL-3), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It exerts its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1. PRL-3 is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   5 NRPAPVEVSYRHMRFLITHNPSNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535   1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543527  85 LSLLKAKFYNDPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535  81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   1 MARMNRPAPVEVSYRHMRFLITHNPSNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKV 80
Cdd:cd18537   1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  81 VEDWLSLLKAKFYNDPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRF 160
Cdd:cd18537  81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                ....*..
gi 31543527 161 KDPHTHK 167
Cdd:cd18537 161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   11 EVSYRHMRFLITHNPSNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKA 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   91 KF--YNDPGSCVAVHCVAGLGRAPVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFkdphthk 167
Cdd:PTZ00242  90 EFakQSTPPETIAVHCVAGLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG------- 162

                 ....*.
gi 31543527  168 trCCVM 173
Cdd:PTZ00242 163 --CTIM 166

C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division control protein 14 (CDC14) family is highly conserved in all eukaryotes, although the roles of its members seem to have diverged during evolution. Yeast Cdc14, the best characterized member of this family, is a dual-specificity phosphatase that plays key roles in cell cycle control. It preferentially dephosphorylates cyclin-dependent kinase (CDK) targets, which makes it the main antagonist of CDK in the cell. Cdc14 functions at the end of mitosis and it triggers the events that completely eliminates the activity of CDK and other mitotic kinases. It is also involved in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint, and in chromosome segregation. Cdc14 phosphatases also function in DNA replication, DNA damage checkpoint, and DNA repair. Vertebrates may contain more than one Cdc14 homolog; humans have three (CDC14A, CDC14B, and CDC14C). CDC14 family proteins contain a highly conserved N-terminal pseudophosphatase domain that contributes to substrate specificity and a C-terminal catalytic dual-specificity phosphatase domain with the PTP signature motif.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   9 PVEVSYRHMRFLiTHNPSNatlstFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLL 88
Cdd:cd14499  32 PHDTRKDENGYP-THTPED-----YIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDIC 105

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31543527  89 KakfyNDPGScVAVHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 155
Cdd:cd14499 106 E----NEKGA-IAVHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 168

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  15 RHMRFLITHNPSNaTLSTFIEDLKKYGATTVVRVCEVTydktplekdgitvvdwpfddgapppgkvVEDWLSLLKAKfyN 94
Cdd:cd14494   5 DPLRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLAM----------------------------VDRFLEVLDQA--E 53

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  95 DPGSCVAVHCVAGLGRAPVLVALALIE-SGMKYEDAIQFIRQKRRGAI--NSKQLTYLEK 151
Cdd:cd14494  54 KPGEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 113

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  52 TYDKTPLEKDGITVVDWPFDD-GAPPPGKVvedwLSLLK-AKFYNDPGSCVAVHCVAGLGRAPVLVALALI-ESGMKYED 128
Cdd:cd14506  66 SYLPEAFMRAGIYFYNFGWKDyGVPSLTTI----LDIVKvMAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQ 141

                        90
                ....*....|....*.
gi 31543527 129 AIQFIRQKRRGAINSK 144
Cdd:cd14506 142 AIRLVRSKRPNSIQTR 157

Protein tyrosine phosphatase, catalytic domain, undefined specificity; 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527     67 DWPfDDGAPPPGKVVEDWLSLLKAKFY-NDPGSCVAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQKRR 138
Cdd:smart00012   9 GWP-DHGVPESPDSILELLRAVKKNLNqSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQRP 87

                   ....*..
gi 31543527    139 GAINSKQ 145
Cdd:smart00012  88 GMVQTEE 94

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  37 LKKYGATTVV------RVCEVT-----YDKTPLEKDGITVVDWPFDDGAP---PPGKVVEDWLSllkakfynDPGSCVAV 102
Cdd:cd14515  22 LKKLGITHVLnaaegkKNGEVNtnakfYKGSGIIYLGIPASDLPTFDISQyfdEAADFIDKALS--------DPGGKVLV 93

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 31543527 103 HCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLEK 151
Cdd:cd14515  94 HCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKREIRPNRgflQQLCELND 146

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  97 GSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKRRGAI--NSKQLTYLEKYR 153
Cdd:cd14524  89 GKSVYVHCKAGRGRSATIVACYLIQHkGWSPEEAQEFLRSKRPHILlrLSQREVLEEFYR 148

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  68 WPfDDGAPPPGKVVEDWLSLLKAKFYNDPGSCVaVHCVAGLGRAPVLVAL-ALIESgMKYE------DAIQFIRQKRRGA 140
Cdd:cd00047 112 WP-DHGVPSSPEDLLALVRRVRKEARKPNGPIV-VHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRKQRPGM 188

                        90
                ....*....|
gi 31543527 141 I-NSKQLTYL 149
Cdd:cd00047 189 VqTLEQYEFI 198

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  34 IEDLKKYGATTVVRV---CEVTYDKTPLE-------KDGITVVDWPFDDGAP-------PpgKVVEDWLSLLKAkfyndp 96
Cdd:cd14526  22 VDRLKKEGVTAVLNLqtdSDMEYWGVDIDsirkackESGIRYVRLPIRDFDTedlrqklP--QAVALLYRLLKN------ 93

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 31543527  97 GSCVAVHCVAGLGRAP--VLVALALIeSGMKYEDAIQFIRQKR 137
Cdd:cd14526  94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type tyrosine-protein phosphatase-like D (PTPRD), also known as receptor-type tyrosine-protein phosphatase delta (R-PTP-delta), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules that play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. PTPRD is involved in pre-synaptic differentiation through interaction with SLITRK2. It contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   9 PVEVSYRHMRFLI----THNPSNATLSTFIEDLKKYGATTVVRVCEVTydktplekdgitvvDWPfDDGAPPPGKVVEDW 84
Cdd:cd14628 142 PAERSARYQYFVVdpmaEYNMPQYILREFKVTDARDGQSRTVRQFQFT--------------DWP-EQGVPKSGEGFIDF 206

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 31543527  85 LSLL---KAKFYNDpgSCVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--RGAINSKQLTYLEKYR 153
Cdd:cd14628 207 IGQVhktKEQFGQD--GPISVHCSAGVGRTGVFITLSIVLERMRYEgvvDIFQTVKMLRtqRPAMVQTEDQYQFCYR 281

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527     44 TVVRVCEVTYDKTPLEKDgITVV---DWPfDDGAPPPGKVVedwLSLLKA--KFYNDPGSCVAVHCVAGLGRAPVLVALA 118
Cdd:smart00194 141 YTIRTLEVTNTGCSETRT-VTHYhytNWP-DHGVPESPESI---LDLIRAvrKSQSTSTGPIVVHCSAGVGRTGTFIAID 215

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 31543527    119 LIESGMKYE------DAIQFIRQKRRGAINSK-QLTYL 149
Cdd:smart00194 216 ILLQQLEAGkevdifEIVKELRSQRPGMVQTEeQYIFL 253

PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527   9 PVEVSYRHMRFLI----THNPSNATLSTFIEDLKKYGATTVVRVCEVTydktplekdgitvvDWPfDDGAPPPGKVVEDW 84
Cdd:cd14627 143 PAERSARYQYFVVdpmaEYNMPQYILREFKVTDARDGQSRTVRQFQFT--------------DWP-EQGVPKSGEGFIDF 207

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 31543527  85 LSLL---KAKFYNDpgSCVAVHCVAGLGRAPVLVALALIESGMKYE------DAIQFIRQKRRGAINSK 144
Cdd:cd14627 208 IGQVhktKEQFGQD--GPISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQRPAMVQTE 274

catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) and type 13 (PTPN13, also known as PTPL1) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization. Human PTPN13 is an important regulator of tumor aggressiveness.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  68 WPfDDGAPPPGKVVEDWLSLLKaKFYND-PgscVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGA 140
Cdd:cd14538 115 WP-DHGTPQSADPLLRFIRYMR-RIHNSgP---IVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGM 189

                ....
gi 31543527 141 INSK 144
Cdd:cd14538 190 IQTK 193

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  94 NDPGSCVAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKR-----RGAInsKQLTYLEKYRPKQR 157
Cdd:cd14575  93 SDPHNKLLVHCVMGRSRSATLVlAYLMIYKNMTVVDAIEQVAQRRcilpnRGFL--KQLRELDIQLAEER 160

bacterial protein tyrosine and dual-specificity phosphatases related to Pseudomonas aeruginosa TpbA; This subfamily contains bacterial protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DUSPs) related to Pseudomonas aeruginosa TpbA, a DUSP that negatively regulates biofilm formation by converting extracellular quorum sensing signals and to Mycobacterium tuberculosis PtpB, a PTP virulence factor that attenuates host immune defenses by interfering with signal transduction pathways in macrophages. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides, while DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and PTPs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  37 LKKYGATTVV---RVCEVTYDKTPLEK-DGITVVDWPFDDGAPPPgkvvEDWLSLLKAKFYNDPGSCVAVHCVAGLGRAP 112
Cdd:cd14529  29 LKKLGIKTVIdlrGADERAASEEAAAKiDGVKYVNLPLSATRPTE----SDVQSFLLIMDLKLAPGPVLIHCKHGKDRTG 104

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 31543527 113 VLVALALIESGMKYEDAI-QFIRQKRRGAINSKQLTYLEKYRPKQR 157
Cdd:cd14529 105 LVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  68 WPfDDGAPPPGKVVEDWLSLLKAKFYNDPgscVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14596 114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMI 189

                ....
gi 31543527 142 NSKQ 145
Cdd:cd14596 190 QTKD 193

dual specificity phosphatase domain of class III mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class III MKPs consist of DUSP8, DUSP10/MKP-5 and DUSP16/MKP-7, and are JNK/p38-selective phosphatases, which are found in both the cell nucleus and cytoplasm. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 31543527  97 GSCVAVHCVAGLGRAPVL-VALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14568  79 NKRVLVHCLAGISRSATIaIAYIMKHMRMSLDDAYRFVKEKR 120

protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called tensin-like SH2 domain-containing protein 1 (TENS1) or tumor endothelial marker (TEM6). It is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Tensin-3 contributes to cell migration, anchorage-independent growth, tumorigenesis, and metastasis of cancer cells. It cooperates with Dock5, an exchange factor for the small GTPase Rac, for osteoclast activity to ensure the correct organization of podosomes. Tensin-3 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  11 EVSYRHMRFLITHNPSNATLSTFIEDLK--------KYGAT-TVVRVCEVTYDKTPLEKDgITVVDWPfDDGAPPPGKV- 80
Cdd:cd14561   1 DLTYITERIIAVSFPADCSEETYLHNLQdvtrmlksKHGDNyLVLNLSEKRYELTKLNPK-IMDVGWP-DLHAPPLDKMc 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 31543527  81 -----VEDWLSllkakfyNDPGSCVAVHCVAGLGRAPVLVA 116
Cdd:cd14561  79 tickaMESWLN-------SDPLHVVVIHCRGGKGRIGVVIS 112

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  63 ITVVDWPfDDGAPPPGKVVEDWLSLLKAKFYNDPGScVAVHCVAGLGRAPVLV----ALALIESGMKYE--DAIQFIRQK 136
Cdd:cd14601 111 IQYIAWP-DHGVPDDSSDFLDFVCLVRNKRAGKDEP-VVVHCSAGIGRTGVLItmetAMCLIECNQPVYplDIVRTMRDQ 188

                .
gi 31543527 137 R 137
Cdd:cd14601 189 R 189

dual specificity phosphatase domain of class I mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class I MKPs consist of DUSP1/MKP-1, DUSP2 (PAC1), DUSP4/MKP-2 and DUSP5. They are all mitogen- and stress-inducible nuclear MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 31543527  97 GSCVAVHCVAGLGRAPVlVALA-LIES-GMKYEDAIQFIRQKR 137
Cdd:cd14565  78 GGRVLVHCQAGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  27 NATLSTFIEDLKKYGATTVVRVcevtydkTP------LEKDGITVVDWPFDDgapppgkvveDWLSLLkAKFYNDP---- 96
Cdd:cd14566  12 NAKDSANIDLLKKYNIKYILNV-------TPnlpntfEEDGGFKYLQIPIDD----------HWSQNL-SAFFPEAisfi 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 31543527  97 ------GSCVAVHCVAGLGRA-PVLVALALIESGMKYEDAIQFIRQKRR 138
Cdd:cd14566  74 dearskKCGVLVHCLAGISRSvTVTVAYLMQKLHLSLNDAYDFVKKRKS 122

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 31543527  89 KAKFYNDpgsCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14646  76 KAKASNG---RVLVHCLAGISRsATIAIAYIMKRMDMSLDEAYRFVKEKR 122

catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) and type 6 (PTPN6) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 and PTPN6, are also called SH2 domain-containing tyrosine phosphatase 2 (SHP2) and 1 (SHP1), respectively. They contain two tandem SH2 domains: a catalytic PTP domain, and a C-terminal tail with regulatory properties. Although structurally similar, they have different localization and different roles in signal transduction. PTPN11/SHP2 is expressed ubiquitously and plays a positive role in cell signaling, leading to cell activation, while PTPN6/SHP1 expression is restricted mainly to hematopoietic and epithelial cells and functions as a negative regulator of signaling events.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543527  68 WPfDDGAPP-PGKVvedwLSLL-----KAKFYNDPGSCVaVHCVAGLGR-APVLVALALIE--------SGMKYEDAIQF 132
Cdd:cd14544 150 WP-DHGVPSdPGGV----LNFLedvnqRQESLPHAGPIV-VHCSAGIGRtGTFIVIDMLLDqikrkgldCDIDIQKTIQM 223

                        90
                ....*....|...
gi 31543527 133 IRQKRRGAINSKQ 145
Cdd:cd14544 224 VRSQRSGMVQTEA 236

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP3 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 31543527 100 VAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYL 149
Cdd:cd14579 111 VLVHCREGYSRSPTLViAYLMLRQKMDVKSALSTVRQKREIGPNDgflKQLCQL 164