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 1761178545 124 QAIKGVYSSWVTDNILAMARPSSELLEKYRIIEQFLGQGIKTIINLQRPGEHASCGSALEQESGFTYLPEAFMEAGIYFY 203
Cdd:cd14506     1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 204 NFGWKDYGVASLTAILDMVKVMTFALQE-GKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 282
Cdd:cd14506    81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1761178545 283 LCVREFTQFLAPLRNIFSCCDPKaHAVTLAQYLIRQRHLLHGYEAR 328
Cdd:cd14506   161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

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 1761178545 124 QAIKGVYSSWVTDNILAMARPSSELLEKYRIIEQFLGQGIKTIINLQRPGEHASCGSALEQESGFTYLPEAFMEAGIYFY 203
Cdd:cd14506     1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 204 NFGWKDYGVASLTAILDMVKVMTFALQE-GKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 282
Cdd:cd14506    81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1761178545 283 LCVREFTQFLAPLRNIFSCCDPKaHAVTLAQYLIRQRHLLHGYEAR 328
Cdd:cd14506   161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545  202 FYNFGWKDYGV-ASLTAILDMV----KVMTFALQEGKVAVHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 270
Cdd:smart00404   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 1761178545  271 KRPNSIQTRGQLL 283
Cdd:smart00404  85 QRPGMVQTEEQYL 97

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 189 TYLPEAFMEAGIYFYNFGWKDYGVASLTAI---LDMVK--VMTFALQEGKVAVHCHAGLGRTGVLIACYLVFATRMTADQ 263
Cdd:PTZ00242   51 TYDAELLEKNGIEVHDWPFDDGAPPPKAVIdnwLRLLDqeFAKQSTPPETIAVHCVAGLGRAPILVALALVEYGGMEPLD 130

                          90
                  ....*....|...
gi 1761178545 264 AIIFVRAKRPNSI 276
Cdd:PTZ00242  131 AVGFVREKRKGAI 143

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 1761178545 124 QAIKGVYSSWVTDNILAMARPSSELLEKYRIIEQFLGQGIKTIINLQRPGEHASCGSALEQESGFTYLPEAFMEAGIYFY 203
Cdd:cd14506     1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 204 NFGWKDYGVASLTAILDMVKVMTFALQE-GKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 282
Cdd:cd14506    81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1761178545 283 LCVREFTQFLAPLRNIFSCCDPKaHAVTLAQYLIRQRHLLHGYEAR 328
Cdd:cd14506   161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), 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. DUSP23 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 is able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 132 SWVTDNILA-MARPSSEllEKYRIIEqflGQGIKTIINL-QRPGehascgsaleqesgftyLPEAFMEAGIYFYNFGWKD 209
Cdd:cd14504     2 SWVIPGKLAgMAFPRLP--EHYAYLN---ENGIRHVVTLtEEPP-----------------PEHSDTCPGLRYHHIPIED 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 210 YGVASLTAILDMVKVMTFALQEGK-VAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCVREF 288
Cdd:cd14504    60 YTPPTLEQIDEFLDIVEEANAKNEaVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQF 139

                  ...
gi 1761178545 289 TQF 291
Cdd:cd14504   140 AKT 142

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 155 IEQFLGQGIKTIINLQRPGEhascgsaLEqESGFTYLPEAFMEAGIYFYNFGWKDYGVASLTA-ILDMVKVMTFALQEGK 233
Cdd:cd14505    36 LEELKDQGVDDVVTLCTDGE-------LE-ELGVPDLLEQYQQAGITWHHLPIPDGGVPSDIAqWQELLEELLSALENGK 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1761178545 234 -VAVHCHAGLGRTGVLIACYLVFAT-RMTADQAIIFVRAKRPNSIQTRGQL 282
Cdd:cd14505   108 kVLIHCKGGLGRTGLIAACLLLELGdTLDPEQAIAAVRALRPGAIQTPKQE 158

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 132 SWVTDNILAMARPSSELLEK-YRI----IEQFLGQGIK---TIINLqrpgehascgsaleqeSGFTYLPEAFMEAGIyfY 203
Cdd:cd14497     3 SYITPRIIAMSFPATGYPESlYRNsiddVANFLNTHHPdhyMIFNL----------------SEEEYDDDSKFEGRV--L 64

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1761178545 204 NFGWKDYGVASLTAILDMVKVMTFALQEGK---VAVHCHAGLGRTGVLIACYLVFATR-MTADQAIIFVRAKRPN 274
Cdd:cd14497    65 HYGFPDHHPPPLGLLLEIVDDIDSWLSEDPnnvAVVHCKAGKGRTGTVICAYLLYYGQySTADEALEYFAKKRFK 139

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545  202 FYNFGWKDYGV-ASLTAILDMV----KVMTFALQEGKVAVHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 270
Cdd:smart00404   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 1761178545  271 KRPNSIQTRGQLL 283
Cdd:smart00404  85 QRPGMVQTEEQYL 97

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 132 SWVTDNILAMARP----SSELLEKyriieqflgQGIKTIINLQRPGE-HASCGSALEQESgftylpeafmeAGIYFYNFG 206
Cdd:cd14524     3 DRIDDTVILGALPfrsmTVALVAK---------ENVRGVITMNEEYEtRFFCNSKEEWKA-----------LGVEQLRLP 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 207 WKDY-GVASLTAILDMVKVM-TFALQEGKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLC 284
Cdd:cd14524    63 TVDFtGVPSLEDLEKGVDFIlKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREV 142

                  ....*..
gi 1761178545 285 VREFTQF 291
Cdd:cd14524   143 LEEFYRK 149

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 189 TYLPEAFMEAGIYFYNFGWKDYGVASLTAI---LDMVK--VMTFALQEGKVAVHCHAGLGRTGVLIACYLVFATRMTADQ 263
Cdd:PTZ00242   51 TYDAELLEKNGIEVHDWPFDDGAPPPKAVIdnwLRLLDqeFAKQSTPPETIAVHCVAGLGRAPILVALALVEYGGMEPLD 130

                          90
                  ....*....|...
gi 1761178545 264 AIIFVRAKRPNSI 276
Cdd:PTZ00242  131 AVGFVREKRKGAI 143

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545  203 YNF-GWKDYGV-ASLTAILDMVKVM--TFALQEGKVAVHCHAGLGRTGVLIACYLVFAtRMTADQAI-IF-----VRAKR 272
Cdd:smart00194 162 YHYtNWPDHGVpESPESILDLIRAVrkSQSTSTGPIVVHCSAGVGRTGTFIAIDILLQ-QLEAGKEVdIFeivkeLRSQR 240

                           90
                   ....*....|...
gi 1761178545  273 PNSIQTRGQLLCV 285
Cdd:smart00194 241 PGMVQTEEQYIFL 253

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 132 SWVTDNILAMARPSsELLEK-YR----IIEQFLGQGIKT---IINLqrpgehasCgsaleqeSGFTYLPEAFmeagiyFY 203
Cdd:cd14509     3 TYITPNIIAMGFPA-EGVEGvYRnpidDVQRFLETKHKGhykVYNL--------C-------SERSYDPSKF------NG 60

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1761178545 204 ---NFGWKDYGVASLTAILDMVKVMTFALQEGK---VAVHCHAGLGRTGVLIACYLVFATRM-TADQAIIFVRAKR 272
Cdd:cd14509    61 rvaEYPFDDHNPPPLELIKPFCEDVDEWLKEDEknvAAVHCKAGKGRTGVMICCYLLYLGKFpSAKEALDFYGAKR 136

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1761178545 215 LTAILDMVK--VMTFALQEGKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP 273
Cdd:pfam00782  51 ISKYLEEAVefIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRP 111

RNA 5'-triphosphatase domain; This family of RNA-specific cysteine phosphatases includes baculovirus RNA 5'-triphosphatase, dual specificity protein phosphatase 11 (DUSP11), and the RNA triphosphatase domains of metazoan and plant mRNA capping enzymes. RNA/polynucleotide 5'-triphosphatase (EC 3.1.3.33) catalyzes the removal of the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end. mRNA capping enzyme is a bifunctional enzyme that catalyzes the first two steps of cap formation. DUSP11 has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 190 YLPEAFMEAGIYFYNFGWKDYGVASLTAILDMVKVMTFALQEGK----VAVHCHAGLGRTGVLIACYLVFATRMTADQAI 265
Cdd:cd14502    66 YDPNDLDDDGYVYYKKVCVRKEPPDAEEVNKFIELVDKFLAEDNpdklIAVHCTHGFNRTGFMIVSYLVERLGLTVEQAL 145

                          90
                  ....*....|.
gi 1761178545 266 IFVRAKRPNSI 276
Cdd:cd14502   146 EAFAQARPPGI 156

protein tyrosine phosphatase type IVA family; Protein tyrosine phosphatases type IVA (PTP-IVa), also known as protein-tyrosine phosphatases of regenerating liver (PRLs) constitute a family of small, prenylated phosphatases that are the most oncogenic of all PTPs. They stimulate progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. They associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation. Vertebrates contain three members: PRL-1, PRL-2, and PRL-3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 137 NILAMARPSSELLEKYriIEQFLGQGIKTIINLQRPgehascgsaleqesgfTYLPEAFMEAGIYFYNFGWKDYGVAS-- 214
Cdd:cd14500    14 RFLITDAPTDSNLPLY--IKELKKYNVTDLVRVCEP----------------TYDKEPLEKAGIKVHDWPFDDGSPPPdd 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1761178545 215 -LTAILDMVKVmTFA---LQEGKVAVHCHAGLGRTGVLIACYLVFAtRMTADQAIIFVRAKRPNSIQTRgQL 282
Cdd:cd14500    76 vVDDWLDLLKT-RFKeegKPGACIAVHCVAGLGRAPVLVAIALIEL-GMKPEDAVEFIRKKRRGAINSK-QL 144

PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They 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; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain 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).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 202 FYNFGWKDYGV-ASLTAILDMV----KVMTFALQEGKVAVHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRA 270
Cdd:cd14554   140 FQFTDWPEQGVpKSGEGFIDFIgqvhKTKEQFGQEGPITVHCSAGVGRTGVFITLSIVL-ERMRYEgvvdvfQTVKLLRT 218

                          90
                  ....*....|....*..
gi 1761178545 271 KRPNSIQTRGQ-LLCVR 286
Cdd:cd14554   219 QRPAMVQTEDQyQFCYR 235

catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), type 18 (PTPN18) and type 12 (PTPN12) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. TPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 202 FYNFGWKDYGV-ASLTAILDMVKVM--TFALQEGKVAVHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----V 268
Cdd:cd14542   106 FHYTAWPDHGVpSSVDPILDLVRLVrdYQGSEDVPICVHCSAGCGRTGTI--CAIDYVWNLLKTGKIpeefsLFdlvreM 183

                          90
                  ....*....|...
gi 1761178545 269 RAKRPNSIQTRGQ 281
Cdd:cd14542   184 RKQRPAMVQTKEQ 196

dual specificity phosphatase domain of dual specificity protein phosphatase 10; Dual specificity protein phosphatase 10 (DUSP10), also called mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5), 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. DUSP10/MKP-5 coordinates skeletal muscle regeneration by negatively regulating mitochondria-mediated apoptosis. It is also an important regulator of intestinal epithelial barrier function and a suppressor of colon tumorigenesis. DUSP10/MKP-5 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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 228 ALQEGK-VAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP---NSIQTRGQLLcvrEFTQFLA 293
Cdd:cd14567    76 AHQSGKgVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPiisPNLNFMGQLL---EFEEDLN 142

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1761178545 232 GKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPnSIQTR----GQLL 283
Cdd:cd14568    80 KRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP-TISPNfnflGQLL 134

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 1761178545 207 WKDYGV-ASLTAILDMVKVMTFALQEGKVAVHCHAGLGRTGVLIACYLVFATrMTADQAI-IF-----VRAKRPNSIQTR 279
Cdd:cd14538   115 WPDHGTpQSADPLLRFIRYMRRIHNSGPIVVHCSAGIGRTGVLITIDVALGL-IERDLPFdIQdivkdLREQRQGMIQTK 193

                  ..
gi 1761178545 280 GQ 281
Cdd:cd14538   194 DQ 195

catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type tyrosine-protein phosphatase H (PTPRH or R-PTP-H), also known as stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRH is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. It plays a role in intestinal immunity by regulating CEACAM20 through tyrosine dephosphorylation. It is also a negative regulator of integrin-mediated signaling and may contribute to contact inhibition of cell growth and motility.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 201 YFYNFGWKDYGVAS----LTAILDMVK-VMTFALQEGKVAVHCHAGLGRTGVLIACYlVFATRMTADQAI---IFV---R 269
Cdd:cd14619   131 HFHFTAWPDHGVPSstdtLLAFRRLLRqWLDQTMSGGPTVVHCSAGVGRTGTLIALD-VLLQQLQSEGLLgpfSFVqkmR 209

                          90
                  ....*....|..
gi 1761178545 270 AKRPNSIQTRGQ 281
Cdd:cd14619   210 ENRPLMVQTESQ 221

catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein phosphatase non-receptor type 12 (PTPN12), also called PTP-PEST or protein-tyrosine phosphatase G1 (PTPG1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 202 FYNFGWKDYGV-ASLTAILDMVKVMTFALQEGKV--AVHCHAGLGRTGVLIAC----YLVFATRMTAD----QAIIFVRA 270
Cdd:cd14604   191 FHYVNWPDHDVpSSFDSILDMISLMRKYQEHEDVpiCIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfNLIQEMRT 270

                          90
                  ....*....|.
gi 1761178545 271 KRPNSIQTRGQ 281
Cdd:cd14604   271 QRHSAVQTKEQ 281

catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11), also called SH2 domain-containing tyrosine phosphatase 2 (SHP-2 or SHP2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 promotes the activation of the RAS/Mitogen-Activated Protein Kinases (MAPK) Extracellular-Regulated Kinases 1/2 (ERK1/2) pathway, a canonical signaling cascade that plays key roles in various cellular processes, including proliferation, survival, differentiation, migration, or metabolism. It also regulates the phosphoinositide 3-kinase (PI3K)/AKT pathway, a fundamental cascade that functions in cell survival, proliferation, migration, morphogenesis, and metabolism. PTPN11 dysregulation is associated with several developmental diseases and malignancies, such as Noonan syndrome and juvenile myelomonocytic leukemia. It contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 196 MEAGIYFYNF-GWKDYGVAS----LTAILDMVKVMTFALQE-GKVAVHCHAGLGRTGVLIAC-YLVFATR-------MTA 261
Cdd:cd14605   140 TERTVWQYHFrTWPDHGVPSdpggVLDFLEEVHHKQESIMDaGPVVVHCSAGIGRTGTFIVIdILIDIIRekgvdcdIDV 219

                          90       100
                  ....*....|....*....|
gi 1761178545 262 DQAIIFVRAKRPNSIQTRGQ 281
Cdd:cd14605   220 PKTIQMVRSQRSGMVQTEAQ 239

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 200 IYFYNF-GWKDYGVAS----LTAILDMVKVMTFAL-QEGKVAVHCHAGLGRTGVLIACYLVFATRMTA--------DQAI 265
Cdd:cd14606   157 IWHYQYlSWPDHGVPSepggVLSFLDQINQRQESLpHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKgldcdidiQKTI 236

                          90
                  ....*....|....*.
gi 1761178545 266 IFVRAKRPNSIQTRGQ 281
Cdd:cd14606   237 QMVRAQRSGMVQTEAQ 252

catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type tyrosine-protein phosphatase V (PTPRV or R-PTP-V), also known as embryonic stem cell protein-tyrosine phosphatase (ES cell phosphatase) or osteotesticular protein-tyrosine phosphatase (OST-PTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRV is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. In rodents, it may play a role in the maintenance of pluripotency and may function in signaling pathways during bone remodeling. It is the only PTP whose function has been lost between rodent and human. The human OST-PTP gene is a pseudogene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 207 WKDYGV----ASLTAILDMVKVMTFALQ-EGKVAVHCHAGLGRTGVLIAcYLVFATRMTADQA------IIFVRAKRPNS 275
Cdd:cd14618   137 WPDHGIpestSSLMAFRELVREHVQATKgKGPTLVHCSAGVGRSGTFIA-LDRLLRQLKEEKVvdvfntVYILRMHRYLM 215

                  ....*.
gi 1761178545 276 IQTRGQ 281
Cdd:cd14618   216 IQTLSQ 221

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 2; Receptor-type tyrosine-protein phosphatase A (PTPRA) and E (PTPRE) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA and PTPRE share several functions including regulation of Src family kinases and voltage-gated potassium (Kv) channels. They both contain a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 202 FYNFGWKDYGV-ASLTAILDMVKVMTFALQE---GKVAVHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAK 271
Cdd:cd14552   105 FHFHGWPEVGIpDNGKGMIDLIAAVQKQQQQsgnHPITVHCSAGAGRTGTFCALSTVL-ERVKAEgvldvfQVVKSLRLQ 183

                          90
                  ....*....|
gi 1761178545 272 RPNSIQTRGQ 281
Cdd:cd14552   184 RPHMVQTLEQ 193

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1761178545 234 VAVHCHAGLGRTGVLIACYLVfATRMTADQAIIFVRAKRPNSIQTRgQLLCVREF 288
Cdd:cd18535    96 VAVHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKY 148

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 202 FYNFGWKDYGV-ASLTAILDMVKVMTFALQEG---KVAVHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAK 271
Cdd:cd14622   106 FHFHGWPEIGIpAEGKGMIDLIAAVQKQQQQTgnhPIVVHCSAGAGRTGTFIALSNIL-ERVKAEglldvfQTVKSLRLQ 184

                          90       100
                  ....*....|....*....|.
gi 1761178545 272 RPNSIQTRGQL-LCVREFTQF 291
Cdd:cd14622   185 RPHMVQTLEQYeFCYRVVQDF 205

bacterial tyrosine-protein phosphataseS similar to Neisseria NMA1982; This subfamily is composed of bacterial tyrosine-protein phosphatases similar to Neisseria meningitidis NMA1982, which displays phosphatase activity but whose biological function is still unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1761178545 133 WVTDNILAMARPSSELLEKYRIieqflgQGIKTIINLQRPGEhascGSALEQEsgftylPEAFMEAGIYFYN--FGWKDY 210
Cdd:cd14503     4 KISDRLATAGQPTPEQFAALAA------AGFKTVINLRPDGE----ENALPNE------AAAVTAAGMEYVHipVDWDNP 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1761178545 211 GVASLTAILDMVKvmtfALQEGKVAVHCHAGlGRTGVLIACYLVFATRMTADQAI 265
Cdd:cd14503    68 TPEDVERFFEVMD----AAQGKPVLVHCASN-MRASAFWYLYRALDGGVSEEEAI 117

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), 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 I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 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 1761178545 230 QEGKVAVHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKR----PNsIQTRGQLL 283
Cdd:cd14640    77 CNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRsiisPN-FSFMGQLL 133