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 359465592 130 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 209
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 210 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 288
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465592 289 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 334
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 359465592 130 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 209
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 210 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 288
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465592 289 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 334
Cdd:cd14506  161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592  207 YFYNfGWKDYGV----ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAI-IF-----VRA 276
Cdd:pfam00102 136 FHYT-GWPDHGVpespNSLLDLLRKVRKSSLDGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAEGEVdIFqivkeLRS 213

                          90
                  ....*....|....*
gi 359465592  277 KRPNSIQTRGQLLCV 291
Cdd:pfam00102 214 QRPGMVQTLEQYIFL 228

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 195 TYLPEAFMEAGIYFYNFGWKDYGVASLTTI---LDMVK--VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQ 269
Cdd:PTZ00242  51 TYDAELLEKNGIEVHDWPFDDGAPPPKAVIdnwLRLLDqeFAKQSTPPETIAVHCVAGLGRAPILVALALVEYGGMEPLD 130

                         90
                 ....*....|...
gi 359465592 270 AIIFVRAKRPNSI 282
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 359465592 130 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 209
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 210 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 288
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465592 289 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 334
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 359465592 138 SWVTDNILA-MARPSSELLEKYhiidqFLSHGIKTIINLqrpgehasCGNPLeqesgftyLPEAFMEAGIYFYNFGWKDY 216
Cdd:cd14504    2 SWVIPGKLAgMAFPRLPEHYAY-----LNENGIRHVVTL--------TEEPP--------PEHSDTCPGLRYHHIPIEDY 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 217 GVASLTTILDMVKVMTFALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCVREFT 295
Cdd:cd14504   61 TPPTLEQIDEFLDIVEEANAKNEaVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFA 140

                 ..
gi 359465592 296 QF 297
Cdd:cd14504  141 KT 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 359465592 161 IDQFLSHGIKTIINLQRPGEhascgnpLEqESGFTYLPEAFMEAGIYFYNFGWKDYGV----ASLTTILDMVKVmtfALQ 236
Cdd:cd14505   36 LEELKDQGVDDVVTLCTDGE-------LE-ELGVPDLLEQYQQAGITWHHLPIPDGGVpsdiAQWQELLEELLS---ALE 104

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 359465592 237 EGK-VAIHCHAGLGRTGVLIACYLVFAT-RMTADQAIIFVRAKRPNSIQTRGQL 288
Cdd:cd14505  105 NGKkVLIHCKGGLGRTGLIAACLLLELGdTLDPEQAIAAVRALRPGAIQTPKQE 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 359465592 138 SWVTDNILAMARPSSELLEKYHI--ID---QFL--SHGIK-TIINLqrpgehascgnpleqeSGFTYLPEAFMEAGIYfy 209
Cdd:cd14497    3 SYITPRIIAMSFPATGYPESLYRnsIDdvaNFLntHHPDHyMIFNL----------------SEEEYDDDSKFEGRVL-- 64

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 359465592 210 NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATR-MTADQAIIFVRAKRPN 280
Cdd:cd14497   65 HYGFPDHHPPPLGLLLEIVDDIDSWLSEDPnnvAVVHCKAGKGRTGTVICAYLLYYGQySTADEALEYFAKKRFK 139

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 359465592 138 SWVTDNILAMARP----SSELLEKyhiidqflsHGIKTIINLQRPGEHASCGNPLEQESGftylpeafmeAGIYFYNFGW 213
Cdd:cd14524    3 DRIDDTVILGALPfrsmTVALVAK---------ENVRGVITMNEEYETRFFCNSKEEWKA----------LGVEQLRLPT 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 214 KDY-GVASLTTILDMVKVM-TFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCV 291
Cdd:cd14524   64 VDFtGVPSLEDLEKGVDFIlKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREVL 143

                 ....*.
gi 359465592 292 REFTQF 297
Cdd:cd14524  144 EEFYRK 149

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592  207 YFYNfGWKDYGV----ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAI-IF-----VRA 276
Cdd:pfam00102 136 FHYT-GWPDHGVpespNSLLDLLRKVRKSSLDGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAEGEVdIFqivkeLRS 213

                          90
                  ....*....|....*
gi 359465592  277 KRPNSIQTRGQLLCV 291
Cdd:pfam00102 214 QRPGMVQTLEQYIFL 228

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 359465592   208 FYNFGWKDYGV-ASLTTILDMV----KVMTFALQEGKVAIHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 276
Cdd:smart00012   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 359465592   277 KRPNSIQTRGQLL 289
Cdd:smart00012  85 QRPGMVQTEEQYL 97

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592  156 EKYHIIDQFLS-HGIKTIINLQRpgehaSCGNPLeqeSGFTYL--P-EAFMEAGIYFYnfgwkdygvaslttiLDMVK-- 229
Cdd:pfam00782   5 SKPTASDAFLSkLGITAVINVTR-----EVDLYN---SGILYLriPvEDNHETNISKY---------------LEEAVef 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 359465592  230 VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP 279
Cdd:pfam00782  62 IDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRP 111

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 359465592 138 SWVTDNILAMARPSsELLEKY---HIID--QFLS--HGIK-TIINLqrpgehasCgnpleqeSGFTYLPEAFmeagiyFY 209
Cdd:cd14509    3 TYITPNIIAMGFPA-EGVEGVyrnPIDDvqRFLEtkHKGHyKVYNL--------C-------SERSYDPSKF------NG 60

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 359465592 210 ---NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATRM-TADQAIIFVRAKR 278
Cdd:cd14509   61 rvaEYPFDDHNPPPLELIKPFCEDVDEWLKEDEknvAAVHCKAGKGRTGVMICCYLLYLGKFpSAKEALDFYGAKR 136

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 359465592 161 IDQFLSHGIKTIINLQRPGEHASCGNPLEQesgftyLPEAFMEAGIYFYNFGWKDYGVASLTTILDMVKVMTFAL--QEG 238
Cdd:cd14526   22 VDRLKKEGVTAVLNLQTDSDMEYWGVDIDS------IRKACKESGIRYVRLPIRDFDTEDLRQKLPQAVALLYRLlkNGG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 359465592 239 KVAIHCHAGLGR-TGVLIAcYLVFATRMTADQAIIFVRAKRP 279
Cdd:cd14526   96 TVYVHCTAGLGRaPATVIA-YLYWVLGYSLDEAYYLLTSKRP 136

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 359465592 143 NILAMARPSSELLEKYhiIDQFLSHGIKTIINLQRPgehascgnpleqesgfTYLPEAFMEAGIYFYNFGWKDYGVAS-- 220
Cdd:cd14500   14 RFLITDAPTDSNLPLY--IKELKKYNVTDLVRVCEP----------------TYDKEPLEKAGIKVHDWPFDDGSPPPdd 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 221 -LTTILDMVKVmTFA---LQEGKVAIHCHAGLGRTGVLIACYLVFAtRMTADQAIIFVRAKRPNSIQTRgQLlcvreftQ 296
Cdd:cd14500   76 vVDDWLDLLKT-RFKeegKPGACIAVHCVAGLGRAPVLVAIALIEL-GMKPEDAVEFIRKKRRGAINSK-QL-------Q 145

                 ...
gi 359465592 297 FLT 299
Cdd:cd14500  146 FLE 148

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 359465592 198 PEAFMEAGIYFYNFGWKDYGVASLTTILDMV-KVMTFALQE--GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFV 274
Cdd:cd14515   46 AKFYKGSGIIYLGIPASDLPTFDISQYFDEAaDFIDKALSDpgGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTV 125

                         90
                 ....*....|
gi 359465592 275 RAKR---PNS 281
Cdd:cd14515  126 RKKReirPNR 135

catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein phosphatase non-receptor type 18 (PTPN18), also called brain-derived phosphatase, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. The N-terminal catalytic PTP domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation, and its C-terminal PEST domain promotes K48-linked HER2 ubiquitination and its destruction via the proteasome pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 213 WKDYGVA-SLTTILDMVKVMTFALQEGKV--AIHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----VRAKRP 279
Cdd:cd14603  169 WPDHGIPdSPDCMLAMIELARRLQGSGPEplCVHCSAGCGRTGVI--CTVDYVRQLLLTQRIppdfsIFdvvleMRKQRP 246

                 ....*...
gi 359465592 280 NSIQTRGQ 287
Cdd:cd14603  247 AAVQTEEQ 254

Predicted phosphohydrolase, protein tyrosine phosphatase (PTP) superfamily, DUF442 family [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 140 VTDNILAMARPSSEllekyhIIDQFLSHGIKTIINLQRPGEHAScgnpleQESGFTyLPEAFMEAGIYFYN--FGWKDYG 217
Cdd:COG3453    4 ITDRLSVSGQPTPE------DLAALAAAGFKTVINLRPDGEEPD------QPAAAD-EAAAAEAAGLEYVHipVTGGAIT 70

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 359465592 218 VASLTTILDMVkvmtfALQEGKVAIHCHAGLgRTGVLIACYLVFATRMTADQAI 271
Cdd:COG3453   71 DEDVEAFAAAL-----AAAPGPVLAHCRSGT-RSSALWALYQAGKGGMSPEEAL 118

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 359465592 234 ALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP---NSIQTRGQLLcvrEFTQFLT 299
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 359465592 238 GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPnSIQTR----GQLL 289
Cdd:cd14568   80 KRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP-TISPNfnflGQLL 134

PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR 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. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 236 QEGKVAIHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAKRPNSIQTRGQL-LCVREFTQFL 298
Cdd:cd14629  220 QDGPITVHCSAGVGRTGVFITLSIVL-ERMRYEgvvdmfQTVKTLRTQRPAMVQTEDQYqLCYRAALEYL 288

fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae protein-tyrosine phosphatases 1 (PTP1) and 2 (PTP2), Schizosaccharomyces pombe PTP1, PTP2, and PTP3, and similar fungal proteins. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. PTP2, together with PTP3, is the major phosphatase that dephosphorylates and inactivates the MAP kinase HOG1 and also modulates its subcellular localization.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 359465592 206 IYFYNfgWKDYGV-ASLTTILDMVKV---MTFALQEGKVAI-HCHAGLGRTGVLIA 256
Cdd:cd18533  108 IQYKS--WPDFGVpDSPEDLLTLIKLkreLNDSASLDPPIIvHCSAGVGRTGTFIA 161

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 359465592 236 QEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAIIFVRAKRPNSIQTRgQLLCVREFTQfltplRNIFSCCDPKAH 313
Cdd:PTZ00393 169 NNRAVAVHCVAGLGRAPVLASIVLI-EFGMDPIDAIVFIRDRRKGAINKR-QLQFLKAYKK-----KKKKKNCLRKCH 239

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 359465592 213 WKDYGV-ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATrMTADQAI-IF-----VRAKRPNSIQTR 285
Cdd:cd14538  115 WPDHGTpQSADPLLRFIRYMRRIHNSGPIVVHCSAGIGRTGVLITIDVALGL-IERDLPFdIQdivkdLREQRQGMIQTK 193

                 ..
gi 359465592 286 GQ 287
Cdd:cd14538  194 DQ 195

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 359465592 202 MEAGIYFYNF-GWKDYGVAS----LTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIAC-YLVFATR-------MTA 267
Cdd:cd14605  140 TERTVWQYHFrTWPDHGVPSdpggVLDFLEEVHHKQESIMDaGPVVVHCSAGIGRTGTFIVIdILIDIIRekgvdcdIDV 219

                         90       100
                 ....*....|....*....|
gi 359465592 268 DQAIIFVRAKRPNSIQTRGQ 287
Cdd:cd14605  220 PKTIQMVRSQRSGMVQTEAQ 239

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 1; 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 first catalytic PTP domain (repeat 1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 208 FYNFGWKDYGVASltTILDMVK----VMTFALQ-EGKVAIHCHAGLGRTGVLIACYLVFATrMTADQAI-IF-----VRA 276
Cdd:cd14551  109 FHFTSWPDFGVPF--TPIGMLKflkkVKSANPPrAGPIVVHCSAGVGRTGTFIVIDAMLDM-MHAEGKVdVFgfvsrIRQ 185

                         90
                 ....*....|.
gi 359465592 277 KRPNSIQTRGQ 287
Cdd:cd14551  186 QRSQMVQTDMQ 196

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 359465592 240 VAIHCHAGLGRTGVLIACYLVfATRMTADQAIIFVRAKRPNSIQTRgQLLCVREF 294
Cdd:cd18535   96 VAVHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKY 148

catalytic domain of receptor-type tyrosine-protein phosphatase T, repeat 1; Receptor-type tyrosine-protein phosphatase T (PTPRT), also known as receptor-type tyrosine-protein phosphatase rho (RPTP-rho or PTPrho), belongs to the type IIb subfamily of receptor protein tyrosine 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. PTPRT is highly expressed in the nervous system and it plays a critical role in regulation of synaptic formation and neuronal development. It dephosphorylates a specific tyrosine residue in syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, and regulates its binding to syntaxin 1. PTPRT has been identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 208 FYNFGWKDYGVASLTT-ILDMVKVMTF--ALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIF-----VRAKRP 279
Cdd:cd14630  136 FHFTSWPDHGVPCYATgLLGFVRQVKFlnPPDAGPIVVHCSAGAGRTGCFIAIDIMLDMAENEGVVDIFncvreLRAQRV 215

                         90
                 ....*....|....
gi 359465592 280 NSIQTRGQLLCVRE 293
Cdd:cd14630  216 NMVQTEEQYVFVHD 229

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 359465592 213 WKDYGV----ASLTTILDMVKVMTFALQ-EGKVAIHCHAGLGRTGVLIAcYLVFATRMTADQA------IIFVRAKRPNS 281
Cdd:cd14618  137 WPDHGIpestSSLMAFRELVREHVQATKgKGPTLVHCSAGVGRSGTFIA-LDRLLRQLKEEKVvdvfntVYILRMHRYLM 215

                 ....*.
gi 359465592 282 IQTRGQ 287
Cdd:cd14618  216 IQTLSQ 221

catalytic domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The type II (or R2B) subfamily of receptor protein tyrosine phosphatases (RPTPs) include the prototypical member PTPmu (or PTPRM), PCP-2 (or PTPRU), PTPrho (or PTPRT), and PTPkappa (or PTPRK). 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. Type IIb RPTPs mediate cell-cell adhesion though homophilic interactions; their ligand is an identical molecule on an adjacent cell. No heterophilic interactions between the subfamily members have been observed. They also commonly function as tumor suppressors. They contain an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465592 208 FYNFGWKDYGVASLTT-ILDMVKVMTFAL--QEGKVAIHCHAGLGRTGvliaCYLVFATR--MTADQAIIFV-------R 275
Cdd:cd14555  104 FHFTGWPDHGVPYHATgLLGFIRRVKASNppSAGPIVVHCSAGAGRTG----CYIVIDIMldMAEREGVVDIyncvkelR 179

                         90
                 ....*....|....*...
gi 359465592 276 AKRPNSIQTRGQLLCVRE 293
Cdd:cd14555  180 SRRVNMVQTEEQYIFIHD 197