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 30089952 128 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 207
Cdd:cd14506   1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 208 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 286
Cdd:cd14506  81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 30089952 287 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 332
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 30089952 128 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 207
Cdd:cd14506   1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 208 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 286
Cdd:cd14506  81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 30089952 287 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 332
Cdd:cd14506 161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952   205 YFYNfGWKDYGV----ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAI-IF-----VRA 274
Cdd:pfam00102 136 FHYT-GWPDHGVpespNSLLDLLRKVRKSSLDGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAEGEVdIFqivkeLRS 213

                          90
                  ....*....|....*
gi 30089952   275 KRPNSIQTRGQLLCV 289
Cdd:pfam00102 214 QRPGMVQTLEQYIFL 228

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952  193 TYLPEAFMEAGIYFYNFGWKDYGVASLTTI---LDMVK--VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQ 267
Cdd:PTZ00242  51 TYDAELLEKNGIEVHDWPFDDGAPPPKAVIdnwLRLLDqeFAKQSTPPETIAVHCVAGLGRAPILVALALVEYGGMEPLD 130

                         90
                 ....*....|...
gi 30089952  268 AIIFVRAKRPNSI 280
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 30089952 128 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 207
Cdd:cd14506   1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 208 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 286
Cdd:cd14506  81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 30089952 287 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 332
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 30089952 136 SWVTDNILA-MARPSSELLEKYhiidqFLSHGIKTIINLqrpgehasCGNPLeqesgftyLPEAFMEAGIYFYNFGWKDY 214
Cdd:cd14504   2 SWVIPGKLAgMAFPRLPEHYAY-----LNENGIRHVVTL--------TEEPP--------PEHSDTCPGLRYHHIPIEDY 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 215 GVASLTTILDMVKVMTFALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCVREFT 293
Cdd:cd14504  61 TPPTLEQIDEFLDIVEEANAKNEaVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFA 140

                ..
gi 30089952 294 QF 295
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 30089952 159 IDQFLSHGIKTIINLQRPGEhascgnpLEqESGFTYLPEAFMEAGIYFYNFGWKDYGV----ASLTTILDMVKVmtfALQ 234
Cdd:cd14505  36 LEELKDQGVDDVVTLCTDGE-------LE-ELGVPDLLEQYQQAGITWHHLPIPDGGVpsdiAQWQELLEELLS---ALE 104

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 30089952 235 EGK-VAIHCHAGLGRTGVLIACYLVFAT-RMTADQAIIFVRAKRPNSIQTRGQL 286
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 30089952 136 SWVTDNILAMARPSSELLEKYHI--ID---QFL--SHGIK-TIINLqrpgehascgnpleqeSGFTYLPEAFMEAGIYfy 207
Cdd:cd14497   3 SYITPRIIAMSFPATGYPESLYRnsIDdvaNFLntHHPDHyMIFNL----------------SEEEYDDDSKFEGRVL-- 64

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30089952 208 NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATR-MTADQAIIFVRAKRPN 278
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 30089952 136 SWVTDNILAMARP----SSELLEKyhiidqflsHGIKTIINLQRPGEHASCGNPLEQESGftylpeafmeAGIYFYNFGW 211
Cdd:cd14524   3 DRIDDTVILGALPfrsmTVALVAK---------ENVRGVITMNEEYETRFFCNSKEEWKA----------LGVEQLRLPT 63

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 212 KDY-GVASLTTILDMVKVM-TFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCV 289
Cdd:cd14524  64 VDFtGVPSLEDLEKGVDFIlKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREVL 143

                ....*.
gi 30089952 290 REFTQF 295
Cdd:cd14524 144 EEFYRK 149

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952   205 YFYNfGWKDYGV----ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAI-IF-----VRA 274
Cdd:pfam00102 136 FHYT-GWPDHGVpespNSLLDLLRKVRKSSLDGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAEGEVdIFqivkeLRS 213

                          90
                  ....*....|....*
gi 30089952   275 KRPNSIQTRGQLLCV 289
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 30089952    206 FYNFGWKDYGV-ASLTTILDMV----KVMTFALQEGKVAIHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 274
Cdd:smart00012   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 30089952    275 KRPNSIQTRGQLL 287
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 30089952   154 EKYHIIDQFLS-HGIKTIINLQRpgehaSCGNPLeqeSGFTYL--P-EAFMEAGIYFYnfgwkdygvaslttiLDMVK-- 227
Cdd:pfam00782   5 SKPTASDAFLSkLGITAVINVTR-----EVDLYN---SGILYLriPvEDNHETNISKY---------------LEEAVef 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 30089952   228 VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP 277
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 30089952 136 SWVTDNILAMARPSsELLEKY---HIID--QFLS--HGIK-TIINLqrpgehasCgnpleqeSGFTYLPEAFmeagiyFY 207
Cdd:cd14509   3 TYITPNIIAMGFPA-EGVEGVyrnPIDDvqRFLEtkHKGHyKVYNL--------C-------SERSYDPSKF------NG 60

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30089952 208 ---NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATRM-TADQAIIFVRAKR 276
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 30089952 159 IDQFLSHGIKTIINLQRPGEHASCGNPLEQesgftyLPEAFMEAGIYFYNFGWKDYGVASLTTILDMVKVMTFAL--QEG 236
Cdd:cd14526  22 VDRLKKEGVTAVLNLQTDSDMEYWGVDIDS------IRKACKESGIRYVRLPIRDFDTEDLRQKLPQAVALLYRLlkNGG 95

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 30089952 237 KVAIHCHAGLGR-TGVLIAcYLVFATRMTADQAIIFVRAKRP 277
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 30089952 141 NILAMARPSSELLEKYhiIDQFLSHGIKTIINLQRPgehascgnpleqesgfTYLPEAFMEAGIYFYNFGWKDYGVAS-- 218
Cdd:cd14500  14 RFLITDAPTDSNLPLY--IKELKKYNVTDLVRVCEP----------------TYDKEPLEKAGIKVHDWPFDDGSPPPdd 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30089952 219 -LTTILDMVKVmTFA---LQEGKVAIHCHAGLGRTGVLIACYLVFAtRMTADQAIIFVRAKRPNSIQTRgQLlcvreftQ 294
Cdd:cd14500  76 vVDDWLDLLKT-RFKeegKPGACIAVHCVAGLGRAPVLVAIALIEL-GMKPEDAVEFIRKKRRGAINSK-QL-------Q 145

                ...
gi 30089952 295 FLT 297
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 30089952 196 PEAFMEAGIYFYNFGWKDYGVASLTTILDMV-KVMTFALQE--GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFV 272
Cdd:cd14515  46 AKFYKGSGIIYLGIPASDLPTFDISQYFDEAaDFIDKALSDpgGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTV 125

                        90
                ....*....|
gi 30089952 273 RAKR---PNS 279
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 30089952 211 WKDYGVA-SLTTILDMVKVMTFALQEGKV--AIHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----VRAKRP 277
Cdd:cd14603 169 WPDHGIPdSPDCMLAMIELARRLQGSGPEplCVHCSAGCGRTGVI--CTVDYVRQLLLTQRIppdfsIFdvvleMRKQRP 246

                ....*...
gi 30089952 278 NSIQTRGQ 285
Cdd:cd14603 247 AAVQTEEQ 254

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 30089952 206 FYNFGWKDYGV-ASLTTILDMVKVM--TFALQEGKVAIHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----V 272
Cdd:cd14542 106 FHYTAWPDHGVpSSVDPILDLVRLVrdYQGSEDVPICVHCSAGCGRTGTI--CAIDYVWNLLKTGKIpeefsLFdlvreM 183

                        90
                ....*....|...
gi 30089952 273 RAKRPNSIQTRGQ 285
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 30089952 232 ALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP---NSIQTRGQLLcvrEFTQFLT 297
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 30089952 236 GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPnSIQTR----GQLL 287
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 30089952 234 QEGKVAIHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAKRPNSIQTRGQL-LCVREFTQFL 296
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 30089952 204 IYFYNfgWKDYGV-ASLTTILDMVKV---MTFALQEGKVAI-HCHAGLGRTGVLIA 254
Cdd:cd18533 108 IQYKS--WPDFGVpDSPEDLLTLIKLkreLNDSASLDPPIIvHCSAGVGRTGTFIA 161

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30089952  234 QEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAIIFVRAKRPNSIQTRgQLLCVREFTQfltplRNIFSCCDPKAH 311
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 30089952 211 WKDYGV-ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATrMTADQAI-IF-----VRAKRPNSIQTR 283
Cdd:cd14538 115 WPDHGTpQSADPLLRFIRYMRRIHNSGPIVVHCSAGIGRTGVLITIDVALGL-IERDLPFdIQdivkdLREQRQGMIQTK 193

                ..
gi 30089952 284 GQ 285
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 30089952 200 MEAGIYFYNF-GWKDYGVAS----LTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIAC-YLVFATR-------MTA 265
Cdd:cd14605 140 TERTVWQYHFrTWPDHGVPSdpggVLDFLEEVHHKQESIMDaGPVVVHCSAGIGRTGTFIVIdILIDIIRekgvdcdIDV 219

                        90       100
                ....*....|....*....|
gi 30089952 266 DQAIIFVRAKRPNSIQTRGQ 285
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 30089952 206 FYNFGWKDYGVASltTILDMVK----VMTFALQ-EGKVAIHCHAGLGRTGVLIACYLVFATrMTADQAI-IF-----VRA 274
Cdd:cd14551 109 FHFTSWPDFGVPF--TPIGMLKflkkVKSANPPrAGPIVVHCSAGVGRTGTFIVIDAMLDM-MHAEGKVdVFgfvsrIRQ 185

                        90
                ....*....|.
gi 30089952 275 KRPNSIQTRGQ 285
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 30089952 238 VAIHCHAGLGRTGVLIACYLVfATRMTADQAIIFVRAKRPNSIQTRgQLLCVREF 292
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 30089952 206 FYNFGWKDYGVASLTT-ILDMVKVMTF--ALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIF-----VRAKRP 277
Cdd:cd14630 136 FHFTSWPDHGVPCYATgLLGFVRQVKFlnPPDAGPIVVHCSAGAGRTGCFIAIDIMLDMAENEGVVDIFncvreLRAQRV 215

                        90
                ....*....|....
gi 30089952 278 NSIQTRGQLLCVRE 291
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 30089952 211 WKDYGV----ASLTTILDMVKVMTFALQ-EGKVAIHCHAGLGRTGVLIAcYLVFATRMTADQA------IIFVRAKRPNS 279
Cdd:cd14618 137 WPDHGIpestSSLMAFRELVREHVQATKgKGPTLVHCSAGVGRSGTFIA-LDRLLRQLKEEKVvdvfntVYILRMHRYLM 215

                ....*.
gi 30089952 280 IQTRGQ 285
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 30089952 206 FYNFGWKDYGVASLTT-ILDMVKVMTFAL--QEGKVAIHCHAGLGRTGvliaCYLVFATR--MTADQAIIFV-------R 273
Cdd:cd14555 104 FHFTGWPDHGVPYHATgLLGFIRRVKASNppSAGPIVVHCSAGAGRTG----CYIVIDIMldMAEREGVVDIyncvkelR 179

                        90
                ....*....|....*...
gi 30089952 274 AKRPNSIQTRGQLLCVRE 291
Cdd:cd14555 180 SRRVNMVQTEEQYIFIHD 197