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 359465590  76 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 155
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 156 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 234
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465590 235 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 280
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 359465590  76 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 155
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 156 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 234
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465590 235 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 280
Cdd:cd14506  161 LCVREFAQFLLPLRNVFACPDPK-AAVTLRQYLIRQRHLLHGYEAR 205

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590   154 FYNFGWKDYGV-ASLTTILDMV----KVMTFALQEGKVAIHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 222
Cdd:smart00404   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 359465590   223 KRPNSIQTRGQLL 235
Cdd:smart00404  85 QRPGMVQTEEQYL 97

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 141 TYLPEAFMEAGIYFYNFGWKDYGVASLTTI---LDMVK--VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQ 215
Cdd:PTZ00242  51 TYDAELLEKNGIEVHDWPFDDGAPPPKAVIdnwLRLLDqeFAKQSTPPETIAVHCVAGLGRAPILVALALVEYGGMEPLD 130

                         90
                 ....*....|...
gi 359465590 216 AIIFVRAKRPNSI 228
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 359465590  76 QAIKGVYSSWVTDNILAMARPSSELLEKYHIIDQFLSHGIKTIINLQRPGEHASCGNPLEQESGFTYLPEAFMEAGIYFY 155
Cdd:cd14506    1 QAIKGLYSSWITDDILAMARPSTELIDKYGIIEQFKEKGIKTVINLQEPGEHASCGPGLEPESGFSYLPEAFMRAGIYFY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 156 NFGWKDYGVASLTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQL 234
Cdd:cd14506   81 NFGWKDYGVPSLTTILDIVKVMAFALQEgGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIQTRGQV 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 359465590 235 LCVREFTQFLTPLRNIFSCCDPKaHAVTLPQYLIRQRHLLHGYEAR 280
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 359465590  84 SWVTDNILA-MARPSSELLEKYhiidqFLSHGIKTIINLqrpgehasCGNPLeqesgftyLPEAFMEAGIYFYNFGWKDY 162
Cdd:cd14504    2 SWVIPGKLAgMAFPRLPEHYAY-----LNENGIRHVVTL--------TEEPP--------PEHSDTCPGLRYHHIPIEDY 60

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 163 GVASLTTILDMVKVMTFALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCVREFT 241
Cdd:cd14504   61 TPPTLEQIDEFLDIVEEANAKNEaVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFA 140

                 ..
gi 359465590 242 QF 243
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 359465590 107 IDQFLSHGIKTIINLQRPGEhascgnpLEqESGFTYLPEAFMEAGIYFYNFGWKDYGV----ASLTTILDMVKVmtfALQ 182
Cdd:cd14505   36 LEELKDQGVDDVVTLCTDGE-------LE-ELGVPDLLEQYQQAGITWHHLPIPDGGVpsdiAQWQELLEELLS---ALE 104

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 359465590 183 EGK-VAIHCHAGLGRTGVLIACYLVFAT-RMTADQAIIFVRAKRPNSIQTRGQL 234
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 359465590  84 SWVTDNILAMARPSSELLEKYHI--ID---QFL--SHGIK-TIINLqrpgehascgnpleqeSGFTYLPEAFMEAGIYfy 155
Cdd:cd14497    3 SYITPRIIAMSFPATGYPESLYRnsIDdvaNFLntHHPDHyMIFNL----------------SEEEYDDDSKFEGRVL-- 64

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 359465590 156 NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATR-MTADQAIIFVRAKRPN 226
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 359465590  84 SWVTDNILAMARP----SSELLEKyhiidqflsHGIKTIINLQRPGEHASCGNPLEQESGftylpeafmeAGIYFYNFGW 159
Cdd:cd14524    3 DRIDDTVILGALPfrsmTVALVAK---------ENVRGVITMNEEYETRFFCNSKEEWKA----------LGVEQLRLPT 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 160 KDY-GVASLTTILDMVKVM-TFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPNSIQTRGQLLCV 237
Cdd:cd14524   64 VDFtGVPSLEDLEKGVDFIlKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREVL 143

                 ....*.
gi 359465590 238 REFTQF 243
Cdd:cd14524  144 EEFYRK 149

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590   154 FYNFGWKDYGV-ASLTTILDMV----KVMTFALQEGKVAIHCHAGLGRTGVLIA----CYLVFATRMTAD--QAIIFVRA 222
Cdd:smart00404   5 YHYTGWPDHGVpESPDSILELLravkKNLNQSESSGPVVVHCSAGVGRTGTFVAidilLQQLEAEAGEVDifDTVKELRS 84

                           90
                   ....*....|...
gi 359465590   223 KRPNSIQTRGQLL 235
Cdd:smart00404  85 QRPGMVQTEEQYL 97

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590  153 YFYNfGWKDYGV----ASLTTILDMVKVMTFALQEGKVAIHCHAGLGRTGVLIACYLVfATRMTADQAI-IF-----VRA 222
Cdd:pfam00102 136 FHYT-GWPDHGVpespNSLLDLLRKVRKSSLDGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAEGEVdIFqivkeLRS 213

                          90
                  ....*....|....*
gi 359465590  223 KRPNSIQTRGQLLCV 237
Cdd:pfam00102 214 QRPGMVQTLEQYIFL 228

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 359465590  102 EKYHIIDQFLS-HGIKTIINLQRpgehaSCGNPLeqeSGFTYL--P-EAFMEAGIYFYnfgwkdygvaslttiLDMVK-- 175
Cdd:pfam00782   5 SKPTASDAFLSkLGITAVINVTR-----EVDLYN---SGILYLriPvEDNHETNISKY---------------LEEAVef 61

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 359465590  176 VMTFALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP 225
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 359465590  84 SWVTDNILAMARPSsELLEKY---HIID--QFLS--HGIK-TIINLqrpgehasCgnpleqeSGFTYLPEAFmeagiyFY 155
Cdd:cd14509    3 TYITPNIIAMGFPA-EGVEGVyrnPIDDvqRFLEtkHKGHyKVYNL--------C-------SERSYDPSKF------NG 60

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 359465590 156 ---NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFATRM-TADQAIIFVRAKR 224
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 359465590 107 IDQFLSHGIKTIINLQRPGEHASCGNPLEQesgftyLPEAFMEAGIYFYNFGWKDYGVASLTTILDMVKVMTFAL--QEG 184
Cdd:cd14526   22 VDRLKKEGVTAVLNLQTDSDMEYWGVDIDS------IRKACKESGIRYVRLPIRDFDTEDLRQKLPQAVALLYRLlkNGG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 359465590 185 KVAIHCHAGLGR-TGVLIAcYLVFATRMTADQAIIFVRAKRP 225
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 359465590  89 NILAMARPSSELLEKYhiIDQFLSHGIKTIINLQRPgehascgnpleqesgfTYLPEAFMEAGIYFYNFGWKDYGVAS-- 166
Cdd:cd14500   14 RFLITDAPTDSNLPLY--IKELKKYNVTDLVRVCEP----------------TYDKEPLEKAGIKVHDWPFDDGSPPPdd 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 167 -LTTILDMVKVmTFA---LQEGKVAIHCHAGLGRTGVLIACYLVFAtRMTADQAIIFVRAKRPNSIQTRgQLlcvreftQ 242
Cdd:cd14500   76 vVDDWLDLLKT-RFKeegKPGACIAVHCVAGLGRAPVLVAIALIEL-GMKPEDAVEFIRKKRRGAINSK-QL-------Q 145

                 ...
gi 359465590 243 FLT 245
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 359465590 144 PEAFMEAGIYFYNFGWKDYGVASLTTILDMV-KVMTFALQE--GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFV 220
Cdd:cd14515   46 AKFYKGSGIIYLGIPASDLPTFDISQYFDEAaDFIDKALSDpgGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTV 125

                         90
                 ....*....|
gi 359465590 221 RAKR---PNS 227
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 359465590 159 WKDYGVA-SLTTILDMVKVMTFALQEGKV--AIHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----VRAKRP 225
Cdd:cd14603  169 WPDHGIPdSPDCMLAMIELARRLQGSGPEplCVHCSAGCGRTGVI--CTVDYVRQLLLTQRIppdfsIFdvvleMRKQRP 246

                 ....*...
gi 359465590 226 NSIQTRGQ 233
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 359465590 154 FYNFGWKDYGV-ASLTTILDMVKVM--TFALQEGKVAIHCHAGLGRTGVLiaCYLVFATRMTADQAI-----IF-----V 220
Cdd:cd14542  106 FHYTAWPDHGVpSSVDPILDLVRLVrdYQGSEDVPICVHCSAGCGRTGTI--CAIDYVWNLLKTGKIpeefsLFdlvreM 183

                         90
                 ....*....|...
gi 359465590 221 RAKRPNSIQTRGQ 233
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 359465590 180 ALQEGK-VAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRP---NSIQTRGQLLcvrEFTQFLT 245
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 359465590 184 GKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIFVRAKRPnSIQTR----GQLL 235
Cdd:cd14568   80 KRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP-TISPNfnflGQLL 134

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590  84 SWVTDNILAMARPSSellekyhiidqflshgiktiinlqrpGEHASCGNPLEQESGF--TYLPEAFM----------EAG 151
Cdd:cd14510   17 TYVTDRVIAMSFPSS--------------------------GKQAFYRNPIEEVVRFldTKHPDHYKvynlcsergyDPK 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 152 IYFYNFG---WKDYGVASLTTILDMVK-VMTFALQEGK--VAIHCHAGLGRTGVLIACYLVFATRM-TADQAIIFVRAKR 224
Cdd:cd14510   71 YFHNRVErvpIDDHNVPTLDEMLSFTAeVREWMAADPKnvVAIHCKGGKGRTGTMVCAWLIYSGQFeSAKEALEYFGERR 150

                        170       180
                 ....*....|....*....|....*.
gi 359465590 225 PN--------SIQTRGQLLCVREFTQ 242
Cdd:cd14510  151 TDksvsskfqGVETPSQSRYVGYFEK 176

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 359465590 152 IYFYNfgWKDYGV-ASLTTILDMVKV---MTFALQEGKVAI-HCHAGLGRTGVLIA 202
Cdd:cd18533  108 IQYKS--WPDFGVpDSPEDLLTLIKLkreLNDSASLDPPIIvHCSAGVGRTGTFIA 161

protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular proteins (tensin-1, -2, -3 and -4) act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of tensin expression has been implicated in human cancer. Tensin-1, -2, and -3 contain an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. In addition, tensin-2 contains a zinc finger N-terminal to its PTP domain. Tensin-4 is not included in this model as it does not contain a PTP-like domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590  84 SWVTDNILAMARPSSELLEKYHIIDQFLSHGIKT-------IINLQRPGEHASCGNPLEQEsgftylpeafmeagiyfyn 156
Cdd:cd14508    3 TYITERIIALSFPSTCSEQTYRHNLREAAHLLQSkhgdnymVFNLSERRHDLRSLNPKVLD------------------- 63

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 359465590 157 FGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVF-ATRMTADQAI 217
Cdd:cd14508   64 FGWPELHAPPLEKLCSICKNMDSWLNADPqnvVVLHCKGGKGRLGVVVSAYMHYsKISATADQAL 128

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 359465590 182 QEGKVAIHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAKRPNSIQTRGQ 233
Cdd:cd14628  219 QDGPISVHCSAGVGRTGVFITLSIVL-ERMRYEgvvdifQTVKMLRTQRPAMVQTEDQ 275

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 359465590 148 MEAGIYFYNF-GWKDYGVAS----LTTILDMVKVMTFALQE-GKVAIHCHAGLGRTGVLIAC-YLVFATR-------MTA 213
Cdd:cd14605  140 TERTVWQYHFrTWPDHGVPSdpggVLDFLEEVHHKQESIMDaGPVVVHCSAGIGRTGTFIVIdILIDIIRekgvdcdIDV 219

                         90       100
                 ....*....|....*....|
gi 359465590 214 DQAIIFVRAKRPNSIQTRGQ 233
Cdd:cd14605  220 PKTIQMVRSQRSGMVQTEAQ 239

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 359465590 182 QEGKVAIHCHAGLGRTGVLIACYLVFaTRMTAD------QAIIFVRAKRPNSIQTRGQL-LCVREFTQFL 244
Cdd:cd14627  220 QDGPISVHCSAGVGRTGVFITLSIVL-ERMRYEgvvdifQTVKMLRTQRPAMVQTEDEYqFCYQAALEYL 288

protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. It plays an essential role in TGF-beta-induced myofibroblast differentiation and myofibroblast-mediated formation of extracellular fibronectin and collagen matrix. It also positively regulates RhoA activity through its interaction with DLC1, a RhoGAP-containing tumor suppressor; the tensin-1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis. Tensin-1 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 359465590 156 NFGWKDYGVASLTTILDMVKVMTFALQEGK---VAIHCHAGLGRTGVLIACYLVFAT-RMTADQAIIFVRAKR 224
Cdd:cd14560   63 DFGWPDLHAPALEKICSICKAMDTWLNADPhnvVVIHNKGNRGRTGVVIAAYMHYSNiSASADQALDRFAMKR 135

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 359465590 154 FYNFGWKDYGVASLTT-ILDMVKVMTF--ALQEGKVAIHCHAGLGRTGVLIACYLVFATRMTADQAIIF-----VRAKRP 225
Cdd:cd14630  136 FHFTSWPDHGVPCYATgLLGFVRQVKFlnPPDAGPIVVHCSAGAGRTGCFIAIDIMLDMAENEGVVDIFncvreLRAQRV 215

                         90
                 ....*....|....
gi 359465590 226 NSIQTRGQLLCVRE 239
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 359465590 159 WKDYGV----ASLTTILDMVKVMTFALQ-EGKVAIHCHAGLGRTGVLIAcYLVFATRMTADQA------IIFVRAKRPNS 227
Cdd:cd14618  137 WPDHGIpestSSLMAFRELVREHVQATKgKGPTLVHCSAGVGRSGTFIA-LDRLLRQLKEEKVvdvfntVYILRMHRYLM 215

                 ....*.
gi 359465590 228 IQTRGQ 233
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 359465590 154 FYNFGWKDYGVASLTT-ILDMVKVMTFAL--QEGKVAIHCHAGLGRTGvliaCYLVFATR--MTADQAIIFV-------R 221
Cdd:cd14555  104 FHFTGWPDHGVPYHATgLLGFIRRVKASNppSAGPIVVHCSAGAGRTG----CYIVIDIMldMAEREGVVDIyncvkelR 179

                         90
                 ....*....|....*...
gi 359465590 222 AKRPNSIQTRGQLLCVRE 239
Cdd:cd14555  180 SRRVNMVQTEEQYIFIHD 197