protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  11 EITYKNMRFLITHNPTNATLHKFIEELKKYGVTTVVRVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQIVDDWLNLLRV 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 339515647  91 KFREE--PGCCIAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKRRGAFNSKQLFYLEKYRPKMRLRF 160
Cdd:PTZ00242  90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG 162

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647    64 QVLDWPfDDGAPPSNQIVDDWLNLLRVKFREEPGCC-IAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 135
Cdd:smart00404   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|..
gi 339515647   136 KRRGAFNSKQLF 147
Cdd:smart00404  85 QRPGMVQTEEQY 96

protein tyrosine phosphatase type IVA 2; Protein tyrosine phosphatase type IVA 2 (PTP-IVa2), also known as protein-tyrosine phosphatase of regenerating liver 2 (PRL-2), stimulates progression from G1 into S phase during mitosis and promotes tumors. It regulates tumor cell migration and invasion through an ERK-dependent signaling pathway. Its overexpression correlates with breast tumor formation and progression. PRL-2 is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647   4 MNRPAPVEITYKNMRFLITHNPTNATLHKFIEELKKYGVTTVVRVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQIVDD 83
Cdd:cd18536    1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 339515647  84 WLNLLRVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLFYLEKYRPKMRL 158
Cdd:cd18536   81 WLNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRL 155

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647   5 NRPAPVEITYKNMRFLITHNPTNATLHKFIEELKKYGVTTVVRVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQIVDDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 339515647  85 LNLLRVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLFYLEKYRPKMRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647   9 PVEITYKNMRFLITHNPTNATLHKFIEELKKYGVTTVVRVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQIVDDWLNLL 88
Cdd:PTZ00393  84 PTKIEHGKIKILILDAPTNDLLPLYIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIV 163

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 339515647  89 RVKFREEpgCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLFYLEKYRPK 155
Cdd:PTZ00393 164 NNVIKNN--RAVAVHCVAGLGRAPVLASIVLIEFGMDPIDAIVFIRDRRKGAINKRQLQFLKAYKKK 228

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  35 EELKKYGVTTVVRVCEATYDANLVVKE-GIQVLDWPFDDGAPPSnqiVDDWLNLLR-VKFREEPGCCIAVHCVAGLGRAP 112
Cdd:COG2453   19 ADLKREGIDAVVSLTEEEELLLGLLEEaGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGIGRTG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 339515647 113 VLVALALIECGMKYEDAVQFIRQKRRGAFNSK-QLFYLEKYRPKM 156
Cdd:COG2453   96 TVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFAKRL 140

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 339515647  34 IEELKKYGVTTVVRVCE----ATYDANLVVKE----GIQVLDWPFDDGAPPSN-----QIVDDWLNLLRVKFReepgccI 100
Cdd:cd14505   36 LEELKDQGVDDVVTLCTdgelEELGVPDLLEQyqqaGITWHHLPIPDGGVPSDiaqwqELLEELLSALENGKK------V 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 339515647 101 AVHCVAGLGRAPVLVALALIECG--MKYEDAVQFIRQKRRGAF-NSKQLFYL 149
Cdd:cd14505  110 LIHCKGGLGRTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIqTPKQENFL 161

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647    64 QVLDWPfDDGAPPSNQIVDDWLNLLRVKFREEPGCC-IAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 135
Cdd:smart00404   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|..
gi 339515647   136 KRRGAFNSKQLF 147
Cdd:smart00404  85 QRPGMVQTEEQY 96

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. 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. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  34 IEELKKYGVTTVVRVCEATYDANLvvKEGIQVLDWPFDDGA--------PPSNQIVDDWLnllrvkfreEPGCCIAVHCV 105
Cdd:cd14498   19 KELLKKLGITHILNVAGEPPPNKF--PDGIKYLRIPIEDSPdedilshfEEAIEFIEEAL---------KKGGKVLVHCQ 87

                         90       100       110
                 ....*....|....*....|....*....|...
gi 339515647 106 AGLGRAPVLVALALI-ECGMKYEDAVQFIRQKR 137
Cdd:cd14498   88 AGVSRSATIVIAYLMkKYGWSLEEALELVKSRR 120

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 339515647  34 IEELKKYGVTTVVRVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQIVDDWLNLlrVKFREEPGCCIAVHCVAGLGRAPV 113
Cdd:cd14504   21 YAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDI--VEEANAKNEAVLVHCLAGKGRTGT 98

                         90       100
                 ....*....|....*....|....*..
gi 339515647 114 LVALALIECG-MKYEDAVQFIRQKRRG 139
Cdd:cd14504   99 MLACYLVKTGkISAVDAINEIRRIRPG 125

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  35 EELKKYGVTTVV----RVCEATYDANLVVKEGIQVLDWPFDDGAPPSNQiVDDWLNLLRVKFREEPgccIAVHCVAGLGR 110
Cdd:cd14529   27 ALLKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESD-VQSFLLIMDLKLAPGP---VLIHCKHGKDR 102

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 339515647 111 APVLVALALIECGMKYEDAV-QFIRQKRRGAFNSKQLFYLEKYRPKMR 157
Cdd:cd14529  103 TGLVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

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 339515647  68 WPfDDGAPPSNQIVDDWLNLLRVKFREEPgccIAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQKRRGAF 141
Cdd:cd14538  115 WP-DHGTPQSADPLLRFIRYMRRIHNSGP---IVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMI 190

                 ...
gi 339515647 142 NSK 144
Cdd:cd14538  191 QTK 193

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647    63 IQVLDWPfDDGAPPSnqiVDDWLNLLRV--KFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYE------DAVQFIR 134
Cdd:smart00194 162 YHYTNWP-DHGVPES---PESILDLIRAvrKSQSTSTGPIVVHCSAGVGRTGTFIAIDILLQQLEAGkevdifEIVKELR 237

                           90
                   ....*....|.
gi 339515647   135 QKRRGAFNSKQ 145
Cdd:smart00194 238 SQRPGMVQTEE 248

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647   9 PVEITyknmRFLITHNPTNATlhkFIEELKKYGVTTVVRVceaTYD-ANLVVK-EGIQVLDWPfddgappsnqIVDDWL- 85
Cdd:cd14566    1 PVEIL----PFLYLGNAKDSA---NIDLLKKYNIKYILNV---TPNlPNTFEEdGGFKYLQIP----------IDDHWSq 60

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 339515647  86 NLLR-----VKFREEP---GCCIAVHCVAGLGRA-PVLVALALIECGMKYEDAVQFIRQKRR 138
Cdd:cd14566   61 NLSAffpeaISFIDEArskKCGVLVHCLAGISRSvTVTVAYLMQKLHLSLNDAYDFVKKRKS 122

PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  47 RVCEATYDANLVVKEgIQVLDWPfDDGAPPSNQIVDDWLNLLRvKFREEPGCC--IAVHCVAGLGRAPVLVALALIECGM 124
Cdd:cd14554  125 KVTDARDGQSRTVRQ-FQFTDWP-EQGVPKSGEGFIDFIGQVH-KTKEQFGQEgpITVHCSAGVGRTGVFITLSIVLERM 201

                 ....*.
gi 339515647 125 KYEDAV 130
Cdd:cd14554  202 RYEGVV 207

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
                 ....*....|....*....|....*....|....*....|...
gi 339515647  97 GCCIAVHCVAGLGRAP--VLVALALIeCGMKYEDAVQFIRQKR 137
Cdd:cd14526   94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

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 339515647  64 QVLDWPFDDGAPPSNQI-------VDDWLnllrvkfREEPGCCIAVHCVAGLGRAPVLVALALIECGM--KYEDAVQFIR 134
Cdd:cd14509   61 RVAEYPFDDHNPPPLELikpfcedVDEWL-------KEDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYG 133

                 ...
gi 339515647 135 QKR 137
Cdd:cd14509  134 AKR 136

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 339515647  64 QVLDWPfDDGAPPSNQIVDDWLNLLRvKFREEPG--CCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIR 134
Cdd:cd14628  187 QFTDWP-EQGVPKSGEGFIDFIGQVH-KTKEQFGqdGPISVHCSAGVGRTGVFITLSIVLERMRYEGVVDIFQ 257

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 339515647   4 MNRPA--PVEITYKN-----MRFLITHNPtnatlhkfieelKKYgvtTVVRVCEATYDANLVVKEgiQVLDWPFDDGAPP 76
Cdd:cd14497   12 MSFPAtgYPESLYRNsiddvANFLNTHHP------------DHY---MIFNLSEEEYDDDSKFEG--RVLHYGFPDHHPP 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  77 S----NQIVDD---WLNllrvkfrEEPGCCIAVHCVAGLGRAPVLVALALIECGM--KYEDAVQFIRQKR 137
Cdd:cd14497   75 PlgllLEIVDDidsWLS-------EDPNNVAVVHCKAGKGRTGTVICAYLLYYGQysTADEALEYFAKKR 137

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 339515647   37 LKKYGVTTVVRVCEATYDANLVVKE-GIQVLDWPFDDGAPPSNQIVD--DWLnllrvkfrEEPGCCIAVHCVAGLGRAPV 113
Cdd:pfam00782  14 LSKLGITAVINVTREVDLYNSGILYlRIPVEDNHETNISKYLEEAVEfiDDA--------RQKGGKVLVHCQAGISRSAT 85

                          90       100
                  ....*....|....*....|....*
gi 339515647  114 LVALALIEC-GMKYEDAVQFIRQKR 137
Cdd:pfam00782  86 LIIAYLMKTrNLSLNEAYSFVKERR 110

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), 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. DUSP13A 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. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  36 ELKKYGVTTVV------RVCEATYD--ANLVVKEGIQVLDWPFDDGAP---PSNQIVDDWLNllrvkfreEPGCCIAVHC 104
Cdd:cd14580   21 GLWKLGITHVLnaahgkLFCQGGDDfyGTSVDYYGVPANDLPDFDISPyfySAAEFIHRALN--------TPGAKVLVHC 92

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 339515647 105 VAGLGRAPVLV-ALALIECGMKYEDAVQFIRQKRR 138
Cdd:cd14580   93 AVGVSRSATLVlAYLMIYHQLSLVQAIKTVKERRW 127

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  32 KFIEELKKYGVTTVVRVCEATYDaNLVVKE--GIQVLDWPfDDGAPPSnqiVDDWLNLLRVK----FREEPGCCIAVHCV 105
Cdd:cd18533   76 ELVSEEENDDGGFIVREFELSKE-DGKVKKvyHIQYKSWP-DFGVPDS---PEDLLTLIKLKrelnDSASLDPPIIVHCS 150

                         90
                 ....*....|..
gi 339515647 106 AGLGRAPVLVAL 117
Cdd:cd18533  151 AGVGRTGTFIAL 162

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  66 LDWPfDDGAPPSNQIVDDWLNLLRvKFREEPGCCIAVHCVAGLGRAPVLVAL----ALIECGMKYED-----AVQFIRQK 136
Cdd:cd14604  194 VNWP-DHDVPSSFDSILDMISLMR-KYQEHEDVPICIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfnLIQEMRTQ 271

                         90
                 ....*....|...
gi 339515647 137 RRGAFNSKQLFYL 149
Cdd:cd14604  272 RHSAVQTKEQYEL 284

catalytic domain of receptor-type tyrosine-protein phosphatase Q; Receptor-type tyrosine-protein phosphatase Q (PTPRQ or R-PTP-Q), also called phosphatidylinositol phosphatase PTPRQ, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRQ 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 (18 in PTPRQ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It displays low tyrosine-protein phosphatase activity; rather, it functions as a phosphatidylinositol phosphatase required for auditory processes. It regulates the levels of phosphatidylinositol 4,5-bisphosphate (PIP2) in the basal region of hair bundles. It can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  34 IEELK--KYGVTTVVRVCEATydanlvvkegiqvlDWPfDDGAPPSNQIVDDWLNLLRVKfREEPGCCIAVHCVAGLGRA 111
Cdd:cd14616  114 IRDLKieRHGDYMMVRQCNFT--------------SWP-EHGVPESSAPLIHFVKLVRAS-RAHDNTPMIVHCSAGVGRT 177

                 ....*.
gi 339515647 112 PVLVAL 117
Cdd:cd14616  178 GVFIAL 183

catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type tyrosine-protein phosphatase J (PTPRJ or R-PTP-J), also known as receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) or density-enhanced phosphatase 1 (DEP-1) OR CD148, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRJ 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 (eight in PTPRJ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed in various cell types including epithelial, hematopoietic, and endothelial cells. It plays a role in cell adhesion, migration, proliferation and differentiation. It dephosphorylates or contributes to the dephosphorylation of various substrates including protein kinases such as FLT3, PDGFRB, MET, RET (variant MEN2A), VEGFR-2, LYN, SRC, MAPK1, MAPK3, and EGFR, as well as PIK3R1 and PIK3R2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 339515647  68 WPfDDGAPPSNQIVDDWLNLLRVKFREEP-GCCIAVHCVAGLGRAPVLVALALIECGMKYEDAV 130
Cdd:cd14615  135 WP-DHGVPETTDLLINFRHLVREYMKQNPpNSPILVHCSAGVGRTGTFIAIDRLIYQIENENVV 197

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  64 QVLDWPfDDGAPPSNQIVddwLNLL-----RVKFREEPGCcIAVHCVAGLGR-APVLVALALIE--------CGMKYEDA 129
Cdd:cd14544  146 QYLSWP-DHGVPSDPGGV---LNFLedvnqRQESLPHAGP-IVVHCSAGIGRtGTFIVIDMLLDqikrkgldCDIDIQKT 220

                         90
                 ....*....|
gi 339515647 130 VQFIRQKRRG 139
Cdd:cd14544  221 IQMVRSQRSG 230

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  64 QVLDWPfDDGAPPSNQIVDDWLNLLRVKFREEPGCC-IAVHCVAGLGRAPVLVALALI---------ECGMKYEDAVQFI 133
Cdd:cd14606  161 QYLSWP-DHGVPSEPGGVLSFLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIVIDMLmenistkglDCDIDIQKTIQMV 239

                 ....*.
gi 339515647 134 RQKRRG 139
Cdd:cd14606  240 RAQRSG 245

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and 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. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 339515647  35 EELKKYGVTTVVRVCEATYDANLvvkEGIQVLDWPFDDGapPSNQIvDDWLNLL--RVKFREEPGCCIAVHCVAGLGRAP 112
Cdd:cd14514   19 PLLLSRGITCIINATTELPDPSY---PGIEYLRVPVEDS--PHADL-SPHFDEVadKIHQVKRRGGRTLVHCVAGVSRSA 92

                         90       100       110
                 ....*....|....*....|....*....|
gi 339515647 113 VLVALALiecgMKYE-----DAVQFIRQKR 137
Cdd:cd14514   93 TLCLAYL----MKYEgmtlrEAYKHVKAAR 118

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 339515647  97 GCCIAVHCVAGLGRAPVlVALA-LIEC-GMKYEDAVQFIRQKR 137
Cdd:cd14565   78 GGRVLVHCQAGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119