protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It 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 971389846   1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQI 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 ....*..
gi 971389846 161 KDSNGHR 167
Cdd:cd18537  161 KDSNGHR 167

protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It 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 971389846   1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQI 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 ....*..
gi 971389846 161 KDSNGHR 167
Cdd:cd18537  161 KDSNGHR 167

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  35 EELKKYGVTTVVRVC-EATYDTAPVEKEGIQVLDWPFDDGAPPSnqiVDDWLNLLK-VKFREEPGCCIAVHCVAGLGRAP 112
Cdd:COG2453   19 ADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGIGRTG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 971389846 113 VLVALALIECGMKYEDAVQFIRQKRRGAFNSK-QLLYLEKYRPKM 156
Cdd:COG2453   96 TVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFAKRL 140

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846   29 TLNKFIEELKKYgVTTVVRVCEATYDTAPVEKEgIQVLDWPfDDGAPPS-NQIVD--DWLNLLKVKFREEPgccIAVHCV 105
Cdd:pfam00102 104 TLKKEKEDEKDY-TVRTLEVSNGGSEETRTVKH-FHYTGWP-DHGVPESpNSLLDllRKVRKSSLDGRSGP---IVVHCS 177

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 971389846  106 AGLGRAPVLVALALIECGMKYE------DAVQFIRQKRRGAFNSK-QLLYL 149
Cdd:pfam00102 178 AGIGRTGTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVQTLeQYIFL 228

protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It 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 971389846   1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQI 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 ....*..
gi 971389846 161 KDSNGHR 167
Cdd:cd18537  161 KDSNGHR 167

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 971389846   5 NRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQIVDDW 84
Cdd:cd14500    1 LRPAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 971389846  85 LNLLKVKFREE--PGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRL 158
Cdd:cd14500   81 LDLLKTRFKEEgkPGACIAVHCVAGLGRAPVLVAIALIELGMKPEDAVEFIRKKRRGAINSKQLQFLEKYKPKKKL 156

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  11 EITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLLKV 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 971389846  91 KFREE--PGCCIAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160
Cdd:PTZ00242  90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG 162

C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division control protein 14 (CDC14) family is highly conserved in all eukaryotes, although the roles of its members seem to have diverged during evolution. Yeast Cdc14, the best characterized member of this family, is a dual-specificity phosphatase that plays key roles in cell cycle control. It preferentially dephosphorylates cyclin-dependent kinase (CDK) targets, which makes it the main antagonist of CDK in the cell. Cdc14 functions at the end of mitosis and it triggers the events that completely eliminates the activity of CDK and other mitotic kinases. It is also involved in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint, and in chromosome segregation. Cdc14 phosphatases also function in DNA replication, DNA damage checkpoint, and DNA repair. Vertebrates may contain more than one Cdc14 homolog; humans have three (CDC14A, CDC14B, and CDC14C). CDC14 family proteins contain a highly conserved N-terminal pseudophosphatase domain that contributes to substrate specificity and a C-terminal catalytic dual-specificity phosphatase domain with the PTP signature motif.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  22 THNPtnatlNKFIEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLLkvkfrEEPGCCIA 101
Cdd:cd14499   44 THTP-----EDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDIC-----ENEKGAIA 113

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 971389846 102 VHCVAGLGRAPVLVALALI-ECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMR 157
Cdd:cd14499  114 VHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEARLW 170

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  17 MRFLITHNPTNaTLNKFIEELKKYGVTTVVRVCEAtydtapvekegiqvldwpfddgappsnqIVDDWLNLLKVKfrEEP 96
Cdd:cd14494    7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLA----------------------------MVDRFLEVLDQA--EKP 55

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 971389846  97 GCCIAVHCVAGLGRAPVLVALALIECG-MKYEDAVQFIRQKRRG--AFNSKQLLYLEK 151
Cdd:cd14494   56 GEPVLVHCKAGVGRTGTLVACYLVLLGgMSAEEAVRIVRLIRPGgiPQTIEQLDFLIK 113

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 971389846  25 PTNATLNKF--IEELKKYGVTTVVRVCEA----------------TYDTAPVEKEGIQVLDWPFDD-GAPPSNQIVDdwl 85
Cdd:cd14506   21 PSTELIDKYgiIEQFKEKGIKTVINLQEPgehascgpglepesgfSYLPEAFMRAGIYFYNFGWKDyGVPSLTTILD--- 97

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 971389846  86 nLLKV-KFREEPGCCIAVHCVAGLGRAPVLVALALI-ECGMKYEDAVQFIRQKRRGAFNSK-QLLYLE 150
Cdd:cd14506   98 -IVKVmAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQAIRLVRSKRPNSIQTRgQVLCVR 164

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 971389846    64 QVLDWPfDDGAPPSNQIVDDWLNLLKVKFREEPGCC-IAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 135
Cdd:smart00012   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|....*
gi 971389846   136 KRRGAFNSK-QLLYL 149
Cdd:smart00012  85 QRPGMVQTEeQYLFL 99

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 971389846  34 IEELKKYGVTTVVRVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLlkVKFREEPGCCIAVHCVAGLGRAPV 113
Cdd:cd14504   21 YAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDI--VEEANAKNEAVLVHCLAGKGRTGT 98

                         90       100
                 ....*....|....*....|....*..
gi 971389846 114 LVALALIECG-MKYEDAVQFIRQKRRG 139
Cdd:cd14504   99 MLACYLVKTGkISAVDAINEIRRIRPG 125

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  63 IQVLDWPfDDGAPPSNQIVDDWLNLLKvKFREEPGCCIAVHCVAGLGRAPVLVAL-ALIECgMKYE------DAVQFIRQ 135
Cdd:cd00047  107 LHYTGWP-DHGVPSSPEDLLALVRRVR-KEARKPNGPIVVHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRK 183

                         90
                 ....*....|....*
gi 971389846 136 KRRGAF-NSKQLLYL 149
Cdd:cd00047  184 QRPGMVqTLEQYEFI 198

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 971389846  35 EELKKYGVTTVV----RVCEATYDTAPVEKEGIQVLDWPFDDGAPPSNQiVDDWLNLLKVKFREEPgccIAVHCVAGLGR 110
Cdd:cd14529   27 ALLKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESD-VQSFLLIMDLKLAPGP---VLIHCKHGKDR 102

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 971389846 111 APVLVALALIECGMKYEDAV-QFIRQKRRGAFNSKQLLYLEKYRPKMR 157
Cdd:cd14529  103 TGLVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

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 971389846   9 PVEITykNMRFLithnpTNATLNKFIEELKKYGVTTVVRVceaTYDTAPV--EKEGIQVLDWPfddgappsnqIVDDWL- 85
Cdd:cd14566    1 PVEIL--PFLYL-----GNAKDSANIDLLKKYNIKYILNV---TPNLPNTfeEDGGFKYLQIP----------IDDHWSq 60

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 971389846  86 NLLK-----VKFREEP---GCCIAVHCVAGLGRA-PVLVALALIECGMKYEDAVQFIRQKRR 138
Cdd:cd14566   61 NLSAffpeaISFIDEArskKCGVLVHCLAGISRSvTVTVAYLMQKLHLSLNDAYDFVKKRKS 122

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  95 EPGCCIAVHCVAGLGRAPVLVALALIEC-GMKYEDAVQFIRQKRRG-AFNSKQLLYLEKY 152
Cdd:cd14524   87 EKGKSVYVHCKAGRGRSATIVACYLIQHkGWSPEEAQEFLRSKRPHiLLRLSQREVLEEF 146

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 971389846  68 WPfDDGAPPSNQIVDDWLNLLKVKFREEPgccIAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQKRRGAF 141
Cdd:cd14538  115 WP-DHGTPQSADPLLRFIRYMRRIHNSGP---IVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMI 190

                 ...
gi 971389846 142 NSK 144
Cdd:cd14538  191 QTK 193

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  34 IEELKKYGVTTVVRVCeATYD--TAPVEKEGIQVLDWP-FDDGAPPSNQIVD--DWLNLLKVKFREepgccIAVHCVAGL 108
Cdd:PRK12361 113 LEKLKSNKITAILDVT-AEFDglDWSLTEEDIDYLNIPiLDHSVPTLAQLNQaiNWIHRQVRANKS-----VVVHCALGR 186

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 971389846 109 GRApVLVALALIECGMK---YEDAVQFIRQKRRGA-FNSKQLLYLEKYRPKMRLRFKDS 163
Cdd:PRK12361 187 GRS-VLVLAAYLLCKDPdltVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

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 971389846  34 IEELKKYGVTTVVRVCEAT--------YDT--APVEKEGIQVLDWPFDDGAPPS-----NQIVDDWLNLLKvkfreePGC 98
Cdd:cd14526   22 VDRLKKEGVTAVLNLQTDSdmeywgvdIDSirKACKESGIRYVRLPIRDFDTEDlrqklPQAVALLYRLLK------NGG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 971389846  99 CIAVHCVAGLGRAP--VLVALALIeCGMKYEDAVQFIRQKR 137
Cdd:cd14526   96 TVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  63 IQVLDWPfDDGAPPSNQIVDDWLNLLKVKFREEPgccIAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQK 136
Cdd:cd14596  109 LQFTTWP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQ 184

                 ....*....
gi 971389846 137 RRGAFNSKQ 145
Cdd:cd14596  185 RYGMIQTKD 193

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  64 QVLDWPfDDGAPPSNQIVDDWLNLLKvKFREEPG--CCIAVHCVAGLGRAPVLVALALIECGMKYE---DAVQFIRQKR- 137
Cdd:cd14628  187 QFTDWP-EQGVPKSGEGFIDFIGQVH-KTKEQFGqdGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvDIFQTVKMLRt 264

                         90       100
                 ....*....|....*....|
gi 971389846 138 -RGAFNSKQLLYLEKYRPKM 156
Cdd:cd14628  265 qRPAMVQTEDQYQFCYRAAL 284

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 971389846  32 KFIEELKKYGVTTVVRVCEATYDTAPVEK-EGIQVLDWPfDDGAPPSnqiVDDWLNLLKVK-------FREEPgccIAVH 103
Cdd:cd18533   76 ELVSEEENDDGGFIVREFELSKEDGKVKKvYHIQYKSWP-DFGVPDS---PEDLLTLIKLKrelndsaSLDPP---IIVH 148

                         90
                 ....*....|....
gi 971389846 104 CVAGLGRAPVLVAL 117
Cdd:cd18533  149 CSAGVGRTGTFIAL 162

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 971389846   4 MNRPA--PVEITYKN-----MRFLITHNPTNATLNKFIEElkKYGVTTVVrvceatydtapvekEGiQVLDWPFDDGAPP 76
Cdd:cd14497   12 MSFPAtgYPESLYRNsiddvANFLNTHHPDHYMIFNLSEE--EYDDDSKF--------------EG-RVLHYGFPDHHPP 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  77 S----NQIVDD---WLNllkvkfrEEPGCCIAVHCVAGLGRAPVLVALALIECGM--KYEDAVQFIRQKR-----RGAFN 142
Cdd:cd14497   75 PlgllLEIVDDidsWLS-------EDPNNVAVVHCKAGKGRTGTVICAYLLYYGQysTADEALEYFAKKRfkeglPGVTI 147

                 ....*...
gi 971389846 143 SKQLLYLE 150
Cdd:cd14497  148 PSQLRYLQ 155

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  35 EELKKYGVTTVVRVC---------EATYDTAPVEKEGIQVLDWPFDDGAppsnqivdDWLNllKVKfreEPGCCIAVHCV 105
Cdd:cd14565   20 EVLKALGITAVLNVSrncpnhfedHFQYKSIPVEDSHNADISSWFEEAI--------GFID--KVK---ASGGRVLVHCQ 86

                         90       100       110
                 ....*....|....*....|....*....|....
gi 971389846 106 AGLGRAPVlVALA-LIEC-GMKYEDAVQFIRQKR 137
Cdd:cd14565   87 AGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

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 971389846  45 VVRVCEATYDTAPVEKEGIQVLDWPfDDGAPPSNQIVDDWLNLLKVKFREEPGCC-IAVHCVAGLGRAPVLVALALI--- 120
Cdd:cd14606  142 TLQVSPLDNGELIREIWHYQYLSWP-DHGVPSEPGGVLSFLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIVIDMLmen 220

                         90       100
                 ....*....|....*....|....*
gi 971389846 121 ------ECGMKYEDAVQFIRQKRRG 139
Cdd:cd14606  221 istkglDCDIDIQKTIQMVRAQRSG 245

dual specificity phosphatase domain of mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs, which are involved in gene regulation, cell proliferation, programmed cell death and stress responses, as an important feedback control mechanism that limits MAPK cascades. MKPs, also referred to as typical DUSPs, 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. 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. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 971389846  97 GCCIAVHCVAGLGR-APVLVALALIECGMKYEDAVQFIRQKR 137
Cdd:cd14512   79 NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

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 971389846  35 EELKKYGVTTVVRVC-EATYDTAPvekeGIQVLDWPFDDGapPSNQIvDDWLNLL--KVKFREEPGCCIAVHCVAGLGRA 111
Cdd:cd14514   19 PLLLSRGITCIINATtELPDPSYP----GIEYLRVPVEDS--PHADL-SPHFDEVadKIHQVKRRGGRTLVHCVAGVSRS 91

                         90       100       110
                 ....*....|....*....|....*....|.
gi 971389846 112 PVLVALALiecgMKYE-----DAVQFIRQKR 137
Cdd:cd14514   92 ATLCLAYL----MKYEgmtlrEAYKHVKAAR 118

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They 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. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 971389846  93 REEPGCCIaVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKR 137
Cdd:cd14519   74 RLNGGNVL-VHCLAGVSRSVTIVAAYLMTvTDLGWRDALKAVRAAR 118

catalytic domain of tyrosine-protein phosphatase non-receptor type 3; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3), also called protein-tyrosine phosphatase H1 (PTP-H1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN3 and p38gamma cooperate to promote Ras-induced oncogenesis. PTPN3 is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. Its PDZ domain binds with the PDZ-binding motif of p38gamma and enables efficient tyrosine dephosphorylation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  63 IQVLDWPfDDGAPPSNQIVDDWLNLLKVKFRE-EPgccIAVHCVAGLGRAPVLVALALIECGMKYE------DAVQFIRQ 135
Cdd:cd14600  174 LQYVAWP-DHGVPDDSSDFLEFVNYVRSKRVEnEP---VLVHCSAGIGRTGVLVTMETAMCLTERNqpvyplDIVRKMRD 249

                 ..
gi 971389846 136 KR 137
Cdd:cd14600  250 QR 251

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, 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. DUSP13B 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. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971389846  37 LKKYGVTTVVRVCEATY--DTAP-------VEKEGIQVLDWPFDDGAP---PSNQIVDDWLNllkvkfreEPGCCIAVHC 104
Cdd:cd14577   39 LIQLGITHIVNAASGKFhvNTGPkfyrdmnIDYYGVEADDNPFFDLSVyfyPVARFIRAALS--------SPNGRVLVHC 110

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 971389846 105 VAGLGRAPVLV-ALALIECGMKYEDAVQFIRQKRRGAFNS---KQLLYLEK 151
Cdd:cd14577  111 AMGISRSATLVlAFLMICEDLTLVDAIQTVRAHRDICPNSgflRQLRELDN 161