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 304361762   1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDD 80
Cdd:cd18536    1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 304361762  81 WLNLLKTKFREEPGCCVAVHCVAGLGR-------------------------KRRGAFNSKQLLYLEKYRPKMRL 130
Cdd:cd18536   81 WLNLLKTKFREEPGCCVAVHCVAGLGRapvlvalaliecgmkyedavqfirqKRRGAFNSKQLLYLEKYRPKMRL 155

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 304361762   1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDD 80
Cdd:cd18536    1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 304361762  81 WLNLLKTKFREEPGCCVAVHCVAGLGR-------------------------KRRGAFNSKQLLYLEKYRPKMRL 130
Cdd:cd18536   81 WLNLLKTKFREEPGCCVAVHCVAGLGRapvlvalaliecgmkyedavqfirqKRRGAFNSKQLLYLEKYRPKMRL 155

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 304361762  32 EELKKYGVTTLVRVC-DATYDKAPVEKEGIHVLDWPF-DDGAPPPNQIVD--DWL-NLLKtkfREEPgccVAVHCVAGLG 106
Cdd:COG2453   19 ADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIpDFGAPDDEQLQEavDFIdEALR---EGKK---VLVHCRGGIG 92

                 .
gi 304361762 107 R 107
Cdd:COG2453   93 R 93

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 304361762   26 TLNKFTEELKKYGVTTLvRVCDATYDKAPVEKEgIHVLDWPfDDGAPP-PNQIVD--DWLNLLKTKFREEPgccVAVHCV 102
Cdd:pfam00102 104 TLKKEKEDEKDYTVRTL-EVSNGGSEETRTVKH-FHYTGWP-DHGVPEsPNSLLDllRKVRKSSLDGRSGP---IVVHCS 177

                  ....*
gi 304361762  103 AGLGR 107
Cdd:pfam00102 178 AGIGR 182

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 304361762   1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDD 80
Cdd:cd18536    1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 304361762  81 WLNLLKTKFREEPGCCVAVHCVAGLGR-------------------------KRRGAFNSKQLLYLEKYRPKMRL 130
Cdd:cd18536   81 WLNLLKTKFREEPGCCVAVHCVAGLGRapvlvalaliecgmkyedavqfirqKRRGAFNSKQLLYLEKYRPKMRL 155

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 304361762   2 NRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDW 81
Cdd:cd14500    1 LRPAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 304361762  82 LNLLKTKFREE--PGCCVAVHCVAGLGR-------------------------KRRGAFNSKQLLYLEKYRPKMRL 130
Cdd:cd14500   81 LDLLKTRFKEEgkPGACIAVHCVAGLGRapvlvaialielgmkpedavefirkKRRGAINSKQLQFLEKYKPKKKL 156

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 304361762   8 EISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLLKT 87
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 304361762  88 KFREE--PGCCVAVHCVAGLGR--------------------------KRRGAFNSKQLLYLEKYRPKMRLRF 132
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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 304361762  35 KKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLLktkfrEEPGCCVAVHCVAGLGR 107
Cdd:cd14499   55 KKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDIC-----ENEKGAIAVHCKAGLGR 122

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 304361762  32 EELKKYGVTTLVRVCdatydkapvEKEGIHVLDWPFDDGAPPPN-----QIVDDWLNLLKTKFReepgccVAVHCVAGLG 106
Cdd:cd14505   54 GELEELGVPDLLEQY---------QQAGITWHHLPIPDGGVPSDiaqwqELLEELLSALENGKK------VLIHCKGGLG 118

                 .
gi 304361762 107 R 107
Cdd:cd14505  119 R 119

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 304361762  32 EELKKYGVTTLV----RVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQiVDDWLNLLKTKFREEPgccVAVHCVAGLGR 107
Cdd:cd14529   27 ALLKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESD-VQSFLLIMDLKLAPGP---VLIHCKHGKDR 102

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
                   ....*....|....*....|....*....|....*....|....*...
gi 304361762    61 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGR 107
Cdd:smart00012   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGR 52

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 304361762  62 VLDWPFDDGAPPPNQI-------VDDWLnllktkfREEPGCCVAVHCVAGLGRKrrGAFNSKQLLYLEKYR 125
Cdd:cd14509   62 VAEYPFDDHNPPPLELikpfcedVDEWL-------KEDEKNVAAVHCKAGKGRT--GVMICCYLLYLGKFP 123

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 304361762  15 RFLITHNPTNATLNKFTEElkKYGVTTLVrvcdatydkapvekEGiHVLDWPFDDGAPPP----NQIVDD---WLNllkt 87
Cdd:cd14497   33 NFLNTHHPDHYMIFNLSEE--EYDDDSKF--------------EG-RVLHYGFPDHHPPPlgllLEIVDDidsWLS---- 91

                         90       100
                 ....*....|....*....|
gi 304361762  88 kfrEEPGCCVAVHCVAGLGR 107
Cdd:cd14497   92 ---EDPNNVAVVHCKAGKGR 108