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 1622958303   1 MNDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 80
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 125
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

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 1622958303   1 MNDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 80
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 125
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303   3 DLKKYGATTVVRVC-EVTYDKTPLEKDGITVVDWPFDDGAPPPgkvVEDWLSLVK-AKFCEAPGSCVAVHCVAGLGRAPV 80
Cdd:COG2453    20 DLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGIGRTGT 96

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 120
Cdd:COG2453    97 VAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622958303  48 VEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQkRRGAIN 109
Cdd:pfam00782  51 ISKYLEEAVEFidDARQKGGKVLVHCQAGISRSATLIIAYLMKTrNLSLNEAYSFVKE-RRPGIS 114

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 1622958303   1 MNDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 80
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 125
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

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 1622958303   1 MNDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 80
Cdd:cd18537    34 IEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPV 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFKDPHTHK 134
Cdd:cd18537   114 LVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFKDSNGHR 167

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303   1 MNDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEA--PGSCVAVHCVAGLGRA 78
Cdd:PTZ00242   33 IKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEFAKQstPPETIAVHCVAGLGRA 112

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622958303  79 PVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFkdphthktrCCVM 140
Cdd:PTZ00242  113 PILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG---------CTIM 166

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 1622958303   5 KKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLvkakfCEAPGSCVAVHCVAGLGRAPVLVAL 84
Cdd:cd14499    55 KKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIAVHCKAGLGRTGTLIAC 129

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1622958303  85 ALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 122
Cdd:cd14499   130 YLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 168

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 1622958303   1 MNDLKKYGATTVVRVC---EVTYDKTP-----LEKDGITVVDWPFDDGAPPP-----GKVVEDWLSLVKAkfceapGSCV 67
Cdd:cd14505    36 LEELKDQGVDDVVTLCtdgELEELGVPdlleqYQQAGITWHHLPIPDGGVPSdiaqwQELLEELLSALEN------GKKV 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622958303  68 AVHCVAGLGRAPVLVALALIESG--MKYEDAIQFIRQKRRGAI-NSKQLTYL 116
Cdd:cd14505   110 LIHCKGGLGRTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIqTPKQENFL 161

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 1622958303  19 TYDKTPLEKDGITVVDWPFDD-GAPPPGKVvedwLSLVK-AKFCEAPGSCVAVHCVAGLGRAPVLVALALI-ESGMKYED 95
Cdd:cd14506    66 SYLPEAFMRAGIYFYNFGWKDyGVPSLTTI----LDIVKvMAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQ 141

                          90
                  ....*....|....*.
gi 1622958303  96 AIQFIRQKRRGAINSK 111
Cdd:cd14506   142 AIRLVRSKRPNSIQTR 157

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 1622958303   34 DWPfDDGAPPPGKVVEDWLSLVKAKFCEAPGSC-VAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQKRR 105
Cdd:smart00012   9 GWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQRP 87

                   ....*..
gi 1622958303  106 GAINSKQ 112
Cdd:smart00012  88 GMVQTEE 94

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 1622958303   4 LKKYGATTVVRVCEVTYDktPLEKDGITVVDWPFDDgapppgKVVEDWLSLVK--AKF---CEAPGSCVAVHCVAGLGRA 78
Cdd:cd14498    22 LKKLGITHILNVAGEPPP--NKFPDGIKYLRIPIED------SPDEDILSHFEeaIEFieeALKKGGKVLVHCQAGVSRS 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1622958303  79 PVLVALALIES-GMKYEDAIQFIRQKRRGA-INS---KQL 113
Cdd:cd14498    94 ATIVIAYLMKKyGWSLEEALELVKSRRPIIsPNPgflKQL 133

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 1622958303  32 VVDWPFDDGAPPPgkvvedwLSLVKAkFCE--------APGSCVAVHCVAGLGRAPVLVALALIESGM--KYEDAIQFIR 101
Cdd:cd14509    62 VAEYPFDDHNPPP-------LELIKP-FCEdvdewlkeDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYG 133

                          90       100
                  ....*....|....*....|...
gi 1622958303 102 QKRrgAINSKQLTYlekyrPKQR 124
Cdd:cd14509   134 AKR--TKNKKGVTI-----PSQR 149

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 1622958303  35 WPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSCVAVHCVAGLGRAPVLVAL-ALIESgMKYE------DAIQFIRQKRRGA 107
Cdd:cd00047   112 WP-DHGVPSSPEDLLALVRRVR-KEARKPNGPIVVHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRKQRPGM 188

                          90
                  ....*....|
gi 1622958303 108 I-NSKQLTYL 116
Cdd:cd00047   189 VqTLEQYEFI 198

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303    4 LKKYGATTVVRVCEVtydKTPLEKDGITVVDWPFDDGappPGKVVEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVL 81
Cdd:smart00195  22 LKKLGITHVINVTNE---VPNYNGSDFTYLGVPIDDN---TETKISPYFPEAVEFieDAESKGGKVLVHCQAGVSRSATL 95

                           90       100
                   ....*....|....*....|....*....
gi 1622958303   82 VALALIES-GMKYEDAIQFIRQkRRGAIN 109
Cdd:smart00195  96 IIAYLMKTrNMSLNDAYDFVKD-RRPIIS 123

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303   5 KKYGATTVVRVCEVTYDKTPLEKdgiTV-----VDWPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSC-VAVHCVAGLGRA 78
Cdd:pfam00102 109 KEDEKDYTVRTLEVSNGGSEETR---TVkhfhyTGWP-DHGVPESPNSLLDLLRKVR-KSSLDGRSGpIVVHCSAGIGRT 183

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1622958303  79 PVLVALALIESGMKYE------DAIQFIRQKRRGAINSK-QLTYL 116
Cdd:pfam00102 184 GTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVQTLeQYIFL 228

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622958303  60 CEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIrQKRRGAINSKQ--LTYLEKYRP 121
Cdd:cd14522    85 CLQTGGKVLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYV-QQRRFCINPNEgfVHQLKEYEA 148

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 1622958303  34 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--RGA 107
Cdd:cd14628   190 DWP-EQGVPKSGEGFIDFIGQVhKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvDIFQTVKMLRtqRPA 268

                          90
                  ....*....|...
gi 1622958303 108 INSKQLTYLEKYR 120
Cdd:cd14628   269 MVQTEDQYQFCYR 281

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303  34 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE------DAIQFIRQKRRG 106
Cdd:cd14627   191 DWP-EQGVPKSGEGFIDFIGQVhKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQRPA 269

                  ....*
gi 1622958303 107 AINSK 111
Cdd:cd14627   270 MVQTE 274

PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303  34 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--RGA 107
Cdd:cd14629   191 DWP-EQGVPKTGEGFIDFIGQVhKTKEQFGQDGPITVHCSAGVGRTGVFITLSIVLERMRYEgvvDMFQTVKTLRtqRPA 269

                          90
                  ....*....|...
gi 1622958303 108 INSKQLTYLEKYR 120
Cdd:cd14629   270 MVQTEDQYQLCYR 282

hypothetical protein; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622958303  67 VAVHCVAGLGRApVLVALALIESGMK---YEDAIQFIRQKRRGA-INSKQLTYLEKYRPKQRLRFKDP 130
Cdd:PRK12361  178 VVVHCALGRGRS-VLVLAAYLLCKDPdltVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

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 1622958303  35 WPfDDGAPPPGKVVEDWLSLVKAKFCEAPgscVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 108
Cdd:cd14596   114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMI 189

                  ....
gi 1622958303 109 NSKQ 112
Cdd:cd14596   190 QTKD 193

dual-specificity phosphatase domain of dual specificity protein phosphatase 11 and similar proteins; dual specificity protein phosphatase 11 (DUSP11), also known as RNA/RNP complex-1-interacting phosphatase or phosphatase that interacts with RNA/RNP complex 1 (PIR1), has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity. It has activity for short RNAs but is less active toward mononucleotide triphosphates, suggesting that its primary function in vivo is to dephosphorylate RNA 5'-ends. It may play a role in nuclear mRNA metabolism. Also included in this subfamily is baculovirus RNA 5'-triphosphatase for Autographa californica nuclear polyhedrosis virus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622958303  43 PPGKVVEDWLSLVKaKF---CEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKR 104
Cdd:cd17665    90 PDDKTIQSFKDAVK-DFlekNKDNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154

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 1622958303  60 CEAPGSCVAVHCVAGLGRAPVlVALA-LIES-GMKYEDAIQFIRQKR 104
Cdd:cd14565    74 VKASGGRVLVHCQAGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

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 1622958303  64 GSCVaVHCVAGLGRApVLVALALIES--GMKYEDAIQFIRQKR 104
Cdd:cd14519    78 GNVL-VHCLAGVSRS-VTIVAAYLMTvtDLGWRDALKAVRAAR 118

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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622958303  56 KAKFCeapGSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 104
Cdd:cd14512    74 EAKAS---NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

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 1622958303  33 VDWPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSCVAVHCVAGLGRAPVLVAL----ALIESGMKYED-----AIQFIRQK 103
Cdd:cd14604   194 VNWP-DHDVPSSFDSILDMISLMR-KYQEHEDVPICIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfnLIQEMRTQ 271

                  ....*....
gi 1622958303 104 RRGAINSKQ 112
Cdd:cd14604   272 RHSAVQTKE 280

dual specificity phosphatase domain of slingshot family phosphatases; The slingshot (SSH) family of dual specificity protein phosphatases is composed of Drosophila slingshot phosphatase and its vertebrate homologs: SSH1, SSH2 and SSH3. Its members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. In Drosophila, loss of ssh gene function causes prominent elevation in the levels of P-cofilin and filamentous actin and disorganized epidermal cell morphogenesis, including bifurcation phenotypes of bristles and wing hairs. SSH family phosphatases contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. In addition, many members contain a C-terminal tail. The SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated activation, and subcellular localization of SSHs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622958303  64 GSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIrQKRRGAINSKQ--LTYLEKY 119
Cdd:cd14513    78 GSKVLVHCKMGVSRsASTVIAYAMKEYGWSLEQALEHV-KERRSCIKPNPgfLRQLITY 135

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 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 highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622958303   3 DLKKYGATTVVRVCEVTYDKTPLEKDgITVVDWPFDDGAPPP-GKVVEDWLSLVKakFCEAPGSCVAVHCVAGLGRA-PV 80
Cdd:cd14582    22 DLEQLSRNKITHIISIHESPQPLLQD-ITYLRIPLPDTPEAPiKKHFKECISFIH--QCRLNGGNCLVHCLAGISRStTI 98

                          90       100
                  ....*....|....*....|....
gi 1622958303  81 LVALALIESGMKYEDAIQFIRQKR 104
Cdd:cd14582    99 VVAYVMAVTELSWQEVLEAIRAVR 122

dual specificity phosphatase domain of dual specificity protein phosphatase 10; Dual specificity protein phosphatase 10 (DUSP10), also called mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP10/MKP-5 coordinates skeletal muscle regeneration by negatively regulating mitochondria-mediated apoptosis. It is also an important regulator of intestinal epithelial barrier function and a suppressor of colon tumorigenesis. DUSP10/MKP-5 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1622958303  64 GSCVAVHCVAGLGRAP-VLVALALIESGMKYEDAIQFIRQKR 104
Cdd:cd14567    80 GKGVLVHCQAGVSRSAtIVIAYLMKHTRMTMTDAYKFVKNKR 121

dual specificity phosphatase domain of dual specificity protein phosphatase 5; Dual specificity protein phosphatase 5 (DUSP5) functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other mitogen-activated protein kinase (MAPK) phosphatases (MKPs), it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP5 preferentially dephosphorylates extracellular signal-regulated kinase (ERK), and is involved in ERK signaling and ERK-dependent inflammatory gene expression in adipocytes. It also plays a role in regulating pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain. DUSP5 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622958303  50 DWLSLVKAKfceapGSCVAVHCVAGLGRAPVLVALALIESG-MKYEDAIQFIRQKR 104
Cdd:cd14639    69 DFIDCVRRA-----GGKVLVHCEAGISRSPTICMAYLMKTKrFRLEEAFDYIKQRR 119