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 1972305363  22 PAPSEIAWGKMRFLITDRPNNSSIQSYIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWFQ 101
Cdd:cd14500     3 PAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLD 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1972305363 102 LCMTSFKEH--PDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGALNQKQLKFLETYKANGEL 173
Cdd:cd14500    83 LLKTRFKEEgkPGACIAVHCVAGLGRAPVLVAIALIELGMKPEDAVEFIRKKRRGAINSKQLQFLEKYKPKKKL 156

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 1972305363  22 PAPSEIAWGKMRFLITDRPNNSSIQSYIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWFQ 101
Cdd:cd14500     3 PAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLD 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1972305363 102 LCMTSFKEH--PDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGALNQKQLKFLETYKANGEL 173
Cdd:cd14500    83 LLKTRFKEEgkPGACIAVHCVAGLGRAPVLVAIALIELGMKPEDAVEFIRKKRRGAINSKQLQFLEKYKPKKKL 156

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305363  29 WGKMRFLITDRPNnssiqSYIEELEKHGARAVVRVCEPTYDTL-ALKEAGIDVLDWQFSDGSPPPPEVIKS---WFQLCM 104
Cdd:COG2453     3 IIPGLLAGGPLPG-----GGEADLKREGIDAVVSLTEEEELLLgLLEEAGLEYLHLPIPDFGAPDDEQLQEavdFIDEAL 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1972305363 105 TSfkehpDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGA-LNQKQLKFLETYKAN 170
Cdd:COG2453    78 RE-----GKKVLVHCRGGIGRTGTVAAAYLVLLGLSAEEALARVRAARPGAvETPAQRAFLERFAKR 139

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1972305363 109 EHPDKSIAVHCVAGLGRAPVLVAIALIEAGMKYE------DAVEMIRTQRRGAL-NQKQLKFL 164
Cdd:pfam00102 166 DGRSGPIVVHCSAGIGRTGTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVqTLEQYIFL 228

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 1972305363  22 PAPSEIAWGKMRFLITDRPNNSSIQSYIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWFQ 101
Cdd:cd14500     3 PAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLD 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1972305363 102 LCMTSFKEH--PDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGALNQKQLKFLETYKANGEL 173
Cdd:cd14500    83 LLKTRFKEEgkPGACIAVHCVAGLGRAPVLVAIALIELGMKPEDAVEFIRKKRRGAINSKQLQFLEKYKPKKKL 156

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 1972305363  21 KPAPSEIAWGKMRFLITDRPNNSSIQSYIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWF 100
Cdd:cd18535     2 RPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWL 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1972305363 101 QLCMTSFKEHPDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGALNQKQLKFLETYKANGEL 173
Cdd:cd18535    82 SLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 1972305363  21 KPAPSEIAWGKMRFLITDRPNNSSIQSYIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWF 100
Cdd:cd18537     6 RPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQIVDDWL 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1972305363 101 QLCMTSFKEHPDKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRTQRRGALNQKQLKFLETYKANGELR 174
Cdd:cd18537    86 NLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLR 159

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 1972305363  48 YIEELEKHGARAVVRVCEPTYDTLALKEAGIDVLDWQFSDGSPPPPEVIKSWFQLCmtsfkEHPDKSIAVHCVAGLGRAP 127
Cdd:cd14499    50 YIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDIC-----ENEKGAIAVHCKAGLGRTG 124

                  ....*...
gi 1972305363 128 VLVAIALI 135
Cdd:cd14499   125 TLIACYLM 132

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 1972305363  33 RFLITDRpnnsSIQSYIEELEKHGARAVVRVCE---------PTYDTLAlKEAGIDVLDWQFSDGSPPPPEvikSWFQLC 103
Cdd:cd14505    24 KFKDHRR----DLQADLEELKDQGVDDVVTLCTdgeleelgvPDLLEQY-QQAGITWHHLPIPDGGVPSDI---AQWQEL 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1972305363 104 MTSFKE--HPDKSIAVHCVAGLGRAPVLVAIALIEAG--MKYEDAVEMIRTQRRGAL-NQKQLKFL 164
Cdd:cd14505    96 LEELLSalENGKKVLIHCKGGLGRTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIqTPKQENFL 161

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 1972305363   80 VLDWQfSDGSPPPPEVIKSWFQLCMTSFKEHPDK-SIAVHCVAGLGRAPVLVAIALIEAGMKYE-------DAVEMIRTQ 151
Cdd:smart00012   7 YTGWP-DHGVPESPDSILELLRAVKKNLNQSESSgPVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQ 85

                           90
                   ....*....|....
gi 1972305363  152 RRGALNQK-QLKFL 164
Cdd:smart00012  86 RPGMVQTEeQYLFL 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 1972305363  49 IEELEKHGARAVVRVCE--PTYDTLalKEAGIDVLDWQFSDGSPPPPEVIKSwfqlCMTSFKEHPDKS--IAVHCVAGLG 124
Cdd:cd14504    21 YAYLNENGIRHVVTLTEepPPEHSD--TCPGLRYHHIPIEDYTPPTLEQIDE----FLDIVEEANAKNeaVLVHCLAGKG 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1972305363 125 RAPVLVAIALIEAG-MKYEDAVEMIRTQRRG-ALNQKQLKFLETY 167
Cdd:cd14504    95 RTGTMLACYLVKTGkISAVDAINEIRRIRPGsIETSEQEKFVIQF 139

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 1972305363  49 IEELEKHGARAVVRVCEPTYDtlALKEAGIDVLDWQFSDGsppPPEVIKSWFQLCmTSF-KEH--PDKSIAVHCVAGLGR 125
Cdd:cd14498    19 KELLKKLGITHILNVAGEPPP--NKFPDGIKYLRIPIEDS---PDEDILSHFEEA-IEFiEEAlkKGGKVLVHCQAGVSR 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1972305363 126 APVLVAIALIEA-GMKYEDAVEMIRTQRRGA-LN---QKQLK 162
Cdd:cd14498    93 SATIVIAYLMKKyGWSLEEALELVKSRRPIIsPNpgfLKQLK 134

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 1972305363  87 DGSPPPPEVIKSWFQLCMTsFKEHPDKSIAVHCVAGLGRAPVLVAI-ALIEAgMKYE------DAVEMIRTQRRGAL-NQ 158
Cdd:cd00047   115 HGVPSSPEDLLALVRRVRK-EARKPNGPIVVHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRKQRPGMVqTL 192

                  ....*.
gi 1972305363 159 KQLKFL 164
Cdd:cd00047   193 EQYEFI 198

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1972305363  108 KEHPDKSIAVHCVAGLGRAPVLVAIA----LIEAGMKY--EDAVEMIRTQRRGAL-NQKQLKFLetYKA 169
Cdd:smart00194 190 QSTSTGPIVVHCSAGVGRTGTFIAIDillqQLEAGKEVdiFEIVKELRSQRPGMVqTEEQYIFL--YRA 256

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1972305363 115 IAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEM------IRTQRRGALnQKQLKFLETYKA 169
Cdd:cd14554   177 ITVHCSAGVGRTGVFITLSIVLERMRYEGVVDVfqtvklLRTQRPAMV-QTEDQYQFCYRA 236

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 1972305363  80 VLDWQFSD----GSPPPPEVIKSWF-QLCMTSFKEHPDKSIAVHCVAGLGRAPVLVAIALIEAGMKYE------DAVEMI 148
Cdd:cd14628   183 VRQFQFTDwpeqGVPKSGEGFIDFIgQVHKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKML 262

                          90       100
                  ....*....|....*....|.
gi 1972305363 149 RTQrRGALNQKQLKFLETYKA 169
Cdd:cd14628   263 RTQ-RPAMVQTEDQYQFCYRA 282

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1972305363 104 MTSFKEHPDKSIAVHCVAGLGRAPVLVAI----ALIEAGMKYED-----AVEMIRTQRRGALNQKQ 160
Cdd:cd14604   215 MRKYQEHEDVPICIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfnLIQEMRTQRHSAVQTKE 280

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1972305363 112 DKSIAVHCVAGLGRAPVLVAIALIEAGMKYEDAVEMIRT-----QRRGALNQKQLKFLETYKA 169
Cdd:cd14629   221 DGPITVHCSAGVGRTGVFITLSIVLERMRYEGVVDMFQTvktlrTQRPAMVQTEDQYQLCYRA 283

N-terminal triphosphatase domain of mRNA capping enzyme; mRNA capping enzyme, also known as RNA guanylyltransferase and 5'-phosphatase (RNGTT) or mammalian mRNA capping enzyme (Mce1) in mammals, is a bifunctional enzyme that catalyzes the first two steps of cap formation: (1) by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end using the polynucleotide 5'-phosphatase activity (EC 3.1.3.33) of the N-terminal triphosphatase domain; and (2) by transferring the GMP moiety of GTP to the 5'-diphosphate terminus through the C-terminal mRNA guanylyltransferase domain (EC 2.7.7.50). The enzyme is also referred to as CEL-1 in Caenorhabditis elegans.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305363  50 EELEKHGARAVVRVCeptydtlalkeAGidvldwqfsDGSPPPPEVIKSWFQLCMTSFKEHPDKSIAVHCVAGLGRAPVL 129
Cdd:cd17664    69 NEVEKEGCKYIKLQC-----------KG---------HGECPSPEQTETFIRLCENFIEKNPLELIGVHCTHGFNRTGFL 128

                  ....*..
gi 1972305363 130 VAIALIE 136
Cdd:cd17664   129 ICAYLVE 135

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 1972305363  50 EELEKHGARAVV--RVCEP--TYDTLALKEAGIDVLDWQFSDGSPPPPEVikSWFQLCMtsFKEHPDKSIAVHCVAGLGR 125
Cdd:cd14529    27 ALLKKLGIKTVIdlRGADEraASEEAAAKIDGVKYVNLPLSATRPTESDV--QSFLLIM--DLKLAPGPVLIHCKHGKDR 102

                          90       100
                  ....*....|....*....|.
gi 1972305363 126 APVLVAIALIEAGMKYEDAVE 146
Cdd:cd14529   103 TGLVSALYRIVYGGSKEEANE 123

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1972305363 113 KSIAVHCVAGLGRAPVLVAIALIEA-GMKYEDAVEMIRtQRRGALN 157
Cdd:pfam00782  70 GKVLVHCQAGISRSATLIIAYLMKTrNLSLNEAYSFVK-ERRPGIS 114

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972305363 108 KEHPDKSIAVHCVAGLGRAPVL----VAIALIEAGMKYE--DAVEMIRTQRRGALNQKQlKFLETYKA 169
Cdd:cd14596   135 KVHNTGPIVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMIQTKD-QYLFCYKV 201

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1972305363 110 HPDKSIAVHCVAGLGRAPVLV-AIALIEAGMKYEDAVEMIRTQR-----RGALNQ 158
Cdd:cd14515    86 DPGGKVLVHCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKReirpnRGFLQQ 140

unknown subfamily of bacterial and plant dual specificity protein phosphatases; This subfamily is composed of uncharacterized bacterial and plant dual-specificity protein phosphatases. DUSPs function as a protein-serine/threonine phosphatases (EC 3.1.3.16) and a protein-tyrosine-phosphatases (EC 3.1.3.48).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305363  87 DGSPPPPEVIKSWFQLCMTSFKEHpdKSIAVHCVAGLGRAPVLVAIALIEAGM--KYEDAVEMIRTQRRGA-LNQKQLKF 163
Cdd:cd14527    53 DLVAPTPEQLERAVAWIEELRAQG--GPVLVHCALGYGRSATVVAAWLLAYGRakSVAEAEALIRAARPQVvLNPAQRKA 130

                  ..
gi 1972305363 164 LE 165
Cdd:cd14527   131 LE 132

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
                  ....*....|....*....|....*....|....*....|....
gi 1972305363 115 IAVHCVAGLGRAPVLVAIALIEA-GMKYEDAVEMIRtQRRGALN 157
Cdd:cd14522    92 VLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYVQ-QRRFCIN 134

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and type 4 (PTPN4) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 and PTPN4 are large modular proteins containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1972305363 117 VHCVAGLGRAPVLV----AIALIEAGMKYeDAVEMIRTQR--RGALNQ--KQLKF 163
Cdd:cd14541   148 VHCSAGIGRTGVLItmetAMCLIEANEPV-YPLDIVRTMRdqRAMLIQtpSQYRF 201

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1972305363 115 IAVHCVAGLGRAPVLVAIALI-----EAG----MKYEDAVEMIRTQRRGALN-QKQLKFLetYKA 169
Cdd:cd14544   182 IVVHCSAGIGRTGTFIVIDMLldqikRKGldcdIDIQKTIQMVRSQRSGMVQtEAQYKFI--YVA 244