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 528509783   5 NRPAPVEVCYKNMRFLITHNPTNSTLSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509783  85 LSLLKRRFIEEPGCCVAVHCVAGLGRAPVLVAVALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 528509783   5 NRPAPVEVCYKNMRFLITHNPTNSTLSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509783  85 LSLLKRRFIEEPGCCVAVHCVAGLGRAPVLVAVALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  31 SSFIEDLKKYGVTTVVRVC-EITYDKTPLEKNGITVVDWPFDDGAPPPskvVEDWLSLLkrRFIEE---PGCCVAVHCVA 106
Cdd:COG2453   15 GGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAV--DFIDEalrEGKKVLVHCRG 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 528509783 107 GLGRAPVLVAVALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 153
Cdd:COG2453   90 GIGRTGTVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 137

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783   37 LKKYGVTTVVRVCEITYDKTP-LEKNGITVVDWPFDDgapppskvVEDWLSLLKRrFIE---EPGCCVAVHCVAGLGRAP 112
Cdd:pfam00782  14 LSKLGITAVINVTREVDLYNSgILYLRIPVEDNHETN--------ISKYLEEAVE-FIDdarQKGGKVLVHCQAGISRSA 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528509783  113 VLVAVALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  85 TLIIAYLMKTrNLSLNEAYSFVKE-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 528509783   5 NRPAPVEVCYKNMRFLITHNPTNSTLSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509783  85 LSLLKRRFIEEPGCCVAVHCVAGLGRAPVLVAVALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 528509783   1 MARMNRPAPVEVCYKNMRFLITHNPTNSTLSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKV 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  81 VEDWLSLLKRRFIEEPGCCVAVHCVAGLGRAPVLVAVALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRY 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 .
gi 528509783 161 K 161
Cdd:cd18537  161 K 161

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  11 EVCYKNMRFLITHNPTNSTLSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKVVEDWLSLLKR 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  91 RFIEE--PGCCVAVHCVAGLGRAPVLVAVALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRykhphifk 167
Cdd:PTZ00242  90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAA-------- 161

                 ....*.
gi 528509783 168 nKCCIM 173
Cdd:PTZ00242 162 -GCTIM 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 528509783  22 THNPtnstlSSFIEDLKKYGVTTVVRVCEITYDKTPLEKNGITVVDWPFDDGAPPPSKVVEDWLSLlkrrfIEEPGCCVA 101
Cdd:cd14499   44 THTP-----EDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIA 113

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 528509783 102 VHCVAGLGRAPVLVAVALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 155
Cdd:cd14499  114 VHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 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 528509783  34 IEDLKKYGVTTVVRVC---EITYDKTP-----LEKNGITVVDWPFDDGAPPP-----SKVVEDWLSLLKRrfieepGCCV 100
Cdd:cd14505   36 LEELKDQGVDDVVTLCtdgELEELGVPdlleqYQQAGITWHHLPIPDGGVPSdiaqwQELLEELLSALEN------GKKV 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 528509783 101 AVHCVAGLGRAPVLVAVALIESG--MKYEDAIQFIRQKRRGAI-NSKQLTYL 149
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 528509783  34 IEDLKKYGVTTVVRVCE----------------ITYDKTPLEKNGITVVDWPFDD-GAPPPS------KVVEDWLSLLKR 90
Cdd:cd14506   32 IEQFKEKGIKTVINLQEpgehascgpglepesgFSYLPEAFMRAGIYFYNFGWKDyGVPSLTtildivKVMAFALQEGGK 111

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 528509783  91 rfieepgccVAVHCVAGLGRAPVLVAVALI-ESGMKYEDAIQFIRQKRRGAINSK 144
Cdd:cd14506  112 ---------VAVHCHAGLGRTGVLIACYLVyALRMSADQAIRLVRSKRPNSIQTR 157

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 528509783  37 LKKYGVTTVVRVCEITYDktPLEKNGITVVDWPFDDgapppsKVVEDWLSLLKR--RFIEE---PGCCVAVHCVAGLGRA 111
Cdd:cd14498   22 LKKLGITHILNVAGEPPP--NKFPDGIKYLRIPIED------SPDEDILSHFEEaiEFIEEalkKGGKVLVHCQAGVSRS 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 528509783 112 PVLVAVALIES-GMKYEDAIQFIRQKRRGA-INS---KQL 146
Cdd:cd14498   94 ATIVIAYLMKKyGWSLEEALELVKSRRPIIsPNPgflKQL 133

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 528509783    67 DWPfDDGAPPPSKVVEDWLSLLKRRF-IEEPGCCVAVHCVAGLGRAPVLVAVALIESGMKYE-------DAIQFIRQKRR 138
Cdd:smart00012   9 GWP-DHGVPESPDSILELLRAVKKNLnQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQRP 87

                   ....*..
gi 528509783   139 GAINSKQ 145
Cdd:smart00012  88 GMVQTEE 94

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783   37 LKKYGVTTVVRVCEITYDKTP-LEKNGITVVDWPFDDgapppskvVEDWLSLLKRrFIE---EPGCCVAVHCVAGLGRAP 112
Cdd:pfam00782  14 LSKLGITAVINVTREVDLYNSgILYLRIPVEDNHETN--------ISKYLEEAVE-FIDdarQKGGKVLVHCQAGISRSA 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528509783  113 VLVAVALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  85 TLIIAYLMKTrNLSLNEAYSFVKE-RRPGIS 114

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783    37 LKKYGVTTVVRVceiTYDKTPLEKNGITVVDWPFDDGappPSKVVEDWLSLLKRrFIEE---PGCCVAVHCVAGLGRAPV 113
Cdd:smart00195  22 LKKLGITHVINV---TNEVPNYNGSDFTYLGVPIDDN---TETKISPYFPEAVE-FIEDaesKGGKVLVHCQAGVSRSAT 94

                           90       100
                   ....*....|....*....|....*
gi 528509783   114 LVAVALIES-GMKYEDAIQFIRQKR 137
Cdd:smart00195  95 LIIAYLMKTrNMSLNDAYDFVKDRR 119

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 528509783  65 VVDWPFDDGAPPPSKV-------VEDWLSllkrrfiEEPGCCVAVHCVAGLGRAPVLVAVALIESGM--KYEDAIQFIRQ 135
Cdd:cd14509   62 VAEYPFDDHNPPPLELikpfcedVDEWLK-------EDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYGA 134

                         90       100
                 ....*....|....*....|....*
gi 528509783 136 KRrgAINSKQLTYlekyrPKQRlRY 160
Cdd:cd14509  135 KR--TKNKKGVTI-----PSQR-RY 151

dual specificity phosphatase domain of class III 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 III MKPs consist of DUSP8, DUSP10/MKP-5 and DUSP16/MKP-7, and are JNK/p38-selective phosphatases, which are found in both the cell nucleus and cytoplasm. 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 528509783  92 FIEE---PGCCVAVHCVAGLGRAPVLvAVALI--ESGMKYEDAIQFIRQKR 137
Cdd:cd14568   71 FIEKaraSNKRVLVHCLAGISRSATI-AIAYImkHMRMSLDDAYRFVKEKR 120

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528509783  90 RRFIEE---PGCCVAVHCVAGLGRAPVLVAVALIES-GMKYEDAIQFIrQKRRGAINSKQ--LTYLEKYRP 154
Cdd:cd14522   79 KEFIDDclqTGGKVLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYV-QQRRFCINPNEgfVHQLKEYEA 148

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  30 LSSFIEDLKKYGVTTVVRVC------EITYDKTPLEKNGITVvdwpFDDGAPPPSKVVE--DWLSLLKRRfieepGCCVA 101
Cdd:PRK12361 109 FPADLEKLKSNKITAILDVTaefdglDWSLTEEDIDYLNIPI----LDHSVPTLAQLNQaiNWIHRQVRA-----NKSVV 179

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528509783 102 VHCVAGLGRAPVLVAVALI--ESGMKYEDAIQFIRQKRRGA-INSKQLTYLEKYRPKQRLRYKHP 163
Cdd:PRK12361 180 VHCALGRGRSVLVLAAYLLckDPDLTVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

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 528509783  92 FIEEP---GCCVAVHCVAGLGR-APVLVAVALIESGMKYEDAIQFIRQKR 137
Cdd:cd14512   71 FIEEAkasNGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  56 TPLEKN------GITVVDWPfDDGAPPPSKVVEDWLSLL--KRRFIEEPgccVAVHCVAGLGRAPVLV----AVALIESG 123
Cdd:cd14601   98 TNLEKNesrpltQIQYIAWP-DHGVPDDSSDFLDFVCLVrnKRAGKDEP---VVVHCSAGIGRTGVLItmetAMCLIECN 173

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 528509783  68 WPfDDGAPPPSKVVEDWLSLLKRRFIEEPgccVAVHCVAGLGRAPVLVAV----ALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14596  114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLICVdvllSLIEKDLSFNikDIVREMRQQRYGMI 189

                 ....
gi 528509783 142 NSKQ 145
Cdd:cd14596  190 QTKD 193

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 528509783  92 FIEEPGCC---VAVHCVAGLGRAPVLVAVALIE-SGMKYEDAIQFIRQKR 137
Cdd:cd14567   72 FIEEAHQSgkgVLVHCQAGVSRSATIVIAYLMKhTRMTMTDAYKFVKNKR 121

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528509783 100 VAVHCVAGLGRAPVLV-AVALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLEK 151
Cdd:cd14577  106 VLVHCAMGISRSATLVlAFLMICEDLTLVDAIQTVRAHRDICPNSgflRQLRELDN 161

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  66 VDWPfDDGAPPPSKVVEDWLSLLKRRFiEEPGCC--VAVHCVAGLGRAPVLVAVALIESGMKYEDA------IQFIRQKR 137
Cdd:cd14554  143 TDWP-EQGVPKSGEGFIDFIGQVHKTK-EQFGQEgpITVHCSAGVGRTGVFITLSIVLERMRYEGVvdvfqtVKLLRTQR 220

                         90
                 ....*....|....*.
gi 528509783 138 RGAINSKQlTYLEKYR 153
Cdd:cd14554  221 PAMVQTED-QYQFCYR 235

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 528509783  76 PPSKVVEDWLSLLKRrFIEE---PGCCVAVHCVAGLGRAPVLVAVALIES-GMKYEDAIQFIRQKR 137
Cdd:cd17665   90 PDDKTIQSFKDAVKD-FLEKnkdNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154

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 528509783  67 DWPfDDGAPPPSKVVEDWLSLL---KRRFIEEPGccVAVHCVAGLGRAPVLVAVALIESGMKYE------DAIQFIRQKR 137
Cdd:cd14627  191 DWP-EQGVPKSGEGFIDFIGQVhktKEQFGQDGP--ISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQR 267

                 ....*..
gi 528509783 138 RGAINSK 144
Cdd:cd14627  268 PAMVQTE 274

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509783  90 RRFIEEPGCCVAVHCVAGLGRAPVLV-AVALIESGMKYEDAIQFIRQKR-----RGAInsKQLTYLEKYRPKQR 157
Cdd:cd14575   89 HQALSDPHNKLLVHCVMGRSRSATLVlAYLMIYKNMTVVDAIEQVAQRRcilpnRGFL--KQLRELDIQLAEER 160

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783  31 SSFIEDLKKYGVTTVVRV-CEI-TYDKTPLEKNGITVVDwpfddgaPPPSKVVEDWLSllKRRFIEEP---GCCVAVHCV 105
Cdd:cd14513   16 ASNLEELQNNGVKYILNVtREIdNFFPGRFTYHNIRVWD-------EESTNLLPYWNE--TYRFIKEArrkGSKVLVHCK 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 528509783 106 AGLGR-APVLVAVALIESGMKYEDAIQFIrQKRRGAINSKQ--LTYLEKY 152
Cdd:cd14513   87 MGVSRsASTVIAYAMKEYGWSLEQALEHV-KERRSCIKPNPgfLRQLITY 135

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
                 ....*....|....*....|....*....|....*....
gi 528509783 100 VAVHCVAGLGRAPVLVAVALIE-SGMKYEDAIQFIRQKR 137
Cdd:cd14519   80 VLVHCLAGVSRSVTIVAAYLMTvTDLGWRDALKAVRAAR 118

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509783   4 MNRPAP-VEVCYKN-----MRFLITHNPtNSTLssfiedlkkygvttVVRVC-EITYDKTPLEKNgitVVDWPFDDGAPP 76
Cdd:cd14510   26 MSFPSSgKQAFYRNpieevVRFLDTKHP-DHYK--------------VYNLCsERGYDPKYFHNR---VERVPIDDHNVP 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 528509783  77 P-------SKVVEDWLSllkrrfiEEPGCCVAVHCVAGLGRAPVLVAVALIESGM 124
Cdd:cd14510   88 TldemlsfTAEVREWMA-------ADPKNVVAIHCKGGKGRTGTMVCAWLIYSGQ 135