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 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14640    21 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVLVHCQAGISRSATICLAYL 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLT 121
Cdd:cd14640   101 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), 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 I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14640    21 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVLVHCQAGISRSATICLAYL 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLT 121
Cdd:cd14640   101 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671    1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:smart00195  21 LLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYL 100

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2292593671   81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:smart00195 101 MKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 136

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDcpnhFEG--------HYQYKCIPVEDnHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSA 73
Cdd:PRK12361  116 LKSNKITAILDVTAE----FDGldwslteeDIDYLNIPILD-HSVPTLAQLNQAINWIHRQVRANKSVVVHCALGRGRSV 190

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2292593671  74 TICLAYLMMKKRVR-LEEAFEFVKQRRSIISPNF 106
Cdd:PRK12361  191 LVLAAYLLCKDPDLtVEEVLQQIKQIRKTARLNK 224

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), 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 I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14640    21 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVLVHCQAGISRSATICLAYL 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLT 121
Cdd:cd14640   101 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

dual specificity phosphatase domain of dual specificity protein phosphatase 1; Dual specificity protein phosphatase 1 (DUSP1), also called mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1), 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 I subfamily and is a mitogen- and stress-inducible nuclear MKP. Human MKP-1 dephosphorylates MAPK1/ERK2, regulating its activity during the meiotic cell cycle. Although initially MKP-1 was considered to be ERK-specific, it has been shown that MKP-1 also dephosphorylates both JNK and p38 MAPKs. DUSP1/MKP-1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. It is a central regulator of a variety of functions in the immune, metabolic, cardiovascular, and nervous systems. It 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14638    21 MLDTLGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAGGRVFVHCQAGISRSATICLAYL 100

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLTTSCAAEAASP 131
Cdd:cd14638   101 MRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQVLAPSCSAEAGSP 151

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPN-HFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14512    22 MQQLGIGYVLNVSNTCPNpDFIGLFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASNGGVLVHCLAGISRSATIAIAYL 101

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQF 115
Cdd:cd14512   102 MKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 136

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 2292593671   1 MLDALGITALLNVSSDCPNHFEgHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:pfam00782  13 FLSKLGITAVINVTREVDLYNS-GILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYL 91

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:pfam00782  92 MKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 2292593671   1 MLDALGITALLNVSSDCPN-HFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAY 79
Cdd:cd14498    21 LLKKLGITHILNVAGEPPPnKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKGGKVLVHCQAGVSRSATIVIAY 100

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2292593671  80 LMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQ 114
Cdd:cd14498   101 LMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPNHFE--GHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAY 79
Cdd:cd14566    22 LKKYNIKYILNVTPNLPNTFEedGGFKYLQIPIDDHWSQNLSAFFPEAISFIDEARSKKCGVLVHCLAGISRSVTVTVAY 101

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2292593671  80 LMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQF 115
Cdd:cd14566   102 LMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLDF 137

dual specificity phosphatase domain of dual specificity protein phosphatase 7; Dual specificity protein phosphatase 7 (DUSP7), also called mitogen-activated protein kinase (MAPK) phosphatase X (MKP-X) or dual specificity protein phosphatase PYST2, 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 II subfamily and is an ERK-selective cytoplasmic MKP. DUSP7 has been shown as an essential regulator of multiple steps in oocyte meiosis. Due to alternative promoter usage, the PYST2 gene gives rise to two isoforms, PYST2-S and PYST2-L. PYST2-L is over-expressed in leukocytes derived from AML and ALL patients as well as in some solid tumors and lymphoblastoid cell lines; it plays a role in cell-crowding. It 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFE--GHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLA 78
Cdd:cd14643    26 VLGKYGIKYILNVTPNLPNMFEhdGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGILVHCLAGISRSVTVTVA 105

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2292593671  79 YLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:cd14643   106 YLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFE 143

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLM 81
Cdd:cd14514    21 LLSRGITCIINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRTLVHCVAGVSRSATLCLAYLM 100

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2292593671  82 MKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQ 114
Cdd:cd14514   101 KYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVS--------SDCPNHFEGH-YQYKCIPVEDNHKADISSWFMEAIEYID-AVKDCRGRVLVHCQAGISR 71
Cdd:cd14515    22 LKKLGITHVLNAAegkkngevNTNAKFYKGSgIIYLGIPASDLPTFDISQYFDEAADFIDkALSDPGGKVLVHCVEGVSR 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2292593671  72 SATICLAYLMMKKRVRLEEAFEFVKQRRSIIsPNFSFMGQLLQFESQ 118
Cdd:cd14515   102 SATLVLAYLMIYQNMTLEEAIRTVRKKREIR-PNRGFLQQLCELNDK 147

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), 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. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   6 GITALLNVSSDCPN-HFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKK 84
Cdd:cd14646    28 GIGYVLNASNTCPKpDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRM 107

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2292593671  85 RVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQV 119
Cdd:cd14646   108 DMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKI 142

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd14573    22 LLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRTLLHCVAGVSRSATLCLAYL 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLTTSCAAEAASPSGPL 135
Cdd:cd14573   102 MKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGKNTVHMITSPVGMI 156

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 2292593671   6 GITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKKR 85
Cdd:cd14513    26 GVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGSKVLVHCKMGVSRSASTVIAYAMKEYG 105

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2292593671  86 VRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:cd14513   106 WSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   5 LGITALLNVSSDCPNHF-EGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMK 83
Cdd:cd14517    36 LKIKAHINVSMDADELFkSGNDQVLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYH 115

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2292593671  84 KRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLTTS 123
Cdd:cd14517   116 YKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, 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. DUSP12 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 targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   6 GITALLNVSSDCPNH--FEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDcRGRVLVHCQAGISRSATICLAYLMMK 83
Cdd:cd14520    26 GITHVLTVDSEEPIDapPVGKLVRKFVPALDEESTDLLSRLDECLDFIDEGRA-EGAVLVHCHAGVSRSAAVVTAYLMKT 104

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2292593671  84 KRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFES 117
Cdd:cd14520   105 EQLSFEEALASLRECKPDVKPNDGFLKQLKLYEA 138

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDC------PNhFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSAT 74
Cdd:cd14522    27 VLLKHGITHIVCVRQNIeanfikPN-FPDHFRYLVLDVADNPTENIIRHFPTVKEFIDDCLQTGGKVLVHGNAGISRSAA 105

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2292593671  75 ICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:cd14522   106 LVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

dual specificity phosphatase domain of plant IBR5-like protein phosphatases; This subfamily is composed of Arabidopsis thaliana INDOLE-3-BUTYRIC ACID (IBA) RESPONSE 5 (IBR5) and similar plant proteins. IBR5 protein is also called SKP1-interacting partner 33. The IBR5 gene encodes a dual-specificity phosphatase (DUSP) which acts as a positive regulator of plant responses to auxin and abscisic acid. DUSPs 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. IBR5 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. It has been shown to target MPK12, which is a negative regulator of auxin signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEGHYQYKCIpvednhKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYL 80
Cdd:cd18534    22 LLKAQGITRILNTVPDCQNLYKNSFTYHVL------SEEKTVPFAEAVDFIEQCRKDKARVLVHCMSGQSRSPAVVIAYL 95

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2292593671  81 MMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQF 115
Cdd:cd18534    96 MKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), 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. DUSP13A 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. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   5 LGITALLNVS------SDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYI-DAVKDCRGRVLVHCQAGISRSATICL 77
Cdd:cd14580    25 LGITHVLNAAhgklfcQGGDDFYGTSVDYYGVPANDLPDFDISPYFYSAAEFIhRALNTPGAKVLVHCAVGVSRSATLVL 104

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2292593671  78 AYLMMKKRVRLEEAFEFVKQRRSiISPNFSFMGQLLQFESQV 119
Cdd:cd14580   105 AYLMIYHQLSLVQAIKTVKERRW-IFPNRGFLKQLRKLDQQL 145

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPNHFEG----HYQYKCIPVEDNHKADISSWfMEAIEYIDAVKDCRGRVLVHCQAGISRSATICL 77
Cdd:COG2453    21 LKREGIDAVVSLTEEEELLLGLleeaGLEYLHLPIPDFGAPDDEQL-QEAVDFIDEALREGKKVLVHCRGGIGRTGTVAA 99

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2292593671  78 AYLMMKKrVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:COG2453   100 AYLVLLG-LSAEEALARVRAARPGAVETPAQRAFLERFA 137

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPNHFEG--HY-----QYKCIPVEDNHKADISSWFMEAIEYID-AVKDCRGRVLVHCQAGISRSA 73
Cdd:cd14575    32 LQKLGITHILNAAHGKWNVDTGaeYYkdmtiHYYGVEADDLPTFNLSQFFYSAAEFIHqALSDPHNKLLVHCVMGRSRSA 111

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2292593671  74 TICLAYLMMKKRVRLEEAFEFVKQRRSIIsPNFSFMGQLLQFESQV 119
Cdd:cd14575   112 TLVLAYLMIYKNMTVVDAIEQVAQRRCIL-PNRGFLKQLRELDIQL 156

dual specificity phosphatase domain of slingshot homolog 3; Dual specificity protein phosphatase slingshot homolog 3 (SSH3), also called SSH-like protein 3, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. The Xenopus homolog (xSSH) is involved in the gastrulation movement. Mouse SSH3 dephosphorylates actin-depolymerizing factor (ADF) and cofilin but is dispensable for development. There are at least two human SSH3 isoforms reported: hSSH-3L (long) and hSSH-3. As SSH family phosphatases, they 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, hSSH-3L contains a C-terminal tail while hSSH-3 does not.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   7 ITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKKRV 86
Cdd:cd14571    30 VSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRVLVHCKMGVSRSASTVIAYAMKQYGW 109

                          90       100
                  ....*....|....*....|....*.
gi 2292593671  87 RLEEAFEFVKQRRSIISPNFSFMGQL 112
Cdd:cd14571   110 TLEQALRHVRERRPIVQPNPGFLRQL 135

dual specificity protein phosphatase 22; Dual specificity protein phosphatase 22 (DUSP22), also called JNK-stimulatory phosphatase-1 (JSP-1), low molecular weight dual specificity phosphatase 2 (LMW-DSP2), mitogen-activated protein kinase phosphatase x (MKP-x) or VHR-related MKPx (VHX), 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. DUSP22 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. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. It also regulates cell death by acting as a scaffold protein for the ASK1-MKK7-JNK signal transduction pathway independently of its phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   6 GITALLNVSSDCPNHFEGhYQYKCIPVEDNHKADISSWFMEAIEYIdavKDCRGR---VLVHCQAGISRSATICLAYLMM 82
Cdd:cd14581    29 NITHILSVHDSARPMLEG-MTYLCIPAADSPSQNLTQHFKESIKFI---HECRLRgegCLVHCLAGVSRSVTLVVAYIMT 104

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2292593671  83 KKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 116
Cdd:cd14581   105 VTDFGWEDALSAVKAARSCANPNMGFQRQLQEFE 138

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13B is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   1 MLDALGITALLNVSSDCPNHFEG-------HYQYKCIPVEDNHKADISSWFMEAIEYIDA-VKDCRGRVLVHCQAGISRS 72
Cdd:cd14577    38 VLIQLGITHIVNAASGKFHVNTGpkfyrdmNIDYYGVEADDNPFFDLSVYFYPVARFIRAaLSSPNGRVLVHCAMGISRS 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2292593671  73 ATICLAYLMMKKRVRLEEAFEFVKQRRSiISPNFSFMGQLLQFE 116
Cdd:cd14577   118 ATLVLAFLMICEDLTLVDAIQTVRAHRD-ICPNSGFLRQLRELD 160

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 2292593671   2 LDALGITALLNVSS--DCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAY 79
Cdd:cd14582    23 LEQLSRNKITHIISihESPQPLLQDITYLRIPLPDTPEAPIKKHFKECISFIHQCRLNGGNCLVHCLAGISRSTTIVVAY 102

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2292593671  80 LMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQF 115
Cdd:cd14582   103 VMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671  46 EAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRR-SIISPNFSFMGQLLQ 114
Cdd:cd14494    44 RFLEVLDQAEKPGEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRpGGIPQTIEQLDFLIK 113

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   2 LDALGITALLNVSSDCPNHFEG--------HYQ-----YKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAG 68
Cdd:cd14526    25 LKKEGVTAVLNLQTDSDMEYWGvdidsirkACKesgirYVRLPIRDFDTEDLRQKLPQAVALLYRLLKNGGTVYVHCTAG 104

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2292593671  69 ISRSATICLAYLMMKKRVRLEEAFEFVKQRRS 100
Cdd:cd14526   105 LGRAPATVIAYLYWVLGYSLDEAYYLLTSKRP 136

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2292593671   24 HYQYKCIPveDNHKADISSWFMEAIEYIDAVK---DCRGRVLVHCQAGISRSATICLAYLMM---KKRVRLEEAFEFVKQ 97
Cdd:smart00404   4 HYHYTGWP--DHGVPESPDSILELLRAVKKNLnqsESSGPVVVHCSAGVGRTGTFVAIDILLqqlEAEAGEVDIFDTVKE 81