dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  42 VTRILGGLYLGGIQPIVDHTPLSAQfKISHILSIIKFQVIPEYlvRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSCLF 121
Cdd:cd14518    1 LSRILGGLYLGGIEPLNRNRLLKAE-NITHILSVIPGDVPEEY--FKGYEHKQIEIDDVEDENILQHFPETNRFIDSALF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 122 PNEKEYDprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSRMG 201
Cdd:cd14518   78 GNGKDED------EEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYHEMG 151

                 .
gi 410730565 202 G 202
Cdd:cd14518  152 C 152

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  42 VTRILGGLYLGGIQPIVDHTPLSAQfKISHILSIIKFQVIPEYlvRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSCLF 121
Cdd:cd14518    1 LSRILGGLYLGGIEPLNRNRLLKAE-NITHILSVIPGDVPEEY--FKGYEHKQIEIDDVEDENILQHFPETNRFIDSALF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 122 PNEKEYDprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSRMG 201
Cdd:cd14518   78 GNGKDED------EEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYHEMG 151

                 .
gi 410730565 202 G 202
Cdd:cd14518  152 C 152

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 410730565   49 LYLGGIQPIVDhtPLSAQFKISHILSIIKfqVIPEYLvrKGYTLKNIPIDDDHTTDILQYFNETNSFIDSClfpnekeyd 128
Cdd:pfam00782   1 LYLGSKPTASD--AFLSKLGITAVINVTR--EVDLYN--SGILYLRIPVEDNHETNISKYLEEAVEFIDDA--------- 65

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 410730565  129 privnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:pfam00782  66 --------RQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQL 123

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  42 VTRILGGLYLGGIQPIVDHTPLSAQfKISHILSIIKFQVIPEYlvRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSCLF 121
Cdd:cd14518    1 LSRILGGLYLGGIEPLNRNRLLKAE-NITHILSVIPGDVPEEY--FKGYEHKQIEIDDVEDENILQHFPETNRFIDSALF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 122 PNEKEYDprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSRMG 201
Cdd:cd14518   78 GNGKDED------EEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYHEMG 151

                 .
gi 410730565 202 G 202
Cdd:cd14518  152 C 152

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565    42 VTRILGGLYLGGIQPIVDhTPLSAQFKISHILSIIKFQVIPEYlvrKGYTLKNIPIDDDHTTDILQYFNETNSFIDSClf 121
Cdd:smart00195   1 PSEILPHLYLGSYSDALN-LALLKKLGITHVINVTNEVPNYNG---SDFTYLGVPIDDNTETKISPYFPEAVEFIEDA-- 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 410730565   122 pnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSRM 200
Cdd:smart00195  75 ---------------ESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  43 TRILGGLYLGGIQPIVDHTpLSAQFKISHILSIIKFQVIPEYLVRKGYtlKNIPIDDDHTTDILQYFNETNSFIDSClfp 122
Cdd:cd14568    2 TRILPHLYLGSQRDVLDKD-LMQRNGISYVLNVSNTCPKPDFIPDSHF--LRIPVNDSYCEKLLPWLDKAVEFIEKA--- 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 410730565 123 nekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIF 197
Cdd:cd14568   76 --------------RASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEF 136

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It 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. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  42 VTRILGGLYLGGIQPIVDHTPLSaQFKISHILSIikfqvipEYLVRKGY----TLKNIPIDDDHTTDILQYFNETNSFID 117
Cdd:cd14523    2 VGVIKPWLLLSSQDVAHDLETLK-KHKVTHILNV-------AYGVENAFpddfTYKTISILDLPETDITSYFPECFEFID 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 118 sclfpnekeydprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIF 197
Cdd:cd14523   74 -----------------EAKSQDGVVLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEY 136

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 410730565  44 RILGGLYLGGIQPIVDHTPLSaQFKISHILSIIkfQVIPEYLVR-KGYTLKNIPIDDDHTTDILQYFNETNSFIDsclfp 122
Cdd:cd14566    3 EILPFLYLGNAKDSANIDLLK-KYNIKYILNVT--PNLPNTFEEdGGFKYLQIPIDDHWSQNLSAFFPEAISFID----- 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 410730565 123 nekeydprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLkNSIYA-IKRKLPKIEPNENFMEQL 194
Cdd:cd14566   75 ------------EARSKKCGVLVHCLAGISRSVTVTVAYLMQKLHLSL-NDAYDfVKKRKSNISPNFNFMGQL 134

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  43 TRILGGLYLGGIQPIVDHTPLSAqFKISHILSIIKFQvipeYLVRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSClfp 122
Cdd:cd14519    2 NKILPGLYVGNFRDAKDAEQLRE-NGITHILSIHDSA----RPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEA--- 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 410730565 123 nekeydpRIvnfkkkqQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIF 197
Cdd:cd14519   74 -------RL-------NGGNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEF 134

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 410730565  45 ILGGLYLGGIQPIVDHT-PLSAQFKISHILSIikFQVIPEYLVRKGYTLK----NIPIDDDHTTDILQYFNETNSFIDSC 119
Cdd:cd14522    8 ILPGLYLGPYSAAMKSKlEVLLKHGITHIVCV--RQNIEANFIKPNFPDHfrylVLDVADNPTENIIRHFPTVKEFIDDC 85

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 410730565 120 LfpnekeydprivnfkkkQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:cd14522   86 L-----------------QTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQL 143

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  42 VTRILGGLYLGGIQPIVDHTPLSaQFKISHILSIIkfQVIPEYL-VRKGYTLKNIPIDDDHTTDILQYFNETNSFIDscl 120
Cdd:cd14567    1 LTPILPFLYLGNERDAQDIDTLQ-RLNIGYVLNVT--THLPLYHeGKGGFRYKRLPATDSNKQNLRQYFEEAFEFIE--- 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 410730565 121 fpnekeydprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:cd14567   75 --------------EAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQL 134

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 410730565  42 VTRILGGLYLGGIQPIVDHTPLSAQfKISHILSIikfQVIPEYLVRKgYTLKNIPIDDDHTTDILQYFNETNSFIDSClf 121
Cdd:cd14582    5 MTKVLPGLYLGNFIDAKDLEQLSRN-KITHIISI---HESPQPLLQD-ITYLRIPLPDTPEAPIKKHFKECISFIHQC-- 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 410730565 122 pnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFS 198
Cdd:cd14582   78 ---------------RLNGGNCLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEFG 139

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 410730565  43 TRILGGLYLGGIQPIVDHTPLSAQfKISHILSIIKF--QVIPEYlvrkgYTLKNIPIDDDHTTDILQYFNETNSFIDSCl 120
Cdd:cd14571    5 SRIFPYLYLGSEWNAANLEELQRN-RVSHILNVTREidNFFPER-----FTYMNIRVYDEEATQLLPHWKETHRFIEAA- 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 410730565 121 fpnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFS 198
Cdd:cd14571   78 ----------------RAQGTRVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQ 139

dual specificity phosphatase domain of dual specificity protein phosphatase 9; Dual specificity protein phosphatase 9 (DUSP9), also called mitogen-activated protein kinase (MAPK) phosphatase 4 (MKP-4), 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. DUSP9 is a mediator of bone morphogenetic protein (BMP) signaling to control the appropriate ERK activity critical for the determination of embryonic stem cell fate. Down-regulation of DUSP9 expression has been linked to severe pre-eclamptic placenta as well as cancers such as hepatocellular carcinoma. DUSP9 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 410730565  44 RILGGLYLGGIQPIVDHTPLsAQFKISHILSIIKfqVIPEYLVRKG-YTLKNIPIDDDHTTDILQYFNETNSFIDSCLfp 122
Cdd:cd14644    5 QILPNLYLGSARDSANLETL-AKLGIRYILNVTP--NLPNFFEKNGdFHYKQIPISDHWSQNLSQFFPEAIEFIDEAL-- 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 410730565 123 nekeydprivnfkkkQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSR 199
Cdd:cd14644   80 ---------------SQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEK 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 410730565  90 YTLKNIPIDDDHTTDILQYFNETNSFIDSClfpnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLS 169
Cdd:cd14640   45 YQYKCIPVEDNHKADISSWFMEAIEYIDSV-----------------KDCNGRVLVHCQAGISRSATICLAYLMMKKRVR 107

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 410730565 170 LKNSIYAIKRKLPKIEPNENFMeqleifsrmgGQYVDFENQ 210
Cdd:cd14640  108 LEEAFEFVKQRRSIISPNFSFM----------GQLLQFESQ 138

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), 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. DUSP3 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 favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  66 QFKISHIL------SIIKFQVIPEYLVRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSCLfpnekeydprivnfkkKQQ 139
Cdd:cd14579   44 RLGITHVLnaaegkSFMHVNTNAEFYEDTGITYHGIKANDTQHFNLSAYFEEAADFIDKAL----------------AQK 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 410730565 140 NGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKlPKIEPNENFMEQL 194
Cdd:cd14579  108 NGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQK-REIGPNDGFLKQL 161

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  71 HILSIIKFQVIPEYLVRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSClfpnekeydprivnfkkKQQNGAIYVHCHAG 150
Cdd:cd14639   26 HITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCV-----------------RRAGGKVLVHCEAG 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 410730565 151 VSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:cd14639   89 ISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQL 132

dual specificity phosphatase domain of slingshot homolog 1; Dual specificity protein phosphatase slingshot homolog 1 (SSH1), also called SSH-like protein 1, 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. SSH1 links NOD1 signaling to actin remodeling, facilitating the changes that leads to NF-kappaB activation and innate immune responses. There are at least two human SSH1 isoforms reported: hSSH-1L (long) and hSSH-1S (short). 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. They also contain C-terminal tails, differing in the lengths of the tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  90 YTLKNIPIDDDHTTDILQYFNETNSFIDsclfpnekeydprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLS 169
Cdd:cd14570   48 FAYHNIRVYDEETTDLLAHWNDAYHFIN-----------------KAKKNHSKCLVHCKMGVSRSASTVIAYAMKEFGWS 110

                         90       100
                 ....*....|....*....|....*
gi 410730565 170 LKNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:cd14570  111 LEKAYNFVKQKRSITRPNAGFMRQL 135

dual specificity phosphatase domain of dual specificity protein phosphatase 2; Dual specificity protein phosphatase 2 (DUSP2), also called dual specificity protein phosphatase PAC-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 mitogen-activated protein kinase (MAPK) phosphatases (MKPs), it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP2 can preferentially dephosphorylate ERK1/2 and p38, but not JNK in vitro. It is predominantly expressed in hematopoietic tissues with high T-cell content, such as thymus, spleen, lymph nodes, peripheral blood and other organs such as the brain and liver. It has a critical and positive role in inflammatory responses. DUSP2 mRNA and protein are significantly reduced in most solid cancers including breast, colon, lung, ovary, kidney and prostate, and the suppression of DUSP2 is associated with tumorigenesis and malignancy. DUSP2 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 410730565  93 KNIPIDDDHTTDILQYFNETNSFIDSClfpnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKN 172
Cdd:cd14641   51 KSIPVEDSHMADISAWFQEAIDFIDSV-----------------KNSGGRVLVHCQAGISRSATICLAYLIQSQRVRLDE 113

                         90       100
                 ....*....|....*....|....*
gi 410730565 173 SIYAIKRKLPKIEPNENFMEQLEIF 197
Cdd:cd14641  114 AFDFVKQRRGVISPNFSFMGQLLQF 138

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 410730565  91 TLKNIPIDDDHTTDILQYFNETNSFIDsclfpnekeydprivnfKKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSL 170
Cdd:cd14517   58 QVLHIPVEDSVEADLLSFFERACSFID-----------------KHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSL 120

                         90       100
                 ....*....|....*....|....
gi 410730565 171 KNSIYAIKRKLPKIEPNENFMEQL 194
Cdd:cd14517  121 KDAWKYLLKCKNNMRPNRGFVKQL 144

dual specificity protein phosphatase 26; Dual specificity protein phosphatase 26 (DUSP26), also called mitogen-activated protein kinase (MAPK) phosphatase 8 (MKP-8) or low-molecular-mass dual-specificity phosphatase 4 (LDP-4), 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. DUSP26 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 a brain phosphatase highly overexpressed in neuroblastoma and has also been identified as a p53 phosphatase, dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  48 GLYLGGiQPIVDHTPLSAQFKISHILSII--KFQVIPEYLVRKGYTLKNIPIDDDHTTDILQYFNETNSFIDSCLfpnek 125
Cdd:cd14578    7 GLYLGD-QDIAANRRELRRLGITHILNAShsKWRGGAEYYEGLNIRYLGIEAHDSPAFDMSIHFYPAADFIHRAL----- 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 410730565 126 eydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKlPKIEPNENFMEQL 194
Cdd:cd14578   81 -----------SQPGGKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDH-RGIIPNRGFLRQL 137

dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that 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 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  95 IPIDDDHTTDILQYFNETNSFIDSCLfpnekeydprivnfkkkQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSI 174
Cdd:cd14574   50 VPVFDDPAEDLYRHFEQCADAIEAAV-----------------RRGGKCLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAF 112

                         90       100
                 ....*....|....*....|...
gi 410730565 175 YAIKRKLPKIEPNENFMEQLEIF 197
Cdd:cd14574  113 QVVKAARPVAEPNPGFWSQLQRY 135

dual specificity protein phosphatase 14; dual specificity protein phosphatase 14 (DUSP14), also called mitogen-activated protein kinase (MAPK) phosphatase 6 (MKP-6) or MKP-1-like protein tyrosine phosphatase (MKP-L), 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. DUSP14 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. DUSP14 dephosphorylates JNK, ERK, and p38 in vitro. It also 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 130 RIVNFKKKqqNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSR 199
Cdd:cd14572   77 KIHSVGRK--HGATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYER 144

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 410730565  95 IPIDDDHTTDILQYFNETNSFIDSCLfpnekeydprivnfkkKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSI 174
Cdd:cd14580   56 VPANDLPDFDISPYFYSAAEFIHRAL----------------NTPGAKVLVHCAVGVSRSATLVLAYLMIYHQLSLVQAI 119

                         90       100
                 ....*....|....*....|
gi 410730565 175 YAIKRKlPKIEPNENFMEQL 194
Cdd:cd14580  120 KTVKER-RWIFPNRGFLKQL 138

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565 132 VNF--KKKQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSIYAIKRKLPKIEPNENFMEQLEIFSR 199
Cdd:cd14524   79 VDFilKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREVLEEFYR 148

dual specificity phosphatase-like domain of inactive dual specificity protein phosphatase 27; Inactive dual specificity protein phosphatase 27 (DUSP27) may play a role in myofiber maturation. It is a pseudophosphatase containing a substitution of the active site cysteine into a serine. It is a large protein of more than 1000 amino acids in length with an N-terminal dual specificity phosphatase-like domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 410730565  95 IPIDDDHTTDILQYFNETNSFIDSCLFpnekeydprivnfkkkQQNGAIYVHCHAGVSRSATFMIAYLMYRYGLSLKNSI 174
Cdd:cd14576   66 IEVDDFPDVDISKHFRKGAEFLDEALL----------------TYRGKVLVSSEMGISRSAVLVAAYLMIFHNMTIMEAL 129

                         90       100
                 ....*....|....*....|
gi 410730565 175 YAIKRKLPkIEPNENFMEQL 194
Cdd:cd14576  130 MTLRKKRA-IYPNEGFLKQL 148