Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region (UCR) found in Phosphodiesterase 4 (PDE4) enzymes. PDE4 is a contributor to intracellular signalling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain pfam00233. Due to alternative promoters/start sites and variable mRNA splicing, transcription from the four PDE4 genes results in the expression of more than 25 different isoforms of PDE4. Each isoform has a unique N-terminal region that determines its specific subcellular localization by mediating interactions with scaffolding proteins. The isoforms are further classified into long, short, and supershort forms based on the presence or absence of two upstream conserved regions (UCRs, known as UCR1 and UCR2). Long splice variants contain both UCR1 and UCR2, short variants lack UCR1, and the supershort forms of PDE4 additionally lack part of UCR2. The extent to which UCRs are present determines critical functional differences between the isoforms. Phosphorylation by protein kinase A (PKA) at a conserved site on UCR1 activates all long PDE4 isoforms. Mutation and deletion studies have shown that long forms of PDE4 are dimeric, with key dimerization interactions mediated by UCR1 and UCR2, and that the C-terminal half of UCR2 could play a negative regulatory role.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217268050   1 METLEELDWCLDQLETIQTYRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLD 62
Cdd:pfam18100  58 VETLEELDWCLDQLETIQTHRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNTFLD 119

Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region (UCR) found in Phosphodiesterase 4 (PDE4) enzymes. PDE4 is a contributor to intracellular signalling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain pfam00233. Due to alternative promoters/start sites and variable mRNA splicing, transcription from the four PDE4 genes results in the expression of more than 25 different isoforms of PDE4. Each isoform has a unique N-terminal region that determines its specific subcellular localization by mediating interactions with scaffolding proteins. The isoforms are further classified into long, short, and supershort forms based on the presence or absence of two upstream conserved regions (UCRs, known as UCR1 and UCR2). Long splice variants contain both UCR1 and UCR2, short variants lack UCR1, and the supershort forms of PDE4 additionally lack part of UCR2. The extent to which UCRs are present determines critical functional differences between the isoforms. Phosphorylation by protein kinase A (PKA) at a conserved site on UCR1 activates all long PDE4 isoforms. Mutation and deletion studies have shown that long forms of PDE4 are dimeric, with key dimerization interactions mediated by UCR1 and UCR2, and that the C-terminal half of UCR2 could play a negative regulatory role.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217268050   1 METLEELDWCLDQLETIQTYRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLD 62
Cdd:pfam18100  58 VETLEELDWCLDQLETIQTHRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNTFLD 119

Metal dependent phosphohydrolases with conserved 'HD' motif; Includes eukaryotic cyclic nucleotide phosphodiesterases (PDEc). This profile/HMM does not detect HD homologues in bacterial glycine aminoacyl-tRNA synthetases (beta subunit).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268050  185 AYHNSLHAADVAQSTHVLLSTPALD----AVFTDLeilaaifaaaIHDVDHPGVSNQFLINTnselalmyndeSVLENHH 260
Cdd:smart00471   2 DYHVFEHSLRVAQLAAALAEELGLLdielLLLAAL----------LHDIGKPGTPDSFLVKT-----------SVLEDHH 60

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268050  261 LAVGFKLLQEEHCDIFMNLtkkqrqtlrkmvidmvLATDMSKHMSLLADLKTMVETkkvtssgvllldnytdriqVLRNM 340
Cdd:smart00471  61 FIGAEILLEEEEPRILEEI----------------LRTAILSHHERPDGLRGEPIT-------------------LEARI 105

                          170
                   ....*....|....*....
gi 2217268050  341 VHCADLSNPTKSLELYRQW 359
Cdd:smart00471 106 VKVADRLDALRADRRYRRV 124

Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region (UCR) found in Phosphodiesterase 4 (PDE4) enzymes. PDE4 is a contributor to intracellular signalling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain pfam00233. Due to alternative promoters/start sites and variable mRNA splicing, transcription from the four PDE4 genes results in the expression of more than 25 different isoforms of PDE4. Each isoform has a unique N-terminal region that determines its specific subcellular localization by mediating interactions with scaffolding proteins. The isoforms are further classified into long, short, and supershort forms based on the presence or absence of two upstream conserved regions (UCRs, known as UCR1 and UCR2). Long splice variants contain both UCR1 and UCR2, short variants lack UCR1, and the supershort forms of PDE4 additionally lack part of UCR2. The extent to which UCRs are present determines critical functional differences between the isoforms. Phosphorylation by protein kinase A (PKA) at a conserved site on UCR1 activates all long PDE4 isoforms. Mutation and deletion studies have shown that long forms of PDE4 are dimeric, with key dimerization interactions mediated by UCR1 and UCR2, and that the C-terminal half of UCR2 could play a negative regulatory role.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217268050   1 METLEELDWCLDQLETIQTYRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLD 62
Cdd:pfam18100  58 VETLEELDWCLDQLETIQTHRSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNTFLD 119

Metal dependent phosphohydrolases with conserved 'HD' motif; Includes eukaryotic cyclic nucleotide phosphodiesterases (PDEc). This profile/HMM does not detect HD homologues in bacterial glycine aminoacyl-tRNA synthetases (beta subunit).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268050  185 AYHNSLHAADVAQSTHVLLSTPALD----AVFTDLeilaaifaaaIHDVDHPGVSNQFLINTnselalmyndeSVLENHH 260
Cdd:smart00471   2 DYHVFEHSLRVAQLAAALAEELGLLdielLLLAAL----------LHDIGKPGTPDSFLVKT-----------SVLEDHH 60

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217268050  261 LAVGFKLLQEEHCDIFMNLtkkqrqtlrkmvidmvLATDMSKHMSLLADLKTMVETkkvtssgvllldnytdriqVLRNM 340
Cdd:smart00471  61 FIGAEILLEEEEPRILEEI----------------LRTAILSHHERPDGLRGEPIT-------------------LEARI 105

                          170
                   ....*....|....*....
gi 2217268050  341 VHCADLSNPTKSLELYRQW 359
Cdd:smart00471 106 VKVADRLDALRADRRYRRV 124