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Conserved domains on  [gi|283135369]
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Chain C, cAMP-specific 3',5'-cyclic phosphodiesterase 4D

Protein Classification

3',5'-cyclic nucleotide phosphodiesterase( domain architecture ID 10446396)

3',5'-cyclic nucleotide phosphodiesterase catalyzes the hydrolysis of cAMP or cGMP to produce adenosine 5'-phosphate or guanosine 5'-phosphate, respectively

CATH:  1.10.1300.10
EC:  3.1.4.-
Gene Ontology:  GO:0046872|GO:0004114
PubMed:  11008484|9868367
SCOP:  4001423

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PDEase_I pfam00233
3'5'-cyclic nucleotide phosphodiesterase;
83-323 1.42e-121

3'5'-cyclic nucleotide phosphodiesterase;


:

Pssm-ID: 459723  Cd Length: 238  Bit Score: 350.70  E-value: 1.42e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369   83 YHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVGF 162
Cdd:pfam00233   1 YHNWRHAFDVTQTMYYLLKTGKLKEVLTDLEILALLIAALCHDVDHPGTNNAFLIKTKSPLAILYNDSSVLENHHCATAF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  163 KLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSgvllLDNYSDRIQVL-QNMVHCA 241
Cdd:pfam00233  81 QILQDEECNIFSNLSDEEYKEVRKLIISLILATDMAKHFELLKKFKSLLESKKTLDF----LENEEDRRLLLlSMLIKAA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  242 DLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCD-KHNASVEKSQVGFIDYIVHPLWETWADLVhPDAQDIL 320
Cdd:pfam00233 157 DISNPTRPWEISKKWADLVAEEFFRQGDLEKELGLPVSPLMDrEKKTSLPKSQIGFIDFIVLPLFEALAKLF-PELQPLL 235


                  ...
gi 283135369  321 DTL 323
Cdd:pfam00233 236 DQL 238
PDE4_UCR super family cl39490
Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region ...
 342-364 2.60e-04

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.


The actual alignment was detected with superfamily member pfam18100:

Pssm-ID: 465648  Cd Length: 119  Bit Score: 40.43  E-value: 2.60e-04
                          10        20
                  ....*....|....*....|...
gi 283135369  342 LDEQNRdsQGNQVSEFISNTFLD 364
Cdd:pfam18100  99 LSEMSR--SGNQVSEFISNTFLD 119
 
Name Accession Description Interval E-value
PDEase_I pfam00233
3'5'-cyclic nucleotide phosphodiesterase;
83-323 1.42e-121

3'5'-cyclic nucleotide phosphodiesterase;


Pssm-ID: 459723  Cd Length: 238  Bit Score: 350.70  E-value: 1.42e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369   83 YHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVGF 162
Cdd:pfam00233   1 YHNWRHAFDVTQTMYYLLKTGKLKEVLTDLEILALLIAALCHDVDHPGTNNAFLIKTKSPLAILYNDSSVLENHHCATAF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  163 KLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSgvllLDNYSDRIQVL-QNMVHCA 241
Cdd:pfam00233  81 QILQDEECNIFSNLSDEEYKEVRKLIISLILATDMAKHFELLKKFKSLLESKKTLDF----LENEEDRRLLLlSMLIKAA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  242 DLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCD-KHNASVEKSQVGFIDYIVHPLWETWADLVhPDAQDIL 320
Cdd:pfam00233 157 DISNPTRPWEISKKWADLVAEEFFRQGDLEKELGLPVSPLMDrEKKTSLPKSQIGFIDFIVLPLFEALAKLF-PELQPLL 235


                  ...
gi 283135369  321 DTL 323
Cdd:pfam00233 236 DQL 238
HDc cd00077
Metal dependent phosphohydrolases with conserved 'HD' motif
 83-265 7.54e-11

Metal dependent phosphohydrolases with conserved 'HD' motif


Pssm-ID: 238032 [Multi-domain]  Cd Length: 145  Bit Score: 59.66  E-value: 7.54e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  83 YHNNIHAADVVQSTHVLlstpALEAVFTDLEILAAIFASAIHDVDHPGVSNQFlintnselalmYNDSSVLENHHLAVGF 162
Cdd:cd00077    1 EHRFEHSLRVAQLARRL----AEELGLSEEDIELLRLAALLHDIGKPGTPDAI-----------TEEESELEKDHAIVGA 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369 163 KLLQEEncdifqnltkkQRQSLRKMVIDIVLATDMSkHMNLLADLKTMVETKKvtssgvllldnysDRIQVLQNMVHCAD 242
Cdd:cd00077   66 EILREL-----------LLEEVIKLIDELILAVDAS-HHERLDGLGYPDGLKG-------------EEITLEARIVKLAD 120

                        170       180
                 ....*....|....*....|....*
gi 283135369 243 LSNPTKPLQLY--RQWTDRIMEEFF 265
Cdd:cd00077  121 RLDALRRDSREkrRRIAEEDLEELL 145
HDc smart00471
Metal dependent phosphohydrolases with conserved 'HD' motif; Includes eukaryotic cyclic ...
 82-256 1.28e-06

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).


Pssm-ID: 214679 [Multi-domain]  Cd Length: 124  Bit Score: 46.91  E-value: 1.28e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369    82 AYHNNIHAADVVQSTHVLLSTPALeavftdLEILAAIFASAIHDVDHPGVSNQFLINTnselalmyndsSVLENHHLAVG 161
Cdd:smart00471   2 DYHVFEHSLRVAQLAAALAEELGL------LDIELLLLAALLHDIGKPGTPDSFLVKT-----------SVLEDHHFIGA 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369   162 FKLLQEENCDIFQNLtkkqrqslrkmvidivLATDMSKHMNLLADLKTMVETkkvtssgvllldnysdriqVLQNMVHCA 241
Cdd:smart00471  65 EILLEEEEPRILEEI----------------LRTAILSHHERPDGLRGEPIT-------------------LEARIVKVA 109

                          170
                   ....*....|....*
gi 283135369   242 DLSNPTKPLQLYRQW 256
Cdd:smart00471 110 DRLDALRADRRYRRV 124
PDE4_UCR pfam18100
Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region ...
 342-364 2.60e-04

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.


Pssm-ID: 465648  Cd Length: 119  Bit Score: 40.43  E-value: 2.60e-04
                          10        20
                  ....*....|....*....|...
gi 283135369  342 LDEQNRdsQGNQVSEFISNTFLD 364
Cdd:pfam18100  99 LSEMSR--SGNQVSEFISNTFLD 119
 
Name Accession Description Interval E-value
PDEase_I pfam00233
3'5'-cyclic nucleotide phosphodiesterase;
83-323 1.42e-121

3'5'-cyclic nucleotide phosphodiesterase;


Pssm-ID: 459723  Cd Length: 238  Bit Score: 350.70  E-value: 1.42e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369   83 YHNNIHAADVVQSTHVLLSTPALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVGF 162
Cdd:pfam00233   1 YHNWRHAFDVTQTMYYLLKTGKLKEVLTDLEILALLIAALCHDVDHPGTNNAFLIKTKSPLAILYNDSSVLENHHCATAF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  163 KLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSgvllLDNYSDRIQVL-QNMVHCA 241
Cdd:pfam00233  81 QILQDEECNIFSNLSDEEYKEVRKLIISLILATDMAKHFELLKKFKSLLESKKTLDF----LENEEDRRLLLlSMLIKAA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  242 DLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMCD-KHNASVEKSQVGFIDYIVHPLWETWADLVhPDAQDIL 320
Cdd:pfam00233 157 DISNPTRPWEISKKWADLVAEEFFRQGDLEKELGLPVSPLMDrEKKTSLPKSQIGFIDFIVLPLFEALAKLF-PELQPLL 235


                  ...
gi 283135369  321 DTL 323
Cdd:pfam00233 236 DQL 238
HDc cd00077
Metal dependent phosphohydrolases with conserved 'HD' motif
 83-265 7.54e-11

Metal dependent phosphohydrolases with conserved 'HD' motif


Pssm-ID: 238032 [Multi-domain]  Cd Length: 145  Bit Score: 59.66  E-value: 7.54e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369  83 YHNNIHAADVVQSTHVLlstpALEAVFTDLEILAAIFASAIHDVDHPGVSNQFlintnselalmYNDSSVLENHHLAVGF 162
Cdd:cd00077    1 EHRFEHSLRVAQLARRL----AEELGLSEEDIELLRLAALLHDIGKPGTPDAI-----------TEEESELEKDHAIVGA 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369 163 KLLQEEncdifqnltkkQRQSLRKMVIDIVLATDMSkHMNLLADLKTMVETKKvtssgvllldnysDRIQVLQNMVHCAD 242
Cdd:cd00077   66 EILREL-----------LLEEVIKLIDELILAVDAS-HHERLDGLGYPDGLKG-------------EEITLEARIVKLAD 120

                        170       180
                 ....*....|....*....|....*
gi 283135369 243 LSNPTKPLQLY--RQWTDRIMEEFF 265
Cdd:cd00077  121 RLDALRRDSREkrRRIAEEDLEELL 145
HDc smart00471
Metal dependent phosphohydrolases with conserved 'HD' motif; Includes eukaryotic cyclic ...
 82-256 1.28e-06

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).


Pssm-ID: 214679 [Multi-domain]  Cd Length: 124  Bit Score: 46.91  E-value: 1.28e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369    82 AYHNNIHAADVVQSTHVLLSTPALeavftdLEILAAIFASAIHDVDHPGVSNQFLINTnselalmyndsSVLENHHLAVG 161
Cdd:smart00471   2 DYHVFEHSLRVAQLAAALAEELGL------LDIELLLLAALLHDIGKPGTPDSFLVKT-----------SVLEDHHFIGA 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283135369   162 FKLLQEENCDIFQNLtkkqrqslrkmvidivLATDMSKHMNLLADLKTMVETkkvtssgvllldnysdriqVLQNMVHCA 241
Cdd:smart00471  65 EILLEEEEPRILEEI----------------LRTAILSHHERPDGLRGEPIT-------------------LEARIVKVA 109

                          170
                   ....*....|....*
gi 283135369   242 DLSNPTKPLQLYRQW 256
Cdd:smart00471 110 DRLDALRADRRYRRV 124
PDE4_UCR pfam18100
Phosphodiesterase 4 upstream conserved regions (UCR); This is the upstream conserved region ...
 342-364 2.60e-04

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.


Pssm-ID: 465648  Cd Length: 119  Bit Score: 40.43  E-value: 2.60e-04
                          10        20
                  ....*....|....*....|...
gi 283135369  342 LDEQNRdsQGNQVSEFISNTFLD 364
Cdd:pfam18100  99 LSEMSR--SGNQVSEFISNTFLD 119
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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