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Reviewed, UniProtKB/Swiss-Prot Q08499 (PDE4D_HUMAN)

Last modified November 25, 2008. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4D
    EC=3.1.4.17
Alternative name(s):
    DPDE3
    PDE43
Gene names
Name: PDE4D
Synonyms: DPDE3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length809 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Regulates the levels of cAMP in the cell.

Catalytic activity

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate.

Cofactor

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.

Enzyme regulation

Inhibited by rolipram. Activated by phosphatidic acid.

Pathway

Purine metabolism; cAMP degradation; AMP from cAMP: step 1/1.

Subunit structure

Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 2 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP By similarity. Isoform 5 binds GNB2L1 via its unique N-terminus. Binds ARRB2.

Subcellular location

CytoplasmBy similarity. MembraneBy similarity. Cytoplasm › cytoskeletonBy similarity. CentrosomeBy similarity. Note= Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome By similarity.

Tissue specificity

Widespread; most abundant in skeletal muscle. Isoform 8 is detected in brain. Isoform 9 is detected in brain, placenta, lung and kidney. Isoform 11 is detected in heart and skeletal muscle.

Post-translational modification

Isoform 2 and isoform 11 are activated by phosphorylation (in vitro), but not isoform 8. Isoform 7 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.

Involvement in disease

Genetic variations in PDE4D might be associated with susceptibility to stroke type 1 (STRK1) [MIM:606799]. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ref.16 states that association with stroke has to be considered with caution.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

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Ontologies

Keywords

   Cellular componentCytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityAlternative splicing
   LigandMetal-binding
cAMP
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processsignal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular componentcentrosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

insoluble fraction Ref.4

Traceable author statement. Source: ProtInc

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

soluble fraction Ref.4

Traceable author statement. Source: ProtInc

   Molecular function3',5'-cyclic-AMP phosphodiesterase activity Ref.4

Traceable author statement. Source: ProtInc

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

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Alternative products

This entry describes 12 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q08499-1)

Also known as: hPDE4D4;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q08499-2)

Also known as: hPDE4D3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MMHVNNFFRRHSWIC
Notes: Activated by phosphorylation at Ser-53. Mutagenesis of Ser-53 abolishes activation.
Isoform 3 (identifier: Q08499-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-205: Missing.
Isoform 4 (identifier: Q08499-4)

Also known as: hPDE4D1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-269: MEAEGSSAPA...QPSINKATIT → MKEQPSCAGT...TESPFPCLFA
Isoform 5 (identifier: Q08499-5)

Also known as: hPDE4D2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-302: Missing.
Isoform 6 (identifier: Q08499-6)

Also known as: hPDE4D5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
Notes: Phosphorylated on Ser-59.
Isoform 7 (identifier: Q08499-7)

Also known as: PDE4DN3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-279: EEAYQKLASE → GLYNGIIAFL
     280-809: Missing.
Notes: Phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.
Isoform 8 (identifier: Q08499-8)

Also known as: PDE4D6;

The sequence of this isoform differs from the canonical sequence as follows:
     1-291: Missing.
     292-306: ETLQTRHSVSEMASN → MPEANYLLSVSWGYI
Isoform 9 (identifier: Q08499-9)

Also known as: PDE4D8;

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.
     123-152: RTSYAVETGHRPGLKKSRMSWPSSFQGLRR → MAFVWDPLGATVPGPSTRAKSRLRFSKSYS
Isoform 10 (identifier: Q08499-10)

Also known as: PDE4D9;

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.
     131-152: GHRPGLKKSRMSWPSSFQGLRR → MSIIMKPRSRSTSSLRTAEAVC
Isoform 11 (identifier: Q08499-11)

Also known as: PDE4D7;

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
     62-152: PPSPQPQPQC...WPSSFQGLRR → MKRNTCDLLS...IAITSAESSG
Isoform 12 (identifier: Q08499-12)

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: MEAEGSSAPA...WPSSFQGLRR → MAQQTSPDTL...QRRFTVAHTC
     270-283: EEAYQKLASETLEE → GSWMELNPYTLLDM
     284-809: Missing.
Notes: Phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 809809cAMP-specific 3',5'-cyclic phosphodiesterase 4D
PRO_0000198814

Regions

Compositional bias42 – 8847Pro-rich

Sites

Metal binding4661Divalent metal cation 1
Metal binding5021Divalent metal cation 1
Metal binding5031Divalent metal cation 1
Metal binding5031Divalent metal cation 2
Metal binding6201Divalent metal cation 1
Binding site4621cAMP
Binding site6201cAMP
Binding site6231cAMP
Binding site6711cAMP

Amino acid modifications

Modified residue181Phosphoserine
Modified residue201Phosphoserine
Modified residue251Phosphothreonine
Modified residue1971Phosphoserine
Modified residue2021Phosphoserine

Natural variations

Alternative sequence1 – 302302Missing in isoform 5.
VSP_004580
Alternative sequence1 – 291291Missing in isoform 8.
VSP_012383
Alternative sequence1 – 269269MEAEG…KATIT → MKEQPSCAGTGHPMAGYGRM APFELASGPVKRLRTESPFP CLFA in isoform 4.
VSP_004579
Alternative sequence1 – 205205Missing in isoform 3.
VSP_004578
Alternative sequence1 – 152152MEAEG…QGLRR → MMHVNNFFRRHSWIC in isoform 2.
VSP_004577
Alternative sequence1 – 152152MEAEG…QGLRR → MAQQTSPDTLTVPEVDNPHC PNPWLNEDLVKSLRENLLQH EKSKTARKSVSPKLSPVISP RNSPRLLRRMLLSSNIPKQR RFTVAHTC in isoform 6, isoform 7 and isoform 12.
VSP_012384
Alternative sequence1 – 130130Missing in isoform 10.
VSP_012385
Alternative sequence1 – 122122Missing in isoform 9.
VSP_012386
Alternative sequence1 – 6161Missing in isoform 11.
VSP_012387
Alternative sequence62 – 15291PPSPQ…QGLRR → MKRNTCDLLSRSKSASEETL HSSNEEEDPFRGMEPYLVRR LSCRNIQLPPLAFRQLEQAD LKSESENIQRPTSLPLKILP LIAITSAESSG in isoform 11.
VSP_012388
Alternative sequence123 – 15230RTSYA…QGLRR → MAFVWDPLGATVPGPSTRAK SRLRFSKSYS in isoform 9.
VSP_012389
Alternative sequence131 – 15222GHRPG…QGLRR → MSIIMKPRSRSTSSLRTAEA VC in isoform 10.
VSP_012390
Alternative sequence270 – 28314EEAYQ…ETLEE → GSWMELNPYTLLDM in isoform 12.
VSP_023326
Alternative sequence270 – 27910EEAYQKLASE → GLYNGIIAFL in isoform 7.
VSP_012391
Alternative sequence280 – 809530Missing in isoform 7.
VSP_012392
Alternative sequence284 – 809526Missing in isoform 12.
VSP_023327
Alternative sequence292 – 30615ETLQT…EMASN → MPEANYLLSVSWGYI in isoform 8.
VSP_012393

Experimental info

Mutagenesis5271D → R: Abolishes homodimerization
Mutagenesis5631R → D: Abolishes homodimerization
Sequence conflict5101S → F in AAH36319. Ref.10
Sequence conflict5491D → G in AAN10119. Ref.6
Sequence conflict6441R → P Ref.2
Sequence conflict7691C → R in AAA97890, AAA97891 and AAA97892. Ref.3

Secondary structure

1 ................................................. 809
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (hPDE4D4) [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 7A4773DD3A044F57

FASTA80991,115
        10         20         30         40         50         60 
MEAEGSSAPA RAGSGEGSDS AGGATLKAPK HLWRHEQHHQ YPLRQPQFRL LHPHHHLPPP 

        70         80         90        100        110        120 
PPPSPQPQPQ CPLQPPPPPP LPPPPPPPGA ARGRYASSGA TGRVRHRGYS DTERYLYCRA 

       130        140        150        160        170        180 
MDRTSYAVET GHRPGLKKSR MSWPSSFQGL RRFDVDNGTS AGRSPLDPMT SPGSGLILQA 

       190        200        210        220        230        240 
NFVHSQRRES FLYRSDSDYD LSPKSMSRNS SIASDIHGDD LIVTPFAQVL ASLRTVRNNF 

       250        260        270        280        290        300 
AALTNLQDRA PSKRSPMCNQ PSINKATITE EAYQKLASET LEELDWCLDQ LETLQTRHSV 

       310        320        330        340        350        360 
SEMASNKFKR MLNRELTHLS EMSRSGNQVS EFISNTFLDK QHEVEIPSPT QKEKEKKKRP 

       370        380        390        400        410        420 
MSQISGVKKL MHSSSLTNSS IPRFGVKTEQ EDVLAKELED VNKWGLHVFR IAELSGNRPL 

       430        440        450        460        470        480 
TVIMHTIFQE RDLLKTFKIP VDTLITYLMT LEDHYHADVA YHNNIHAADV VQSTHVLLST 

       490        500        510        520        530        540 
PALEAVFTDL EILAAIFASA IHDVDHPGVS NQFLINTNSE LALMYNDSSV LENHHLAVGF 

       550        560        570        580        590        600 
KLLQEENCDI FQNLTKKQRQ SLRKMVIDIV LATDMSKHMN LLADLKTMVE TKKVTSSGVL 

       610        620        630        640        650        660 
LLDNYSDRIQ VLQNMVHCAD LSNPTKPLQL YRQWTDRIME EFFRQGDRER ERGMEISPMC 

       670        680        690        700        710        720 
DKHNASVEKS QVGFIDYIVH PLWETWADLV HPDAQDILDT LEDNREWYQS TIPQSPSPAP 

       730        740        750        760        770        780 
DDPEEGRQGQ TEKFQFELTL EEDGESDTEK DSGSQVEEDT SCSDSKTLCT QDSESTEIPL 

       790        800 
DEQVEEEAVG EEEESQPEAC VIDDRSPDT

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Isoform 2 (hPDE4D3) [UniParc].

Checksum: 24174F02715A412A
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67276,369