Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q08493 (PDE4C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4C

EC=3.1.4.53
Alternative name(s):
DPDE1
PDE21
Gene names
Name:PDE4C
Synonyms:DPDE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length712 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. Ref.7

Catalytic activity

Adenosine 3',5'-cyclic phosphate + H2O = 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. Ref.7

Enzyme regulation

Inhibited by rolipram.

Pathway

Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Subunit structure

Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2 By similarity.

Subcellular location

Cell projectioncilium By similarity.

Tissue specificity

Expressed in various tissues but not in cells of the immune system.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform PDE4C1 (identifier: Q08493-1)

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 PDE4C2 (identifier: Q08493-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.
Isoform PDE4C3 (identifier: Q08493-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: MENLGVGEGA...LSWPVSSCRR → MQGPPAPAPV...RRFTVAHPLC
Isoform PDE4C4 (identifier: Q08493-4)

The sequence of this isoform is not available.
Isoform PDE4C5 (identifier: Q08493-5)

The sequence of this isoform is not available.
Isoform PDE4C6 (identifier: Q08493-6)

The sequence of this isoform is not available.
Isoform PDE4C7 (identifier: Q08493-7)

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 712712cAMP-specific 3',5'-cyclic phosphodiesterase 4C
PRO_0000198811

Regions

Nucleotide binding388 – 3925cAMP By similarity

Sites

Active site3881Proton donor By similarity
Metal binding3921Divalent metal cation 1
Metal binding4281Divalent metal cation 1
Metal binding4291Divalent metal cation 1
Metal binding4291Divalent metal cation 2
Metal binding5461Divalent metal cation 1
Binding site4291cAMP By similarity
Binding site5461cAMP By similarity
Binding site5971cAMP By similarity
Site5491Binds AMP, but not cAMP By similarity

Natural variations

Alternative sequence1 – 106106Missing in isoform PDE4C2.
VSP_004575
Alternative sequence1 – 8181MENLG…SSCRR → MQGPPAPAPVPGPGSPRGSP RGSPGLFRKLLVNQSIRLQR RFTVAHPLC in isoform PDE4C3.
VSP_004574
Natural variant1311S → L.
Corresponds to variant rs10413646 [ dbSNP | Ensembl ].
VAR_050473
Natural variant2891R → Q.
Corresponds to variant rs34503849 [ dbSNP | Ensembl ].
VAR_050474
Natural variant3441R → Q.
Corresponds to variant rs2229228 [ dbSNP | Ensembl ].
VAR_034374
Natural variant3441R → W.
Corresponds to variant rs11879710 [ dbSNP | Ensembl ].
VAR_061497

Experimental info

Sequence conflict2041K → N in AAD47053. Ref.2
Sequence conflict2041K → N in AAD47054. Ref.2
Sequence conflict2111D → Y in AAD47053. Ref.2
Sequence conflict2111D → Y in AAD47054. Ref.2
Sequence conflict339 – 3402EL → DV in CAA86601. Ref.1
Sequence conflict444 – 4463NSE → K in AAC83047. Ref.4
Sequence conflict446 – 4472EL → DV in CAA86601. Ref.1

Secondary structure

............................................. 712
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE4C1 [UniParc].

Last modified March 27, 2002. Version 2.
Checksum: 1932116C9CE0322C

FASTA71279,902
        10         20         30         40         50         60 
MENLGVGEGA EACSRLSRSR GRHSMTRAPK HLWRQPRRPI RIQQRFYSDP DKSAGCRERD 

        70         80         90        100        110        120 
LSPRPELRKS RLSWPVSSCR RFDLENGLSC GRRALDPQSS PGLGRIMQAP VPHSQRRESF 

       130        140        150        160        170        180 
LYRSDSDYEL SPKAMSRNSS VASDLHGEDM IVTPFAQVLA SLRTVRSNVA ALARQQCLGA 

       190        200        210        220        230        240 
AKQGPVGNPS SSNQLPPAED TGQKLALETL DELDWCLDQL ETLQTRHSVG EMASNKFKRI 

       250        260        270        280        290        300 
LNRELTHLSE TSRSGNQVSE YISRTFLDQQ TEVELPKVTA EEAPQPMSRI SGLHGLCHSA 

       310        320        330        340        350        360 
SLSSATVPRF GVQTDQEEQL AKELEDTNKW GLDVFKVAEL SGNRPLTAII FSIFQERDLL 

       370        380        390        400        410        420 
KTFQIPADTL ATYLLMLEGH YHANVAYHNS LHAADVAQST HVLLATPALE AVFTDLEILA 

       430        440        450        460        470        480 
ALFASAIHDV DHPGVSNQFL INTNSELALM YNDASVLENH HLAVGFKLLQ AENCDIFQNL 

       490        500        510        520        530        540 
SAKQRLSLRR MVIDMVLATD MSKHMNLLAD LKTMVETKKV TSLGVLLLDN YSDRIQVLQN 

       550        560        570        580        590        600 
LVHCADLSNP TKPLPLYRQW TDRIMAEFFQ QGDRERESGL DISPMCDKHT ASVEKSQVGF 

       610        620        630        640        650        660 
IDYIAHPLWE TWADLVHPDA QDLLDTLEDN REWYQSKIPR SPSDLTNPER DGPDRFQFEL 

       670        680        690        700        710 
TLEEAEEEDE EEEEEGEETA LAKEALELPD TELLSPEAGP DPGDLPLDNQ RT 

« Hide

Isoform PDE4C2 [UniParc].

Checksum: 3C42FC9F237333E1
Show »

FASTA60667,791
Isoform PDE4C3 [UniParc].

Checksum: E555883F32D17B64
Show »

FASTA68075,614
Isoform PDE4C4 (Sequence not available).
Isoform PDE4C5 (Sequence not available).
Isoform PDE4C6 (Sequence not available).
Isoform PDE4C7 (Sequence not available).

References

« Hide 'large scale' references
[1]"Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C)."
Engels P., Sullivan M., Mueller T., Luebbert H.
FEBS Lett. 358:305-310(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4C1).
Tissue: Substantia nigra.
[2]"Genomic organisation of the human cyclic AMP-specific phosphodiesterase PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and JUND."
Sullivan M., Olsen A.S., Houslay M.D.
Cell. Signal. 11:735-742(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS PDE4C1; PDE4C2 AND PDE4C3).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE4C1).
Tissue: Tongue.
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs."
Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K.
Mol. Cell. Biol. 13:6558-6571(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 462-712.
[7]"Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors."
Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J., Ke H.
Biochem. J. 408:193-201(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 306-663 IN COMPLEX WITH METAL IONS, FUNCTION, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z46632 mRNA. Translation: CAA86601.1.
AF157816 expand/collapse EMBL AC list , AF157811, AF157814, AF157815 Genomic DNA. Translation: AAD47053.1.
AF157816 expand/collapse EMBL AC list , AF157812, AF157814, AF157815 Genomic DNA. Translation: AAD47054.1.
AF157816, AF157814, AF157815 Genomic DNA. Translation: AAD47055.1.
AK095384 mRNA. Translation: BAG53036.1.
AC005759 Genomic DNA. Translation: AAC83047.1.
CH471106 Genomic DNA. Translation: EAW84677.1.
L20968 mRNA. Translation: AAA03591.1.
PIRS71626.
RefSeqNP_000914.2. NM_000923.4.
NP_001092288.1. NM_001098818.2.
NP_001092289.1. NM_001098819.2.
UniGeneHs.132584.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LXUmodel-A306-649[»]
2QYMX-ray1.90A306-663[»]
ProteinModelPortalQ08493.
SMRQ08493. Positions 234-640.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111169. 2 interactions.
STRING9606.ENSP00000347689.

Chemistry

BindingDBQ08493.
ChEMBLCHEMBL2095153.
DrugBankDB00651. Dyphylline.
GuidetoPHARMACOLOGY1302.

PTM databases

PhosphoSiteQ08493.

Polymorphism databases

DMDM20141263.

Proteomic databases

PaxDbQ08493.
PRIDEQ08493.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262805; ENSP00000262805; ENSG00000105650. [Q08493-3]
ENST00000355502; ENSP00000347689; ENSG00000105650. [Q08493-1]
ENST00000447275; ENSP00000402091; ENSG00000105650. [Q08493-2]
ENST00000594465; ENSP00000470210; ENSG00000105650. [Q08493-1]
ENST00000594617; ENSP00000469696; ENSG00000105650. [Q08493-1]
GeneID5143.
KEGGhsa:5143.
UCSCuc002nif.4. human. [Q08493-1]
uc002nii.4. human. [Q08493-3]

Organism-specific databases

CTD5143.
GeneCardsGC19M018318.
HGNCHGNC:8782. PDE4C.
HPAHPA048975.
MIM600128. gene.
neXtProtNX_Q08493.
PharmGKBPA264.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG122287.
HOVERGENHBG108239.
InParanoidQ08493.
KOK01120.
OMAGENCDIF.
OrthoDBEOG7HQNBC.
PhylomeDBQ08493.
TreeFamTF314638.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressQ08493.
BgeeQ08493.
CleanExHS_PDE4C.
GenevestigatorQ08493.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ08493.
GeneWikiPDE4C.
GenomeRNAi5143.
NextBio19838.
PROQ08493.
SOURCESearch...

Entry information

Entry namePDE4C_HUMAN
AccessionPrimary (citable) accession number: Q08493
Secondary accession number(s): B3KTC4 expand/collapse secondary AC list , Q9UN44, Q9UN45, Q9UN46, Q9UPJ6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 27, 2002
Last modified: March 19, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM