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Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4C

Gene

PDE4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.1 Publication

Catalytic activityi

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

Cofactori

a divalent metal cation1 PublicationNote: 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.1 Publication

Enzyme regulationi

Inhibited by rolipram.

Pathwayi: 3',5'-cyclic AMP degradation

This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)
This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei388Proton donorBy similarity1
Metal bindingi392Divalent metal cation 11
Metal bindingi428Divalent metal cation 11
Metal bindingi429Divalent metal cation 11
Metal bindingi429Divalent metal cation 21
Binding sitei429cAMPBy similarity1
Metal bindingi546Divalent metal cation 11
Binding sitei546cAMPBy similarity1
Sitei549Binds AMP, but not cAMPBy similarity1
Binding sitei597cAMPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi388 – 392cAMPBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02781-MONOMER.
BRENDAi3.1.4.53. 2681.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-418555. G alpha (s) signalling events.
SIGNORiQ08493.
UniPathwayiUPA00762; UER00747.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4C (EC:3.1.4.53)
Alternative name(s):
DPDE1
PDE21
Gene namesi
Name:PDE4C
Synonyms:DPDE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:8782. PDE4C.

Subcellular locationi

GO - Cellular componenti

  • cilium Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000105650.
PharmGKBiPA264.

Chemistry databases

ChEMBLiCHEMBL291.
DrugBankiDB00201. Caffeine.
DB00651. Dyphylline.
DB05266. Ibudilast.
DB01088. Iloprost.
DB00920. Ketotifen.
DB01656. Roflumilast.
GuidetoPHARMACOLOGYi1302.

Polymorphism and mutation databases

BioMutaiPDE4C.
DMDMi20141263.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988111 – 712cAMP-specific 3',5'-cyclic phosphodiesterase 4CAdd BLAST712

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei73PhosphoserineBy similarity1
Modified residuei641PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ08493.
PeptideAtlasiQ08493.
PRIDEiQ08493.

PTM databases

iPTMnetiQ08493.
PhosphoSitePlusiQ08493.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000105650.
CleanExiHS_PDE4C.
ExpressionAtlasiQ08493. baseline and differential.
GenevisibleiQ08493. HS.

Organism-specific databases

HPAiHPA048975.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
SRIP306263EBI-10225541,EBI-750459

Protein-protein interaction databases

BioGridi111169. 1 interactor.
IntActiQ08493. 4 interactors.
STRINGi9606.ENSP00000347689.

Chemistry databases

BindingDBiQ08493.

Structurei

Secondary structure

1712
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi317 – 323Combined sources7
Helixi324 – 326Combined sources3
Helixi334 – 340Combined sources7
Helixi345 – 356Combined sources12
Helixi359 – 362Combined sources4
Helixi367 – 379Combined sources13
Beta strandi385 – 389Combined sources5
Helixi390 – 404Combined sources15
Helixi407 – 409Combined sources3
Turni410 – 412Combined sources3
Helixi415 – 427Combined sources13
Turni428 – 431Combined sources4
Helixi435 – 437Combined sources3
Helixi456 – 467Combined sources12
Helixi468 – 470Combined sources3
Turni476 – 479Combined sources4
Helixi482 – 497Combined sources16
Helixi501 – 503Combined sources3
Helixi504 – 516Combined sources13
Helixi531 – 546Combined sources16
Helixi549 – 551Combined sources3
Helixi554 – 569Combined sources16
Helixi600 – 603Combined sources4
Helixi605 – 616Combined sources12
Turni617 – 620Combined sources4
Helixi621 – 630Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LXUmodel-A306-649[»]
2QYMX-ray1.90A306-663[»]
ProteinModelPortaliQ08493.
SMRiQ08493.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08493.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG108239.
KOiK13293.
OMAiEDTNRWG.
OrthoDBiEOG091G06CD.
PhylomeDBiQ08493.
TreeFamiTF314638.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PDE4C1 (identifier: Q08493-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MENLGVGEGA EACSRLSRSR GRHSMTRAPK HLWRQPRRPI RIQQRFYSDP
60 70 80 90 100
DKSAGCRERD LSPRPELRKS RLSWPVSSCR RFDLENGLSC GRRALDPQSS
110 120 130 140 150
PGLGRIMQAP VPHSQRRESF LYRSDSDYEL SPKAMSRNSS VASDLHGEDM
160 170 180 190 200
IVTPFAQVLA SLRTVRSNVA ALARQQCLGA AKQGPVGNPS SSNQLPPAED
210 220 230 240 250
TGQKLALETL DELDWCLDQL ETLQTRHSVG EMASNKFKRI LNRELTHLSE
260 270 280 290 300
TSRSGNQVSE YISRTFLDQQ TEVELPKVTA EEAPQPMSRI SGLHGLCHSA
310 320 330 340 350
SLSSATVPRF GVQTDQEEQL AKELEDTNKW GLDVFKVAEL SGNRPLTAII
360 370 380 390 400
FSIFQERDLL KTFQIPADTL ATYLLMLEGH YHANVAYHNS LHAADVAQST
410 420 430 440 450
HVLLATPALE AVFTDLEILA ALFASAIHDV DHPGVSNQFL INTNSELALM
460 470 480 490 500
YNDASVLENH HLAVGFKLLQ AENCDIFQNL SAKQRLSLRR MVIDMVLATD
510 520 530 540 550
MSKHMNLLAD LKTMVETKKV TSLGVLLLDN YSDRIQVLQN LVHCADLSNP
560 570 580 590 600
TKPLPLYRQW TDRIMAEFFQ QGDRERESGL DISPMCDKHT ASVEKSQVGF
610 620 630 640 650
IDYIAHPLWE TWADLVHPDA QDLLDTLEDN REWYQSKIPR SPSDLTNPER
660 670 680 690 700
DGPDRFQFEL TLEEAEEEDE EEEEEGEETA LAKEALELPD TELLSPEAGP
710
DPGDLPLDNQ RT
Length:712
Mass (Da):79,902
Last modified:March 27, 2002 - v2
Checksum:i1932116C9CE0322C
GO
Isoform PDE4C2 (identifier: Q08493-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.

Show »
Length:606
Mass (Da):67,791
Checksum:i3C42FC9F237333E1
GO
Isoform PDE4C3 (identifier: Q08493-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: MENLGVGEGA...LSWPVSSCRR → MQGPPAPAPV...RRFTVAHPLC

Show »
Length:680
Mass (Da):75,614
Checksum:iE555883F32D17B64
GO
Isoform PDE4C4 (identifier: Q08493-4)
Sequence is not available
Length:
Mass (Da):
Isoform PDE4C5 (identifier: Q08493-5)
Sequence is not available
Length:
Mass (Da):
Isoform PDE4C6 (identifier: Q08493-6)
Sequence is not available
Length:
Mass (Da):
Isoform PDE4C7 (identifier: Q08493-7)
Sequence is not available
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204K → N in AAD47053 (PubMed:10574328).Curated1
Sequence conflicti204K → N in AAD47054 (PubMed:10574328).Curated1
Sequence conflicti211D → Y in AAD47053 (PubMed:10574328).Curated1
Sequence conflicti211D → Y in AAD47054 (PubMed:10574328).Curated1
Sequence conflicti339 – 340EL → DV in CAA86601 (PubMed:7843419).Curated2
Sequence conflicti444 – 446NSE → K in AAC83047 (PubMed:15057824).Curated3
Sequence conflicti446 – 447EL → DV in CAA86601 (PubMed:7843419).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050473131S → L.Corresponds to variant rs10413646dbSNPEnsembl.1
Natural variantiVAR_050474289R → Q.Corresponds to variant rs34503849dbSNPEnsembl.1
Natural variantiVAR_034374344R → Q.Corresponds to variant rs2229228dbSNPEnsembl.1
Natural variantiVAR_061497344R → W.Corresponds to variant rs11879710dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045751 – 106Missing in isoform PDE4C2. CuratedAdd BLAST106
Alternative sequenceiVSP_0045741 – 81MENLG…SSCRR → MQGPPAPAPVPGPGSPRGSP RGSPGLFRKLLVNQSIRLQR RFTVAHPLC in isoform PDE4C3. CuratedAdd BLAST81

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46632 mRNA. Translation: CAA86601.1.
AF157816
, AF157811, AF157814, AF157815 Genomic DNA. Translation: AAD47053.1.
AF157816
, 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.
CCDSiCCDS12373.1. [Q08493-1]
CCDS42523.1. [Q08493-3]
CCDS46016.1. [Q08493-2]
PIRiS71626.
RefSeqiNP_000914.2. NM_000923.5. [Q08493-1]
NP_001092288.1. NM_001098818.3. [Q08493-3]
NP_001092289.1. NM_001098819.3. [Q08493-2]
NP_001317101.1. NM_001330172.1.
XP_011526358.1. XM_011528056.2. [Q08493-2]
UniGeneiHs.132584.

Genome annotation databases

EnsembliENST00000262805; ENSP00000262805; ENSG00000105650. [Q08493-3]
ENST00000355502; ENSP00000347689; ENSG00000105650. [Q08493-1]
ENST00000447275; ENSP00000402091; ENSG00000105650. [Q08493-2]
ENST00000594465; ENSP00000470210; ENSG00000105650. [Q08493-1]
ENST00000594617; ENSP00000469696; ENSG00000105650. [Q08493-1]
GeneIDi5143.
KEGGihsa:5143.
UCSCiuc002nii.5. human. [Q08493-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46632 mRNA. Translation: CAA86601.1.
AF157816
, AF157811, AF157814, AF157815 Genomic DNA. Translation: AAD47053.1.
AF157816
, 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.
CCDSiCCDS12373.1. [Q08493-1]
CCDS42523.1. [Q08493-3]
CCDS46016.1. [Q08493-2]
PIRiS71626.
RefSeqiNP_000914.2. NM_000923.5. [Q08493-1]
NP_001092288.1. NM_001098818.3. [Q08493-3]
NP_001092289.1. NM_001098819.3. [Q08493-2]
NP_001317101.1. NM_001330172.1.
XP_011526358.1. XM_011528056.2. [Q08493-2]
UniGeneiHs.132584.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LXUmodel-A306-649[»]
2QYMX-ray1.90A306-663[»]
ProteinModelPortaliQ08493.
SMRiQ08493.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111169. 1 interactor.
IntActiQ08493. 4 interactors.
STRINGi9606.ENSP00000347689.

Chemistry databases

BindingDBiQ08493.
ChEMBLiCHEMBL291.
DrugBankiDB00201. Caffeine.
DB00651. Dyphylline.
DB05266. Ibudilast.
DB01088. Iloprost.
DB00920. Ketotifen.
DB01656. Roflumilast.
GuidetoPHARMACOLOGYi1302.

PTM databases

iPTMnetiQ08493.
PhosphoSitePlusiQ08493.

Polymorphism and mutation databases

BioMutaiPDE4C.
DMDMi20141263.

Proteomic databases

PaxDbiQ08493.
PeptideAtlasiQ08493.
PRIDEiQ08493.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262805; ENSP00000262805; ENSG00000105650. [Q08493-3]
ENST00000355502; ENSP00000347689; ENSG00000105650. [Q08493-1]
ENST00000447275; ENSP00000402091; ENSG00000105650. [Q08493-2]
ENST00000594465; ENSP00000470210; ENSG00000105650. [Q08493-1]
ENST00000594617; ENSP00000469696; ENSG00000105650. [Q08493-1]
GeneIDi5143.
KEGGihsa:5143.
UCSCiuc002nii.5. human. [Q08493-1]

Organism-specific databases

CTDi5143.
GeneCardsiPDE4C.
HGNCiHGNC:8782. PDE4C.
HPAiHPA048975.
MIMi600128. gene.
neXtProtiNX_Q08493.
OpenTargetsiENSG00000105650.
PharmGKBiPA264.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689. Eukaryota.
ENOG410XRI7. LUCA.
GeneTreeiENSGT00760000118889.
HOVERGENiHBG108239.
KOiK13293.
OMAiEDTNRWG.
OrthoDBiEOG091G06CD.
PhylomeDBiQ08493.
TreeFamiTF314638.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.
BioCyciZFISH:HS02781-MONOMER.
BRENDAi3.1.4.53. 2681.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-418555. G alpha (s) signalling events.
SIGNORiQ08493.

Miscellaneous databases

EvolutionaryTraceiQ08493.
GeneWikiiPDE4C.
GenomeRNAii5143.
PROiQ08493.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105650.
CleanExiHS_PDE4C.
ExpressionAtlasiQ08493. baseline and differential.
GenevisibleiQ08493. HS.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDE4C_HUMAN
AccessioniPrimary (citable) accession number: Q08493
Secondary accession number(s): B3KTC4
, Q9UN44, Q9UN45, Q9UN46, Q9UPJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 27, 2002
Last modified: November 30, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.