Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A

Gene

Pde8a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development. Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling. Protects against cell death induced by hydrogen peroxide and staurosporine.By similarity

Catalytic activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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.By similarity

Activity regulationi

Inhibited by dipyridimole. Insensitive to selective PDE inhibitor rolipram and to the non-selective inhibitor, IBMX.

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 4D (Pde4d), 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), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (Pde7a), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (Pde10a), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (Pde7b), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (Pde4a), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (Pde4c)
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 sitei551Proton donorBy similarity1
Metal bindingi555Divalent metal cation 1; via tele nitrogenBy similarity1
Metal bindingi591Divalent metal cation 1; via tele nitrogenBy similarity1
Metal bindingi592Divalent metal cation 1By similarity1
Metal bindingi592Divalent metal cation 2By similarity1
Metal bindingi720Divalent metal cation 1By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandcAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53 3474
ReactomeiR-MMU-418555 G alpha (s) signalling events
UniPathwayi
UPA00762;UER00747

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC:3.1.4.53)
Short name:
MmPDE8
Gene namesi
Name:Pde8a
Synonyms:Pde8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1277116 Pde8a

Pathology & Biotechi

Disruption phenotypei

Reduced phosphorylation of Mapk1/Erk2 and Mapk3/Erk1, both basal levels and those induced by EGF treatment.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988391 – 823High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8AAdd BLAST823

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei355Phosphoserine; by PKABy similarity1
Modified residuei382PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei456PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-355 by PKA under elevated cAMP conditions, this enhances catalytic activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO88502
PaxDbiO88502
PeptideAtlasiO88502
PRIDEiO88502

PTM databases

iPTMnetiO88502
PhosphoSitePlusiO88502

Expressioni

Tissue specificityi

Highest levels in testis > eye > liver > skeletal muscle > heart > 7-day embryo > kidney > ovary > brain. In the testis, expressed specifically in the seminiferous epithelium in a spatial and temporal manner.

Developmental stagei

Levels of expression decrease sometime between embryo day 7 and day 11. In the testis, expression restricted to middle and late pachytene spermatocytes.

Gene expression databases

BgeeiENSMUSG00000025584 Expressed in 257 organ(s), highest expression level in testis
CleanExiMM_PDE8A
GenevisibleiO88502 MM

Interactioni

Subunit structurei

Interacts with RAF1. The interaction promotes RAF1 activity.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202082, 1 interactor
STRINGi10090.ENSMUSP00000026672

Structurei

3D structure databases

ProteinModelPortaliO88502
SMRiO88502
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 280PASPROSITE-ProRule annotationAdd BLAST72
Domaini283 – 325PACAdd BLAST43
Domaini475 – 814PDEasePROSITE-ProRule annotationAdd BLAST340

Domaini

Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1229 Eukaryota
ENOG410XP9B LUCA
GeneTreeiENSGT00760000118889
HOVERGENiHBG053544
InParanoidiO88502
KOiK18437
OMAiHYVSISR
OrthoDBiEOG091G0337
PhylomeDBiO88502
TreeFamiTF314638

Family and domain databases

CDDicd00077 HDc, 1 hit
cd00130 PAS, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF13426 PAS_9, 1 hit
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
SUPFAMiSSF55785 SSF55785, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50112 PAS, 1 hit
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

Sequencei

Sequence statusi: Complete.

O88502-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGCAPSIHTS ENRTFSHSDG EDEDVDVDVP GPAPRSIQRW STAPGLVEPQ
60 70 80 90 100
PRDNGASKVS VADVQFGPMR FHQDQLQVLL VFTKEDSQCN GFHRACEKAG
110 120 130 140 150
FKCTVTKEVQ TVLTCFQDKL HDIIIIDHRY PRQMDAETLC RSIRSSKFSE
160 170 180 190 200
NTVIVGVVRR VDKEESSLMP FLAAGFTRRF IENPNVMACY NELLQLACGE
210 220 230 240 250
VRSQLKLRAC NSVFTALEKS QEAIEITSED HIIQYANPAF ESTMGYQSGE
260 270 280 290 300
LIGKELAQVP INEKKGDLLD AINSCVTVDK EWQGVYHTQK KNGDNIQQNV
310 320 330 340 350
KIIPVIGQGG KIRHYVSIIR VCNGNNKVET TTECVQTDSQ TDNQAGKHKD
360 370 380 390 400
RRKHSMDAKA VSSRTSDVSS QRRHSSLARI HSMMIEAPIT KVINIINAAQ
410 420 430 440 450
ENSPVPVTEA LNRVLDILRT TELYSPQFNA QDDPHATDLV GGLMSDGLRR
460 470 480 490 500
FSGNEYILAT KNLPPLSNNL ATPVSLHDVP PRIALAIENE EQWDFDIFEL
510 520 530 540 550
EVATQNRPLI YLGLKTFARF GMCEFLQCSE TTLRSWFQMI ESNYHSSNPY
560 570 580 590 600
HNSTHAADVL HATAYFLSRD KIKETLDRID EVAALIAATV HDVDHPGRTN
610 620 630 640 650
SFLCNAGNQL AVLYNDTAVL ESHHVALAFQ LTLENDQCNI FKQMERNDYR
660 670 680 690 700
TLRQSIIDMV LATEMTKHFE HVNKFINSIN KPLTAQESEE PDRSLEDIKA
710 720 730 740 750
MLKTPESRAL IKRMMIKCAD VSNPCRPLEH CIEWAARISE EYFSQTDEEK
760 770 780 790 800
QLDLPVVMPV FDRNTCSIPK SQISFIDYFI TDMFDAWDAF VDLPNLMQHL
810 820
DDNFRYWKGL DEKKLRSLRP PPE
Length:823
Mass (Da):93,171
Last modified:November 1, 1998 - v1
Checksum:i7FD9BE4BAEB9BCF2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF067806 mRNA Translation: AAC40194.1
BC125578 mRNA Translation: AAI25579.1
BC132145 mRNA Translation: AAI32146.1
CCDSiCCDS40005.1
RefSeqiNP_032829.1, NM_008803.2
UniGeneiMm.371577

Genome annotation databases

EnsembliENSMUST00000026672; ENSMUSP00000026672; ENSMUSG00000025584
GeneIDi18584
KEGGimmu:18584
UCSCiuc009ibt.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF067806 mRNA Translation: AAC40194.1
BC125578 mRNA Translation: AAI25579.1
BC132145 mRNA Translation: AAI32146.1
CCDSiCCDS40005.1
RefSeqiNP_032829.1, NM_008803.2
UniGeneiMm.371577

3D structure databases

ProteinModelPortaliO88502
SMRiO88502
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202082, 1 interactor
STRINGi10090.ENSMUSP00000026672

PTM databases

iPTMnetiO88502
PhosphoSitePlusiO88502

Proteomic databases

MaxQBiO88502
PaxDbiO88502
PeptideAtlasiO88502
PRIDEiO88502

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026672; ENSMUSP00000026672; ENSMUSG00000025584
GeneIDi18584
KEGGimmu:18584
UCSCiuc009ibt.1 mouse

Organism-specific databases

CTDi5151
MGIiMGI:1277116 Pde8a

Phylogenomic databases

eggNOGiKOG1229 Eukaryota
ENOG410XP9B LUCA
GeneTreeiENSGT00760000118889
HOVERGENiHBG053544
InParanoidiO88502
KOiK18437
OMAiHYVSISR
OrthoDBiEOG091G0337
PhylomeDBiO88502
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayi
UPA00762;UER00747

BRENDAi3.1.4.53 3474
ReactomeiR-MMU-418555 G alpha (s) signalling events

Miscellaneous databases

ChiTaRSiPde8a mouse
PROiPR:O88502
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025584 Expressed in 257 organ(s), highest expression level in testis
CleanExiMM_PDE8A
GenevisibleiO88502 MM

Family and domain databases

CDDicd00077 HDc, 1 hit
cd00130 PAS, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF13426 PAS_9, 1 hit
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
SUPFAMiSSF55785 SSF55785, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50112 PAS, 1 hit
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDE8A_MOUSE
AccessioniPrimary (citable) accession number: O88502
Secondary accession number(s): Q059P6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: November 7, 2018
This is version 156 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again