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Reviewed, UniProtKB/Swiss-Prot O60658 (PDE8A_HUMAN)

Last modified January 19, 2010. Version 107. 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

Names and origin

Protein namesRecommended name:
    High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
    EC=3.1.4.17
Gene names
Name: PDE8A
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length829 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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.

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.

Enzyme regulation

Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and zaprinast as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP.

Pathway

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

Tissue specificity

Expressed in most tissues except thymus and peripheral blood leukocytes. Highest levels in testis, ovary, small intestine and colon.

Domain

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

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 1 PAS (PER-ARNT-SIM) domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60658-1)

Also known as: PDE8A1;

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: O60658-2)

Also known as: PDE8A2;

The sequence of this isoform differs from the canonical sequence as follows:
     239-284: Missing.
Isoform 3 (identifier: O60658-3)

Also known as: PDE8A3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-380: Missing.
Isoform 4-5 (identifier: O60658-4)

Also known as: PDE8A4; PDE8A5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-247: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 829829High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
PRO_0000198838

Regions

Domain213 – 28371PAS
Domain287 – 32943PAC
Region531 – 813283Catalytic By similarity

Sites

Active site5561Proton donor By similarity
Metal binding5601Divalent metal cation 1
Metal binding5961Divalent metal cation 1
Metal binding5971Divalent metal cation 1
Metal binding5971Divalent metal cation 2
Metal binding7261Divalent metal cation 1

Amino acid modifications

Modified residue201Phosphoserine Ref.8
Modified residue3861Phosphoserine Ref.9
Modified residue4071Phosphoserine Ref.8
Modified residue4571Phosphoserine Ref.8 Ref.9

Natural variations

Alternative sequence1 – 380380Missing in isoform 3.
VSP_004596
Alternative sequence1 – 247247Missing in isoform 4-5.
VSP_004595
Alternative sequence239 – 28446Missing in isoform 2.
VSP_004597

Experimental info

Mutagenesis7481Y → F: Increases sensitivity to several nonselective or family selective PDE inhibitors.
Sequence conflict551L → V in AAK57641. Ref.2
Sequence conflict1121E → G in AAH60762. Ref.5
Sequence conflict3441H → R in AAK57641. Ref.2
Sequence conflict3441H → R in AAC39763. Ref.6
Sequence conflict3991I → V in AAK57641. Ref.2
Sequence conflict3991I → V in AAC39763. Ref.6

Secondary structure

............................................................ 829
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE8A1) [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 99BD05EA185A42CD

FASTA82993,304
        10         20         30         40         50         60 
MGCAPSIHIS ERLVAEDAPS PAAPPLSSGG PRLPQGQKTA ALPRTRGAGL LESELRDGSG 

        70         80         90        100        110        120 
KKVAVADVQF GPMRFHQDQL QVLLVFTKED NQCNGFCRAC EKAGFKCTVT KEAQAVLACF 

       130        140        150        160        170        180 
LDKHHDIIII DHRNPRQLDA EALCRSIRSS KLSENTVIVG VVRRVDREEL SVMPFISAGF 

       190        200        210        220        230        240 
TRRYVENPNI MACYNELLQL EFGEVRSQLK LRACNSVFTA LENSEDAIEI TSEDRFIQYA 

       250        260        270        280        290        300 
NPAFETTMGY QSGELIGKEL GEVPINEKKA DLLDTINSCI RIGKEWQGIY YAKKKNGDNI 

       310        320        330        340        350        360 
QQNVKIIPVI GQGGKIRHYV SIIRVCNGNN KAEKISECVQ SDTHTDNQTG KHKDRRKGSL 

       370        380        390        400        410        420 
DVKAVASRAT EVSSQRRHSS MARIHSMTIE APITKVINII NAAQESSPMP VTEALDRVLE 

       430        440        450        460        470        480 
ILRTTELYSP QFGAKDDDPH ANDLVGGLMS DGLRRLSGNE YVLSTKNTQM VSSNIITPIS 

       490        500        510        520        530        540 
LDDVPPRIAR AMENEEYWDF DIFELEAATH NRPLIYLGLK MFARFGICEF LHCSESTLRS 

       550        560        570        580        590        600 
WLQIIEANYH SSNPYHNSTH SADVLHATAY FLSKERIKET LDPIDEVAAL IAATIHDVDH 

       610        620        630        640        650        660 
PGRTNSFLCN AGSELAILYN DTAVLESHHA ALAFQLTTGD DKCNIFKNME RNDYRTLRQG 

       670        680        690        700        710        720 
IIDMVLATEM TKHFEHVNKF VNSINKPLAT LEENGETDKN QEVINTMLRT PENRTLIKRM 

       730        740        750        760        770        780 
LIKCADVSNP CRPLQYCIEW AARISEEYFS QTDEEKQQGL PVVMPVFDRN TCSIPKSQIS 

       790        800        810        820 
FIDYFITDMF DAWDAFVDLP DLMQHLDNNF KYWKGLDEMK LRNLRPPPE 

« Hide

Isoform 2 (PDE8A2).

Checksum: 67BB1FBE670D7EFE
Show »

FASTA78388,293
Isoform 3 (PDE8A3).

Checksum: 585A7C35597FAFF9
Show »

FASTA44951,254
Isoform 4-5 (PDE8A4) (PDE8A5).

Checksum: D9B28D458CC0582B
Show »

FASTA58266,013

References

« Hide 'large scale' references
[1]"Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution."
Wang P., Wu P., Egan R.W., Billah M.M.
Gene 280:183-194(2001) [PubMed: 11738832] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4-5).
Tissue: Testis.
[2]"T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3."
Glavas N.A., Ostenson C., Schaefer J.B., Vasta V., Beavo J.A.
Proc. Natl. Acad. Sci. U.S.A. 98:6319-6324(2001) [PubMed: 11371644] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Hippocampus.
[4]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].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver and Placenta.
[6]"Isolation and characterization of PDE8A, a novel human cAMP-specific phosphodiesterase."
Fisher D.A., Smith J.F., Pillar J.S., St Denis S.H., Cheng J.B.
Biochem. Biophys. Res. Commun. 246:570-577(1998) [PubMed: 9618252] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 117-829 (ISOFORMS 1 AND 2).
[7]The European IMAGE consortium
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 554-829.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20; SER-407 AND SER-457, MASS SPECTROMETRY.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386 AND SER-457, MASS SPECTROMETRY.
[10]"Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity."
Wang H., Yan Z., Yang S., Cai J., Robinson H., Ke H.
Biochemistry 47:12760-12768(2008) [PubMed: 18983167] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 482-819 IN COMPLEX WITH METAL IONS AND THE INHIBITOR IBMX, FUNCTION, COFACTOR, MUTAGENESIS OF TYR-748.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF388183 mRNA. Translation: AAL18610.1.
AF388184 mRNA. Translation: AAL18611.1.
AF388185 mRNA. Translation: AAL18612.1.
AF388186 mRNA. Translation: AAL18613.1.
AF388187 mRNA. Translation: AAL18614.1.
AF332653 mRNA. Translation: AAK57641.1.
AK127232 mRNA. Translation: BAG54458.1.
CH471101 Genomic DNA. Translation: EAX01967.1.
BC060762 mRNA. Translation: AAH60762.1.
BC075822 mRNA. Translation: AAH75822.1.
AF056490 mRNA. Translation: AAC39763.1.
AL109687 mRNA. Translation: CAB52020.1.
AL109778 mRNA. Translation: CAB52432.1.
IPIIPI00030976.
IPI00182447.
IPI00218161.
IPI00218162.
PIRJW0088.
RefSeqNP_002596.1.
NP_775656.1.
UniGeneHs.9333

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LHQmodel-A482-821[»]
1LXXmodel-A488-821[»]
3ECMX-ray1.90A482-819[»]
3ECNX-ray2.10A/B482-819[»]
SMRO60658. Positions 205-324.
ModBaseSearch...

Protein-protein interaction databases

STRINGO60658.

PTM databases

PhosphoSiteO60658.

Proteomic databases

PRIDEO60658.

Genome annotation databases

EnsemblENST00000310298; ENSP00000311453; ENSG00000073417; Homo sapiens. [Genome view]
ENST00000394553; ENSP00000378056; ENSG00000073417; Homo sapiens. [Genome view]
GeneID5151.
KEGGhsa:5151.
UCSCuc002blh.1. human.
uc002bli.1. human.

Organism-specific databases

CTD5151.
GeneCardsGC15P083324.
H-InvDBHIX0012539.
HGNCHGNC:8793. PDE8A.
HPAHPA007722.
MIM602972. gene.
PharmGKBPA33141.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG18615.
HOVERGENO60658.
InParanoidO60658.
OMADKHHDII.
OrthoDBEOG9THZC7.
PhylomeDBO60658.

Enzyme and pathway databases

BRENDA3.1.4.17. 247.
ReactomeREACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpressO60658.
BgeeO60658.
CleanExHS_PDE8A.
GenevestigatorO60658.
GermOnlineENSG00000073417. Homo sapiens.

Family and domain databases

InterProIPR003607. Metal-dep_PHydrolase_HD_dom.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR002073. PDEase.
IPR001789. Sig_transdc_resp-reg_receiver.
[Graphical view]
PfamPF00989. PAS. 1 hit.
PF00233. PDEase_I. 1 hit.
PF00072. Response_reg. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]
PROSITEPS50113. PAC. False negative.
PS50112. PAS. 1 hit.
PS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio19878.
SOURCESearch...

Entry information

Entry namePDE8A_HUMAN
AccessionPrimary (citable) accession number: O60658
Secondary accession number(s): B3KXE6 expand/collapse secondary AC list , Q6P9H3, Q969I1, Q96PC9, Q96PD0, Q96PD1, Q96T71, Q9UMB7, Q9UMC3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2002
Last modified: January 19, 2010
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents