Reviewed, UniProtKB/Swiss-Prot O60658 (PDE8A_HUMAN)

Names and origin

Protein names

Recommended name:
    High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
    EC=3.1.4.17

Gene names

Name:

PDE8A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	829 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase, which has a high affinity for cAMP, 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	Divalent cations. Magnesium or manganese yield for maximum activity, in vitro.
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; cAMP degradation; AMP from cAMP: 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. Contains 1 PAC (PAS-associated C-terminal) domain. Contains 1 PAS (PER-ARNT-SIM) domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Manganese Metal-binding cAMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cAMP catabolic process Inferred from electronic annotation. Source: InterPro regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro two-component signal transduction system (phosphorelay) Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	3',5'-cyclic-nucleotide phosphodiesterase activity Ref.3 Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW two-component response regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 829

829

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

PRO_0000198838

Regions

Domain

213 – 283

71

PAS

Domain

287 – 329

43

PAC

Region

531 – 813

283

Catalytic By similarity

Sites

Metal binding

556

1

Magnesium or manganese 1 Potential

Metal binding

560

1

Magnesium or manganese 1 Potential

Metal binding

585

1

Magnesium or manganese 1 Potential

Metal binding

596

1

Magnesium or manganese 2 Potential

Metal binding

600

1

Magnesium or manganese 2 Potential

Metal binding

626

1

Magnesium or manganese 2 Potential

Amino acid modifications

Modified residue

20

1

Phosphoserine Ref.5

Modified residue

386

1

Phosphoserine Ref.6

Modified residue

407

1

Phosphoserine Ref.5

Modified residue

457

1

Phosphoserine Ref.5 Ref.6

Natural variations

Alternative sequence

1 – 380

380

Missing in isoform 3.

VSP_004596

Alternative sequence

1 – 247

247

Missing in isoform 4-5.

VSP_004595

Alternative sequence

239 – 284

46

Missing in isoform 2.

VSP_004597

Experimental info

Sequence conflict

344

1

H → R in AAC39763. Ref.3

Sequence conflict

399

1

I → V in AAC39763. Ref.3

Secondary structure

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829

Helix Strand Turn

Details...

Helix

484 – 491

8

Helix

492 – 494

3

Helix

502 – 508

7

Turn

509 – 511

3

Helix

513 – 524

12

Helix

527 – 530

4

Helix

535 – 547

13

Beta strand

553 – 557

5

Helix

558 – 572

15

Helix

575 – 577

3

Turn

578 – 580

3

Helix

583 – 595

13

Turn

596 – 599

4

Helix

605 – 610

6

Helix

614 – 618

5

Turn

619 – 621

3

Helix

624 – 635

12

Beta strand

638 – 642

5

Turn

645 – 648

4

Helix

651 – 666

16

Helix

670 – 672

3

Beta strand

673 – 675

3

Turn

679 – 681

3

Helix

688 – 690

3

Helix

691 – 696

6

Helix

711 – 726

16

Helix

729 – 731

3

Helix

734 – 757

24

Turn

769 – 771

3

Helix

774 – 784

11

Helix

786 – 796

11

Helix

801 – 807

7

Turn

808 – 811

4

Helix

814 – 817

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PDE8A1) [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 99BD05EA185A42CD	FASTA	829	93,304
	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
	Isoform 2 (PDE8A2). Checksum: 67BB1FBE670D7EFE	FASTA	783	88,293
	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 TSEDRFIQEW 250 260 270 280 290 300 QGIYYAKKKN GDNIQQNVKI IPVIGQGGKI RHYVSIIRVC NGNNKAEKIS ECVQSDTHTD 310 320 330 340 350 360 NQTGKHKDRR KGSLDVKAVA SRATEVSSQR RHSSMARIHS MTIEAPITKV INIINAAQES 370 380 390 400 410 420 SPMPVTEALD RVLEILRTTE LYSPQFGAKD DDPHANDLVG GLMSDGLRRL SGNEYVLSTK 430 440 450 460 470 480 NTQMVSSNII TPISLDDVPP RIARAMENEE YWDFDIFELE AATHNRPLIY LGLKMFARFG 490 500 510 520 530 540 ICEFLHCSES TLRSWLQIIE ANYHSSNPYH NSTHSADVLH ATAYFLSKER IKETLDPIDE 550 560 570 580 590 600 VAALIAATIH DVDHPGRTNS FLCNAGSELA ILYNDTAVLE SHHAALAFQL TTGDDKCNIF 610 620 630 640 650 660 KNMERNDYRT LRQGIIDMVL ATEMTKHFEH VNKFVNSINK PLATLEENGE TDKNQEVINT 670 680 690 700 710 720 MLRTPENRTL IKRMLIKCAD VSNPCRPLQY CIEWAARISE EYFSQTDEEK QQGLPVVMPV 730 740 750 760 770 780 FDRNTCSIPK SQISFIDYFI TDMFDAWDAF VDLPDLMQHL DNNFKYWKGL DEMKLRNLRP PPE
	Isoform 3 (PDE8A3). Checksum: 585A7C35597FAFF9	FASTA	449	51,254
	10 20 30 40 50 60 MARIHSMTIE APITKVINII NAAQESSPMP VTEALDRVLE ILRTTELYSP QFGAKDDDPH 70 80 90 100 110 120 ANDLVGGLMS DGLRRLSGNE YVLSTKNTQM VSSNIITPIS LDDVPPRIAR AMENEEYWDF 130 140 150 160 170 180 DIFELEAATH NRPLIYLGLK MFARFGICEF LHCSESTLRS WLQIIEANYH SSNPYHNSTH 190 200 210 220 230 240 SADVLHATAY FLSKERIKET LDPIDEVAAL IAATIHDVDH PGRTNSFLCN AGSELAILYN 250 260 270 280 290 300 DTAVLESHHA ALAFQLTTGD DKCNIFKNME RNDYRTLRQG IIDMVLATEM TKHFEHVNKF 310 320 330 340 350 360 VNSINKPLAT LEENGETDKN QEVINTMLRT PENRTLIKRM LIKCADVSNP CRPLQYCIEW 370 380 390 400 410 420 AARISEEYFS QTDEEKQQGL PVVMPVFDRN TCSIPKSQIS FIDYFITDMF DAWDAFVDLP 430 440 DLMQHLDNNF KYWKGLDEMK LRNLRPPPE
	Isoform 4-5 (PDE8A4) (PDE8A5). Checksum: D9B28D458CC0582B	FASTA	582	66,013
	10 20 30 40 50 60 MGYQSGELIG KELGEVPINE KKADLLDTIN SCIRIGKEWQ GIYYAKKKNG DNIQQNVKII 70 80 90 100 110 120 PVIGQGGKIR HYVSIIRVCN GNNKAEKISE CVQSDTHTDN QTGKHKDRRK GSLDVKAVAS 130 140 150 160 170 180 RATEVSSQRR HSSMARIHSM TIEAPITKVI NIINAAQESS PMPVTEALDR VLEILRTTEL 190 200 210 220 230 240 YSPQFGAKDD DPHANDLVGG LMSDGLRRLS GNEYVLSTKN TQMVSSNIIT PISLDDVPPR 250 260 270 280 290 300 IARAMENEEY WDFDIFELEA ATHNRPLIYL GLKMFARFGI CEFLHCSEST LRSWLQIIEA 310 320 330 340 350 360 NYHSSNPYHN STHSADVLHA TAYFLSKERI KETLDPIDEV AALIAATIHD VDHPGRTNSF 370 380 390 400 410 420 LCNAGSELAI LYNDTAVLES HHAALAFQLT TGDDKCNIFK NMERNDYRTL RQGIIDMVLA 430 440 450 460 470 480 TEMTKHFEHV NKFVNSINKP LATLEENGET DKNQEVINTM LRTPENRTLI KRMLIKCADV 490 500 510 520 530 540 SNPCRPLQYC IEWAARISEE YFSQTDEEKQ QGLPVVMPVF DRNTCSIPKS QISFIDYFIT 550 560 570 580 DMFDAWDAFV DLPDLMQHLD NNFKYWKGLD EMKLRNLRPP PE

References

	« Hide 'large scale' referencesShow '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]	"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.
[3]	"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).
[4]	The European IMAGE consortium Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 554-829.
[5]	"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.
[6]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
AF056490 mRNA. Translation: AAC39763.1.
BC075822 mRNA. Translation: AAH75822.1.
AL109687 mRNA. Translation: CAB52020.1.
AL109778 mRNA. Translation: CAB52432.1.

IPI

IPI00030976.
IPI00182447.
IPI00218161.
IPI00218162.

PIR

JW0088.

RefSeq

NP_002596.1.

UniGene

Hs.9333

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LHQ	model	-	A	482-821	[»]
1LXX	model	-	A	488-821	[»]
3ECM	X-ray	1.90	A	482-819	[»]
3ECN	X-ray	2.10	A/B	482-819	[»]

ModBase

Search...

PTM databases

PhosphoSite

O60658.

Proteomic databases

PRIDE

O60658.

Genome annotation databases

Ensembl

ENSG00000073417. Homo sapiens. [Contig view]

GeneID

5151.

KEGG

hsa:5151.

Organism-specific databases

GeneCards

GC15P083324.

H-InvDB

HIX0012539.

HGNC

HGNC:8793. PDE8A.

HPA

HPA007722.

MIM

602972. gene.

PharmGKB

PA33141.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O60658.

OMA

O60658. MERNDYR.

Enzyme and pathway databases

BRENDA

3.1.4.17. 247.

Gene expression databases

ArrayExpress

O60658.

Bgee

O60658.

CleanEx

HS_PDE8A.

GermOnline

ENSG00000073417. Homo sapiens.

Family and domain databases

InterPro

IPR003607. Met-dep_phosphohydro_HD.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR002073. PDEase.
IPR013938. PDEase_PDE8.
IPR001789. Sig_transdc_resp-reg_receiver.
[Graphical view]

Pfam

PF00989. PAS. 1 hit.
PF08629. PDE8. 1 hit.
PF00233. PDEase_I. 1 hit.
PF00072. Response_reg. 1 hit.
[Graphical view]

PRINTS

PR00387. PDIESTERASE1.

SMART

SM00471. HDc. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00229. sensory_box. 1 hit.

PROSITE

PS50113. PAC. False negative.
PS50112. PAS. 1 hit.
PS00126. PDEASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

19878.

SOURCE

Search...

Entry information

Entry name

PDE8A_HUMAN

Accession

Primary (citable) accession number: O60658
Secondary accession number(s): Q969I1 , Q96PC9, Q96PD0, Q96PD1, Q9UMB7, Q9UMC3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	September 19, 2002
Last modified:	May 5, 2009
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)