Reviewed, UniProtKB/Swiss-Prot Q07343 (PDE4B_HUMAN)

Names and origin

Protein names

Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4B
    EC=3.1.4.17
Alternative name(s):
    DPDE4
    PDE32

Gene names

Name:	PDE4B
Synonyms:	DPDE4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence 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 mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
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 rolipram.
Pathway	Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Tissue specificity	Expressed in brain, heart, lung and skeletal muscle.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding cAMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Ref.2 Inferred from Experiment. Source: Reactome insoluble fraction Ref.2 Traceable author statement. Source: ProtInc soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	3',5'-cyclic-AMP phosphodiesterase activity Ref.2 Inferred from Experiment. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform PDE4B1 (identifier: Q07343-1)

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 PDE4B2 (identifier: Q07343-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-211: MKKSRSVMTV...QPPVSRVNPQ → MKKEHGGTFS...PNYMPVCLFA

Isoform PDE4B3 (identifier: Q07343-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MKKSRSVMTV...SIAITTVSQE → MTAKDSSKEL...QRRRFTVAHT

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 736

736

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

PRO_0000198809

Regions

Nucleotide binding

406 – 410

5

cAMP

Sites

Active site

406

1

Proton donor

Metal binding

410

1

Divalent metal cation 1

Metal binding

446

1

Divalent metal cation 1

Metal binding

447

1

Divalent metal cation 1

Metal binding

447

1

Divalent metal cation 2

Metal binding

564

1

Divalent metal cation 1

Binding site

447

1

cAMP

Binding site

564

1

cAMP

Binding site

615

1

cAMP

Site

567

1

Binds AMP, but not cAMP By similarity

Amino acid modifications

Modified residue

184

1

Phosphothreonine By similarity

Modified residue

272

1

Phosphoserine By similarity

Modified residue

274

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

1 – 211

211

MKKSR…RVNPQ → MKKEHGGTFSSTGISGGSGD SAMDSLQPLQPNYMPVCLFA in isoform PDE4B2.

VSP_004572

Alternative sequence

1 – 93

93

MKKSR…TVSQE → MTAKDSSKELTASEPEVCIK TFKEQMHLELELPRLPGNRP TSPKISPRSSPRNSPCFFRK LLVNKSIRQRRRFTVAHT in isoform PDE4B3.

VSP_004571

Natural variant

703

1

S → C: dbSNP rs2227297.

VAR_034373

Secondary structure

1

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736

Helix Strand Turn

Details...

Turn

325 – 329

5

Helix

332 – 341

10

Helix

342 – 344

3

Helix

352 – 358

7

Helix

363 – 374

12

Helix

377 – 380

4

Helix

385 – 397

13

Beta strand

403 – 407

5

Helix

408 – 422

15

Helix

425 – 427

3

Turn

428 – 430

3

Helix

433 – 445

13

Turn

446 – 449

4

Helix

455 – 460

6

Helix

464 – 468

5

Turn

469 – 471

3

Helix

474 – 485

12

Helix

486 – 488

3

Turn

494 – 497

4

Helix

500 – 515

16

Helix

519 – 521

3

Helix

522 – 534

13

Helix

549 – 564

16

Helix

567 – 569

3

Helix

572 – 595

24

Turn

606 – 608

3

Helix

611 – 621

11

Helix

623 – 634

12

Turn

635 – 638

4

Helix

639 – 655

17

Helix

671 – 677

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE4B1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 208FCE9CD40EF5EB	FASTA	736	83,343
	10 20 30 40 50 60 MKKSRSVMTV MADDNVKDYF ECSLSKSYSS SSNTLGIDLW RGRRCCSGNL QLPPLSQRQS 70 80 90 100 110 120 ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG PSPGRSPLDP QASSSAGLVL 130 140 150 160 170 180 HATFPGHSQR RESFLYRSDS DYDLSPKAMS RNSSLPSEQH GDDLIVTPFA QVLASLRSVR 190 200 210 220 230 240 NNFTILTNLH GTSNKRSPAA SQPPVSRVNP QEESYQKLAM ETLEELDWCL DQLETIQTYR 250 260 270 280 290 300 SVSEMASNKF KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK 310 320 330 340 350 360 KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL NIFNVAGYSH 370 380 390 400 410 420 NRPLTCIMYA IFQERDLLKT FRISSDTFIT YMMTLEDHYH SDVAYHNSLH AADVAQSTHV 430 440 450 460 470 480 LLSTPALDAV FTDLEILAAI FAAAIHDVDH PGVSNQFLIN TNSELALMYN DESVLENHHL 490 500 510 520 530 540 AVGFKLLQEE HCDIFMNLTK KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS 550 560 570 580 590 600 SGVLLLDNYT DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI 610 620 630 640 650 660 SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN WYQSMIPQSP 670 680 690 700 710 720 SPPLDEQNRD CQGLMEKFQF ELTLDEEDSE GPEKEGEGHS YFSSTKTLCV IDPENRDSLG 730 ETDIDIATED KSPVDT
	Isoform PDE4B2. Checksum: 5087570D9EB3711E	FASTA	565	64,480
	10 20 30 40 50 60 MKKEHGGTFS STGISGGSGD SAMDSLQPLQ PNYMPVCLFA EESYQKLAME TLEELDWCLD 70 80 90 100 110 120 QLETIQTYRS VSEMASNKFK RMLNRELTHL SEMSRSGNQV SEYISNTFLD KQNDVEIPSP 130 140 150 160 170 180 TQKDREKKKK QQLMTQISGV KKLMHSSSLN NTSISRFGVN TENEDHLAKE LEDLNKWGLN 190 200 210 220 230 240 IFNVAGYSHN RPLTCIMYAI FQERDLLKTF RISSDTFITY MMTLEDHYHS DVAYHNSLHA 250 260 270 280 290 300 ADVAQSTHVL LSTPALDAVF TDLEILAAIF AAAIHDVDHP GVSNQFLINT NSELALMYND 310 320 330 340 350 360 ESVLENHHLA VGFKLLQEEH CDIFMNLTKK QRQTLRKMVI DMVLATDMSK HMSLLADLKT 370 380 390 400 410 420 MVETKKVTSS GVLLLDNYTD RIQVLRNMVH CADLSNPTKS LELYRQWTDR IMEEFFQQGD 430 440 450 460 470 480 KERERGMEIS PMCDKHTASV EKSQVGFIDY IVHPLWETWA DLVQPDAQDI LDTLEDNRNW 490 500 510 520 530 540 YQSMIPQSPS PPLDEQNRDC QGLMEKFQFE LTLDEEDSEG PEKEGEGHSY FSSTKTLCVI 550 560 DPENRDSLGE TDIDIATEDK SPVDT
	Isoform PDE4B3. Checksum: 49618FFEAFF33D30	FASTA	721	82,096
	10 20 30 40 50 60 MTAKDSSKEL TASEPEVCIK TFKEQMHLEL ELPRLPGNRP TSPKISPRSS PRNSPCFFRK 70 80 90 100 110 120 LLVNKSIRQR RRFTVAHTCF DVENGPSPGR SPLDPQASSS AGLVLHATFP GHSQRRESFL 130 140 150 160 170 180 YRSDSDYDLS PKAMSRNSSL PSEQHGDDLI VTPFAQVLAS LRSVRNNFTI LTNLHGTSNK 190 200 210 220 230 240 RSPAASQPPV SRVNPQEESY QKLAMETLEE LDWCLDQLET IQTYRSVSEM ASNKFKRMLN 250 260 270 280 290 300 RELTHLSEMS RSGNQVSEYI SNTFLDKQND VEIPSPTQKD REKKKKQQLM TQISGVKKLM 310 320 330 340 350 360 HSSSLNNTSI SRFGVNTENE DHLAKELEDL NKWGLNIFNV AGYSHNRPLT CIMYAIFQER 370 380 390 400 410 420 DLLKTFRISS DTFITYMMTL EDHYHSDVAY HNSLHAADVA QSTHVLLSTP ALDAVFTDLE 430 440 450 460 470 480 ILAAIFAAAI HDVDHPGVSN QFLINTNSEL ALMYNDESVL ENHHLAVGFK LLQEEHCDIF 490 500 510 520 530 540 MNLTKKQRQT LRKMVIDMVL ATDMSKHMSL LADLKTMVET KKVTSSGVLL LDNYTDRIQV 550 560 570 580 590 600 LRNMVHCADL SNPTKSLELY RQWTDRIMEE FFQQGDKERE RGMEISPMCD KHTASVEKSQ 610 620 630 640 650 660 VGFIDYIVHP LWETWADLVQ PDAQDILDTL EDNRNWYQSM IPQSPSPPLD EQNRDCQGLM 670 680 690 700 710 720 EKFQFELTLD EEDSEGPEKE GEGHSYFSST KTLCVIDPEN RDSLGETDID IATEDKSPVD T

References

[1]	"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: 8413254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE4B1 AND PDE4B2). Tissue: Brain.
[2]	"Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3." Huston E., Lumb S., Russell A., Catterall C., Ross A.H., Steele M.R., Bolger G.B., Perry M.J., Owens R.J., Houslay M.D. Biochem. J. 328:549-558(1997) [PubMed: 9371714] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B3).
[3]	"A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA." McLaughlin M.M., Cieslinski L.B., Burman M., Torphy T.J., Livi G.P. J. Biol. Chem. 268:6470-6476(1993) [PubMed: 8384210] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B2). Tissue: Brain.
[4]	"Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity." Xu R.X., Hassell A.M., Vanderwall D., Lambert M.H., Holmes W.D., Luther M.A., Rocque W.J., Milburn M.V., Zhao Y., Ke H., Nolte R.T. Science 288:1822-1825(2000) [PubMed: 10846163] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS, FUNCTION, COFACTOR.
[5]	"Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram." Xu R.X., Rocque W.J., Lambert M.H., Vanderwall D.E., Luther M.A., Nolte R.T. J. Mol. Biol. 337:355-365(2004) [PubMed: 15003452] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP; METAL IONS AND THE INHIBITOR ROLIPRAM, FUNCTION, COFACTOR.
[6]	"A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases." Zhang K.Y.J., Card G.L., Suzuki Y., Artis D.R., Fong D., Gillette S., Hsieh D., Neiman J., West B.L., Zhang C., Milburn M.V., Kim S.-H., Schlessinger J., Bollag G. Mol. Cell 15:279-286(2004) [PubMed: 15260978] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP AND METAL IONS.
[7]	"Structural basis for the activity of drugs that inhibit phosphodiesterases." Card G.L., England B.P., Suzuki Y., Fong D., Powell B., Lee B., Luu C., Tabrizizad M., Gillette S., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J. Structure 12:2233-2247(2004) [PubMed: 15576036] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[8]	"A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design." Card G.L., Blasdel L., England B.P., Zhang C., Suzuki Y., Gillette S., Fong D., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J. Nat. Biotechnol. 23:201-207(2005) [PubMed: 15685167] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 324-700 IN COMPLEX WITH METAL IONS AND INHIBITORS.
[9]	"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: 17727341] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 324-659 IN COMPLEX WITH METAL IONS AND THE INHIBITOR NVP.
[10]	"Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors." Hamblin J.N., Angell T.D.R., Ballantine S.P., Cook C.M., Cooper A.W.J., Dawson J., Delves C.J., Jones P.S., Lindvall M., Lucas F.S., Mitchell C.J., Neu M.Y., Ranshaw L.E., Solanke Y.E., Somers D.O., Wiseman J.O. Bioorg. Med. Chem. Lett. 18:4237-4241(2008) [PubMed: 18539455] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 324-675 IN COMPLEX WITH METAL IONS AND INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L20966 mRNA. Translation: AAA03589.1.
L20971 mRNA. Translation: AAA03593.1.
M97515 mRNA. Translation: AAA36426.1.
U85048 mRNA. Translation: AAB96381.1.

IPI

IPI00016604.
IPI00183599.
IPI00220621.

PIR

I61354.

RefSeq

NP_001032416.1.
NP_001032417.1.
NP_001032418.1.
NP_002591.2.

UniGene

Hs.198072

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F0J	X-ray	1.77	A/B	324-700	[»]
1JP1	model	-	A	324-700	[»]
1JP2	model	-	A	324-700	[»]
1RO6	X-ray	2.00	A/B	324-700	[»]
1RO9	X-ray	2.13	A/B	324-700	[»]
1ROR	X-ray	2.00	A/B	324-700	[»]
1TB5	X-ray	2.15	A/B	324-700	[»]
1XLX	X-ray	2.19	A/B	324-700	[»]
1XLZ	X-ray	2.06	A/B	324-700	[»]
1XM4	X-ray	2.31	A/B	324-700	[»]
1XM6	X-ray	1.92	A/B	324-700	[»]
1XMU	X-ray	2.30	A/B	324-700	[»]
1XMY	X-ray	2.40	A/B	324-700	[»]
1XN0	X-ray	2.31	A/B	324-700	[»]
1XOS	X-ray	2.28	A	324-700	[»]
1XOT	X-ray	2.34	A/B	324-700	[»]
1Y2H	X-ray	2.40	A/B	324-700	[»]
1Y2J	X-ray	2.55	A/B	324-700	[»]
2CHM	X-ray	1.60	A	450-475	[»]
2QYL	X-ray	1.95	A	324-659	[»]
3D3P	X-ray	1.75	A	324-675	[»]
3HC8	X-ray	1.79	A	451-474	[»]
3HDZ	X-ray	1.80	A	451-474	[»]
3KKT	X-ray	2.48	A/B	324-700	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q07343. 3 interactions.

STRING

Q07343.

PTM databases

PhosphoSite

Q07343.

Proteomic databases

PRIDE

Q07343.

Genome annotation databases

Ensembl

ENST00000329654; ENSP00000332116; ENSG00000184588; Homo sapiens. [Genome view]
ENST00000371049; ENSP00000360088; ENSG00000184588; Homo sapiens. [Genome view]

GeneID

5142.

KEGG

hsa:5142.

UCSC

uc001dcn.1. human.

Organism-specific databases

CTD

5142.

GeneCards

GC01P065970.

H-InvDB

HIX0000677.

HGNC

HGNC:8781. PDE4B.

HPA

HPA003005.

MIM

600127. gene.

PharmGKB

PA33129.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14687.

HOGENOM

HBG315913.

HOVERGEN

Q07343.

InParanoid

Q07343.

OMA

GEGHNYF.

OrthoDB

EOG9BK7PW.

PhylomeDB

Q07343.

Enzyme and pathway databases

BRENDA

3.1.4.17. 247.

Reactome

REACT_14797. Signaling by GPCR.
REACT_15295. Opioid Signalling.

Gene expression databases

ArrayExpress

Q07343.

Bgee

Q07343.

CleanEx

HS_PDE4B.

Genevestigator

Q07343.

GermOnline

ENSG00000184588. Homo sapiens.

Family and domain databases

InterPro

IPR003607. Metal-dep_PHydrolase_HD_dom.
IPR002073. PDEase.
[Graphical view]

Pfam

PF00233. PDEase_I. 1 hit.
[Graphical view]

PRINTS

PR00387. PDIESTERASE1.

SMART

SM00471. HDc. 1 hit.
[Graphical view]

PROSITE

PS00126. PDEASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00131. Adenosine monophosphate.
DB01427. Amrinone.
DB00201. Caffeine.
DB01166. Cilostazol.
DB00651. Dyphylline.
DB00824. Enprofylline.
DB01113. Papaverine.
DB00806. Pentoxifylline.
DB00277. Theophylline.

NextBio

19828.

SOURCE

Search...

Entry information

Entry name

PDE4B_HUMAN

Accession

Primary (citable) accession number: Q07343
Secondary accession number(s): O15443

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	February 9, 2010
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.