Reviewed, UniProtKB/Swiss-Prot Q08493 (PDE4C_HUMAN)

Names and origin

Protein names

Recommended name:
    cAMP-specific 3',5'-cyclic phosphodiesterase 4C
    EC=3.1.4.17
Alternative name(s):
    DPDE1
    PDE21

Gene names

Name:	PDE4C
Synonyms:	DPDE1

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

General annotation (Comments)

Catalytic activity	Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.
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 various tissues but not in cells of the immune system.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	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 Inferred from Experiment. Source: Reactome
Molecular function	3',5'-cyclic-AMP phosphodiesterase activity Inferred from Experiment. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform PDE4C1 (identifier: Q08493-1)

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 PDE4C2 (identifier: Q08493-2)

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

Isoform PDE4C3 (identifier: Q08493-3)

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

Isoform PDE4C4 (identifier: Q08493-4)

The sequence of this isoform is not available.

Isoform PDE4C5 (identifier: Q08493-5)

The sequence of this isoform is not available.

Isoform PDE4C6 (identifier: Q08493-6)

The sequence of this isoform is not available.

Isoform PDE4C7 (identifier: Q08493-7)

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 712

712

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

PRO_0000198811

Amino acid modifications

Modified residue

164

1

Phosphothreonine Ref.6

Modified residue

646

1

Phosphothreonine Ref.5

Natural variations

Alternative sequence

1 – 106

106

Missing in isoform PDE4C2.

VSP_004575

Alternative sequence

1 – 81

81

MENLG…SSCRR → MQGPPAPAPVPGPGSPRGSP RGSPGLFRKLLVNQSIRLQR RFTVAHPLC in isoform PDE4C3.

VSP_004574

Natural variant

131

1

S → L: dbSNP rs10413646.

VAR_050473

Natural variant

289

1

R → Q: dbSNP rs34503849.

VAR_050474

Natural variant

344

1

R → Q: dbSNP rs2229228.

VAR_034374

Experimental info

Sequence conflict

204

1

K → N in AAD47053. Ref.2

Sequence conflict

204

1

K → N in AAD47054. Ref.2

Sequence conflict

211

1

D → Y in AAD47053. Ref.2

Sequence conflict

211

1

D → Y in AAD47054. Ref.2

Sequence conflict

339 – 340

2

EL → DV in CAA86601. Ref.1

Sequence conflict

444 – 446

3

NSE → K in AAC83047. Ref.3

Sequence conflict

446 – 447

2

EL → DV in CAA86601. Ref.1

Secondary structure

1

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712

Helix Strand Turn

Details...

Helix

307 – 310

4

Helix

314 – 323

10

Helix

324 – 326

3

Helix

334 – 340

7

Turn

341 – 343

3

Helix

345 – 356

12

Helix

359 – 362

4

Helix

367 – 379

13

Beta strand

385 – 389

5

Helix

390 – 404

15

Helix

407 – 409

3

Turn

410 – 412

3

Helix

415 – 427

13

Turn

428 – 431

4

Helix

437 – 442

6

Helix

446 – 450

5

Turn

451 – 453

3

Helix

456 – 467

12

Helix

468 – 470

3

Turn

476 – 479

4

Helix

482 – 497

16

Helix

501 – 503

3

Helix

504 – 516

13

Helix

531 – 546

16

Helix

549 – 551

3

Helix

554 – 577

24

Turn

588 – 590

3

Helix

593 – 603

11

Helix

605 – 615

11

Turn

616 – 620

5

Helix

621 – 636

16

Helix

638 – 640

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE4C1 [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 1932116C9CE0322C	FASTA	712	79,902
	10 20 30 40 50 60 MENLGVGEGA EACSRLSRSR GRHSMTRAPK HLWRQPRRPI RIQQRFYSDP DKSAGCRERD 70 80 90 100 110 120 LSPRPELRKS RLSWPVSSCR RFDLENGLSC GRRALDPQSS PGLGRIMQAP VPHSQRRESF 130 140 150 160 170 180 LYRSDSDYEL SPKAMSRNSS VASDLHGEDM IVTPFAQVLA SLRTVRSNVA ALARQQCLGA 190 200 210 220 230 240 AKQGPVGNPS SSNQLPPAED TGQKLALETL DELDWCLDQL ETLQTRHSVG EMASNKFKRI 250 260 270 280 290 300 LNRELTHLSE TSRSGNQVSE YISRTFLDQQ TEVELPKVTA EEAPQPMSRI SGLHGLCHSA 310 320 330 340 350 360 SLSSATVPRF GVQTDQEEQL AKELEDTNKW GLDVFKVAEL SGNRPLTAII FSIFQERDLL 370 380 390 400 410 420 KTFQIPADTL ATYLLMLEGH YHANVAYHNS LHAADVAQST HVLLATPALE AVFTDLEILA 430 440 450 460 470 480 ALFASAIHDV DHPGVSNQFL INTNSELALM YNDASVLENH HLAVGFKLLQ AENCDIFQNL 490 500 510 520 530 540 SAKQRLSLRR MVIDMVLATD MSKHMNLLAD LKTMVETKKV TSLGVLLLDN YSDRIQVLQN 550 560 570 580 590 600 LVHCADLSNP TKPLPLYRQW TDRIMAEFFQ QGDRERESGL DISPMCDKHT ASVEKSQVGF 610 620 630 640 650 660 IDYIAHPLWE TWADLVHPDA QDLLDTLEDN REWYQSKIPR SPSDLTNPER DGPDRFQFEL 670 680 690 700 710 TLEEAEEEDE EEEEEGEETA LAKEALELPD TELLSPEAGP DPGDLPLDNQ RT
	Isoform PDE4C2. Checksum: 3C42FC9F237333E1	FASTA	606	67,791
	10 20 30 40 50 60 MQAPVPHSQR RESFLYRSDS DYELSPKAMS RNSSVASDLH GEDMIVTPFA QVLASLRTVR 70 80 90 100 110 120 SNVAALARQQ CLGAAKQGPV GNPSSSNQLP PAEDTGQKLA LETLDELDWC LDQLETLQTR 130 140 150 160 170 180 HSVGEMASNK FKRILNRELT HLSETSRSGN QVSEYISRTF LDQQTEVELP KVTAEEAPQP 190 200 210 220 230 240 MSRISGLHGL CHSASLSSAT VPRFGVQTDQ EEQLAKELED TNKWGLDVFK VAELSGNRPL 250 260 270 280 290 300 TAIIFSIFQE RDLLKTFQIP ADTLATYLLM LEGHYHANVA YHNSLHAADV AQSTHVLLAT 310 320 330 340 350 360 PALEAVFTDL EILAALFASA IHDVDHPGVS NQFLINTNSE LALMYNDASV LENHHLAVGF 370 380 390 400 410 420 KLLQAENCDI FQNLSAKQRL SLRRMVIDMV LATDMSKHMN LLADLKTMVE TKKVTSLGVL 430 440 450 460 470 480 LLDNYSDRIQ VLQNLVHCAD LSNPTKPLPL YRQWTDRIMA EFFQQGDRER ESGLDISPMC 490 500 510 520 530 540 DKHTASVEKS QVGFIDYIAH PLWETWADLV HPDAQDLLDT LEDNREWYQS KIPRSPSDLT 550 560 570 580 590 600 NPERDGPDRF QFELTLEEAE EEDEEEEEEG EETALAKEAL ELPDTELLSP EAGPDPGDLP LDNQRT
	Isoform PDE4C3. Checksum: E555883F32D17B64	FASTA	680	75,614
	10 20 30 40 50 60 MQGPPAPAPV PGPGSPRGSP RGSPGLFRKL LVNQSIRLQR RFTVAHPLCF DLENGLSCGR 70 80 90 100 110 120 RALDPQSSPG LGRIMQAPVP HSQRRESFLY RSDSDYELSP KAMSRNSSVA SDLHGEDMIV 130 140 150 160 170 180 TPFAQVLASL RTVRSNVAAL ARQQCLGAAK QGPVGNPSSS NQLPPAEDTG QKLALETLDE 190 200 210 220 230 240 LDWCLDQLET LQTRHSVGEM ASNKFKRILN RELTHLSETS RSGNQVSEYI SRTFLDQQTE 250 260 270 280 290 300 VELPKVTAEE APQPMSRISG LHGLCHSASL SSATVPRFGV QTDQEEQLAK ELEDTNKWGL 310 320 330 340 350 360 DVFKVAELSG NRPLTAIIFS IFQERDLLKT FQIPADTLAT YLLMLEGHYH ANVAYHNSLH 370 380 390 400 410 420 AADVAQSTHV LLATPALEAV FTDLEILAAL FASAIHDVDH PGVSNQFLIN TNSELALMYN 430 440 450 460 470 480 DASVLENHHL AVGFKLLQAE NCDIFQNLSA KQRLSLRRMV IDMVLATDMS KHMNLLADLK 490 500 510 520 530 540 TMVETKKVTS LGVLLLDNYS DRIQVLQNLV HCADLSNPTK PLPLYRQWTD RIMAEFFQQG 550 560 570 580 590 600 DRERESGLDI SPMCDKHTAS VEKSQVGFID YIAHPLWETW ADLVHPDAQD LLDTLEDNRE 610 620 630 640 650 660 WYQSKIPRSP SDLTNPERDG PDRFQFELTL EEAEEEDEEE EEEGEETALA KEALELPDTE 670 680 LLSPEAGPDP GDLPLDNQRT
	Isoform PDE4C4 (Sequence not available).	FASTA	–	–
	Isoform PDE4C5 (Sequence not available).	FASTA	–	–
	Isoform PDE4C6 (Sequence not available).	FASTA	–	–
	Isoform PDE4C7 (Sequence not available).	FASTA	–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C)." Engels P., Sullivan M., Mueller T., Luebbert H. FEBS Lett. 358:305-310(1995) [PubMed: 7843419] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4C1). Tissue: Substantia nigra.
[2]	"Genomic organisation of the human cyclic AMP-specific phosphodiesterase PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and JUND." Sullivan M., Olsen A.S., Houslay M.D. Cell. Signal. 11:735-742(1999) [PubMed: 10574328] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS PDE4C1; PDE4C2 AND PDE4C3).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] OF 462-712.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-646, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-164, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
AC005759 Genomic DNA. Translation: AAC83047.1.
L20968 mRNA. Translation: AAA03591.1.

IPI

IPI00298070.
IPI00328206.
IPI00472785.

PIR

S71626.

RefSeq

NP_000914.2.

UniGene

Hs.132584

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LXU	model	-	A	306-649	[»]
2QYM	X-ray	1.90	A	306-663	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q08493.

PTM databases

PhosphoSite

Q08493.

Proteomic databases

PRIDE

Q08493.

Genome annotation databases

Ensembl

ENST00000262805; ENSP00000262805; ENSG00000105650; Homo sapiens. [Genome view]
ENST00000336173; ENSP00000336624; ENSG00000105650; Homo sapiens. [Genome view]
ENST00000355502; ENSP00000347689; ENSG00000105650; Homo sapiens. [Genome view]
ENST00000447275; ENSP00000402091; ENSG00000105650; Homo sapiens. [Genome view]

GeneID

5143.

KEGG

hsa:5143.

UCSC

uc002nik.2. human.

Organism-specific databases

CTD

5143.

GeneCards

GC19M018181.

H-InvDB

HIX0014907.

HGNC

HGNC:8782. PDE4C.

MIM

600128. gene.

PharmGKB

PA264.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q08493.

OMA

AIMFSIF.

Enzyme and pathway databases

BRENDA

3.1.4.17. 247.

Reactome

REACT_14797. Signaling by GPCR.
REACT_15295. Opioid Signalling.

Gene expression databases

ArrayExpress

Q08493.

Bgee

Q08493.

CleanEx

HS_PDE4C.

Genevestigator

Q08493.

GermOnline

ENSG00000105650. Homo sapiens.

Family and domain databases

InterPro

IPR003607. Met-dep_phosphohydro_HD.
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

DB00651. Dyphylline.

NextBio

19838.

SOURCE

Search...

Entry information

Entry name

PDE4C_HUMAN

Accession

Primary (citable) accession number: Q08493
Secondary accession number(s): Q9UN44 , Q9UN45, Q9UN46, Q9UPJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	March 27, 2002
Last modified:	November 3, 2009
This is version 85 of the entry and version 2 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.