Reviewed, UniProtKB/Swiss-Prot Q13946 (PDE7A_HUMAN)

Names and origin

Protein names

Recommended name:
    High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
    EC=3.1.4.17
Alternative name(s):
    HCP1
    TM22

Gene names

Name:

PDE7A

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	482 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 is highly specific for cAMP and may have a role in muscle signal transduction.
Catalytic activity	Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.
Cofactor	Divalent cations.
Enzyme regulation	Insensitive to all selective PDE inhibitors.
Pathway	Purine metabolism; cAMP degradation; AMP from cAMP: step 1/1.
Subunit structure	Interacts with CBFA2T3. Ref.6
Subcellular location	Note: PDE7A1 (57 kDa) is located mostly to soluble cellular fractions. PDE7A2 (50 kDa) is located to particulate cellular fractions.
Tissue specificity	PDE7A1 is found at high levels in skeletal muscle and at low levels in a variety of tissues including brain and heart. It is expressed as well in two T-cell lines. PDE7A2 is found abundantly in skeletal muscle and at low levels in heart.
Developmental stage	Developmentally regulated. PDE7A1 and PDE7A2 are found in several fetal tissues, expression is reduced throughout development. It persists strongly only in adult skeletal muscle.
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.

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 Non-traceable author statement. Source: UniProtKB
Cellular component	cell fraction Non-traceable author statement. Source: UniProtKB
Molecular function	3',5'-cyclic-AMP phosphodiesterase activity Ref.1 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform PDE7A1 (identifier: Q13946-1)

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 PDE7A2 (identifier: Q13946-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MEVCYQLPVLPLDRPVPQHVLSRRGAISFSSSSALFGCPNPRQLSQ → MGITLIWCLALVLIKWITSK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 482

482

High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A

PRO_0000198833

Regions

Region

187 – 451

265

Catalytic By similarity

Compositional bias

28 – 33

6

Poly-Ser

Amino acid modifications

Modified residue

84

1

Phosphoserine Potential

Natural variations

Alternative sequence

1 – 46

46

MEVCY…RQLSQ → MGITLIWCLALVLIKWITSK in isoform PDE7A2.

VSP_004593

Natural variant

76

1

G → E: dbSNP rs11557049.

VAR_056661

Secondary structure

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482

Helix Strand Turn

Details...

Helix

140 – 148

9

Turn

149 – 152

4

Helix

158 – 164

7

Helix

169 – 180

12

Helix

183 – 186

4

Helix

191 – 203

13

Beta strand

209 – 213

5

Helix

214 – 228

15

Helix

231 – 234

4

Helix

239 – 251

13

Turn

252 – 255

4

Helix

261 – 266

6

Helix

270 – 274

5

Turn

275 – 277

3

Helix

280 – 296

17

Turn

297 – 301

5

Helix

304 – 319

16

Helix

323 – 325

3

Helix

326 – 339

14

Helix

347 – 362

16

Helix

365 – 367

3

Helix

370 – 393

24

Turn

404 – 406

3

Helix

409 – 419

11

Helix

421 – 431

11

Helix

435 – 453

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE7A1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 3B3C8F6E9154F88C	FASTA	482	55,505
	10 20 30 40 50 60 MEVCYQLPVL PLDRPVPQHV LSRRGAISFS SSSALFGCPN PRQLSQRRGA ISYDSSDQTA 70 80 90 100 110 120 LYIRMLGDVR VRSRAGFESE RRGSHPYIDF RIFHSQSEIE VSVSARNIRR LLSFQRYLRS 130 140 150 160 170 180 SRFFRGTAVS NSLNILDDDY NGQAKCMLEK VGNWNFDIFL FDRLTNGNSL VSLTFHLFSL 190 200 210 220 230 240 HGLIEYFHLD MMKLRRFLVM IQEDYHSQNP YHNAVHAADV TQAMHCYLKE PKLANSVTPW 250 260 270 280 290 300 DILLSLIAAA THDLDHPGVN QPFLIKTNHY LATLYKNTSV LENHHWRSAV GLLRESGLFS 310 320 330 340 350 360 HLPLESRQQM ETQIGALILA TDISRQNEYL SLFRSHLDRG DLCLEDTRHR HLVLQMALKC 370 380 390 400 410 420 ADICNPCRTW ELSKQWSEKV TEEFFHQGDI EKKYHLGVSP LCDRHTESIA NIQIGFMTYL 430 440 450 460 470 480 VEPLFTEWAR FSNTRLSQTM LGHVGLNKAS WKGLQREQSS SEDTDAAFEL NSQLLPQENR LS
	Isoform PDE7A2. Checksum: CAA62B0BFEF074AF	FASTA	456	52,725
	10 20 30 40 50 60 MGITLIWCLA LVLIKWITSK RRGAISYDSS DQTALYIRML GDVRVRSRAG FESERRGSHP 70 80 90 100 110 120 YIDFRIFHSQ SEIEVSVSAR NIRRLLSFQR YLRSSRFFRG TAVSNSLNIL DDDYNGQAKC 130 140 150 160 170 180 MLEKVGNWNF DIFLFDRLTN GNSLVSLTFH LFSLHGLIEY FHLDMMKLRR FLVMIQEDYH 190 200 210 220 230 240 SQNPYHNAVH AADVTQAMHC YLKEPKLANS VTPWDILLSL IAAATHDLDH PGVNQPFLIK 250 260 270 280 290 300 TNHYLATLYK NTSVLENHHW RSAVGLLRES GLFSHLPLES RQQMETQIGA LILATDISRQ 310 320 330 340 350 360 NEYLSLFRSH LDRGDLCLED TRHRHLVLQM ALKCADICNP CRTWELSKQW SEKVTEEFFH 370 380 390 400 410 420 QGDIEKKYHL GVSPLCDRHT ESIANIQIGF MTYLVEPLFT EWARFSNTRL SQTMLGHVGL 430 440 450 NKASWKGLQR EQSSSEDTDA AFELNSQLLP QENRLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae." Michaeli T., Bloom T.J., Martins T., Loughney K., Ferguson K., Riggs M., Rodgers L., Beavo J.A., Wigler M. J. Biol. Chem. 268:12925-12932(1993) [PubMed: 8389765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE7A1).
[2]	"Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart." Han P., Zhu X., Michaeli T. J. Biol. Chem. 272:16152-16157(1997) [PubMed: 9195912] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE7A2). Tissue: Skeletal muscle.
[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. , 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 PDE7A1). Tissue: Thymus.
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] 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 PDE7A2).
[6]	"A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines." Asirvatham A.L., Galligan S.G., Schillace R.V., Davey M.P., Vasta V., Beavo J.A., Carr D.W. J. Immunol. 173:4806-4814(2004) [PubMed: 15470020] [Abstract] Cited for: INTERACTION WITH CBFA2T3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L12052 mRNA. Translation: AAA35644.2.
U67932 mRNA. Translation: AAB65772.1.
AK292680 mRNA. Translation: BAF85369.1.
AC055822 Genomic DNA. No translation available.
AC100812 Genomic DNA. No translation available.
BC126360 mRNA. Translation: AAI26361.1.

IPI

IPI00217833.
IPI00219721.

RefSeq

NP_002594.1.

UniGene

Hs.584788

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZKL	X-ray	1.67	A	130-482	[»]
3G3N	X-ray	2.40	A	139-456	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q13946.

Proteomic databases

PRIDE

Q13946.

Genome annotation databases

Ensembl

ENSG00000205268. Homo sapiens. [Contig view]

GeneID

5150.

UCSC

uc003xvp.1. human.
uc003xvq.1. human.

Organism-specific databases

GeneCards

GC08M066793.

H-InvDB

HIX0007547.

HGNC

HGNC:8791. PDE7A.

MIM

171885. gene.

PharmGKB

PA33139.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13946.

HOVERGEN

Q13946.

OMA

Q13946. SHMPLES.

Enzyme and pathway databases

BRENDA

3.1.4.17. 247.

Gene expression databases

ArrayExpress

Q13946.

Bgee

Q13946.

CleanEx

HS_PDE7A.

GermOnline

ENSG00000205268. 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.
DB00920. Ketotifen.

NextBio

19872.

SOURCE

Search...

Entry information

Entry name

PDE7A_HUMAN

Accession

Primary (citable) accession number: Q13946
Secondary accession number(s): A0AVH6, A8K9G5, O15380

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	July 7, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)