Q13946 (PDE7A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	482 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 have a role in muscle signal transduction. Ref.9
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. Ref.9
Enzyme regulation	Insensitive to all selective PDE inhibitors.
Pathway	Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Subunit structure	Interacts with CBFA2T3. Ref.7
Subcellular location	Isoform PDE7A1: Cytoplasm › cytosol. Note: PDE7A1 (57 kDa) is located mostly to soluble cellular fractions. Isoform PDE7A2: Cytoplasm. Note: 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. PDE7 subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding cAMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cAMP catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway signal transduction Non-traceable author statement. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	3',5'-cyclic-AMP phosphodiesterase activity Traceable author statement Ref.1. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 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

Isoform PDE7A3 (identifier: Q13946-3)

The sequence of this isoform differs from the canonical sequence as follows:
     416-424: FMTYLVEPL → NYTYLDIAG
     425-482: Missing.

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

Sites

Active site

212

1

Proton donor By similarity

Metal binding

216

1

Divalent metal cation 1

Metal binding

252

1

Divalent metal cation 1

Metal binding

253

1

Divalent metal cation 1

Metal binding

253

1

Divalent metal cation 2

Metal binding

362

1

Divalent metal cation 1

Amino acid modifications

Modified residue

84

1

Phosphoserine Potential

Natural variations

Alternative sequence

1 – 46

46

MEVCY…RQLSQ → MGITLIWCLALVLIKWITSK in isoform PDE7A2.

VSP_004593

Alternative sequence

416 – 424

9

FMTYLVEPL → NYTYLDIAG in isoform PDE7A3.

VSP_038645

Alternative sequence

425 – 482

58

Missing in isoform PDE7A3.

VSP_038646

Natural variant

76

1

G → E.
Corresponds to variant rs11557049 [ dbSNP | Ensembl ].

VAR_056661

Experimental info

Sequence conflict

204

1

D → G in BAF83490. Ref.4

Secondary structure

1

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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 [UniParc]. 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
	Isoform PDE7A3 [UniParc]. Checksum: A7DBF40D08A7B561	FASTA	424	48,828
	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 NIQIGNYTYL DIAG

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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE7A2). Tissue: Skeletal muscle.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE7A3).
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE7A1). Tissue: Kidney and Thymus.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE7A2).
[7]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBFA2T3.
[8]	"Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide phosphodiesterases 4 and 7." Wang H., Liu Y., Chen Y., Robinson H., Ke H. J. Biol. Chem. 280:30949-30955(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 130-482 IN COMPLEX WITH METAL IONS AND THE INHIBITOR IBMX.
[9]	"Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors." Castano T., Wang H., Campillo N.E., Ballester S., Gonzalez-Garcia C., Hernandez J., Perez C., Cuenca J., Perez-Castillo A., Martinez A., Huertas O., Gelpi J.L., Luque F.J., Ke H., Gil C. ChemMedChem 4:866-876(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 139-456 IN COMPLEX WITH METAL IONS, FUNCTION, COFACTOR.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L12052 mRNA. Translation: AAA35644.2.
U67932 mRNA. Translation: AAB65772.1.
AF332652 mRNA. Translation: AAK57640.1.
AK290801 mRNA. Translation: BAF83490.1.
AK292680 mRNA. Translation: BAF85369.1.
AC055822 Genomic DNA. No translation available.
AC100812 Genomic DNA. No translation available.
BC126360 mRNA. Translation: AAI26361.1.

IPI

IPI00183153.
IPI00217833.
IPI00219721.

RefSeq

NP_001229247.1. NM_001242318.2.
NP_002594.1. NM_002603.3.

UniGene

Hs.527119.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q13946.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13946. 1 interaction.

STRING

9606.ENSP00000368730.

PTM databases

PhosphoSite

Q13946.

Polymorphism databases

DMDM

3182958.

Proteomic databases

PaxDb

Q13946.

PRIDE

Q13946.

Protocols and materials databases

DNASU

5150.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379419; ENSP00000368730; ENSG00000205268.
ENST00000396642; ENSP00000379881; ENSG00000205268.
ENST00000401827; ENSP00000385632; ENSG00000205268.

GeneID

5150.

KEGG

hsa:5150.

UCSC

uc003xvp.3. human.
uc003xvq.3. human.
uc003xvr.3. human.

Organism-specific databases

CTD

5150.

GeneCards

GC08M066629.

HGNC

HGNC:8791. PDE7A.

HPA

CAB018770.
HPA027340.

MIM

171885. gene.

neXtProt

NX_Q13946.

PharmGKB

PA33139.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300643.

HOGENOM

HOG000220881.

HOVERGEN

HBG053543.

InParanoid

Q13946.

KO

K01120.

OMA

SHMPLES.

OrthoDB

EOG48KRBC.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

UniPathway

UPA00762; UER00747.

Gene expression databases

ArrayExpress

Q13946.

Bgee

Q13946.

CleanEx

HS_PDE7A.

Genevestigator

Q13946.

GermOnline

ENSG00000205268. Homo sapiens.

Family and domain databases

Gene3D

1.10.1300.10. 1 hit.

InterPro

IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[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

BindingDB

Q13946.

ChEMBL

CHEMBL3012.

DrugBank

DB00651. Dyphylline.
DB00920. Ketotifen.

EvolutionaryTrace

Q13946.

GenomeRNAi

5150.

NextBio

19872.

SOURCE

Search...

Entry information

Entry name

PDE7A_HUMAN

Accession

Primary (citable) accession number: Q13946
Secondary accession number(s): A0AVH6 , A8K436, A8K9G5, O15380, Q96T72

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.