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Q13946 (PDE7A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A

EC=3.1.4.53
Alternative name(s):
HCP1
TM22
Gene names
Name:PDE7A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length482 AA.
Sequence statusComplete.
Protein existenceEvidence 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: Cytoplasmcytosol. 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 componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandcAMP
Metal-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcAMP catabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_function3',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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 482482High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
PRO_0000198833

Regions

Region187 – 451265Catalytic By similarity
Compositional bias28 – 336Poly-Ser

Sites

Active site2121Proton donor By similarity
Metal binding2161Divalent metal cation 1
Metal binding2521Divalent metal cation 1
Metal binding2531Divalent metal cation 1
Metal binding2531Divalent metal cation 2
Metal binding3621Divalent metal cation 1

Amino acid modifications

Modified residue841Phosphoserine Potential

Natural variations

Alternative sequence1 – 4646MEVCY…RQLSQ → MGITLIWCLALVLIKWITSK in isoform PDE7A2.
VSP_004593
Alternative sequence416 – 4249FMTYLVEPL → NYTYLDIAG in isoform PDE7A3.
VSP_038645
Alternative sequence425 – 48258Missing in isoform PDE7A3.
VSP_038646
Natural variant761G → E.
Corresponds to variant rs11557049 [ dbSNP | Ensembl ].
VAR_056661

Experimental info

Sequence conflict2041D → G in BAF83490. Ref.4

Secondary structure

............................................... 482
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PDE7A1 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 3B3C8F6E9154F88C

FASTA48255,505
        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 

« Hide

Isoform PDE7A2 [UniParc].

Checksum: CAA62B0BFEF074AF
Show »

FASTA45652,725
Isoform PDE7A3 [UniParc].

Checksum: A7DBF40D08A7B561
Show »

FASTA42448,828

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001229247.1. NM_001242318.2.
NP_002594.1. NM_002603.3.
UniGeneHs.527119.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZKLX-ray1.67A130-482[»]
3G3NX-ray2.40A139-456[»]
ProteinModelPortalQ13946.
SMRQ13946. Positions 77-457.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111176. 1 interaction.
IntActQ13946. 1 interaction.
STRING9606.ENSP00000368730.

Chemistry

BindingDBQ13946.
ChEMBLCHEMBL2363066.
DrugBankDB00651. Dyphylline.
DB00920. Ketotifen.
GuidetoPHARMACOLOGY1305.

PTM databases

PhosphoSiteQ13946.

Polymorphism databases

DMDM3182958.

Proteomic databases

PaxDbQ13946.
PRIDEQ13946.

Protocols and materials databases

DNASU5150.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379419; ENSP00000368730; ENSG00000205268. [Q13946-2]
ENST00000396642; ENSP00000379881; ENSG00000205268. [Q13946-3]
ENST00000401827; ENSP00000385632; ENSG00000205268. [Q13946-1]
GeneID5150.
KEGGhsa:5150.
UCSCuc003xvp.3. human. [Q13946-2]
uc003xvq.3. human. [Q13946-1]
uc003xvr.3. human. [Q13946-3]

Organism-specific databases

CTD5150.
GeneCardsGC08M066629.
HGNCHGNC:8791. PDE7A.
HPACAB018770.
HPA027340.
MIM171885. gene.
neXtProtNX_Q13946.
PharmGKBPA33139.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300643.
HOGENOMHOG000220881.
HOVERGENHBG053543.
InParanoidQ13946.
KOK01120.
OMALCDRQTE.
OrthoDBEOG7M98G3.
PhylomeDBQ13946.
TreeFamTF314638.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
UniPathwayUPA00762; UER00747.

Gene expression databases

ArrayExpressQ13946.
BgeeQ13946.
CleanExHS_PDE7A.
GenevestigatorQ13946.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13946.
GeneWikiPDE7A.
GenomeRNAi5150.
NextBio19872.
PROQ13946.
SOURCESearch...

Entry information

Entry namePDE7A_HUMAN
AccessionPrimary (citable) accession number: Q13946
Secondary accession number(s): A0AVH6 expand/collapse secondary AC list , A8K436, A8K9G5, O15380, Q96T72
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM