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Protein

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

Gene

PDE7A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.1 Publication

Catalytic activityi

Adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate.

Cofactori

a divalent metal cation1 PublicationNote: 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.1 Publication

Activity regulationi

Insensitive to all selective PDE inhibitors.

Pathwayi: 3',5'-cyclic AMP degradation

This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A)
This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei212Proton donorBy similarity1
Metal bindingi216Divalent metal cation 11
Metal bindingi252Divalent metal cation 11
Metal bindingi253Divalent metal cation 11
Metal bindingi253Divalent metal cation 21
Metal bindingi362Divalent metal cation 11

GO - Molecular functioni

  • 3',5'-cyclic-AMP phosphodiesterase activity Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandcAMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.53 2681
ReactomeiR-HSA-418555 G alpha (s) signalling events
UniPathwayi
UPA00762;UER00747

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (EC:3.1.4.53)
Alternative name(s):
HCP1
TM22
Gene namesi
Name:PDE7A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000205268.10
HGNCiHGNC:8791 PDE7A
MIMi171885 gene
neXtProtiNX_Q13946

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi5150
OpenTargetsiENSG00000205268
PharmGKBiPA33139

Chemistry databases

ChEMBLiCHEMBL3012
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine
DB00651 Dyphylline
GuidetoPHARMACOLOGYi1305

Polymorphism and mutation databases

BioMutaiPDE7A
DMDMi3182958

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988331 – 482High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7AAdd BLAST482

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei84PhosphoserineSequence analysis1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13946
MaxQBiQ13946
PaxDbiQ13946
PeptideAtlasiQ13946
PRIDEiQ13946
ProteomicsDBi59762
59763 [Q13946-2]
59764 [Q13946-3]

PTM databases

iPTMnetiQ13946
PhosphoSitePlusiQ13946

Expressioni

Tissue specificityi

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 stagei

Developmentally regulated. PDE7A1 and PDE7A2 are found in several fetal tissues, expression is reduced throughout development. It persists strongly only in adult skeletal muscle.

Gene expression databases

BgeeiENSG00000205268 Expressed in 198 organ(s), highest expression level in secondary oocyte
CleanExiHS_PDE7A
ExpressionAtlasiQ13946 baseline and differential
GenevisibleiQ13946 HS

Organism-specific databases

HPAiCAB018770
HPA027340

Interactioni

Subunit structurei

Interacts with CBFA2T3.3 Publications

Protein-protein interaction databases

BioGridi111176, 5 interactors
IntActiQ13946, 1 interactor
STRINGi9606.ENSP00000385632

Chemistry databases

BindingDBiQ13946

Structurei

Secondary structure

1482
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13946
SMRiQ13946
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13946

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini136 – 458PDEasePROSITE-ProRule annotationAdd BLAST323

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi28 – 33Poly-Ser6

Domaini

Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000118889
HOGENOMiHOG000220881
HOVERGENiHBG053543
KOiK18436
OMAiHFILQMA
OrthoDBiEOG091G05SK
PhylomeDBiQ13946
TreeFamiTF314638

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform PDE7A1 (identifier: Q13946-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MEVCYQLPVL PLDRPVPQHV LSRRGAISFS SSSALFGCPN PRQLSQRRGA
60 70 80 90 100
ISYDSSDQTA LYIRMLGDVR VRSRAGFESE RRGSHPYIDF RIFHSQSEIE
110 120 130 140 150
VSVSARNIRR LLSFQRYLRS SRFFRGTAVS NSLNILDDDY NGQAKCMLEK
160 170 180 190 200
VGNWNFDIFL FDRLTNGNSL VSLTFHLFSL HGLIEYFHLD MMKLRRFLVM
210 220 230 240 250
IQEDYHSQNP YHNAVHAADV TQAMHCYLKE PKLANSVTPW DILLSLIAAA
260 270 280 290 300
THDLDHPGVN QPFLIKTNHY LATLYKNTSV LENHHWRSAV GLLRESGLFS
310 320 330 340 350
HLPLESRQQM ETQIGALILA TDISRQNEYL SLFRSHLDRG DLCLEDTRHR
360 370 380 390 400
HLVLQMALKC ADICNPCRTW ELSKQWSEKV TEEFFHQGDI EKKYHLGVSP
410 420 430 440 450
LCDRHTESIA NIQIGFMTYL VEPLFTEWAR FSNTRLSQTM LGHVGLNKAS
460 470 480
WKGLQREQSS SEDTDAAFEL NSQLLPQENR LS
Length:482
Mass (Da):55,505
Last modified:July 15, 1998 - v2
Checksum:i3B3C8F6E9154F88C
GO
Isoform PDE7A2 (identifier: Q13946-2) [UniParc]FASTAAdd to basket

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

Show »
Length:456
Mass (Da):52,725
Checksum:iCAA62B0BFEF074AF
GO
Isoform PDE7A3 (identifier: Q13946-3) [UniParc]FASTAAdd to basket

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

Show »
Length:424
Mass (Da):48,828
Checksum:iA7DBF40D08A7B561
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RG23E5RG23_HUMAN
High affinity cAMP-specific 3',5'-c...
PDE7A
85Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204D → G in BAF83490 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05666176G → E. Corresponds to variant dbSNP:rs11557049Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045931 – 46MEVCY…RQLSQ → MGITLIWCLALVLIKWITSK in isoform PDE7A2. 2 PublicationsAdd BLAST46
Alternative sequenceiVSP_038645416 – 424FMTYLVEPL → NYTYLDIAG in isoform PDE7A3. 1 Publication9
Alternative sequenceiVSP_038646425 – 482Missing in isoform PDE7A3. 1 PublicationAdd BLAST58

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34901.1 [Q13946-2]
CCDS56538.1 [Q13946-1]
RefSeqiNP_001229247.1, NM_001242318.2 [Q13946-1]
NP_002594.1, NM_002603.3 [Q13946-2]
XP_011515842.1, XM_011517540.2 [Q13946-2]
UniGeneiHs.527119

Genome annotation databases

EnsembliENST00000379419; ENSP00000368730; ENSG00000205268 [Q13946-2]
ENST00000396642; ENSP00000379881; ENSG00000205268 [Q13946-3]
ENST00000401827; ENSP00000385632; ENSG00000205268 [Q13946-1]
GeneIDi5150
KEGGihsa:5150
UCSCiuc003xvp.4 human [Q13946-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34901.1 [Q13946-2]
CCDS56538.1 [Q13946-1]
RefSeqiNP_001229247.1, NM_001242318.2 [Q13946-1]
NP_002594.1, NM_002603.3 [Q13946-2]
XP_011515842.1, XM_011517540.2 [Q13946-2]
UniGeneiHs.527119

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZKLX-ray1.67A130-482[»]
3G3NX-ray2.40A139-456[»]
4PM0X-ray2.10A130-482[»]
4Y2BX-ray2.20A130-482[»]
ProteinModelPortaliQ13946
SMRiQ13946
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111176, 5 interactors
IntActiQ13946, 1 interactor
STRINGi9606.ENSP00000385632

Chemistry databases

BindingDBiQ13946
ChEMBLiCHEMBL3012
DrugBankiDB07954 3-isobutyl-1-methyl-7H-xanthine
DB00201 Caffeine
DB00651 Dyphylline
GuidetoPHARMACOLOGYi1305

PTM databases

iPTMnetiQ13946
PhosphoSitePlusiQ13946

Polymorphism and mutation databases

BioMutaiPDE7A
DMDMi3182958

Proteomic databases

EPDiQ13946
MaxQBiQ13946
PaxDbiQ13946
PeptideAtlasiQ13946
PRIDEiQ13946
ProteomicsDBi59762
59763 [Q13946-2]
59764 [Q13946-3]

Protocols and materials databases

DNASUi5150
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379419; ENSP00000368730; ENSG00000205268 [Q13946-2]
ENST00000396642; ENSP00000379881; ENSG00000205268 [Q13946-3]
ENST00000401827; ENSP00000385632; ENSG00000205268 [Q13946-1]
GeneIDi5150
KEGGihsa:5150
UCSCiuc003xvp.4 human [Q13946-1]

Organism-specific databases

CTDi5150
DisGeNETi5150
EuPathDBiHostDB:ENSG00000205268.10
GeneCardsiPDE7A
HGNCiHGNC:8791 PDE7A
HPAiCAB018770
HPA027340
MIMi171885 gene
neXtProtiNX_Q13946
OpenTargetsiENSG00000205268
PharmGKBiPA33139
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000118889
HOGENOMiHOG000220881
HOVERGENiHBG053543
KOiK18436
OMAiHFILQMA
OrthoDBiEOG091G05SK
PhylomeDBiQ13946
TreeFamiTF314638

Enzyme and pathway databases

UniPathwayi
UPA00762;UER00747

BRENDAi3.1.4.53 2681
ReactomeiR-HSA-418555 G alpha (s) signalling events

Miscellaneous databases

ChiTaRSiPDE7A human
EvolutionaryTraceiQ13946
GeneWikiiPDE7A
GenomeRNAii5150
PROiPR:Q13946
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000205268 Expressed in 198 organ(s), highest expression level in secondary oocyte
CleanExiHS_PDE7A
ExpressionAtlasiQ13946 baseline and differential
GenevisibleiQ13946 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
InterProiView protein in InterPro
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDE7A_HUMAN
AccessioniPrimary (citable) accession number: Q13946
Secondary accession number(s): A0AVH6
, A8K436, A8K9G5, O15380, Q96T72
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: November 7, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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