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P54750 (PDE1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A

Short name=Cam-PDE 1A
EC=3.1.4.17
Alternative name(s):
61 kDa Cam-PDE
hCam-1
Gene names
Name:PDE1A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length535 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cGMP than for cAMP.

Catalytic activity

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 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 By similarity.

Enzyme regulation

Type I PDE are activated by the binding of calmodulin in the presence of Ca2+.

Subunit structure

Homodimer By similarity.

Tissue specificity

Several tissues, including brain, kidney, testes and heart.

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandCalmodulin-binding
cAMP
cGMP
Metal-binding
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of phospholipase C activity

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cAMP catabolic process

Inferred from electronic annotation. Source: Ensembl

cGMP catabolic process

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

regulation of smooth muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_function3',5'-cyclic-AMP phosphodiesterase activity

Inferred from electronic annotation. Source: Ensembl

cGMP binding

Inferred from electronic annotation. Source: Ensembl

calcium- and calmodulin-regulated 3',5'-cyclic-GMP phosphodiesterase activity

Inferred from electronic annotation. Source: Ensembl

calmodulin-dependent cyclic-nucleotide phosphodiesterase activity

Traceable author statement Ref.1. Source: ProtInc

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54750-1)

Also known as: PDE1A3; PDE1A6;

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 2 (identifier: P54750-2)

Also known as: PDE1A4; PDE1A5;

The sequence of this isoform differs from the canonical sequence as follows:
     2-34: GSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR
Isoform 3 (identifier: P54750-3)

Also known as: PDE1A10;

The sequence of this isoform differs from the canonical sequence as follows:
     2-72: GSSATEIEEL...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE
Isoform 4 (identifier: P54750-4)

Also known as: PDE1A5;

The sequence of this isoform differs from the canonical sequence as follows:
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS
Isoform 5 (identifier: P54750-5)

Also known as: PDE1A9;

The sequence of this isoform differs from the canonical sequence as follows:
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL
Isoform 6 (identifier: P54750-6)

Also known as: PDE1A1;

The sequence of this isoform differs from the canonical sequence as follows:
     2-34: GSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS
Isoform 7 (identifier: P54750-7)

Also known as: PDE1A8;

The sequence of this isoform differs from the canonical sequence as follows:
     2-34: GSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL
Isoform 8 (identifier: P54750-8)

Also known as: PDE1A11;

The sequence of this isoform differs from the canonical sequence as follows:
     2-72: GSSATEIEEL...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS
Isoform 9 (identifier: P54750-9)

Also known as: PDE1A12;

The sequence of this isoform differs from the canonical sequence as follows:
     2-72: GSSATEIEEL...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 535534Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
PRO_0000198785

Regions

Region24 – 4421Calmodulin-binding By similarity
Region193 – 515323Catalytic By similarity

Sites

Active site2191Proton donor By similarity
Metal binding2231Divalent metal cation 1 By similarity
Metal binding2591Divalent metal cation 1 By similarity
Metal binding2601Divalent metal cation 1 By similarity
Metal binding2601Divalent metal cation 2 By similarity
Metal binding3661Divalent metal cation 1 By similarity

Natural variations

Alternative sequence2 – 7271GSSAT…IDETR → MGKKINKLFCFNFLVQCFRG KSKPSKCQIRKKVKNHIE in isoform 3, isoform 8 and isoform 9.
VSP_004548
Alternative sequence2 – 3433GSSAT…RLKGI → MDDHVTIRKKHLQRPIFR in isoform 2, isoform 6 and isoform 7.
VSP_004547
Alternative sequence522 – 53514EARTS…EFIHQ → GESDLHKNSEDLVNAEEKHD ETHS in isoform 4, isoform 6 and isoform 8.
VSP_004549
Alternative sequence522 – 53514EARTS…EFIHQ → GSVVYEALLPSLSVFTSPLR VWITSSRFLLL in isoform 5, isoform 7 and isoform 9.
VSP_004550

Secondary structure

................................................. 535
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PDE1A3) (PDE1A6) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: B1878145160BB3D7

FASTA53561,252
        10         20         30         40         50         60 
MGSSATEIEE LENTTFKYLT GEQTEKMWQR LKGILRCLVK QLERGDVNVV DLKKNIEYAA 

        70         80         90        100        110        120 
SVLEAVYIDE TRRLLDTEDE LSDIQTDSVP SEVRDWLAST FTRKMGMTKK KPEEKPKFRS 

       130        140        150        160        170        180 
IVHAVQAGIF VERMYRKTYH MVGLAYPAAV IVTLKDVDKW SFDVFALNEA SGEHSLKFMI 

       190        200        210        220        230        240 
YELFTRYDLI NRFKIPVSCL ITFAEALEVG YSKYKNPYHN LIHAADVTQT VHYIMLHTGI 

       250        260        270        280        290        300 
MHWLTELEIL AMVFAAAIHD YEHTGTTNNF HIQTRSDVAI LYNDRSVLEN HHVSAAYRLM 

       310        320        330        340        350        360 
QEEEMNILIN LSKDDWRDLR NLVIEMVLST DMSGHFQQIK NIRNSLQQPE GIDRAKTMSL 

       370        380        390        400        410        420 
ILHAADISHP AKSWKLHYRW TMALMEEFFL QGDKEAELGL PFSPLCDRKS TMVAQSQIGF 

       430        440        450        460        470        480 
IDFIVEPTFS LLTDSTEKIV IPLIEEASKA ETSSYVASSS TTIVGLHIAD ALRRSNTKGS 

       490        500        510        520        530 
MSDGSYSPDY SLAAVDLKSF KNNLVDIIQQ NKERWKELAA QEARTSSQKC EFIHQ 

« Hide

Isoform 2 (PDE1A4) (PDE1A5) [UniParc].

Checksum: 8FFD320EF08C01DE
Show »

FASTA52059,723
Isoform 3 (PDE1A10) [UniParc].

Checksum: 14C0823000447A8E
Show »

FASTA50257,614
Isoform 4 (PDE1A5) [UniParc].

Checksum: BE2A280A504FDB9E
Show »

FASTA54562,309
Isoform 5 (PDE1A9) [UniParc].

Checksum: 0956259BB3F5E938
Show »

FASTA55263,040
Isoform 6 (PDE1A1) [UniParc].

Checksum: 39DB606547FC0CE2
Show »

FASTA53060,780
Isoform 7 (PDE1A8) [UniParc].

Checksum: 9187F614548EB3FF
Show »

FASTA53761,512
Isoform 8 (PDE1A11) [UniParc].

Checksum: 85C9BC1242D9B55B
Show »

FASTA51258,671
Isoform 9 (PDE1A12) [UniParc].

Checksum: 8943F30315077A73
Show »

FASTA51959,402

References

« Hide 'large scale' references
[1]"Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases."
Loughney K., Martins T.J., Harris E.A.S., Sadhu K., Hicks J.B., Sonnenburg W.K., Beavo J.A., Ferguson K.
J. Biol. Chem. 271:796-806(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice variants, their specific expression, genomic organization, and chromosomal localization."
Michibata H., Yanaka N., Kanoh Y., Okumura K., Omori K.
Biochim. Biophys. Acta 1517:278-287(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 9).
Tissue: Heart.
[3]"Isolation and differential tissue distribution of two human cDNAs encoding PDE1 splice variants."
Fidock M.D., Miller M., Lanfear J.
Cell. Signal. 14:53-60(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Uterus.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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] (ISOFORMS 3 AND 4).
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U40370 mRNA. Translation: AAC50436.1.
AB038224 Genomic DNA. Translation: BAB20049.1.
AB038224 Genomic DNA. Translation: BAB20050.1.
AB038224 Genomic DNA. Translation: BAB20051.1.
AB038224 Genomic DNA. Translation: BAB20052.1.
AB038224 Genomic DNA. Translation: BAB20053.1.
AB038224 Genomic DNA. Translation: BAB20054.1.
AB038224 Genomic DNA. Translation: BAB20055.1.
AB038224 Genomic DNA. Translation: BAB20056.1.
AB038224 Genomic DNA. Translation: BAB20057.1.
AJ401610 mRNA. Translation: CAC82208.1.
AL110263 mRNA. Translation: CAB53703.1.
CH471058 Genomic DNA. Translation: EAX10966.1.
CH471058 Genomic DNA. Translation: EAX10974.1.
BC022480 mRNA. Translation: AAH22480.1.
CCDSCCDS2285.1. [P54750-4]
CCDS33344.1. [P54750-1]
CCDS58741.1. [P54750-2]
PIRT14783.
RefSeqNP_001003683.1. NM_001003683.2. [P54750-1]
NP_001245242.1. NM_001258313.1.
NP_001245243.1. NM_001258314.1.
NP_005010.2. NM_005019.4. [P54750-4]
XP_005246692.1. XM_005246635.2. [P54750-5]
XP_005246693.1. XM_005246636.1.
XP_005246694.1. XM_005246637.1.
XP_006712637.1. XM_006712574.1. [P54750-5]
XP_006712638.1. XM_006712575.1. [P54750-5]
XP_006712639.1. XM_006712576.1. [P54750-5]
XP_006712640.1. XM_006712577.1. [P54750-5]
XP_006712641.1. XM_006712578.1. [P54750-4]
XP_006712642.1. XM_006712579.1. [P54750-1]
UniGeneHs.191046.
Hs.742174.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LXQmodel-A154-432[»]
ProteinModelPortalP54750.
SMRP54750. Positions 142-520.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111162. 4 interactions.
IntActP54750. 1 interaction.
MINTMINT-4717501.

Chemistry

BindingDBP54750.
ChEMBLCHEMBL2095150.
GuidetoPHARMACOLOGY1294.

PTM databases

PhosphoSiteP54750.

Polymorphism databases

DMDM1705942.

Proteomic databases

MaxQBP54750.
PaxDbP54750.
PRIDEP54750.

Protocols and materials databases

DNASU5136.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331935; ENSP00000331574; ENSG00000115252. [P54750-4]
ENST00000346717; ENSP00000329112; ENSG00000115252. [P54750-8]
ENST00000351439; ENSP00000309269; ENSG00000115252. [P54750-2]
ENST00000358139; ENSP00000350858; ENSG00000115252. [P54750-1]
ENST00000409365; ENSP00000386767; ENSG00000115252. [P54750-6]
ENST00000410103; ENSP00000387037; ENSG00000115252. [P54750-1]
ENST00000435564; ENSP00000410309; ENSG00000115252. [P54750-4]
ENST00000456212; ENSP00000408874; ENSG00000115252. [P54750-5]
GeneID5136.
KEGGhsa:5136.
UCSCuc002uoq.2. human. [P54750-4]
uc002uor.4. human. [P54750-2]
uc002uos.4. human. [P54750-1]
uc002uou.4. human. [P54750-3]

Organism-specific databases

CTD5136.
GeneCardsGC02M182971.
HGNCHGNC:8774. PDE1A.
HPAHPA022151.
MIM171890. gene.
neXtProtNX_P54750.
PharmGKBPA33122.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG139098.
HOVERGENHBG056120.
KOK13755.
OMAQEEEMNV.
OrthoDBEOG7X9G6J.
PhylomeDBP54750.
TreeFamTF314638.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP54750.
BgeeP54750.
GenevestigatorP54750.

Family and domain databases

Gene3D1.10.1300.10. 2 hits.
InterProIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
IPR013706. PDEase_N.
[Graphical view]
PfamPF00233. PDEase_I. 1 hit.
PF08499. PDEase_I_N. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00471. HDc. 1 hit.
[Graphical view]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDE1A. human.
GeneWikiPDE1A.
GenomeRNAi5136.
NextBio19802.
PROP54750.
SOURCESearch...

Entry information

Entry namePDE1A_HUMAN
AccessionPrimary (citable) accession number: P54750
Secondary accession number(s): D3DPG5 expand/collapse secondary AC list , Q86VZ0, Q9C0K8, Q9C0K9, Q9C0L0, Q9C0L1, Q9C0L2, Q9C0L3, Q9C0L4, Q9UFX3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 148 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

MIM cross-references

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

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM