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Protein

Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A

Gene

PDE1A

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

Functioni

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 activityi

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

Cofactori

a divalent metal cationBy similarityNote: 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

Activity regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei219Proton donorBy similarity1
Metal bindingi223Divalent metal cation 1; via tele nitrogenBy similarity1
Metal bindingi259Divalent metal cation 1; via tele nitrogenBy similarity1
Metal bindingi260Divalent metal cation 1By similarity1
Metal bindingi260Divalent metal cation 2By similarity1
Metal bindingi366Divalent metal cation 1By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Hydrolase
LigandcAMP, cGMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.17 2681
ReactomeiR-HSA-111957 Cam-PDE 1 activation
R-HSA-418457 cGMP effects
R-HSA-418555 G alpha (s) signalling events
SIGNORiP54750

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (EC:3.1.4.17)
Short name:
Cam-PDE 1A
Alternative name(s):
61 kDa Cam-PDE
hCam-1
Gene namesi
Name:PDE1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115252.18
HGNCiHGNC:8774 PDE1A
MIMi171890 gene
neXtProtiNX_P54750

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi5136
OpenTargetsiENSG00000115252
PharmGKBiPA33122

Chemistry databases

ChEMBLiCHEMBL3421
DrugBankiDB01244 Bepridil
DB00201 Caffeine
DB01023 Felodipine
DB00622 Nicardipine
GuidetoPHARMACOLOGYi1294

Polymorphism and mutation databases

BioMutaiPDE1A
DMDMi1705942

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001987851 – 535Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1AAdd BLAST535

Proteomic databases

MaxQBiP54750
PaxDbiP54750
PeptideAtlasiP54750
PRIDEiP54750
ProteomicsDBi56702
56703 [P54750-2]
56704 [P54750-3]
56705 [P54750-4]
56706 [P54750-5]
56707 [P54750-6]
56708 [P54750-7]
56709 [P54750-8]
56710 [P54750-9]

PTM databases

iPTMnetiP54750
PhosphoSitePlusiP54750

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000115252 Expressed in 195 organ(s), highest expression level in Brodmann (1909) area 23
GenevisibleiP54750 HS

Organism-specific databases

HPAiHPA022151

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111162, 4 interactors
IntActiP54750, 1 interactor
STRINGi9606.ENSP00000331574

Chemistry databases

BindingDBiP54750

Structurei

3D structure databases

ProteinModelPortaliP54750
SMRiP54750
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini142 – 522PDEasePROSITE-ProRule annotationAdd BLAST381

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 44Calmodulin-bindingBy similarityAdd BLAST21

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3688 Eukaryota
ENOG410XQDD LUCA
GeneTreeiENSGT00760000118889
HOVERGENiHBG056120
KOiK13755
OMAiRMYRKSY
OrthoDBiEOG091G04C4
PhylomeDBiP54750
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
IPR013706 PDEase_N
PfamiView protein in Pfam
PF00233 PDEase_I, 1 hit
PF08499 PDEase_I_N, 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 (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P54750-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MGSSATEIEE LENTTFKYLT GEQTEKMWQR LKGILRCLVK QLERGDVNVV
60 70 80 90 100
DLKKNIEYAA SVLEAVYIDE TRRLLDTEDE LSDIQTDSVP SEVRDWLAST
110 120 130 140 150
FTRKMGMTKK KPEEKPKFRS IVHAVQAGIF VERMYRKTYH MVGLAYPAAV
160 170 180 190 200
IVTLKDVDKW SFDVFALNEA SGEHSLKFMI YELFTRYDLI NRFKIPVSCL
210 220 230 240 250
ITFAEALEVG YSKYKNPYHN LIHAADVTQT VHYIMLHTGI MHWLTELEIL
260 270 280 290 300
AMVFAAAIHD YEHTGTTNNF HIQTRSDVAI LYNDRSVLEN HHVSAAYRLM
310 320 330 340 350
QEEEMNILIN LSKDDWRDLR NLVIEMVLST DMSGHFQQIK NIRNSLQQPE
360 370 380 390 400
GIDRAKTMSL ILHAADISHP AKSWKLHYRW TMALMEEFFL QGDKEAELGL
410 420 430 440 450
PFSPLCDRKS TMVAQSQIGF IDFIVEPTFS LLTDSTEKIV IPLIEEASKA
460 470 480 490 500
ETSSYVASSS TTIVGLHIAD ALRRSNTKGS MSDGSYSPDY SLAAVDLKSF
510 520 530
KNNLVDIIQQ NKERWKELAA QEARTSSQKC EFIHQ
Length:535
Mass (Da):61,252
Last modified:January 23, 2007 - v2
Checksum:iB1878145160BB3D7
GO
Isoform 2 (identifier: P54750-2) [UniParc]FASTAAdd to basket
Also known as: PDE1A4, PDE1A5

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR

Show »
Length:519
Mass (Da):59,592
Checksum:i51F86B0EF08C01CE
GO
Isoform 3 (identifier: P54750-3) [UniParc]FASTAAdd to basket
Also known as: PDE1A10

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MGSSATEIEE...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE

Show »
Length:501
Mass (Da):57,483
Checksum:i74C082300051D62C
GO
Isoform 4 (identifier: P54750-4) [UniParc]FASTAAdd to basket
Also known as: PDE1A5

The sequence of this isoform differs from the canonical sequence as follows:
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS

Show »
Length:545
Mass (Da):62,309
Checksum:iBE2A280A504FDB9E
GO
Isoform 5 (identifier: P54750-5) [UniParc]FASTAAdd to basket
Also known as: PDE1A9

The sequence of this isoform differs from the canonical sequence as follows:
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL

Show »
Length:552
Mass (Da):63,040
Checksum:i0956259BB3F5E938
GO
Isoform 6 (identifier: P54750-6) [UniParc]FASTAAdd to basket
Also known as: PDE1A1

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS

Show »
Length:529
Mass (Da):60,649
Checksum:i39CF97424CCC0CE2
GO
Isoform 7 (identifier: P54750-7) [UniParc]FASTAAdd to basket
Also known as: PDE1A8

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGI → MDDHVTIRKKHLQRPIFR
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL

Show »
Length:536
Mass (Da):61,380
Checksum:i8CDAD40B298EB3FF
GO
Isoform 8 (identifier: P54750-8) [UniParc]FASTAAdd to basket
Also known as: PDE1A11

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MGSSATEIEE...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE
     522-535: EARTSSQKCEFIHQ → GESDLHKNSEDLVNAEEKHDETHS

Show »
Length:511
Mass (Da):58,540
Checksum:i415D4C1242D9B547
GO
Isoform 9 (identifier: P54750-9) [UniParc]FASTAAdd to basket
Also known as: PDE1A12

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MGSSATEIEE...LEAVYIDETR → MGKKINKLFC...IRKKVKNHIE
     522-535: EARTSSQKCEFIHQ → GSVVYEALLPSLSVFTSPLRVWITSSRFLLL

Show »
Length:518
Mass (Da):59,271
Checksum:i4C1AF30315076AF7
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0045481 – 72MGSSA…IDETR → MGKKINKLFCFNFLVQCFRG KSKPSKCQIRKKVKNHIE in isoform 3, isoform 8 and isoform 9. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_0045471 – 34MGSSA…RLKGI → MDDHVTIRKKHLQRPIFR in isoform 2, isoform 6 and isoform 7. 2 PublicationsAdd BLAST34
Alternative sequenceiVSP_004549522 – 535EARTS…EFIHQ → GESDLHKNSEDLVNAEEKHD ETHS in isoform 4, isoform 6 and isoform 8. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_004550522 – 535EARTS…EFIHQ → GSVVYEALLPSLSVFTSPLR VWITSSRFLLL in isoform 5, isoform 7 and isoform 9. CuratedAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS2285.1 [P54750-4]
CCDS33344.1 [P54750-1]
CCDS58741.1 [P54750-2]
CCDS74612.1 [P54750-3]
CCDS86900.1 [P54750-6]
PIRiT14783
RefSeqiNP_001003683.1, NM_001003683.2 [P54750-1]
NP_001245242.1, NM_001258313.1 [P54750-2]
NP_001245243.1, NM_001258314.1 [P54750-3]
NP_005010.2, NM_005019.4 [P54750-4]
XP_016859784.1, XM_017004295.1 [P54750-4]
XP_016859785.1, XM_017004296.1 [P54750-4]
XP_016859786.1, XM_017004297.1 [P54750-4]
XP_016859787.1, XM_017004298.1 [P54750-4]
XP_016859788.1, XM_017004299.1 [P54750-1]
XP_016859789.1, XM_017004300.1 [P54750-1]
XP_016859790.1, XM_017004301.1 [P54750-1]
XP_016859791.1, XM_017004302.1 [P54750-6]
UniGeneiHs.191046
Hs.742065
Hs.742174

Genome annotation databases

EnsembliENST00000351439; ENSP00000309269; ENSG00000115252 [P54750-2]
ENST00000358139; ENSP00000350858; ENSG00000115252 [P54750-3]
ENST00000409365; ENSP00000386767; ENSG00000115252 [P54750-6]
ENST00000410103; ENSP00000387037; ENSG00000115252 [P54750-1]
ENST00000435564; ENSP00000410309; ENSG00000115252 [P54750-4]
GeneIDi5136
KEGGihsa:5136
UCSCiuc002uoq.3 human [P54750-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPDE1A_HUMAN
AccessioniPrimary (citable) accession number: P54750
Secondary accession number(s): D3DPG5
, Q86VZ0, Q9C0K8, Q9C0K9, Q9C0L0, Q9C0L1, Q9C0L2, Q9C0L3, Q9C0L4, Q9UFX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 184 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
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Main funding by: National Institutes of Health

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