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Protein

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

Gene

PDE1C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 high affinity for both cAMP and cGMP.

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei228 – 2281Proton donorBy similarity
Metal bindingi232 – 2321Divalent metal cation 1By similarity
Metal bindingi268 – 2681Divalent metal cation 1By similarity
Metal bindingi269 – 2691Divalent metal cation 1By similarity
Metal bindingi269 – 2691Divalent metal cation 2By similarity
Metal bindingi376 – 3761Divalent metal cation 1By similarity

GO - Molecular functioni

  • calmodulin-dependent cyclic-nucleotide phosphodiesterase activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calmodulin-binding, cAMP, cGMP, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.17. 2681.
ReactomeiREACT_15408. Cam-PDE 1 activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (EC:3.1.4.17)
Short name:
Cam-PDE 1C
Alternative name(s):
hCam-3
Gene namesi
Name:PDE1C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:8776. PDE1C.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33124.

Chemistry

DrugBankiDB00201. Caffeine.

Polymorphism and mutation databases

BioMutaiPDE1C.
DMDMi2499445.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 709709Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1CPRO_0000198792Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ14123.
PaxDbiQ14123.
PRIDEiQ14123.

PTM databases

PhosphoSiteiQ14123.

Expressioni

Tissue specificityi

Expressed in several tissues, including brain and heart.

Gene expression databases

BgeeiQ14123.
CleanExiHS_PDE1C.
ExpressionAtlasiQ14123. baseline and differential.
GenevisibleiQ14123. HS.

Organism-specific databases

HPAiHPA021751.
HPA052375.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111163. 2 interactions.
STRINGi9606.ENSP00000379496.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LXSmodel-A163-460[»]
ProteinModelPortaliQ14123.
SMRiQ14123. Positions 158-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni202 – 521320CatalyticBy similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG139098.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000231888.
HOVERGENiHBG056120.
KOiK13755.
OrthoDBiEOG7X9G6J.
PhylomeDBiQ14123.
TreeFamiTF314638.

Family and domain databases

Gene3Di1.10.1300.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
IPR013706. PDEase_N.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
PF08499. PDEase_I_N. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Note: Additional isoforms seem to exist.

Isoform PDE1C2 (identifier: Q14123-1) [UniParc]FASTAAdd to basket

Also known as: HCam-3A

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
MESPTKEIEE FESNSLKYLQ PEQIEKIWLR LRGLRKYKKT SQRLRSLVKQ
60 70 80 90 100
LERGEASVVD LKKNLEYAAT VLESVYIDET RRLLDTEDEL SDIQSDAVPS
110 120 130 140 150
EVRDWLASTF TRQMGMMLRR SDEKPRFKSI VHAVQAGIFV ERMYRRTSNM
160 170 180 190 200
VGLSYPPAVI EALKDVDKWS FDVFSLNEAS GDHALKFIFY ELLTRYDLIS
210 220 230 240 250
RFKIPISALV SFVEALEVGY SKHKNPYHNL MHAADVTQTV HYLLYKTGVA
260 270 280 290 300
NWLTELEIFA IIFSAAIHDY EHTGTTNNFH IQTRSDPAIL YNDRSVLENH
310 320 330 340 350
HLSAAYRLLQ DDEEMNILIN LSKDDWREFR TLVIEMVMAT DMSCHFQQIK
360 370 380 390 400
AMKTALQQPE AIEKPKALSL MLHTADISHP AKAWDLHHRW TMSLLEEFFR
410 420 430 440 450
QGDREAELGL PFSPLCDRKS TMVAQSQVGF IDFIVEPTFT VLTDMTEKIV
460 470 480 490 500
SPLIDETSQT GGTGQRRSSL NSISSSDAKR SGVKTSGSEG SAPINNSVIS
510 520 530 540 550
VDYKSFKATW TEVVHINRER WRAKVPKEEK AKKEAEEKAR LAAEEQQKEM
560 570 580 590 600
EAKSQAEEGA SGKAEKKTSG ETKNQVNGTR ANKSDNPRGK NSKAEKSSGE
610 620 630 640 650
QQQNGDFKDG KNKTDKKDHS NIGNDSKKTD GTKQRSHGSP APSTSSTCRL
660 670 680 690 700
TLPVIKPPLR HFKRPAYASS SYAPSVSKKT DEHPARYKML DQRIKMKKIQ

NISHNWNRK
Length:709
Mass (Da):80,760
Last modified:November 1, 1997 - v1
Checksum:i77133D4DDBE5F7C0
GO
Isoform PDE1C1 (identifier: Q14123-2) [UniParc]FASTAAdd to basket

Also known as: HCam-3B

The sequence of this isoform differs from the canonical sequence as follows:
     631-634: GTKQ → DSQE
     635-709: Missing.

Show »
Length:634
Mass (Da):72,208
Checksum:i73F9A72EDCEAF6F7
GO
Isoform 3 (identifier: Q14123-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MESPTKEIEE...LRLRGLRKYK → MTDAGNRKEG...PQLDSSEVLV

Note: No experimental confirmation available.Curated
Show »
Length:769
Mass (Da):86,896
Checksum:i47B4A412522129DA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421Q → F in BAC03734 (PubMed:14702039).Curated
Sequence conflicti126 – 1261R → L in BAC03734 (PubMed:14702039).Curated
Isoform 3 (identifier: Q14123-3)
Sequence conflicti4 – 41A → V in BAC03734 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3838MESPT…LRKYK → MTDAGNRKEGFKKCRSATFS IDGYSFTIVANEAGDKNARP LARFSRSKSQNCLWNSLIDG LTGNVKEKPRPTIVHDPRPP EEILADELPQLDSSEVLV in isoform 3. 1 PublicationVSP_044468Add
BLAST
Alternative sequencei631 – 6344GTKQ → DSQE in isoform PDE1C1. 1 PublicationVSP_004552
Alternative sequencei635 – 70975Missing in isoform PDE1C1. 1 PublicationVSP_004553Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40371 mRNA. Translation: AAC50437.1.
U40372 mRNA. Translation: AAA96961.1.
AK056170 mRNA. Translation: BAG51638.1.
AK091734 mRNA. Translation: BAC03734.1.
AC004931 Genomic DNA. No translation available.
AC005589 Genomic DNA. No translation available.
AC006377 Genomic DNA. No translation available.
AC007033 Genomic DNA. No translation available.
AC007093 Genomic DNA. No translation available.
AC018637 Genomic DNA. No translation available.
CCDSiCCDS5437.1. [Q14123-2]
CCDS55099.1. [Q14123-1]
CCDS55100.1. [Q14123-3]
RefSeqiNP_001177985.1. NM_001191056.2. [Q14123-2]
NP_001177986.1. NM_001191057.2. [Q14123-1]
NP_001177987.2. NM_001191058.2.
NP_001177988.1. NM_001191059.2. [Q14123-1]
NP_005011.1. NM_005020.3. [Q14123-2]
UniGeneiHs.290550.
Hs.728862.

Genome annotation databases

EnsembliENST00000321453; ENSP00000318105; ENSG00000154678.
ENST00000396182; ENSP00000379485; ENSG00000154678. [Q14123-2]
ENST00000396184; ENSP00000379487; ENSG00000154678. [Q14123-2]
ENST00000396191; ENSP00000379494; ENSG00000154678.
GeneIDi5137.
KEGGihsa:5137.
UCSCiuc003tcm.2. human. [Q14123-1]
uc003tco.2. human. [Q14123-3]
uc003tcr.3. human. [Q14123-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40371 mRNA. Translation: AAC50437.1.
U40372 mRNA. Translation: AAA96961.1.
AK056170 mRNA. Translation: BAG51638.1.
AK091734 mRNA. Translation: BAC03734.1.
AC004931 Genomic DNA. No translation available.
AC005589 Genomic DNA. No translation available.
AC006377 Genomic DNA. No translation available.
AC007033 Genomic DNA. No translation available.
AC007093 Genomic DNA. No translation available.
AC018637 Genomic DNA. No translation available.
CCDSiCCDS5437.1. [Q14123-2]
CCDS55099.1. [Q14123-1]
CCDS55100.1. [Q14123-3]
RefSeqiNP_001177985.1. NM_001191056.2. [Q14123-2]
NP_001177986.1. NM_001191057.2. [Q14123-1]
NP_001177987.2. NM_001191058.2.
NP_001177988.1. NM_001191059.2. [Q14123-1]
NP_005011.1. NM_005020.3. [Q14123-2]
UniGeneiHs.290550.
Hs.728862.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LXSmodel-A163-460[»]
ProteinModelPortaliQ14123.
SMRiQ14123. Positions 158-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111163. 2 interactions.
STRINGi9606.ENSP00000379496.

Chemistry

BindingDBiQ14123.
ChEMBLiCHEMBL2097161.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi1296.

PTM databases

PhosphoSiteiQ14123.

Polymorphism and mutation databases

BioMutaiPDE1C.
DMDMi2499445.

Proteomic databases

MaxQBiQ14123.
PaxDbiQ14123.
PRIDEiQ14123.

Protocols and materials databases

DNASUi5137.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321453; ENSP00000318105; ENSG00000154678.
ENST00000396182; ENSP00000379485; ENSG00000154678. [Q14123-2]
ENST00000396184; ENSP00000379487; ENSG00000154678. [Q14123-2]
ENST00000396191; ENSP00000379494; ENSG00000154678.
GeneIDi5137.
KEGGihsa:5137.
UCSCiuc003tcm.2. human. [Q14123-1]
uc003tco.2. human. [Q14123-3]
uc003tcr.3. human. [Q14123-2]

Organism-specific databases

CTDi5137.
GeneCardsiGC07M031759.
HGNCiHGNC:8776. PDE1C.
HPAiHPA021751.
HPA052375.
MIMi602987. gene.
neXtProtiNX_Q14123.
PharmGKBiPA33124.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG139098.
GeneTreeiENSGT00760000118889.
HOGENOMiHOG000231888.
HOVERGENiHBG056120.
KOiK13755.
OrthoDBiEOG7X9G6J.
PhylomeDBiQ14123.
TreeFamiTF314638.

Enzyme and pathway databases

BRENDAi3.1.4.17. 2681.
ReactomeiREACT_15408. Cam-PDE 1 activation.

Miscellaneous databases

ChiTaRSiPDE1C. human.
GeneWikiiPDE1C.
GenomeRNAii5137.
NextBioi19808.
PROiQ14123.
SOURCEiSearch...

Gene expression databases

BgeeiQ14123.
CleanExiHS_PDE1C.
ExpressionAtlasiQ14123. baseline and differential.
GenevisibleiQ14123. HS.

Family and domain databases

Gene3Di1.10.1300.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
IPR013706. PDEase_N.
[Graphical view]
PfamiPF00233. PDEase_I. 1 hit.
PF08499. PDEase_I_N. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORMS PDE1C1 AND PDE1C2).
    Tissue: Heart.
  2. "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] (ISOFORMS PDE1C2 AND 3).
    Tissue: Heart.
  3. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPDE1C_HUMAN
AccessioniPrimary (citable) accession number: Q14123
Secondary accession number(s): B3KPC6
, E9PE92, Q14124, Q8NB10
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 22, 2015
This is version 135 of the entry and version 1 of the sequence. [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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.