Q01064 (PDE1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Short name=Cam-PDE 1B
EC=3.1.4.17

Alternative name(s):
63 kDa Cam-PDE

Gene names

Name:	PDE1B
Synonyms:	PDE1B1, PDES1B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	536 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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 preference for cGMP as a substrate. Ref.8
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. Ref.8
Enzyme regulation	Type I PDE are activated by the binding of calmodulin in the presence of Ca2+.
Subunit structure	Homodimer By similarity.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	Calmodulin-binding Metal-binding cAMP cGMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of phospholipase C activity Traceable author statement. Source: Reactome apoptotic process Traceable author statement Ref.1. Source: ProtInc blood coagulation Traceable author statement. Source: Reactome cAMP catabolic process Inferred from direct assay PubMed 14687666. Source: UniProtKB cGMP catabolic process Inferred from direct assay PubMed 14687666. Source: UniProtKB cellular response to granulocyte macrophage colony-stimulating factor stimulus Inferred from direct assay PubMed 14687666. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from direct assay PubMed 14687666. Source: UniProtKB epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome locomotory behavior Inferred from electronic annotation. Source: Compara monocyte differentiation Inferred from expression pattern PubMed 14687666. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara regulation of neurotransmitter levels Inferred from electronic annotation. Source: Compara response to amphetamine Inferred from electronic annotation. Source: Compara serotonin metabolic process Inferred from electronic annotation. Source: Compara visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA
Molecular_function	3',5'-cyclic-AMP phosphodiesterase activity Inferred from electronic annotation. Source: Compara calcium- and calmodulin-regulated 3',5'-cyclic-GMP phosphodiesterase activity Inferred from electronic annotation. Source: Compara calmodulin-dependent cyclic-nucleotide phosphodiesterase activity Traceable author statement Ref.2. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform PDE1B1 (identifier: Q01064-1)

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 PDE1B2 (identifier: Q01064-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MELSPRSPPEMLEESDCP → MANPVPVQRSHLQGPILR
     19-38: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 536

536

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

PRO_0000198789

Regions

Region

27 – 47

21

Calmodulin-binding Potential

Region

197 – 496

300

Catalytic By similarity

Sites

Active site

223

1

Proton donor By similarity

Metal binding

227

1

Divalent metal cation 1

Metal binding

263

1

Divalent metal cation 1

Metal binding

264

1

Divalent metal cation 1

Metal binding

264

1

Divalent metal cation 2

Metal binding

370

1

Divalent metal cation 1

Amino acid modifications

Modified residue

466

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 18

18

MELSP…ESDCP → MANPVPVQRSHLQGPILR in isoform PDE1B2.

VSP_038643

Alternative sequence

19 – 38

20

Missing in isoform PDE1B2.

VSP_038644

Experimental info

Sequence conflict

225 – 226

2

QI → SM in AAA58405. Ref.2

Sequence conflict

337

1

S → A in AAA58405. Ref.2

Secondary structure

1

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536

Helix Strand Turn

Details...

Helix

152 – 158

7

Turn

159 – 162

4

Helix

168 – 174

7

Helix

179 – 190

12

Helix

193 – 196

4

Helix

201 – 215

15

Turn

216 – 218

3

Beta strand

221 – 224

4

Helix

225 – 242

18

Helix

244 – 247

4

Helix

250 – 262

13

Turn

263 – 266

4

Helix

272 – 278

7

Helix

281 – 286

6

Helix

291 – 303

13

Helix

307 – 309

3

Turn

311 – 314

4

Helix

317 – 332

16

Helix

336 – 338

3

Helix

339 – 351

13

Helix

358 – 370

13

Helix

373 – 375

3

Helix

378 – 402

25

Helix

414 – 427

14

Helix

429 – 444

16

Helix

476 – 501

26

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE1B1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: D15211AC32C756A4	FASTA	536	61,380
	10 20 30 40 50 60 MELSPRSPPE MLEESDCPSP LELKSAPSKK MWIKLRSLLR YMVKQLENGE INIEELKKNL 70 80 90 100 110 120 EYTASLLEAV YIDETRQILD TEDELQELRS DAVPSEVRDW LASTFTQQAR AKGRRAEEKP 130 140 150 160 170 180 KFRSIVHAVQ AGIFVERMFR RTYTSVGPTY STAVLNCLKN LDLWCFDVFS LNQAADDHAL 190 200 210 220 230 240 RTIVFELLTR HNLISRFKIP TVFLMSFLDA LETGYGKYKN PYHNQIHAAD VTQTVHCFLL 250 260 270 280 290 300 RTGMVHCLSE IELLAIIFAA AIHDYEHTGT TNSFHIQTKS ECAIVYNDRS VLENHHISSV 310 320 330 340 350 360 FRLMQDDEMN IFINLTKDEF VELRALVIEM VLATDMSCHF QQVKTMKTAL QQLERIDKPK 370 380 390 400 410 420 ALSLLLHAAD ISHPTKQWLV HSRWTKALME EFFRQGDKEA ELGLPFSPLC DRTSTLVAQS 430 440 450 460 470 480 QIGFIDFIVE PTFSVLTDVA EKSVQPLADE DSKSKNQPSF QWRQPSLDVE VGDPNPDVVS 490 500 510 520 530 FRSTWVKRIQ ENKQKWKERA ASGITNQMSI DELSPCEEEA PPSPAEDEHN QNGNLD
	Isoform PDE1B2 [UniParc]. Checksum: 0A9093462479DC5C	FASTA	516	59,051
	10 20 30 40 50 60 MANPVPVQRS HLQGPILRLR YMVKQLENGE INIEELKKNL EYTASLLEAV YIDETRQILD 70 80 90 100 110 120 TEDELQELRS DAVPSEVRDW LASTFTQQAR AKGRRAEEKP KFRSIVHAVQ AGIFVERMFR 130 140 150 160 170 180 RTYTSVGPTY STAVLNCLKN LDLWCFDVFS LNQAADDHAL RTIVFELLTR HNLISRFKIP 190 200 210 220 230 240 TVFLMSFLDA LETGYGKYKN PYHNQIHAAD VTQTVHCFLL RTGMVHCLSE IELLAIIFAA 250 260 270 280 290 300 AIHDYEHTGT TNSFHIQTKS ECAIVYNDRS VLENHHISSV FRLMQDDEMN IFINLTKDEF 310 320 330 340 350 360 VELRALVIEM VLATDMSCHF QQVKTMKTAL QQLERIDKPK ALSLLLHAAD ISHPTKQWLV 370 380 390 400 410 420 HSRWTKALME EFFRQGDKEA ELGLPFSPLC DRTSTLVAQS QIGFIDFIVE PTFSVLTDVA 430 440 450 460 470 480 EKSVQPLADE DSKSKNQPSF QWRQPSLDVE VGDPNPDVVS FRSTWVKRIQ ENKQKWKERA 490 500 510 ASGITNQMSI DELSPCEEEA PPSPAEDEHN QNGNLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inhibition of calmodulin-dependent phosphodiesterase induces apoptosis in human leukemic cells." Jiang X., Li J., Paskind M., Epstein P.M. Proc. Natl. Acad. Sci. U.S.A. 93:11236-11241(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE1B1).
[2]	"Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1." Yu J., Frazier A.L.B., Wolda S.L., Florio V.A., Martins T.J., Snyder P.B., Harris E.A.S., McCaw K.N., Farrell C.A., Steiner B., Bentley J.K., Beavo J.A., Ferguson K., Gelinas R. Cell. Signal. 9:519-529(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE1B1). Tissue: Brain.
[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 PDE1B2). Tissue: Testis.
[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. , 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 PDE1B2). Tissue: Testis.
[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. , 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 (JUL-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] (ISOFORM PDE1B1). Tissue: Brain.
[7]	"A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase." Repaske D.R., Swinnen J.V., Jin S.-L.C., van Wyk J.J., Conti M. J. Biol. Chem. 267:18683-18688(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 222-337.
[8]	"A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases." Zhang K.Y.J., Card G.L., Suzuki Y., Artis D.R., Fong D., Gillette S., Hsieh D., Neiman J., West B.L., Zhang C., Milburn M.V., Kim S.-H., Schlessinger J., Bollag G. Mol. Cell 15:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 146-506 IN COMPLEX WITH METAL IONS, COFACTOR, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U56976 mRNA. Translation: AAC50769.1.
U86078 mRNA. Translation: AAC51872.1.
AJ401609 mRNA. Translation: CAC82207.1.
AK302931 mRNA. Translation: BAG64092.1.
CH471054 Genomic DNA. Translation: EAW96790.1.
BC032226 mRNA. Translation: AAH32226.1.
M94539 mRNA. Translation: AAA58405.1.

IPI

IPI00005592.
IPI00789728.

PIR

JC6129.

RefSeq

NP_000915.1. NM_000924.3.
NP_001159447.1. NM_001165975.2.

UniGene

Hs.530871.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LXR	model	-	A	158-461	[»]
1TAZ	X-ray	1.77	A	146-506	[»]

ProteinModelPortal

Q01064.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000243052.

PTM databases

PhosphoSite

Q01064.

Polymorphism databases

DMDM

3183514.

Proteomic databases

PaxDb

Q01064.

PRIDE

Q01064.

Protocols and materials databases

DNASU

5153.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000243052; ENSP00000243052; ENSG00000123360.
ENST00000550620; ENSP00000448519; ENSG00000123360.

GeneID

5153.

KEGG

hsa:5153.

UCSC

uc001sgd.2. human.
uc001sge.3. human.

Organism-specific databases

CTD

5153.

GeneCards

GC12P054943.

HGNC

HGNC:8775. PDE1B.

HPA

HPA018492.

MIM

171891. gene.

neXtProt

NX_Q01064.

PharmGKB

PA33123.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG139098.

HOGENOM

HOG000231888.

HOVERGEN

HBG056120.

InParanoid

Q01064.

KO

K13755.

OMA

STAVHNC.

OrthoDB

EOG4FXR79.

PhylomeDB

Q01064.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q01064.

Bgee

Q01064.

CleanEx

HS_PDE1B.

Genevestigator

Q01064.

GermOnline

ENSG00000123360. Homo sapiens.

Family and domain databases

Gene3D

1.10.1300.10. 2 hits.

InterPro

IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
IPR013706. PDEase_N.
[Graphical view]

Pfam

PF00233. PDEase_I. 1 hit.
PF08499. PDEase_I_N. 1 hit.
[Graphical view]

PRINTS

PR00387. PDIESTERASE1.

SMART

SM00471. HDc. 1 hit.
[Graphical view]

PROSITE

PS00126. PDEASE_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q01064.

ChEMBL

CHEMBL4425.

EvolutionaryTrace

Q01064.

GenomeRNAi

5153.

NextBio

19926.

SOURCE

Search...

Entry information

Entry name

PDE1B_HUMAN

Accession

Primary (citable) accession number: Q01064
Secondary accession number(s): Q92825, Q96KP3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.