DB code: M00143

CATH domain 3.40.50.9600 : Rossmann fold
3.40.50.2300 : Rossmann fold
3.30.200.- : Phosphorylase Kinase; domain 1
1.10.510.- : Transferase(Phosphotransferase); domain 1
3.30.70.- : Alpha-Beta Plaits
E.C. 4.6.1.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.2300 : Rossmann fold D00144

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P18910 Atrial natriuretic peptide receptor 1
EC 4.6.1.2
Atrial natriuretic peptide receptor type A
ANP-A
ANPR-A
NPR-A
Guanylate cyclase A
GC-A
NP_036745.1 (Protein)
NM_012613.1 (DNA/RNA sequence)
PF01094 (ANF_receptor)
PF00211 (Guanylate_cyc)
PF07714 (Pkinase_Tyr)
[Graphical View]

KEGG enzyme name
guanylate cyclase
guanylyl cyclase
guanyl cyclase
GTP diphosphate-lyase (cyclizing)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P18910 ANPRA_RAT GTP = 3'',5''-cyclic GMP + diphosphate. Homodimer. Membrane, Single-pass type I membrane protein.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00044 C00081 C00286 C00013 C00942 C00943 C02507
E.C.
Compound GTP ITP dGTP Pyrophosphate 3',5'-Cyclic GMP 3',5'-Cyclic IMP 3',5'-Cyclic dGMP
Type amide group,amine group,nucleotide amide group,nucleotide amide group,amine group,nucleotide phosphate group/phosphate ion amide group,amine group,nucleotide amide group,nucleotide amide group,amine group,nucleotide
ChEBI 15996
 15996
 		16039
 16039
 		16497
 16497
 		29888
 29888
 		16356
 16356
 		27541
 27541
PubChem 6830
 6830
 		8583
 8583
 		65103
 65103
 		1023
 21961011
 1023
 21961011
 		24316
 24316
 		19069
 19069
 		439740
 439740
1dp4A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dp4C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dp4A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dp4C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dp4A01
1dp4C01
1dp4A02
1dp4C02

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 7827054
Journal Biochemistry
Year 1995
Volume 34
Pages 955-64
Authors Mimeault M, De Lean A, Lafleur M, Bonenfant D, Fournier A
Title Evaluation of conformational and binding characteristics of various natriuretic peptides and related analogs.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7721418
Journal Hypertension
Year 1995
Volume 25
Pages 694-8
Authors Miao ZH, Song DL, Douglas JG, Chang CH
Title Mutational inactivation of the catalytic domain of guanylate cyclase-A receptor.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8713120
Journal Biochem Biophys Res Commun
Year 1996
Volume 224
Pages 765-71
Authors Thorpe DS, Niu S, Morkin E
Title Refolding parameters for the allosteric homodimeric guanylyl cyclase catalytic core from the atrial natriuretic peptide receptor.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9914494
Journal Eur J Biochem
Year 1999
Volume 259
Pages 204-11
Authors Kashiwagi M, Miyamoto K, Takei Y, Hirose S
Title Cloning, properties and tissue distribution of natriuretic peptide receptor-A of euryhaline eel, Anguilla japonica.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11078709
Journal Am J Physiol Cell Physiol
Year 2000
Volume 279
Pages C1938-45
Authors Nara M, Dhulipala PD, Ji GJ, Kamasani UR, Wang YX, Matalon S, Kotlikoff MI
Title Guanylyl cyclase stimulatory coupling to K(Ca) channels.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10971587
Journal Eur J Biochem
Year 2000
Volume 267
Pages 5758-68
Authors Miyagi M, Zhang X, Misono KS
Title Glycosylation sites in the atrial natriuretic peptide receptor: oligosaccharide structures are not required for hormone binding.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10648635
Journal Mol Pharmacol
Year 2000
Volume 57
Pages 259-67
Authors Pandey KN, Kumar R, Li M, Nguyen H
Title Functional domains and expression of truncated atrial natriuretic peptide receptor-A: the carboxyl-terminal regions direct the receptor internalization and sequestration in COS-7 cells.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10894551
Journal Nature
Year 2000
Volume 406
Pages 101-4
Authors van den Akker F, Zhang X, Miyagi M, Huo X, Misono KS, Yee VC
Title Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor.
Related PDB 1dp4
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11558678
Journal Can J Physiol Pharmacol
Year 2001
Volume 79
Pages 692-704
Authors van den Akker F
Title Detailed analysis of the atrial natriuretic factor receptor hormone-binding domain crystal structure.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11306239
Journal Cell Signal
Year 2001
Volume 13
Pages 221-31
Authors Silberbach M, Roberts CT Jr
Title Natriuretic peptide signalling: molecular and cellular pathways to growth regulation.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11556325
Journal J Mol Biol
Year 2001
Volume 311
Pages 923-37
Authors van den Akker F
Title Structural insights into the ligand binding domains of membrane bound guanylyl cyclases and natriuretic peptide receptors.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11269661
Journal Mol Cell Biochem
Year 2001
Volume 217
Pages 165-72
Authors Duda T, Yadav P, Jankowska A, Venkataraman V, Sharma RK
Title Three dimensional atomic model and experimental validation for the ATP-Regulated Module (ARM) of the atrial natriuretic factor receptor guanylate cyclase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11573084
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 832
Authors Hollien J
Title Picture story. A hormone receptor springs into action.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11533490
Journal Science
Year 2001
Volume 293
Pages 1657-62
Authors He Xl, Chow Dc, Martick MM, Garcia KC
Title Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11952096
Journal Mol Cell Biochem
Year 2002
Volume 230
Pages 49-60
Authors Misono KS
Title Natriuretic peptide receptor: structure and signaling.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11952097
Journal Mol Cell Biochem
Year 2002
Volume 230
Pages 61-72
Authors Pandey KN
Title Intracellular trafficking and metabolic turnover of ligand-bound guanylyl cyclase/atrial natriuretic peptide receptor-A into subcellular compartments.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of N-terminal extracellular region and C-terminal intracellular region, which has a protein-kinase like domain and a guanylate-cyclase domain. The PDB structure, 1dp4, corresponds to the N-terminal extracellular region, which is hormone-binding domain (see [8] & [9]). Thus, the structure of the catalytic domain of this enzyme has not been determined yet.
This enzyme catalyzes an intramolecular transfer reaction, rather than an elimination reaction.

Created Updated
2004-07-15 2009-02-26