Natriuretic peptides A
Alternative name(s):
CDD-ANF
Prepronatriodilatin
Cleaved into the following 2 chains:
Cardiodilatin-related peptide
Short name=CDP
Atrial natriuretic factor
Short name=ANF
Alternative name(s):
Atrial natriuretic peptide
Short name=ANP
Function
ナトリウム利尿、血管拡張にかかわる。妊娠の成立の際に胎盤の形成に重要。
Hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. Also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3. Ref.15
Subcellular location
Secreted.
Post-translational modification
Cleaved by CORIN upon secretion to produce the functional hormone.
Polymorphism
There are two different prepronatriodilatin alleles. One codes for 2 Arg residues at the C-terminus that are cleaved to form the mature peptide, while the other ends in a termination codon immediately after the last codon of the mature peptide.
Involvement in disease
Atrial fibrillation, familial, 6 (ATFB6) [MIM:612201]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20
Sequence similarities
Belongs to the natriuretic peptide family.
Atrial natriuretic peptide-converting enzyme
EC=3.4.21.-
Alternative name(s):
Corin
Heart-specific serine proteinase ATC2
Pro-ANP-converting enzyme
Transmembrane protease serine 10
Cleaved into the following 5 chains:
Atrial natriuretic peptide-converting enzyme, N-terminal propeptide
Atrial natriuretic peptide-converting enzyme, activated protease fragment
Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment
Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment
Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment
Function
心房性ナトリウム利尿ペプチドのプロセッシングに関与するセリンプロテアーゼ。ナトリウムの排泄、利尿、血管拡張作用。
Serine-type endopeptidase involved in atrial natriuretic peptide hormone (NPPA) processing. Converts through proteolytic cleavage the non-functional propeptide NPPA into the active hormone, thereby regulating blood pressure in heart and promoting natriuresis, diuresis and vasodilation. Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Also acts as a regulator of sodium reabsorption in kidney. May also process pro-NPPB the B-type natriuretic peptide. Ref.5 Ref.10 Ref.11
Isoform 2:has weaker endopeptidase activity compared to isoform 1. Ref.5 Ref.10 Ref.11
Enzyme regulation
Inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine.
Subcellular location
Cell membrane; Single-pass type II membrane protein. Note: May easily detached from the endothelial cell membrane. Ref.8 Ref.9 Ref.10
Isoform 2: Cell membrane; Single-pass type II membrane protein. Note: Less efficiently targeted to the cell membrane compared to isoform 1. Ref.8 Ref.9 Ref.10
Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment: Secreted. Note: Soluble form produced following cleavage by ADAM10. Ref.8 Ref.9 Ref.10
Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment: Secreted. Note: Soluble form produced following autocatalytic cleavage.
Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment: Secreted. Note: Soluble form produced following autocatalytic cleavage.
Tissue specificity
Highly expressed in heart. Expressed in heart myocytes. Also expressed in pregnant uterus. Detected in blood, in plasma as well as in serum (at protein level). Ref.1 Ref.8 Ref.11
Domain
The DDNN motif is required for targeting to the cell membrane and enzyme activation (Ref.10).
Post-translational modification
- N-glycosylated; required for processing and activation. Ref.7 Ref.10
- Activated through proteolytic processing by a trypsin-like protease; cleaved into a N-terminal propeptide and an activated corin protease fragment. Different soluble forms are produced by cleavage and autocatalytic cleavage: Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment is produced by cleavage by ADAM10, while 160 kDa and 100 kDa soluble fragments are produced by autocatalytic cleavage. Cleavage by ADAM10 to produce soluble 180 kDa soluble fragment takes place after the transmembrane region and before FZ 1. Ref.7 Ref.9
A disulfide bond links the activated corin protease fragment and the N-terminal propeptide. The disulfide bond also links the activated corin protease fragment with soluble fragments (100 kDa, 160 kDa and 180 kDa fragments).
Involvement in disease
子癇
Pre-eclampsia/eclampsia 5 (PEE5) [MIM:614595]: A hypertensive disorder of pregnancy characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. It impacts 2 individuals, the mother and her child, both of whom can be severely affected. Preeclampsia is one of the causes of maternal mortality and morbidity worldwide.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Miscellaneous
Initially named CORIN due to its abundant expression in the heart (Ref.1).
Sequence similarities
Belongs to the peptidase S1 family.
Contains 2 FZ (frizzled) domains.
Contains 7 LDL-receptor class A domains.
Contains 1 peptidase S1 domain.
Contains 1 SRCR domain.
Biophysicochemical properties
Kinetic parameters:
KM=1.28 mM for pyroGlu-Phe-Lys-pNA.HCl Ref.6
KM=3.52 mM for pyroGlu-Pro-Arg-pNA.HCl
KM=2.95 mM for H-D-Pro-Phe-Arg-pNA.2HCl
KM=1.92 mM for Bz-Ile-Glu-(gamma-OR)-Gly-Arg-pNA.HCl
KM=16 mM for pyroGlu-Gly-Arg-pNA.HCl
Atrial natriuretic peptide receptor 1
EC=4.6.1.2
Alternative name(s):
Atrial natriuretic peptide receptor type A
Short name=ANP-A
Short name=ANPR-A
Short name=NPR-A
Guanylate cyclase A
Short name=GC-A
Function
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand. Ref.10
Catalytic activity
GTP = 3',5'-cyclic GMP + diphosphate.
Subunit structure
Homodimer By similarity.
Subcellular location
Membrane; Single-pass type I membrane protein.
Post-translational modification
Phosphorylation of the protein kinase-like domain is required for full activation by ANP By similarity.
Sequence similarities
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Contains 1 guanylate cyclase domain.
Contains 1 protein kinase domain.
Atrial natriuretic peptide receptor 3
Alternative name(s):
Atrial natriuretic peptide clearance receptor
Atrial natriuretic peptide receptor type C
Short name=ANP-C
Short name=ANPR-C
Short name=NPR-C
Gene names
Name: NPR3
Synonyms: ANPRC, C5orf23, NPRC
Function
Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects. May regulate diuresis, blood pressure and skeletal development. Does not have guanylate cyclase activity.
Subunit structure
Homodimer; disulfide-linked. Dimers can also be formed through the C-terminal cysteine of isoform 2. Ref.8 Ref.10 Ref.11
Subcellular location
Membrane; Single-pass type I membrane protein.
Miscellaneous
Has low affinity for peptide hormones in the absence of bound chloride.
Sequence similarities
Belongs to the ANF receptor family.
