| IED ID | IndEnz0002005574 |
| Enzyme Type ID | protease005574 |
| Protein Name |
Natriuretic peptides A Atrial natriuretic factor prohormone preproANF proANF Atrial natriuretic peptide prohormone preproANP proANP Atriopeptigen Cardiodilatin CDD preproCDD-ANF Cleaved into: Long-acting natriuretic peptide LANP Long-acting natriuretic hormone LANH Pro atrial natriuretic factor 1-30 proANF 1-30 Pro atrial natriuretic peptide 1-30 proANP 1-30 ; Vessel dilator VSDL Pro atrial natriuretic factor 31-67 proANF 31-67 Pro atrial natriuretic peptide 31-67 proANP 31-67 ; Kaliuretic peptide KP Pro atrial natriuretic factor 79-98 proANF 79-98 Pro atrial natriuretic peptide 79-98 proANP 79-98 ; Urodilatin URO CDD 95-126 CDD-ANP 95-126 Pro atrial natriuretic peptide 95-126 proANP 95-126 ; Auriculin-C Atrial natriuretic factor 1-33 ANF 1-33 ; Auriculin-D Atrial natriuretic factor 3-33 ANF 3-33 ; Atrial natriuretic peptide ANP Alpha-atrial natriuretic peptide Alpha-hANP Atrial natriuretic factor ANF CDD-ANF CDD-ANP 99-126 Cardionatrin Pro atrial natriuretic factor 99-126 proANF 99-126 ; Auriculin-B Atrial natriuretic factor 8-33 ANF 8-33 ; Auriculin-A; Atriopeptin-1 Atriopeptin I ; Atriopeptin-2 Atriopeptin II ; Atriopeptin-3 Atriopeptin III |
| Gene Name | NPPA |
| Organism | Canis lupus familiaris (Dog) (Canis familiaris) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Carnivora Caniformia Canidae (dog coyote wolf fox) Canis Canis lupus (Gray wolf) Canis lupus familiaris (Dog) (Canis familiaris) |
| Enzyme Sequence | MGSPIAASFLLFLAVQLLGQTGANPVYGSVSNADLLDFKNLLDRLEDKMPLEDEAESPQALSEQNAEAGAALSPLPEVPPWTGEVSPAQRDGGALGRSPWDSSDRSALLKSKLRALLAAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY |
| Enzyme Length | 149 |
| Uniprot Accession Number | P07499 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Atrial natriuretic peptide]: Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism (By similarity). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses (By similarity). Regulates vasodilation, natriuresis, diuresis and aldosterone synthesis and is therefore essential for regulating blood pressure, controlling the extracellular fluid volume and maintaining the fluid-electrolyte balance (By similarity). Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (By similarity). Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension (By similarity). In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis (By similarity). This includes up-regulating lipid metabolism and mitochondrial oxygen utilization by activating the AMP-activated protein kinase (AMPK), and increasing energy expenditure by acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown adipose tissue (By similarity). Binds the clearance receptor NPR3 which removes the hormone from circulation (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P05125}.; FUNCTION: [Long-acting natriuretic peptide]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity). However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report, in vivo it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis (By similarity). Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator. Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Vessel dilator]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides. Possibly functions in protein excretion in urine by maintaining the integrity of the proximal tubules and enhancing protein excretion by decreasing proximal tubular protein reabsorption. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Kaliuretic peptide]: May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. May have a role in potassium excretion but not sodium excretion (natriuresis). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Urodilatin]: Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis. Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance. Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1. Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Auriculin-D]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Auriculin-B]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Auriculin-A]: May have a role in cardio-renal homeostasis through regulation of regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, vasodilates intestinal smooth muscle but not smooth muscle strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Atriopeptin-2]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal and vascular smooth muscle strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Atriopeptin-1]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal smooth muscle but not vascular smooth muscle strips. {ECO:0000250|UniProtKB:P01161}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Disulfide bond (1); Modified residue (1); Peptide (12); Propeptide (2); Region (2); Signal peptide (1); Site (2) |
| Keywords | Cell projection;Disulfide bond;Hormone;Phosphoprotein;Reference proteome;Secreted;Signal;Vasoactive;Vasodilator |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Long-acting natriuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Vessel dilator]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Kaliuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Urodilatin]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in urine. Not detected in blood. Increased electrolytes, osmolality and intracellular cAMP levels increase peptide secretion/excretion. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Atrial natriuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Perikaryon {ECO:0000250|UniProtKB:P01160}. Cell projection {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. Detected in urine in one study. However, in another study, was not detected in urine. Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (By similarity). Increased secretion in response to the vasopressin AVP (By similarity). Likely to be secreted in response to an increase in atrial pressure or atrial stretch. In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels. Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161}.; SUBCELLULAR LOCATION: [Atriopeptin-3]: Secreted {ECO:0000250|UniProtKB:P01161}. Note=Detected in blood. Slight increase in secretion in response to the vasopressin AVP. {ECO:0000250|UniProtKB:P01161}. |
| Modified Residue | MOD_RES 127; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P01160 |
| Post Translational Modification | PTM: The precursor molecule is proteolytically cleaved by CORIN at Arg-121 to produce the atrial natriuretic peptide (By similarity). Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide (By similarity). Additional processing gives rise to the auriculin and atriopeptin peptides (By similarity). In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161}.; PTM: [Atrial natriuretic peptide]: Cleavage by MME initiates degradation of the factor and thereby regulates its activity. Degradation by IDE results in reduced activation of NPR1 (in vitro). During IDE degradation, the resulting products can temporarily stimulate NPR2 to produce cGMP, before the fragments are completely degraded and inactivated by IDE (in vitro). {ECO:0000250|UniProtKB:P01160}.; PTM: [Urodilatin]: Degraded by IDE. {ECO:0000250|UniProtKB:P01160}.; PTM: [Urodilatin]: Phosphorylation on Ser-127 decreases vasorelaxant activity. {ECO:0000250|UniProtKB:P01160}. |
| Signal Peptide | SIGNAL 1..23; /evidence=ECO:0000250|UniProtKB:P24259 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 15838287; 17338155; 18681918; 19585255; 21835711; 22578688; |
| Motif | |
| Gene Encoded By | |
| Mass | 15,819 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |