NPPA (natriuretic peptide A)

Gene

• Entrez ID: 4878
• Gene name: Natriuretic peptide A
• Gene symbol: NPPA
• Synonyms: ANF, ANP, ATFB6, ATRST2, CDD, CDD-ANF, CDP, PND
• Chromosome: 1
• Chromosome location: 1p36.22
• Summary: The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1. [provided by RefSeq, Oct 2015]

Transcription factors

Transcription factor	Regulation	Reference
ANKRD1	Repression	18273862
FOS	Unknown	1530876
GATA4	Activation	14573514
HAND2	Activation	12392994
JARID2	Unknown	18805276
NKX2-2	Activation	14573514
TBX5	Activation	14573514;18451335
ZIC3	Unknown	17468179

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003085	Process	Negative regulation of systemic arterial blood pressure	IBA	21873635
GO:0003180	Process	Aortic valve morphogenesis	TAS	29325903
GO:0005102	Function	Signaling receptor binding	IDA	1672777
GO:0005102	Function	Signaling receptor binding	IPI	16870210
GO:0005179	Function	Hormone activity	IBA	21873635
GO:0005184	Function	Neuropeptide hormone activity	IMP	19646991
GO:0005515	Function	Protein binding	IPI	25416956, 32296183
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0006182	Process	CGMP biosynthetic process	IBA	21873635
GO:0006182	Process	CGMP biosynthetic process	IDA	1672777
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0006457	Process	Protein folding	IDA	16870210
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IBA	21873635
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IDA	1672777
GO:0007218	Process	Neuropeptide signaling pathway	IBA	21873635
GO:0007218	Process	Neuropeptide signaling pathway	IDA	19646991
GO:0007565	Process	Female pregnancy	ISS
GO:0008217	Process	Regulation of blood pressure	IDA	6230082, 6547996
GO:0010460	Process	Positive regulation of heart rate	IMP	19646991
GO:0019934	Process	CGMP-mediated signaling	IBA	21873635
GO:0032991	Component	Protein-containing complex	IDA	16870210
GO:0035994	Process	Response to muscle stretch	TAS	15276478
GO:0042311	Process	Vasodilation	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0043508	Process	Negative regulation of JUN kinase activity	IDA	22399583
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0051427	Function	Hormone receptor binding	IBA	21873635
GO:0051427	Function	Hormone receptor binding	IPI	1660465
GO:0060372	Process	Regulation of atrial cardiac muscle cell membrane repolarization	IMP	19646991
GO:0060452	Process	Positive regulation of cardiac muscle contraction	IMP	19646991
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	27559042
GO:0071855	Function	Neuropeptide receptor binding	IMP	19646991
GO:1901841	Process	Regulation of high voltage-gated calcium channel activity	ISS	8301666
GO:1902261	Process	Positive regulation of delayed rectifier potassium channel activity	IDA	8301666, 19646991
GO:1902514	Process	Regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	ISS	8301666
GO:1903766	Process	Positive regulation of potassium ion export across plasma membrane	IDA	8301666, 19646991
GO:1903779	Process	Regulation of cardiac conduction	TAS

Other IDs

• MIM: 108780
• HGNC: 7939
• e!Ensembl: ENSG00000175206

Protein

• UniProt ID: P01160
• Protein name: Natriuretic peptides A (Atrial natriuretic factor prohormone) (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)]
• Protein 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 (PubMed:8653797, PubMed:7595132, PubMed:2825692, PubMed:7720651, PubMed:8087923, PubMed:2532366, PubMed:22307324, PubMed:18835931, PubMed:21672517, PubMed:15741263, PubMed:16875975). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses (PubMed:25401746, PubMed:9893117, PubMed:1672777, PubMed:1660465, PubMed:2162527, PubMed:2825692, PubMed:7720651, PubMed:22307324, PubMed:8384600, PubMed:21098034). 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 (PubMed:8653797, PubMed:7595132, PubMed:2825692, PubMed:7720651, PubMed:2532366, PubMed:8087923). Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (PubMed:16875975). 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 (PubMed:22307324, PubMed:18835931, PubMed:21672517, PubMed:15741263). This includes upregulating 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 (PubMed:22307324, PubMed:18835931, PubMed:21672517, PubMed:15741263). Binds the clearance receptor NPR3 which removes the hormone from circulation (PubMed:1672777). ; [Long-acting natriuretic peptide]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis (PubMed:8653797, PubMed:7955907, PubMed:8087923, PubMed:2825692, PubMed:7595132, PubMed:2532366). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7720651). 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 (PubMed:2162527, PubMed:2825692). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (PubMed:11145122). ; [Vessel dilator]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation (PubMed:8653797, PubMed:7955907, PubMed:8087923, PubMed:2532366, PubMed:7595132). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7720651, PubMed:7595132). 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 (PubMed:7831500). Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides (PubMed:2162527, PubMed:2825692). 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 (PubMed:11145122). ; [Kaliuretic peptide]: May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis (PubMed:8087923, PubMed:2825692, PubMed:7595132). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7720651, PubMed:7595132). May have a role in potassium excretion but not sodium excretion (natriuresis) (PubMed:8087923). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (PubMed:11145122). ; [Urodilatin]: Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis (PubMed:8351194, PubMed:8853410, PubMed:8779891). Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance (PubMed:2528951, PubMed:8351194, PubMed:8853410, PubMed:8779891). Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1 (PubMed:8384600, PubMed:9893117). Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney (PubMed:8779891, PubMed:8384600). ; [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. ; [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. ; [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. ; [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. ; [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.
• PDB: 1ANP, 1YK0, 3N57
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00212	ANP	116 → 146	Atrial natriuretic peptide	Family

• Sequence:

  MSSFSTTTVSFLLLLAFQLLGQTRANPMYNAVSNADLMDFKNLLDHLEEKMPLEDEVVPP
  QVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRSALLKSKLRALLT
  APRSLRRSSCFGGRMDRIGAQSGLGCNSFRY

• Sequence length: 151