General Information

  • ID:  hor002986
  • Uniprot ID:  P01160
  • Protein name:  Atrial natriuretic factor
  • Gene name:  NPPA
  • Organism:  Homo sapiens (Human)
  • Family:  Natriuretic peptide family
  • Source:  Human
  • Expression:  [Urodilatin]: Detected in the kidney distal tubular cells (at protein level) .
  • Disease:  Diseases associated with NPPA include Atrial Standstill 2 and Atrial Fibrillation, Familial, 6.
  • Comments:  NA
  • Taxonomy:  Homo (genus), Homininae (subfamily), Hominidae (family), Hominoidea (superfamily), Catarrhini (parvorder), Simiiformes (infraorder), Haplorrhini (suborder), Primates (order), Euarchontoglires (superorder), Boreoeutheria, Eutheria, Theria, Mammalia (class), Amniota, Tetrapoda, Dipnotetrapodomorpha, Sarcopterygii (superclass), Euteleostomi, Teleostomi, Gnathostomata, Vertebrata, Craniata (subphylum), Chordata (phylum), Deuterostomia, Bilateria, Eumetazoa, Metazoa (kingdom), Opisthokonta, Eukaryota (superkingdom), cellular organisms
  • GO MF:  GO:0005102 signaling receptor binding; GO:0005179 hormone activity; GO:0005184 neuropeptide hormone activity; GO:0005515 protein binding; GO:0051427 hormone receptor binding; GO:0071855 neuropeptide receptor binding
  • GO BP:  GO:0003008 system process; GO:0003085 negative regulation of systemic arterial blood pressure; GO:0003161 cardiac conduction system development; GO:0003180 aortic valve morphogenesis; GO:0006182 cGMP biosynthetic process; GO:0006457 protein folding; GO:0007168 receptor guanylyl cyclase signaling pathway; GO:0007218 neuropeptide signaling pathway; GO:0007565 female pregnancy; GO:0008217 regulation of blood pressure; GO:0010460 positive regulation of heart rate; GO:0014898 cardiac muscle hypertrophy in response to stress; GO:0019934 cGMP-mediated signaling; GO:0035994 response to muscle stretch; GO:0036376 sodium ion export across plasma membrane; GO:0042311 vasodilation; GO:0043508 negative regulation of JUN kinase activity; GO:0045776 negative regulation of blood pressure; GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization; GO:0060452 positive regulation of cardiac muscle contraction; GO:0097746 blood vessel diameter maintenance; GO:1901841 regulation of high voltage-gated calcium channel activity; GO:1902261 positive regulation of delayed rectifier potassium channel activity; GO:1902514 regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; GO:1903766 positive regulation of potassium ion export across plasma membrane
  • GO CC:  GO:0005576 extracellular region; GO:0005615 extracellular space; GO:0005737 cytoplasm; GO:0032991 protein-containing complex; GO:0042995 cell projection; GO:0043204 perikaryon; GO:0062023 collagen-containing extracellular matrix

Sequence Information

  • Sequence:  SLRRSSCFGGRMDRIGAQSGLGCNSFRY
  • Length:  28
  • Propeptide:  MSSFSTTTVSFLLLLAFQLLGQTRANPMYNAVSNADLMDFKNLLDHLEEKMPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY
  • Signal peptide:  MSSFSTTTVSFLLLLAFQLLGQTRA
  • Modification:  T6 Phosphoserine
  • Glycosylation:  NA
  • Mutagenesis:  1-6R->G: Loss of cleavage by CORIN.; 1-3R->G: Loss of cleavage by CORIN.; 24-28R->G: Loss of cleavage by CORIN.

Activity

  • Function:  Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism . Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses. 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 . Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts. Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension. In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis. 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. Binds the clearance receptor NPR3 which removes the hormone from circulation.
  • Mechanism:  NA
  • Cross BBB:  NA
  • Target:  NPR3, NPR1
  • Target Unid:  P17342, P16066
  • IC50: IC50=59pM, Inhibition of aldosterone production ( PubMed ID: 2942845 )
  • EC50: NA
  • ED50: NA
  • kd: Kd=10pM for receptor binding ( PubMed ID: 11054637 )
  • Half life: 22 minutes; /1320 seconds ( PubMed ID: 11054637 )

Structure

  • Disulfide bond:  7-23
  • Structure ID:  AF-O24567-F1(AlphaFold_DB_ID)

  • Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)
    •    AF-O24567-F1.pdbhor002986_AF2.pdbhor002986_ESM.pdb

Physical Information

Mass: 356424 Formula: C127H205N45O39S3
Absent amino acids: EHKPTVW Common amino acids: GRS
pI: 10.95 Basic residues: 5
Polar residues: 14 Hydrophobic residues: 6
Hydrophobicity: -49.64 Boman Index: -8050
Half-Life: 1.9 hour Half-Life Yeast: >20 hour
Half-Life E.Coli: >10 hour Aliphatic Index 45.36
Instability Index: 8255.36 Extinction Coefficient cystines: 1615
Absorbance 280nm: 59.81

Literature

  • PubMed ID:  6230082
  • Title:  Purification and Complete Amino Acid Sequence of Alpha-Human Atrial Natriuretic Polypeptide (alpha-hANP).
  • PubMed ID:  1826098
  • Title:  Hydrolysis of Intact and Cys-Phe-cleaved Human Atrial Natriuretic Peptide in Vitro by Human Tissue Kallikrein
  • PubMed ID:  11054637
  • Title:  
  • PubMed ID:  2942845
  • Title: