Gene: [01p362/NPPA] natriuretic peptide precursor A (cardionatrin; atrial hormone); atrionatriuretic peptide (atriopeptin, prepronatriodilatin); [ANP PND ANF ]

COM

 [1] Atriopeptin (ANP) is a potent vasoactive peptide synthesized in human atrium (heart) and is thought to play a key role in cardiovascular homeostasis by means of extracellular fluid volume and electrolyte homeostatic controlling mechanisms. ANP acts by stimulating cGMP; belongs to the family of natriuretic peptides also including BNP, CNP (see GEM:01p362/NPPB and GEM:02q/NPPC) which interact with their specific receptors (GEM:01q211/NPR1; GEM:09p/NPR2; GEM:05p1/NPR3).
[2] According to comments presented in the relevant SwissProt Data Base entry (SWI:P01160[:CC]), the human genome contains two different pronatriodilatin genes one of which encodes for two additional Arg/R residues at the precursor C-terminus that are cleaved to form the mature peptide, whereas the other gene contains a stop-codon immediately after the last codon of the mature peptide. These data are not yet reflected however in Genome Data Base and Online MIM.
[3] Also see 'Gene polymorphism', 'Peptide product', and 'Pathology' in the given entry and 'Genetic map' in GEM:01p363/D1Z2[:MAG].[GEM:01p362/NPPA:POL,PRT,PAT]"

PRT

 "NPPA precursor protein: =153 aa; =16708 Da.
Sourses:
- Oikawa S, Imai M, Ueno A, Tanaka S, Noguchi T, Nakazato H, Kangawa K,
Fukuda A, Matsuo H;
Nature, 309, 724-726, 1984;
Cloning and sequence analysis of cDNA encoding a precursor for human
atrial natriuretic polypeptide.
- Nakayama K, Ohkubo H, Hirose T, Inayama S, Nakanishi S;
Nature, 310, 699-701, 1984;
mRNA sequence for human cardiodilatin-atrial natriuretic factor
precursor and regulation of precursor mRNA in rat atria.
- Nemer M, Chamberland M, Sirois D, Argentin S, Drouin J, Dixon RAF,
Zivin RA, Condra JH;
Nature, 312, 654-656, 1984;
Gene structure of human cardiac hormone precursor, pronatriodilatin.
- Greenberg BD, Bencen GH, Seilhamer JJ, Lewicki JA, Fiddes JC;
Nature, 312, 656-658, 1984;
Nucleotide sequence of the gene encoding human atrial natriuretic
factor precursor.
- Seidman CE, Bloch KD, Klein KA, Smith JA, Seidman JG;
Science, 226, 1206-1209, 1984;
Nucleotide sequences of the human and mouse atrial natriuretic factor
genes;
/Note: all six of the above mentioned publications described AA-Seq
of 1-151 aa residues, i.e., the polypeptide lacking the last two
amino acids (Arg-Arg/RR)/.
- Zivin RA, Condra JH, Dixon RAF, Seidah NG, Chretien M, Nemer M,
Chamberland M, Drouin J;
Proc Natl Acad Sci USA, 81, 6325-6329, 1984;
Molecular cloning and characterization of DNA sequences encoding rat
and human atrial natriuretic factors;
/Note: AA-Seq of 118-153 aa residues/.
- Maki M, Parmentier M, Inagami T;
Biochem Biophys Res Commun, 125, 797-802, 1984;
Cloning of genomic DNA for human atrial natriuretic factor;
/Note: AA-Seq of 1-75 aa residues/.
- Kangawa K, Matsuo H;
Biochem Biophys Res Commun, 118, 131-139, 1984;
/Note: AA-Seq of 124-151 aa residues/.
.....................................................................
PRT:{-25( 1)=MSSFSTTTVS FLLLLAFQLL GQTRA=
1( 26)=NPMYNAVSNA DLMDFKNLLD HLEEKMPLED=
31( 56)=EVVPPQVLSE PNEEAGAALS PLPEVPPWTG EVSPAQRDGG ALGRGPWDSS=
81(106)=DRSALLKSKL RALLTAPR=
99(124)=SLRRSSCFGG RMDRIGAQSG LGCNSFRY=
127(152)=RR=128(153)}
.....................................................................
Features:
{seg(-25..-1) = SIGNAL-peptide /Note: in the precursor, seg(1..25);
seg(1..30) = CARDIODILATIN-related peptide /: seg(26..55);
seg(99..126) = ATRIAL NATRIURETIC peptide, ALPHA /: seg(124..151);
seg(105..121) = DISULFID bond Cys-Cys/C..C /: seg(130..146);
seg(127..128) = variant missing in one of the two genes /: seg(152..153)}
............................................................................"

POL

 The following RFLPs have been found for NPPA: Bgl II, Bgl I, BsmI (Frossard-1986,1987); XhoI, TaqI (Nemer-1986); ScaI, NsiI (Masharani-1988). The latter authors demonstrated that the ScaI RFLP (at sites ) is diallelic: (1) a 10 kb fragment at the frequency p=0.12, and (2) 7.4/2.6 kb paired fragments at the frequency (1-p)=0.88. The NsiI RFLP (at sites ) is diallelic in relation to presence/absence of a 16 kb fragment at the frequency (1-p)=0.95, in addition to the 6.8 kb constant fragment."

PAT

 According to a recent publication by John-1995, the authors were generated mice with an alteration of the NPPA gene. When homozygous animals were fed standard or intermediate salt diets (0.5 and 2% sodium chloride, respectively), their blood pressures were elevated by 8 to 23 mm of mercury, and they had no circulating atrial natriuretic peptide, ANP. Although heterozygotes had normal amounts of circulating ANP and normal blood pressures on standard salt diets, they became certainly hypertensive with blood pressures elevated by 27 mm of mercury, on higher salt diets
(8% sodium chloride). These results demonstrate that genetically reduced production of ANP can cause salt-dependent hypertension."

ECR

 "[1] Cross-References to Protein DBs:
swp:P01160/ANF_HUMAN/Jul-21-1986/Aug-13-1987/Nov-01-1991.
pir:A01424/AWHU; pir:A22693; pir:A32733.
prosite:PS00263/natriuretic_peptide.
[2] Cross-References to DNA DBs:
emb:K02043/HSANF; emb:X01471/HSANFPRE; emb:K02044/HSANFB;
emb:M30262/HSCDDANF; emb:K02399/HSANFH."

REF

 FUN,EXP,MEB "Ackermann U: Clin Chem, 32, 241-247, 1986
FUN,EXP,MEB "de Bold AJ: Science, 230, 767-770, 1985
LOC,CYG "Dracopoli NC &: Genomics, 9, N4 (Apr), 686-700, 1991
FUN,EXP,MEB "Flynn TG, Davies PL &: Biochem J, 232, 313-321, 1985
POL,MOL "Frossard PM &: NAR, 15, 7656, 1987
POL,MOL "Frossard PM &: NAR, 14, 5121, 1986a
POL,MOL "Frossard PM &: NAR, 14, 9223, 1986b
CLO,GEN,SEQ,STR "Greenberg BD &: Nature, 312, 656-658, 1984
FUN,EXP,MEB "Johansson B &: BBRC, 148, 1087-1092, 1987
PAT,MOD,MOU "John SWM &: Science, 267, N5198 (Feb 3), 679-681, 1995
CLO,SEQ,COD "Kennedy BP &: BBRC, 122, 1076-1082, 1984
FUN,EXP,MEB "Lang RE &: Nature, 314, 264-266, 1985
FUN,EXP,MEB "Laragh JH: New Engl J Med, 313, 1330-1340, 1985
CLO,GEN,SEQ,STR "Maki M &: BBRC, 125, 797-802, 1984
POL,MOL "Masharani U &: Hum Genet, 80, 307, 1988
FUN,EXP,MEB "Napier MA &: PNAS, 81, 5946-5950, 1984
FUN,EXP,MEB "Needleman P, Greenwald JE: New Engl J Med, 314, 828-834, 1986
POL,MOL "Nemer M &: NAR, 14, 8696, 1986a
POL,MOL "Nemer M &: NAR, 14, 8697, 1986b
CLO,GEN,SEQ,STR "Nemer M &: Nature, 312, 654-656, 1984
CLO,SEQ,COD "Oikawa S &: Nature, 309, 724-726, 1984
EVO,SEQ,HUM,MOU "Sachse H &: Nucleos Nuc, 7, 61-73, 1988
EVO,SEQ,HUM,MOU "Seidman CE &: Science, 226, 1206-1209, 1984
FUN,EXP,MEB "Weidmann &: Am J Nephrol, 8, 1-14, 1988
FUN,EXP,MEB "Yamaji T &: J Clin Invest, 76, 1705-1709, 1985
LOC,CYG "Yang-Feng TL &: AJHG, 37, N6 (Nov), 1117-1128, 1985
CLO,SEQ,COD "Zivin RA &: PNAS, 81, 6325-6329, 1984

KEY

 horm, neu, card, ren

CLA

 coding, basic

LOC

 01 p36.2

MIM

 MIM: 108780

SYN

 ANP PND ANF

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