ANF_RAT
ID ANF_RAT Reviewed; 152 AA.
AC P01161;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Natriuretic peptides A {ECO:0000305};
DE AltName: Full=Atrial natriuretic factor prohormone {ECO:0000250|UniProtKB:P01160};
DE Short=preproANF {ECO:0000303|PubMed:6234658};
DE Short=proANF {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Atrial natriuretic peptide prohormone {ECO:0000250|UniProtKB:P01160};
DE Short=preproANP {ECO:0000250|UniProtKB:P01160};
DE Short=proANP {ECO:0000303|PubMed:7831500};
DE AltName: Full=Atriopeptigen {ECO:0000303|PubMed:6419347};
DE AltName: Full=Cardiodilatin {ECO:0000250|UniProtKB:P01160};
DE Short=CDD {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=preproCDD-ANF {ECO:0000250|UniProtKB:P01160};
DE Contains:
DE RecName: Full=Long-acting natriuretic peptide {ECO:0000250|UniProtKB:P01160};
DE Short=LANP {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Long-acting natriuretic hormone {ECO:0000305};
DE Short=LANH {ECO:0000305};
DE AltName: Full=Pro atrial natriuretic factor 1-30 {ECO:0000250|UniProtKB:P01160};
DE Short=proANF 1-30 {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic peptide 1-30 {ECO:0000305};
DE Short=proANP 1-30 {ECO:0000305};
DE Contains:
DE RecName: Full=Vessel dilator {ECO:0000250|UniProtKB:P01160};
DE Short=VSDL {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic factor 31-67 {ECO:0000250|UniProtKB:P01160};
DE Short=proANF 31-67 {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic peptide 31-67 {ECO:0000305};
DE Short=proANP 31-67 {ECO:0000305};
DE Contains:
DE RecName: Full=Kaliuretic peptide {ECO:0000250|UniProtKB:P01160};
DE Short=KP {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic factor 79-98 {ECO:0000250|UniProtKB:P01160};
DE Short=proANF 79-98 {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic peptide 79-98 {ECO:0000305};
DE Short=proANP 79-98 {ECO:0000305};
DE Contains:
DE RecName: Full=Urodilatin {ECO:0000250|UniProtKB:P01160};
DE Short=URO {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=CDD 95-126 {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=CDD-ANP (95-126) {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Pro atrial natriuretic peptide 95-126 {ECO:0000250|UniProtKB:P01160};
DE Short=proANP 95-126 {ECO:0000250|UniProtKB:P01160};
DE Contains:
DE RecName: Full=Auriculin-C {ECO:0000305};
DE AltName: Full=Atrial natriuretic factor 1-33 {ECO:0000303|PubMed:6232612};
DE Short=ANF 1-33 {ECO:0000303|PubMed:6232612};
DE Contains:
DE RecName: Full=Auriculin-D {ECO:0000305};
DE AltName: Full=Atrial natriuretic factor 3-33 {ECO:0000303|PubMed:6232612};
DE Short=ANF 3-33 {ECO:0000303|PubMed:6232612};
DE Contains:
DE RecName: Full=Atrial natriuretic peptide {ECO:0000250|UniProtKB:P01160};
DE Short=ANP {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Alpha-atrial natriuretic peptide {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Alpha-hANP {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Atrial natriuretic factor {ECO:0000303|PubMed:6547210};
DE Short=ANF {ECO:0000303|PubMed:6547210};
DE AltName: Full=CDD-ANF {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=CDD-ANP (99-126) {ECO:0000250|UniProtKB:P01160};
DE AltName: Full=Cardionatrin {ECO:0000303|PubMed:3160114};
DE AltName: Full=Pro atrial natriuretic factor 99-126 {ECO:0000250|UniProtKB:P01160};
DE Short=proANF 99-126 {ECO:0000250|UniProtKB:P01160};
DE Contains:
DE RecName: Full=Auriculin-B {ECO:0000305};
DE AltName: Full=Atrial natriuretic factor 8-33 {ECO:0000303|PubMed:6232612};
DE Short=ANF 8-33 {ECO:0000303|PubMed:6232612};
DE Contains:
DE RecName: Full=Auriculin-A {ECO:0000303|PubMed:6233494};
DE Contains:
DE RecName: Full=Atriopeptin-1 {ECO:0000303|PubMed:6419347};
DE AltName: Full=Atriopeptin I {ECO:0000303|PubMed:6419347};
DE Contains:
DE RecName: Full=Atriopeptin-2 {ECO:0000303|PubMed:6419347};
DE AltName: Full=Atriopeptin II {ECO:0000303|PubMed:6419347};
DE Contains:
DE RecName: Full=Atriopeptin-3 {ECO:0000303|PubMed:3160114};
DE AltName: Full=Atriopeptin III {ECO:0000303|PubMed:3160114};
DE Flags: Precursor;
GN Name=Nppa;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6547210; DOI=10.1038/309719a0;
RA Yamanaka M., Greenberg B., Johnson L., Seilhamer J.J., Brewer M.,
RA Friedemann T., Miller J., Atlas S.A., Laragh J., Lewicki J., Fiddes J.C.;
RT "Cloning and sequence analysis of the cDNA for the rat atrial natriuretic
RT factor precursor.";
RL Nature 309:719-722(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6328328; DOI=10.1038/309722a0;
RA Maki M., Takayanagi R., Misono K.S., Pandey K.N., Tibbetts C., Inagami T.;
RT "Structure of rat atrial natriuretic factor precursor deduced from cDNA
RT sequence.";
RL Nature 309:722-724(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6234658; DOI=10.1126/science.6234658;
RA Seidman C.E., Duby A.D., Choi E., Graham R.M., Haber E., Homcy C.,
RA Smith J.A., Seidman J.G.;
RT "The structure of rat preproatrial natriuretic factor as defined by a
RT complementary DNA clone.";
RL Science 225:324-326(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6239103; DOI=10.1038/312152a0;
RA Kangawa K., Tawaragi Y., Oikawa S., Mizuno A., Sakuragawa Y., Nakazato H.,
RA Fukuda A., Minamino N., Matsuo H.;
RT "Identification of rat gamma atrial natriuretic polypeptide and
RT characterization of the cDNA encoding its precursor.";
RL Nature 312:152-155(1984).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2985557; DOI=10.1016/s0021-9258(18)89107-4;
RA Argentin S., Nemer M., Drouin J., Scott G.K., Kennedy B.P., Davies P.L.;
RT "The gene for rat atrial natriuretic factor.";
RL J. Biol. Chem. 260:4568-4571(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6238331; DOI=10.1073/pnas.81.20.6325;
RA Zivin R.A., Condra J.H., Dixon R.A.F., Seidah N.G., Chretien M., Nemer M.,
RA Chamberland M., Drouin J.;
RT "Molecular cloning and characterization of DNA sequences encoding rat and
RT human atrial natriuretic factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:6325-6329(1984).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2962707; DOI=10.1139/y87-315;
RA Flynn T.G.;
RT "The elucidation of the structure of atrial natriuretic factor, a new
RT peptide hormone.";
RL Can. J. Physiol. Pharmacol. 65:2013-2020(1987).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=1837590; DOI=10.1210/mend-5-9-1292;
RA Dagnino L., Drouin J., Nemer M.;
RT "Differential expression of natriuretic peptide genes in cardiac and
RT extracardiac tissues.";
RL Mol. Endocrinol. 5:1292-1300(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-152.
RX PubMed=2951736; DOI=10.1073/pnas.84.8.2175;
RA Gardner D.G., Vlasuk G.P., Baxter J.D., Fiddes J.C., Lewicki J.A.;
RT "Identification of atrial natriuretic factor gene transcripts in the
RT central nervous system of the rat.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2175-2179(1987).
RN [10]
RP PROTEIN SEQUENCE OF 126-149, SYNTHESIS (AURICULIN-A), FUNCTION
RP (AURICULIN-A), TISSUE SPECIFICITY (AURICULIN-A), AND PROTEOLYTIC PROCESSING
RP (AURICULIN-A).
RX PubMed=6233494; DOI=10.1038/309717a0;
RA Atlas S.A., Kleinert H.D., Camargo M.J., Januszewicz A., Sealey J.E.,
RA Laragh J.H., Schilling J.W., Lewicki J.A., Johnson L.K., Maack T.;
RT "Purification, sequencing and synthesis of natriuretic and vasoactive rat
RT atrial peptide.";
RL Nature 309:717-719(1984).
RN [11]
RP PROTEIN SEQUENCE OF 127-150, FUNCTION (ATRIOPEPTIN-1 AND ATRIOPEPTIN-2),
RP TISSUE SPECIFICITY (ATRIOPEPTIN-1 AND ATRIOPEPTIN-2), AND PROTEOLYTIC
RP PROCESSING (ATRIOPEPTIN-1 AND ATRIOPEPTIN-2).
RX PubMed=6419347; DOI=10.1126/science.6419347;
RA Currie M.G., Geller D.M., Cole B.R., Siegel N.R., Fok K.F., Adams S.P.,
RA Eubanks S.R., Galluppi G.R., Needleman P.;
RT "Purification and sequence analysis of bioactive atrial peptides
RT (atriopeptins).";
RL Science 223:67-69(1984).
RN [12]
RP PROTEIN SEQUENCE OF 118-150, SYNTHESIS (AURICULIN-B), FUNCTION (AURICULIN-B
RP AND AURICULIN-D), TISSUE SPECIFICITY (AURICULIN-B; AURICULIN-C AND
RP AURICULIN-D), AND PROTEOLYTIC PROCESSING (AURICULIN-B; AURICULIN-C AND
RP AURICULIN-D).
RX PubMed=6232612; DOI=10.1073/pnas.81.9.2640;
RA Seidah N.G., Lazure C., Chretien M., Thibault G., Garcia R., Cantin M.,
RA Genest J., Nutt R.F., Brady S.F., Lyle T.A., Paleveda W.J., Colton C.D.,
RA Ciccarone T.M., Veber D.F.;
RT "Amino acid sequence of homologous rat atrial peptides: natriuretic
RT activity of native and synthetic forms.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:2640-2644(1984).
RN [13]
RP PROTEIN SEQUENCE OF 123-150, SYNTHESIS (ATRIAL NATRIURETIC PEPTIDE AND
RP ATRIOPEPTIN-3), AND SUBCELLULAR LOCATION (ATRIAL NATRIURETIC PEPTIDE AND
RP ATRIOPEPTIN-3).
RX PubMed=3160114; DOI=10.1126/science.3160114;
RA Schwartz D., Geller D.M., Manning P.T., Siegel N.R., Fok K.F., Smith C.E.,
RA Needleman P.;
RT "Ser-Leu-Arg-Arg-atriopeptin III: the major circulating form of atrial
RT peptide.";
RL Science 229:397-400(1985).
RN [14]
RP PROTEIN SEQUENCE OF 25-38, SYNTHESIS (ATRIAL NATRIURETIC PEPTIDE), AND
RP SUBCELLULAR LOCATION (ATRIAL NATRIURETIC PEPTIDE).
RX PubMed=2966345; DOI=10.1016/0196-9781(88)90008-3;
RA Thibault G., Murthy K.K., Gutkowska J., Seidah N.G., Lazure C.,
RA Chretien M., Cantin M.;
RT "NH2-terminal fragment of rat pro-atrial natriuretic factor in the
RT circulation: identification, radioimmunoassay and half-life.";
RL Peptides 9:47-53(1988).
RN [15]
RP PROTEIN SEQUENCE OF 99-115, AND TISSUE SPECIFICITY (ATRIAL NATRIURETIC
RP PEPTIDE).
RX PubMed=2525379; DOI=10.1016/0006-291x(89)92661-2;
RA Itoh H., Nakao K., Kambayashi Y., Hosoda K., Saito Y., Yamada T.,
RA Mukoyama M., Arai H., Shirakami G., Suga S., Yoshida I., Inouye K.,
RA Imura H.;
RT "Occurrence of a novel cardiac natriuretic peptide in rats.";
RL Biochem. Biophys. Res. Commun. 161:732-739(1989).
RN [16]
RP PROTEOLYTIC PROCESSING BY MME (ATRIAL NATRIURETIC PEPTIDE), AND CLEAVAGE
RP SITE.
RX PubMed=2966343; DOI=10.1016/0196-9781(88)90024-1;
RA Sonnenberg J.L., Sakane Y., Jeng A.Y., Koehn J.A., Ansell J.A.,
RA Wennogle L.P., Ghai R.D.;
RT "Identification of protease 3.4.24.11 as the major atrial natriuretic
RT factor degrading enzyme in the rat kidney.";
RL Peptides 9:173-180(1988).
RN [17]
RP SYNTHESIS (LONG-ACTING NATRIURETIC PEPTIDE AND VESSEL DILATOR), AND
RP FUNCTION (LONG-ACTING NATRIURETIC PEPTIDE; VESSEL DILATOR AND ATRIAL
RP NATRIURETIC PEPTIDE).
RX PubMed=7831500; DOI=10.1016/0167-0115(94)90612-2;
RA Weir M.L., Honrath U., Flynn T.G., Sonnenberg H.;
RT "Lack of biologic activity or specific binding of amino-terminal pro-ANP
RT segments in the rat.";
RL Regul. Pept. 53:111-122(1994).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 129-149 IN COMPLEX WITH NPR1,
RP RECEPTOR-BINDING (ATRIAL NATRIURETIC PEPTIDE), AND DISULFIDE BOND.
RX PubMed=15117952; DOI=10.1074/jbc.m313222200;
RA Ogawa H., Qiu Y., Ogata C.M., Misono K.S.;
RT "Crystal structure of hormone-bound atrial natriuretic peptide receptor
RT extracellular domain: rotation mechanism for transmembrane signal
RT transduction.";
RL J. Biol. Chem. 279:28625-28631(2004).
CC -!- FUNCTION: [Atrial natriuretic peptide]: Hormone that plays a key role
CC in mediating cardio-renal homeostasis, and is involved in vascular
CC remodeling and regulating energy metabolism (By similarity). Acts by
CC specifically binding and stimulating NPR1 to produce cGMP, which in
CC turn activates effector proteins, such as PRKG1, that drive various
CC biological responses (PubMed:15117952). Regulates vasodilation,
CC natriuresis, diuresis and aldosterone synthesis and is therefore
CC essential for regulating blood pressure, controlling the extracellular
CC fluid volume and maintaining the fluid-electrolyte balance
CC (PubMed:7831500). Also involved in inhibiting cardiac remodeling and
CC cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating
CC the growth of cardiomyocytes and fibroblasts (By similarity). Plays a
CC role in female pregnancy by promoting trophoblast invasion and spiral
CC artery remodeling in uterus, and thus prevents pregnancy-induced
CC hypertension (By similarity). In adipose tissue, acts in various
CC cGMP- and PKG-dependent pathways to regulate lipid metabolism and
CC energy homeostasis (By similarity). This includes up-regulating lipid
CC metabolism and mitochondrial oxygen utilization by activating the AMP-
CC activated protein kinase (AMPK), and increasing energy expenditure by
CC acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown
CC adipose tissue (By similarity). Binds the clearance receptor NPR3 which
CC removes the hormone from circulation (By similarity).
CC {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P05125,
CC ECO:0000269|PubMed:15117952, ECO:0000269|PubMed:7831500}.
CC -!- FUNCTION: [Long-acting natriuretic peptide]: May have a role in cardio-
CC renal homeostasis through regulation of natriuresis, diuresis,
CC vasodilation, and inhibiting aldosterone synthesis (By similarity). In
CC vitro, promotes the production of cGMP and induces vasodilation (By
CC similarity). May promote natriuresis, at least in part, by enhancing
CC prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-
CC ATPase (By similarity). However reports on the involvement of this
CC peptide in mammal blood volume and blood pressure homeostasis are
CC conflicting; according to a report, in vivo it is not sufficient to
CC activate cGMP and does not inhibit collecting duct transport nor effect
CC diuresis and natriuresis (PubMed:7831500). Appears to bind to specific
CC receptors that are distinct from the receptors bound by atrial
CC natriuretic peptide and vessel dilator. Possibly enhances protein
CC excretion in urine by decreasing proximal tubular protein reabsorption
CC (By similarity). {ECO:0000250|UniProtKB:P01160,
CC ECO:0000269|PubMed:7831500}.
CC -!- FUNCTION: [Vessel dilator]: May have a role in cardio-renal homeostasis
CC through regulation of natriuresis, diuresis, and vasodilation (By
CC similarity). In vitro, promotes the production of cGMP and induces
CC vasodilation (By similarity). May promote natriuresis, at least in
CC part, by enhancing prostaglandin E2 synthesis resulting in the
CC inhibition of renal Na+-K+-ATPase (By similarity). However reports on
CC the involvement of this peptide in mammal blood volume and blood
CC pressure homeostasis are conflicting; according to a report, in vivo it
CC is not sufficient to activate cGMP and does not inhibit collecting duct
CC transport nor effect diuresis and natriuresis (PubMed:7831500). Appears
CC to bind to specific receptors that are distinct from the receptors
CC bound by the atrial natriuretic and long-acting natriuretic peptides
CC (By similarity). Possibly functions in protein excretion in urine by
CC maintaining the integrity of the proximal tubules and enhancing protein
CC excretion by decreasing proximal tubular protein reabsorption (By
CC similarity). {ECO:0000250|UniProtKB:P01160,
CC ECO:0000269|PubMed:7831500}.
CC -!- FUNCTION: [Kaliuretic peptide]: May have a role in cardio-renal
CC homeostasis through regulation of diuresis and inhibiting aldosterone
CC synthesis. In vitro, promotes the production of cGMP and induces
CC vasodilation. May promote natriuresis, at least in part, by enhancing
CC prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-
CC ATPase. May have a role in potassium excretion but not sodium excretion
CC (natriuresis). Possibly enhances protein excretion in urine by
CC decreasing proximal tubular protein reabsorption.
CC {ECO:0000250|UniProtKB:P01160}.
CC -!- FUNCTION: [Urodilatin]: Hormone produced in the kidneys that appears to
CC be important for maintaining cardio-renal homeostasis. Mediates
CC vasodilation, natriuresis and diuresis primarily in the renal system,
CC in order to maintain the extracellular fluid volume and control the
CC fluid-electrolyte balance. Specifically binds and stimulates cGMP
CC production by renal transmembrane receptors, likely NPR1. Urodilatin
CC not ANP, may be the natriuretic peptide responsible for the regulation
CC of sodium and water homeostasis in the kidney.
CC {ECO:0000250|UniProtKB:P01160}.
CC -!- FUNCTION: [Auriculin-D]: May have a role in cardio-renal homeostasis
CC through regulation of natriuresis and vasodilation. In vivo promotes
CC natriuresis and in vitro, vasodilates renal artery strips.
CC {ECO:0000269|PubMed:6232612}.
CC -!- FUNCTION: [Auriculin-B]: May have a role in cardio-renal homeostasis
CC through regulation of natriuresis and vasodilation. In vivo promotes
CC natriuresis and in vitro, vasodilates renal artery strips.
CC {ECO:0000269|PubMed:6232612}.
CC -!- FUNCTION: [Auriculin-A]: May have a role in cardio-renal homeostasis
CC through regulation of regulation of natriuresis and vasodilation. In
CC vivo promotes natriuresis. In vitro, vasodilates intestinal smooth
CC muscle but not smooth muscle strips. {ECO:0000269|PubMed:6233494}.
CC -!- FUNCTION: [Atriopeptin-2]: May have a role in cardio-renal homeostasis
CC through regulation of natriuresis and vasodilation. In vivo promotes
CC natriuresis. In vitro, selectively vasodilates intestinal and vascular
CC smooth muscle strips. {ECO:0000269|PubMed:6419347}.
CC -!- FUNCTION: [Atriopeptin-1]: May have a role in cardio-renal homeostasis
CC through regulation of natriuresis and vasodilation. In vivo promotes
CC natriuresis. In vitro, selectively vasodilates intestinal smooth muscle
CC but not vascular smooth muscle strips. {ECO:0000269|PubMed:6419347}.
CC -!- SUBUNIT: [Atrial natriuretic peptide]: Homodimer; disulfide-linked
CC antiparallel dimer. {ECO:0000250|UniProtKB:P01160}.
CC -!- SUBCELLULAR LOCATION: [Long-acting natriuretic peptide]: Secreted
CC {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood.
CC {ECO:0000250|UniProtKB:P01160}.
CC -!- SUBCELLULAR LOCATION: [Vessel dilator]: Secreted
CC {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood.
CC {ECO:0000250|UniProtKB:P01160}.
CC -!- SUBCELLULAR LOCATION: [Kaliuretic peptide]: Secreted
CC {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood.
CC {ECO:0000250|UniProtKB:P01160}.
CC -!- SUBCELLULAR LOCATION: [Urodilatin]: Secreted
CC {ECO:0000250|UniProtKB:P01160}. Note=Detected in urine. Not detected in
CC blood. Increased electrolytes, osmolality and intracellular cAMP levels
CC increase peptide secretion/excretion. {ECO:0000250|UniProtKB:P01160}.
CC -!- SUBCELLULAR LOCATION: [Atrial natriuretic peptide]: Secreted
CC {ECO:0000269|PubMed:2966345, ECO:0000269|PubMed:3160114}. Perikaryon
CC {ECO:0000250|UniProtKB:P01160}. Cell projection
CC {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood (PubMed:2966345,
CC PubMed:3160114). Detected in urine in one study (By similarity).
CC However, in another study, was not detected in urine (By similarity).
CC Detected in cytoplasmic bodies and neuronal processes of pyramidal
CC neurons (layers II-VI) (By similarity). Increased secretion in response
CC to the vasopressin AVP (PubMed:3160114). Also likely to be secreted in
CC response to an increase in atrial pressure or atrial stretch (By
CC similarity). In kidney cells, secretion increases in response to
CC activated guanylyl cyclases and increased intracellular cAMP levels (By
CC similarity). Plasma levels increase 15 minutes after a high-salt meal,
CC and decrease back to normal plasma levels 1 hr later (By similarity).
CC {ECO:0000250|UniProtKB:P01160, ECO:0000269|PubMed:2966345,
CC ECO:0000269|PubMed:3160114}.
CC -!- SUBCELLULAR LOCATION: [Atriopeptin-3]: Secreted
CC {ECO:0000269|PubMed:3160114}. Note=Detected in blood (PubMed:3160114).
CC Slight increase in secretion in response to the vasopressin AVP
CC (PubMed:3160114). {ECO:0000269|PubMed:3160114}.
CC -!- TISSUE SPECIFICITY: High levels of expression in the atria compared to
CC the ventricles (PubMed:1837590). Very low levels of expression detected
CC in extracardiac tissues such as the brain, hypothalamus, pituitary,
CC lung and aorta (PubMed:1837590). {ECO:0000269|PubMed:1837590}.
CC -!- TISSUE SPECIFICITY: [Auriculin-A]: Atria (at protein level).
CC {ECO:0000269|PubMed:6233494}.
CC -!- TISSUE SPECIFICITY: [Auriculin-B]: Atria (at protein level).
CC {ECO:0000269|PubMed:6232612}.
CC -!- TISSUE SPECIFICITY: [Auriculin-C]: Atria (at protein level).
CC {ECO:0000269|PubMed:6232612}.
CC -!- TISSUE SPECIFICITY: [Auriculin-D]: Atria (at protein level).
CC {ECO:0000269|PubMed:6232612}.
CC -!- TISSUE SPECIFICITY: [Atrial natriuretic peptide]: High levels of
CC expression in the atria with very low levels of expression in the
CC ventricles (at protein level) (PubMed:2525379). Relatively low levels
CC of expression detected in the brain compared to the atria (at protein
CC level) (PubMed:2525379). {ECO:0000269|PubMed:2525379}.
CC -!- TISSUE SPECIFICITY: [Atriopeptin-1]: Atria (at protein level).
CC {ECO:0000269|PubMed:6419347}.
CC -!- TISSUE SPECIFICITY: [Atriopeptin-2]: Atria (at protein level).
CC {ECO:0000269|PubMed:6419347}.
CC -!- PTM: The precursor molecule is proteolytically cleaved by CORIN at Arg-
CC 122 to produce the atrial natriuretic peptide. Undergoes further
CC proteolytic cleavage by unknown proteases to give rise to long-acting
CC natriuretic peptide, vessel dilator and kaliuretic peptide (By
CC similarity). Additional processing gives rise to the auriculin and
CC atriopeptin peptides (PubMed:6233494, PubMed:6419347, PubMed:6232612,
CC PubMed:3160114). In the kidneys, alternative processing by an unknown
CC protease results in the peptide urodilatin (By similarity).
CC {ECO:0000250|UniProtKB:P01160, ECO:0000269|PubMed:3160114,
CC ECO:0000269|PubMed:6232612, ECO:0000269|PubMed:6233494,
CC ECO:0000269|PubMed:6419347}.
CC -!- PTM: [Atrial natriuretic peptide]: Cleavage by MME initiates
CC degradation of the factor and thereby regulates its activity
CC (PubMed:2966343). Degradation by IDE results in reduced activation of
CC NPR1 (in vitro) (By similarity). During IDE degradation, the resulting
CC products can temporarily stimulate NPR2 to produce cGMP, before the
CC fragments are completely degraded and inactivated by IDE (in vitro) (By
CC similarity). {ECO:0000250|UniProtKB:P01160,
CC ECO:0000269|PubMed:2966343}.
CC -!- PTM: [Urodilatin]: Degraded by IDE. {ECO:0000250|UniProtKB:P01160}.
CC -!- PTM: [Urodilatin]: Phosphorylation on Ser-128 decreases vasorelaxant
CC activity. {ECO:0000250|UniProtKB:P01160}.
CC -!- SIMILARITY: Belongs to the natriuretic peptide family. {ECO:0000305}.
CC -!- CAUTION: [Long-acting natriuretic peptide]: Results concerning the
CC involvement of this peptide in blood volume and blood pressure
CC homeostasis are conflicting. Several studies utilising in vitro and
CC heterologous expression systems show that it is able to activate cGMP
CC and promote vasodilation and natriuresis (By similarity). However, an
CC in vivo study found that it is not sufficient to induce any diuretic,
CC natriuretic, nor hypotensive responses, and is unable to bind NPR1 nor
CC increase guanylyl cyclase activity (PubMed:7831500).
CC {ECO:0000250|UniProtKB:P01160, ECO:0000269|PubMed:7831500}.
CC -!- CAUTION: [Vessel dilator]: Results concerning the involvement of this
CC peptide in blood volume and blood pressure homeostasis are conflicting.
CC Several studies utilising in vitro and heterologous expression systems
CC show that it is able to activate cGMP and promote vasodilation and
CC natriuresis (By similarity). However, an in vivo study found that it is
CC not sufficient to induce any diuretic, natriuretic, nor hypotensive
CC responses, and is unable to bind NPR1 nor increase guanylyl cyclase
CC activity (PubMed:7831500). {ECO:0000250|UniProtKB:P01160,
CC ECO:0000269|PubMed:7831500}.
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DR EMBL; M15868; AAA40736.1; -; mRNA.
DR EMBL; X00665; CAA25285.1; -; mRNA.
DR EMBL; K02062; AAA40735.1; -; Genomic_DNA.
DR EMBL; X01118; CAA25586.1; -; mRNA.
DR EMBL; M27498; AAA40737.1; -; mRNA.
DR PIR; A22570; AWRT.
DR RefSeq; NP_036744.1; NM_012612.2.
DR PDB; 1T34; X-ray; 2.95 A; H=129-149.
DR PDB; 7BRG; X-ray; 2.45 A; L=123-150.
DR PDB; 7BRL; X-ray; 3.20 A; L=126-139.
DR PDBsum; 1T34; -.
DR PDBsum; 7BRG; -.
DR PDBsum; 7BRL; -.
DR AlphaFoldDB; P01161; -.
DR BMRB; P01161; -.
DR SMR; P01161; -.
DR IntAct; P01161; 1.
DR STRING; 10116.ENSRNOP00000011005; -.
DR BindingDB; P01161; -.
DR ChEMBL; CHEMBL4287; -.
DR iPTMnet; P01161; -.
DR PhosphoSitePlus; P01161; -.
DR PaxDb; P01161; -.
DR PRIDE; P01161; -.
DR Ensembl; ENSRNOT00000011005; ENSRNOP00000011005; ENSRNOG00000008176.
DR GeneID; 24602; -.
DR KEGG; rno:24602; -.
DR UCSC; RGD:3193; rat.
DR CTD; 4878; -.
DR RGD; 3193; Nppa.
DR eggNOG; ENOG502S9RQ; Eukaryota.
DR GeneTree; ENSGT00940000154513; -.
DR HOGENOM; CLU_144536_0_0_1; -.
DR InParanoid; P01161; -.
DR OMA; LSEVPPW; -.
DR OrthoDB; 1596502at2759; -.
DR PhylomeDB; P01161; -.
DR TreeFam; TF106304; -.
DR Reactome; R-RNO-5578768; Physiological factors.
DR EvolutionaryTrace; P01161; -.
DR PRO; PR:P01161; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000008176; Expressed in heart and 4 other tissues.
DR ExpressionAtlas; P01161; baseline and differential.
DR Genevisible; P01161; RN.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0042629; C:mast cell granule; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005179; F:hormone activity; IDA:RGD.
DR GO; GO:0051427; F:hormone receptor binding; ISO:RGD.
DR GO; GO:0005184; F:neuropeptide hormone activity; ISO:RGD.
DR GO; GO:0071855; F:neuropeptide receptor binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IDA:RGD.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISO:RGD.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0006182; P:cGMP biosynthetic process; IMP:RGD.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:RGD.
DR GO; GO:0007565; P:female pregnancy; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; TAS:UniProtKB.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; TAS:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:RGD.
DR GO; GO:1903815; P:negative regulation of collecting lymphatic vessel constriction; IDA:RGD.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IDA:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; ISO:RGD.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IDA:RGD.
DR GO; GO:1902261; P:positive regulation of delayed rectifier potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:RGD.
DR GO; GO:1903595; P:positive regulation of histamine secretion by mast cell; IDA:UniProtKB.
DR GO; GO:1903766; P:positive regulation of potassium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0006457; P:protein folding; ISO:RGD.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IDA:MGI.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0050878; P:regulation of body fluid levels; TAS:RGD.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:1901841; P:regulation of high voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISO:RGD.
DR GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW.
DR InterPro; IPR000663; Natr_peptide.
DR InterPro; IPR030480; Natr_peptide_CS.
DR InterPro; IPR002407; Natriuretic_peptide_atrial.
DR Pfam; PF00212; ANP; 1.
DR PRINTS; PR00711; ANATPEPTIDE.
DR PRINTS; PR00710; NATPEPTIDES.
DR SMART; SM00183; NAT_PEP; 1.
DR PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone; Phosphoprotein;
KW Reference proteome; Secreted; Signal; Vasoactive; Vasodilator.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:2966345"
FT CHAIN 25..150
FT /note="Natriuretic peptides A"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449770"
FT PROPEP 25..122
FT /evidence="ECO:0000305"
FT /id="PRO_0000001505"
FT PEPTIDE 25..54
FT /note="Long-acting natriuretic peptide"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449771"
FT PEPTIDE 55..91
FT /note="Vessel dilator"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449772"
FT PROPEP 92..102
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449773"
FT PEPTIDE 103..122
FT /note="Kaliuretic peptide"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449774"
FT PEPTIDE 118..150
FT /note="Auriculin-C"
FT /evidence="ECO:0000269|PubMed:6232612"
FT /id="PRO_0000449776"
FT PEPTIDE 119..150
FT /note="Urodilatin"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000449775"
FT PEPTIDE 120..144
FT /note="Auriculin-D"
FT /evidence="ECO:0000269|PubMed:6232612"
FT /id="PRO_0000449777"
FT PEPTIDE 123..150
FT /note="Atrial natriuretic peptide"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT /id="PRO_0000391785"
FT PEPTIDE 126..150
FT /note="Auriculin-B"
FT /evidence="ECO:0000269|PubMed:6232612"
FT /id="PRO_0000001506"
FT PEPTIDE 126..149
FT /note="Auriculin-A"
FT /evidence="ECO:0000269|PubMed:6233494"
FT /id="PRO_0000001507"
FT PEPTIDE 127..150
FT /note="Atriopeptin-3"
FT /evidence="ECO:0000269|PubMed:3160114"
FT /id="PRO_0000001508"
FT PEPTIDE 127..149
FT /note="Atriopeptin-2"
FT /evidence="ECO:0000269|PubMed:6419347"
FT /id="PRO_0000001509"
FT PEPTIDE 127..147
FT /note="Atriopeptin-1"
FT /evidence="ECO:0000269|PubMed:6419347"
FT /id="PRO_0000001510"
FT REGION 54..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 146..150
FT /note="Important for degradation of atrial natriuretic
FT peptide by IDE"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT SITE 122..123
FT /note="Cleavage; by CORIN"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT SITE 129..130
FT /note="Cleavage; by MME"
FT /evidence="ECO:0000269|PubMed:2966343"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01160"
FT DISULFID 129..145
FT /evidence="ECO:0000269|PubMed:15117952"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:7BRG"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:7BRG"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:7BRG"
SQ SEQUENCE 152 AA; 16556 MW; D8AAB2191E29519F CRC64;
MGSFSITKGF FLFLAFWLPG HIGANPVYSA VSNTDLMDFK NLLDHLEEKM PVEDEVMPPQ
ALSEQTDEAG AALSSLSEVP PWTGEVNPSQ RDGGALGRGP WDPSDRSALL KSKLRALLAG
PRSLRRSSCF GGRIDRIGAQ SGLGCNSFRY RR
