P18910 (ANPRA_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Atrial natriuretic peptide receptor 1
EC=4.6.1.2

Alternative name(s):
Atrial natriuretic peptide receptor type A
Short name=ANP-A
Short name=ANPR-A
Short name=NPR-A
Guanylate cyclase A
Short name=GC-A

Gene names

Name:

Npr1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1057 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand By similarity.
Catalytic activity	GTP = 3',5'-cyclic GMP + diphosphate.
Subunit structure	Homodimer. Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylation of the protein kinase-like domain is required for full activation by ANP.
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 1 guanylate cyclase domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	cGMP biosynthesis
Cellular component	Membrane
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride GTP-binding Nucleotide-binding
Molecular function	Lyase Receptor Vasoactive
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	dopamine metabolic process Inferred from mutant phenotype. Source: RGD intracellular signal transduction Inferred from direct assay. Source: RGD negative regulation of smooth muscle cell proliferation Inferred from mutant phenotype. Source: RGD positive regulation of cGMP biosynthetic process Inferred from mutant phenotype Ref.1. Source: RGD regulation of blood vessel size Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from direct assay. Source: GOC plasma membrane Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro GTP binding Inferred from direct assay. Source: RGD guanylate cyclase activity Inferred from direct assay Ref.3Ref.1. Source: RGD natriuretic peptide receptor activity Inferred from direct assay. Source: RGD peptide hormone binding Inferred from direct assay. Source: RGD protein kinase activity Inferred from electronic annotation. Source: InterPro protein kinase binding Inferred from mutant phenotype. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Chain

29 – 1057

1029

Atrial natriuretic peptide receptor 1

PRO_0000012362

Regions

Topological domain

29 – 469

441

Extracellular Potential

Transmembrane

470 – 490

21

Helical; Potential

Topological domain

491 – 1057

567

Cytoplasmic Potential

Domain

524 – 801

278

Protein kinase

Domain

872 – 1002

131

Guanylate cyclase

Sites

Binding site

81

1

Chloride

Binding site

113

1

Chloride; via amide nitrogen

Binding site

114

1

Chloride; via amide nitrogen

Amino acid modifications

Modified residue

515

1

Phosphoserine Ref.6

Modified residue

525

1

Phosphoserine Ref.5 Ref.6

Modified residue

528

1

Phosphothreonine Ref.5 Ref.6

Modified residue

530

1

Phosphoserine Ref.5 Ref.6

Modified residue

534

1

Phosphoserine Ref.5 Ref.6

Modified residue

538

1

Phosphoserine Ref.5 Ref.6

Modified residue

541

1

Phosphothreonine Ref.5 Ref.6

Glycosylation

41

1

N-linked (GlcNAc...)

Glycosylation

208

1

N-linked (GlcNAc...) Ref.7 Ref.8

Glycosylation

334

1

N-linked (GlcNAc...) Potential

Glycosylation

375

1

N-linked (GlcNAc...) Potential

Glycosylation

382

1

N-linked (GlcNAc...) Potential

Glycosylation

423

1

N-linked (GlcNAc...)

Disulfide bond

88 ↔ 114

Ref.8

Disulfide bond

192 ↔ 241

Ref.8

Disulfide bond

451 ↔ 460

Ref.8

Experimental info

Mutagenesis

197

1

E → K: Abolishes hormone binding. Ref.7

Mutagenesis

213

1

H → D: Abolishes hormone binding. Ref.7

Mutagenesis

522

1

S → A: No effect on phosphorylation, 15% loss of ANP-dependent activity. Ref.5

Mutagenesis

525

1

S → A: Reduced phosphorylation, 80% loss of ANP-dependent activity. Ref.5

Mutagenesis

525

1

S → E: No effect on ANP-dependent activity. Ref.5

Mutagenesis

528

1

T → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5

Mutagenesis

530

1

S → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5

Mutagenesis

534

1

S → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5

Mutagenesis

538

1

S → A: Reduced phosphorylation, 60% loss of CNP-dependent activity. Ref.5

Mutagenesis

541

1

T → A: Markedly reduced phosphorylation, 50% loss of CNP-dependent activity. Ref.5

Mutagenesis

542

1

T → A: No effect on phosphorylation, 30% loss of ANP-dependent activity. Ref.5

Sequence conflict

366

1

Q → H in AAA41202. Ref.3

Sequence conflict

392

1

L → P in AAA41202. Ref.3

Secondary structure

1

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1057

Helix Strand Turn

Details...

Beta strand

30 – 37

8

Helix

48 – 63

16

Beta strand

73 – 80

8

Beta strand

86 – 88

3

Helix

92 – 104

13

Beta strand

107 – 110

4

Helix

115 – 128

14

Beta strand

132 – 135

4

Helix

140 – 143

4

Turn

145 – 147

3

Beta strand

151 – 153

3

Helix

158 – 172

15

Beta strand

176 – 183

8

Beta strand

186 – 188

3

Helix

191 – 207

17

Beta strand

210 – 216

7

Helix

221 – 223

3

Helix

224 – 234

11

Beta strand

236 – 242

7

Helix

244 – 256

13

Turn

261 – 263

3

Beta strand

265 – 269

5

Beta strand

291 – 293

3

Helix

295 – 301

7

Helix

302 – 304

3

Beta strand

305 – 310

6

Helix

316 – 333

18

Helix

341 – 343

3

Helix

344 – 365

22

Helix

373 – 378

6

Turn

379 – 382

4

Beta strand

383 – 387

5

Beta strand

390 – 394

5

Beta strand

398 – 400

3

Beta strand

404 – 409

6

Turn

411 – 413

3

Beta strand

416 – 422

7

Turn

424 – 426

3

Beta strand

429 – 432

4

Sequences

	Sequence		Length	Mass (Da)
	P18910 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: 9EA9AE685AC05816	FASTA	1,057	118,951
	10 20 30 40 50 60 MPGSRRVRPR LRALLLLPPL LLLRGGHASD LTVAVVLPLT NTSYPWSWAR VGPAVELALA 70 80 90 100 110 120 RVKARPDLLP GWTVRMVLGS SENAAGVCSD TAAPLAAVDL KWEHSPAVFL GPGCVYSAAP 130 140 150 160 170 180 VGRFTAHWRV PLLTAGAPAL GIGVKDEYAL TTRTGPSHVK LGDFVTALHR RLGWEHQALV 190 200 210 220 230 240 LYADRLGDDR PCFFIVEGLY MRVRERLNIT VNHQEFVEGD PDHYPKLLRA VRRKGRVIYI 250 260 270 280 290 300 CSSPDAFRNL MLLALNAGLT GEDYVFFHLD VFGQSLKSAQ GLVPQKPWER GDGQDRSARQ 310 320 330 340 350 360 AFQAAKIITY KEPDNPEYLE FLKQLKLLAD KKFNFTVEDG LKNIIPASFH DGLLLYVQAV 370 380 390 400 410 420 TETLAQGGTV TDGENITQRM WNRSFQGVTG YLKIDRNGDR DTDFSLWDMD PETGAFRVVL 430 440 450 460 470 480 NYNGTSQELM AVSEHKLYWP LGYPPPDVPK CGFDNEDPAC NQDHFSTLEV LALVGSLSLI 490 500 510 520 530 540 SFLIVSFFIY RKMQLEKELV SELWRVRWED LQPSSLERHL RSAGSRLTLS GRGSNYGSLL 550 560 570 580 590 600 TTEGQFQVFA KTAYYKGNLV AVKRVNRKRI ELTRKVLFEL KHMRDVQNEH LTRFVGACTD 610 620 630 640 650 660 PPNICILTEY CPRGSLQDIL ENESITLDWM FRYSLTNDIV KGMLFLHNGA ICSHGNLKSS 670 680 690 700 710 720 NCVVDGRFVL KITDYGLESF RDPEPEQGHT LFAKKLWTAP ELLRMASPPA RGSQAGDVYS 730 740 750 760 770 780 FGIILQEIAL RSGVFYVEGL DLSPKEIIER VTRGEQPPFR PSMDLQSHLE ELGQLMQRCW 790 800 810 820 830 840 AEDPQERPPF QQIRLALRKF NKENSSNILD NLLSRMEQYA NNLEELVEER TQAYLEEKRK 850 860 870 880 890 900 AEALLYQILP HSVAEQLKRG ETVQAEAFDS VTIYFSDIVG FTALSAESTP MQVVTLLNDL 910 920 930 940 950 960 YTCFDAVIDN FDVYKVETIG DAYMVVSGLP VRNGQLHARE VARMALALLD AVRSFRIRHR 970 980 990 1000 1010 1020 PQEQLRLRIG IHTGPVCAGV VGLKMPRYCL FGDTVNTASR MESNGEALKI HLSSETKAVL 1030 1040 1050 EEFDGFELEL RGDVEMKGKG KVRTYWLLGE RGCSTRG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor." Chinkers M., Garbers D.L., Chang M.S., Lowe D.G., Chin H., Goeddel D.V., Schulz S. Nature 338:78-83(1989) [PubMed: 2563900] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide receptor gene." Yamaguchi M., Rutledge L.J., Garbers D.L. J. Biol. Chem. 265:20414-20420(1990) [PubMed: 1978722] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Site-directed mutational analysis of a membrane guanylate cyclase cDNA reveals the atrial natriuretic factor signaling site." Duda T., Goraczniak R.M., Sharma R.K. Proc. Natl. Acad. Sci. U.S.A. 88:7882-7886(1991) [PubMed: 1679239] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"Phosphorylation of the kinase homology domain is essential for activation of the A-type natriuretic peptide receptor." Potter L.R., Hunter T. Mol. Cell. Biol. 18:2164-2172(1998) [PubMed: 9528788] [Abstract] Cited for: PHOSPHORYLATION AT SER-525; THR-528; SER-530; SER-534; SER-538 AND THR-541, MUTAGENESIS OF SER-522; SER-525; THR-528; SER-530; SER-534; SER-538; THR-541 AND THR-542.
[6]	"Mass spectrometric identification of phosphorylation sites in guanylyl cyclase A and B." Yoder A.R., Stone M.D., Griffin T.J., Potter L.R. Biochemistry 49:10137-10145(2010) [PubMed: 20977274] [Abstract] Cited for: PHOSPHORYLATION AT SER-515; SER-525; THR-528; SER-530; SER-534; SER-538 AND THR-541.
[7]	"Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor." van den Akker F., Zhang X., Miyagi M., Huo X., Misono K.S., Yee V.C. Nature 406:101-104(2000) [PubMed: 10894551] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-463 IN COMPLEX WITH CHLORIDE, MUTAGENESIS OF GLU-197 AND HIS-213, SUBUNIT, GLYCOSYLATION AT ASN-208.
[8]	"Crystal structure of hormone-bound atrial natriuretic peptide receptor extracellular domain: rotation mechanism for transmembrane signal transduction." Ogawa H., Qiu Y., Ogata C.M., Misono K.S. J. Biol. Chem. 279:28625-28631(2004) [PubMed: 15117952] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 29-463 IN COMPLEX WITH NPPA AND CHLORIDE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-208.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X14773 mRNA. Translation: CAA32881.1.
J05677 Genomic DNA. Translation: AAA41200.1.
M74535 mRNA. Translation: AAA41202.1.
BC128742 mRNA. Translation: AAI28743.1.

IPI

IPI00196307.

PIR

OYRTR. S03348.

RefSeq

NP_036745.1. NM_012613.1.

UniGene

Rn.10463.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DP4	X-ray	2.00	A/C	29-463	[»]
1T34	X-ray	2.95	A/B	29-463	[»]
1T53	model	-	A	509-799	[»]
3A3K	X-ray	2.50	A/B	29-463	[»]

ProteinModelPortal

P18910.

SMR

P18910. Positions 29-454.

ModBase

Search...

Protein-protein interaction databases

STRING

P18910.

PTM databases

PhosphoSite

P18910.

Proteomic databases

PRIDE

P18910.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000020307; ENSRNOP00000020307; ENSRNOG00000014684.

GeneID

24603.

KEGG

rno:24603.

UCSC

NM_012613. rat.

Organism-specific databases

CTD

4881.

RGD

3195. Npr1.

Phylogenomic databases

eggNOG

maNOG17441.

GeneTree

ENSGT00560000076744.

HOVERGEN

HBG051862.

InParanoid

P18910.

OMA

GRVIYIC.

OrthoDB

EOG4XSKP4.

PhylomeDB

P18910.

Gene expression databases

ArrayExpress

P18910.

Genevestigator

P18910.

GermOnline

ENSRNOG00000014684. Rattus norvegicus.

Family and domain databases

InterPro

IPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR001828. ANF_lig-bd_rcpt.
IPR011009. Kinase-like_dom.
IPR001170. Ntpep_rcpt.
IPR000719. Prot_kinase_cat_dom.
IPR001245. Ser-Thr/Tyr_kinase.
[Graphical view]

Gene3D

G3DSA:3.30.70.1230. A/G_cyclase. 1 hit.

KO

K12323.

Pfam

PF01094. ANF_receptor. 1 hit.
PF00211. Guanylate_cyc. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR00255. NATPEPTIDER.

SMART

SM00044. CYCc. 1 hit.
[Graphical view]

SUPFAM

SSF55073. A/G_cyclase. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00458. ANF_RECEPTORS. 1 hit.
PS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

603816.

Entry information

Entry name

ANPRA_RAT

Accession

Primary (citable) accession number: P18910
Secondary accession number(s): A1A5N8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	November 16, 2011
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program