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P18910 (ANPRA_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1057 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processcGMP biosynthesis
   Cellular componentMembrane
   DomainSignal
Transmembrane
Transmembrane helix
   LigandChloride
GTP-binding
Nucleotide-binding
   Molecular functionLyase
Receptor
Vasoactive
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcGMP biosynthetic process

Inferred from direct assay PubMed 7552344. Source: RGD

cell surface receptor signaling pathway

Inferred from mutant phenotype PubMed 12082097. Source: RGD

dopamine metabolic process

Inferred from mutant phenotype PubMed 15544851. Source: RGD

intracellular signal transduction

Inferred from direct assay PubMed 11788449. Source: RGD

negative regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 19104909. Source: RGD

positive regulation of cGMP biosynthetic process

Inferred from mutant phenotype PubMed 12217425Ref.1. Source: RGD

receptor guanylyl cyclase signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of blood vessel size

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 7552344. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

GTP binding

Inferred from direct assay PubMed 7552344. Source: RGD

guanylate cyclase activity

Inferred from direct assay Ref.3Ref.1PubMed 7552344. Source: RGD

natriuretic peptide receptor activity

Inferred from direct assay PubMed 12217425PubMed 7552344. Source: RGD

peptide hormone binding

Inferred from direct assay PubMed 7552344. Source: RGD

protein kinase activity

Inferred from electronic annotation. Source: InterPro

protein kinase binding

Inferred from mutant phenotype PubMed 12855709. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828
Chain29 – 10571029Atrial natriuretic peptide receptor 1
PRO_0000012362

Regions

Topological domain29 – 469441Extracellular Potential
Transmembrane470 – 49021Helical; Potential
Topological domain491 – 1057567Cytoplasmic Potential
Domain524 – 801278Protein kinase
Domain872 – 1002131Guanylate cyclase

Sites

Binding site811Chloride
Binding site1131Chloride; via amide nitrogen
Binding site1141Chloride; via amide nitrogen

Amino acid modifications

Modified residue5151Phosphoserine Ref.6
Modified residue5251Phosphoserine Ref.5 Ref.6
Modified residue5281Phosphothreonine Ref.5 Ref.6
Modified residue5301Phosphoserine Ref.5 Ref.6
Modified residue5341Phosphoserine Ref.5 Ref.6
Modified residue5381Phosphoserine Ref.5 Ref.6
Modified residue5411Phosphothreonine Ref.5 Ref.6
Glycosylation411N-linked (GlcNAc...)
Glycosylation2081N-linked (GlcNAc...) Ref.7 Ref.8
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation3751N-linked (GlcNAc...) Potential
Glycosylation3821N-linked (GlcNAc...) Potential
Glycosylation4231N-linked (GlcNAc...)
Disulfide bond88 ↔ 114 Ref.8
Disulfide bond192 ↔ 241 Ref.8
Disulfide bond451 ↔ 460 Ref.8

Experimental info

Mutagenesis1971E → K: Abolishes hormone binding. Ref.7
Mutagenesis2131H → D: Abolishes hormone binding. Ref.7
Mutagenesis5221S → A: No effect on phosphorylation, 15% loss of ANP-dependent activity. Ref.5
Mutagenesis5251S → A: Reduced phosphorylation, 80% loss of ANP-dependent activity. Ref.5
Mutagenesis5251S → E: No effect on ANP-dependent activity. Ref.5
Mutagenesis5281T → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5
Mutagenesis5301S → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5
Mutagenesis5341S → A: Reduced phosphorylation, 50% loss of ANP-dependent activity. Ref.5
Mutagenesis5381S → A: Reduced phosphorylation, 60% loss of CNP-dependent activity. Ref.5
Mutagenesis5411T → A: Markedly reduced phosphorylation, 50% loss of CNP-dependent activity. Ref.5
Mutagenesis5421T → A: No effect on phosphorylation, 30% loss of ANP-dependent activity. Ref.5
Sequence conflict3661Q → H in AAA41202. Ref.3
Sequence conflict3921L → P in AAA41202. Ref.3

Secondary structure

......................................................................... 1057
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P18910 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: 9EA9AE685AC05816

FASTA1,057118,951
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
PIROYRTR. S03348.
RefSeqNP_036745.1. NM_012613.1.
XP_006232653.1. XM_006232591.1.
UniGeneRn.10463.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DP4X-ray2.00A/C29-463[»]
1T34X-ray2.95A/B29-463[»]
1T53model-A509-799[»]
3A3KX-ray2.50A/B29-463[»]
ProteinModelPortalP18910.
SMRP18910. Positions 29-454.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP18910. 1 interaction.

PTM databases

PhosphoSiteP18910.

Proteomic databases

PaxDbP18910.
PRIDEP18910.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000020307; ENSRNOP00000020307; ENSRNOG00000014684.
GeneID24603.
KEGGrno:24603.
UCSCRGD:3195. rat.

Organism-specific databases

CTD4881.
RGD3195. Npr1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00710000106571.
HOGENOMHOG000293307.
HOVERGENHBG051862.
InParanoidP18910.
KOK12323.
OMACFFLVEG.
OrthoDBEOG7Z69BJ.
PhylomeDBP18910.
TreeFamTF106338.

Gene expression databases

GenevestigatorP18910.

Family and domain databases

Gene3D3.30.70.1230. 1 hit.
InterProIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR001828. ANF_lig-bd_rcpt.
IPR011009. Kinase-like_dom.
IPR001170. Ntpep_rcpt.
IPR028082. Peripla_BP_I.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00211. Guanylate_cyc. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00255. NATPEPTIDER.
SMARTSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
SSF55073. SSF55073. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00458. ANF_RECEPTORS. 1 hit.
PS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP18910.
NextBio603816.
PROP18910.

Entry information

Entry nameANPRA_RAT
AccessionPrimary (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: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references