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P16066 (ANPRA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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
Synonyms:ANPRA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1061 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. Ref.10

Catalytic activity

GTP = 3',5'-cyclic GMP + diphosphate.

Subunit structure

Homodimer By similarity.

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 By similarity.

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
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandChloride
GTP-binding
Nucleotide-binding
   Molecular functionLyase
Receptor
Vasoactive
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Non-traceable author statement PubMed 12547834. Source: GOC

body fluid secretion

Traceable author statement PubMed 14960748. Source: UniProtKB

cGMP biosynthetic process

Inferred from direct assay Ref.10. Source: UniProtKB

cell surface receptor signaling pathway

Non-traceable author statement PubMed 12547834. Source: UniProtKB

dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

negative regulation of angiogenesis

Traceable author statement PubMed 14737067. Source: UniProtKB

negative regulation of cell growth

Non-traceable author statement PubMed 12727915. Source: UniProtKB

negative regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cGMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of renal sodium excretion

Traceable author statement PubMed 14960748. Source: UniProtKB

positive regulation of urine volume

Traceable author statement PubMed 14737067. Source: UniProtKB

receptor guanylyl cyclase signaling pathway

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of blood pressure

Non-traceable author statement PubMed 12727915. Source: UniProtKB

regulation of blood vessel size

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of vascular permeability

Traceable author statement PubMed 14737067. Source: UniProtKB

regulation of vasodilation

Non-traceable author statement PubMed 7601467. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

Inferred by curator PubMed 12547834. Source: UniProtKB

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

G-protein coupled peptide receptor activity

Non-traceable author statement PubMed 12547834. Source: UniProtKB

GTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

guanylate cyclase activity

Inferred from direct assay Ref.10. Source: UniProtKB

hormone binding

Inferred from physical interaction PubMed 12547834Ref.9. Source: UniProtKB

natriuretic peptide receptor activity

Inferred from direct assay Ref.9Ref.10. Source: UniProtKB

peptide hormone binding

Inferred from electronic annotation. Source: Ensembl

protein kinase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232
Chain33 – 10611029Atrial natriuretic peptide receptor 1
PRO_0000012360

Regions

Topological domain33 – 473441Extracellular Potential
Transmembrane474 – 49421Helical; Potential
Topological domain495 – 1061567Cytoplasmic Potential
Domain528 – 805278Protein kinase
Domain876 – 1006131Guanylate cyclase

Sites

Binding site851Chloride By similarity
Binding site1171Chloride; via amide nitrogen By similarity
Binding site1181Chloride; via amide nitrogen By similarity

Amino acid modifications

Modified residue5191Phosphoserine Ref.11
Modified residue5291Phosphoserine Ref.11
Modified residue5321Phosphothreonine Ref.11
Modified residue5341Phosphoserine Ref.11
Modified residue5381Phosphoserine Ref.11
Modified residue5421Phosphoserine By similarity
Modified residue5451Phosphothreonine By similarity
Glycosylation341N-linked (GlcNAc...) Potential
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation2121N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Glycosylation3791N-linked (GlcNAc...) Potential
Glycosylation3861N-linked (GlcNAc...) Potential
Glycosylation4271N-linked (GlcNAc...) Potential
Disulfide bond92 ↔ 118 By similarity
Disulfide bond196 ↔ 245 By similarity
Disulfide bond455 ↔ 464 By similarity

Natural variations

Natural variant1821A → V. Ref.12
Corresponds to variant rs56019647 [ dbSNP | Ensembl ].
VAR_042214
Natural variant2701F → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.12
VAR_042215
Natural variant7551V → M. Ref.12
VAR_042216
Natural variant9391R → Q. Ref.12
Corresponds to variant rs35240348 [ dbSNP | Ensembl ].
VAR_042217
Natural variant9671E → K. Ref.12
Corresponds to variant rs35479618 [ dbSNP | Ensembl ].
VAR_042218

Experimental info

Sequence conflict3441G → V in AAH63304. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P16066 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: E6B5BD0FCA32F70D

FASTA1,061118,919
        10         20         30         40         50         60 
MPGPRRPAGS RLRLLLLLLL PPLLLLLRGS HAGNLTVAVV LPLANTSYPW SWARVGPAVE 

        70         80         90        100        110        120 
LALAQVKARP DLLPGWTVRT VLGSSENALG VCSDTAAPLA AVDLKWEHNP AVFLGPGCVY 

       130        140        150        160        170        180 
AAAPVGRFTA HWRVPLLTAG APALGFGVKD EYALTTRAGP SYAKLGDFVA ALHRRLGWER 

       190        200        210        220        230        240 
QALMLYAYRP GDEEHCFFLV EGLFMRVRDR LNITVDHLEF AEDDLSHYTR LLRTMPRKGR 

       250        260        270        280        290        300 
VIYICSSPDA FRTLMLLALE AGLCGEDYVF FHLDIFGQSL QGGQGPAPRR PWERGDGQDV 

       310        320        330        340        350        360 
SARQAFQAAK IITYKDPDNP EYLEFLKQLK HLAYEQFNFT MEDGLVNTIP ASFHDGLLLY 

       370        380        390        400        410        420 
IQAVTETLAH GGTVTDGENI TQRMWNRSFQ GVTGYLKIDS SGDRETDFSL WDMDPENGAF 

       430        440        450        460        470        480 
RVVLNYNGTS QELVAVSGRK LNWPLGYPPP DIPKCGFDNE DPACNQDHLS TLEVLALVGS 

       490        500        510        520        530        540 
LSLLGILIVS FFIYRKMQLE KELASELWRV RWEDVEPSSL ERHLRSAGSR LTLSGRGSNY 

       550        560        570        580        590        600 
GSLLTTEGQF QVFAKTAYYK GNLVAVKRVN RKRIELTRKV LFELKHMRDV QNEHLTRFVG 

       610        620        630        640        650        660 
ACTDPPNICI LTEYCPRGSL QDILENESIT LDWMFRYSLT NDIVKGMLFL HNGAICSHGN 

       670        680        690        700        710        720 
LKSSNCVVDG RFVLKITDYG LESFRDLDPE QGHTVYAKKL WTAPELLRMA SPPVRGSQAG 

       730        740        750        760        770        780 
DVYSFGIILQ EIALRSGVFH VEGLDLSPKE IIERVTRGEQ PPFRPSLALQ SHLEELGLLM 

       790        800        810        820        830        840 
QRCWAEDPQE RPPFQQIRLT LRKFNRENSS NILDNLLSRM EQYANNLEEL VEERTQAYLE 

       850        860        870        880        890        900 
EKRKAEALLY QILPHSVAEQ LKRGETVQAE AFDSVTIYFS DIVGFTALSA ESTPMQVVTL 

       910        920        930        940        950        960 
LNDLYTCFDA VIDNFDVYKV ETIGDAYMVV SGLPVRNGRL HACEVARMAL ALLDAVRSFR 

       970        980        990       1000       1010       1020 
IRHRPQEQLR LRIGIHTGPV CAGVVGLKMP RYCLFGDTVN TASRMESNGE ALKIHLSSET 

      1030       1040       1050       1060 
KAVLEEFGGF ELELRGDVEM KGKGKVRTYW LLGERGSSTR G 

« Hide

References

« Hide 'large scale' references
[1]"Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction."
Lowe D.G., Chang M.S., Hellmiss R., Chen E., Singh S., Garbers D.L., Goeddel D.V.
EMBO J. 8:1377-1384(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]"Organization of the human natriuretic peptide receptor A gene."
Takahashi Y., Nakayama T., Soma M., Izumi Y., Kanmatsuse K.
Biochem. Biophys. Res. Commun. 246:736-739(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[3]"Identification of functional polymorphisms in noncoding regions of the human natriuretic peptide receptor A gene."
Maeda N., Knowles J.W.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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.
[8]"Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina."
Pardhasaradhi K., Kutty R.K., Gentleman S., Krishna G.
Cell. Mol. Neurobiol. 14:1-7(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 634-1048.
Tissue: Retina.
[9]"Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera."
Bennett B.D., Bennett G.L., Vitangcol R.V., Jewett J.R., Burnier J., Henzel W., Lowe D.G.
J. Biol. Chem. 266:23060-23067(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: LIGAND-BINDING.
[10]"Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP)."
Koller K.J., Lowe D.G., Bennett G.L., Minamino N., Kangawa K., Matsuo H., Goeddel D.V.
Science 252:120-123(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"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-519; SER-529; THR-532; SER-534 AND SER-538.
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-182; CYS-270; MET-755; GLN-939 AND LYS-967.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15357 mRNA. Translation: CAA33417.1.
AB010491 Genomic DNA. Translation: BAA31199.1.
AF190631 Genomic DNA. Translation: AAF01340.1.
EU326310 Genomic DNA. Translation: ACA05918.1.
AL713889 Genomic DNA. Translation: CAI13613.1.
CH471121 Genomic DNA. Translation: EAW53284.1.
BC063304 mRNA. Translation: AAH63304.1.
S72628 mRNA. Translation: AAD14112.1.
PIROYHUAR. S04459.
RefSeqNP_000897.3. NM_000906.3.
UniGeneHs.490330.

3D structure databases

ProteinModelPortalP16066.
SMRP16066. Positions 34-457, 521-851, 869-1051.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110941. 6 interactions.
DIPDIP-46246N.
IntActP16066. 3 interactions.
MINTMINT-1192002.
STRING9606.ENSP00000357669.

Chemistry

BindingDBP16066.
ChEMBLCHEMBL1988.
DrugBankDB01613. Erythrityl Tetranitrate.
DB00883. Isosorbide Dinitrate.
DB01020. Isosorbide Mononitrate.
DB04899. Nesiritide.
DB00435. Nitric Oxide.
DB00727. Nitroglycerin.
DB00325. Nitroprusside.
GuidetoPHARMACOLOGY1747.

PTM databases

PhosphoSiteP16066.

Polymorphism databases

DMDM113912.

Proteomic databases

PaxDbP16066.
PRIDEP16066.

Protocols and materials databases

DNASU4881.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368680; ENSP00000357669; ENSG00000169418.
GeneID4881.
KEGGhsa:4881.
UCSCuc001fcs.4. human.

Organism-specific databases

CTD4881.
GeneCardsGC01P153651.
HGNCHGNC:7943. NPR1.
HPAHPA031087.
MIM108960. gene.
neXtProtNX_P16066.
PharmGKBPA31736.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000293307.
HOVERGENHBG051862.
InParanoidP16066.
KOK12323.
OMACFFLVEG.
OrthoDBEOG7Z69BJ.
PhylomeDBP16066.
TreeFamTF106338.

Enzyme and pathway databases

SignaLinkP16066.

Gene expression databases

ArrayExpressP16066.
BgeeP16066.
CleanExHS_NPR1.
GenevestigatorP16066.

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

GeneWikiNPR1.
GenomeRNAi4881.
NextBio18788.
PROP16066.
SOURCESearch...

Entry information

Entry nameANPRA_HUMAN
AccessionPrimary (citable) accession number: P16066
Secondary accession number(s): B0ZBF0, Q5SR08, Q6P4Q3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM