P16066 (ANPRA_HUMAN) 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
Synonyms:	ANPRA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1061 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. 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 process	cGMP biosynthesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride GTP-binding Nucleotide-binding
Molecular function	Lyase Receptor Vasoactive
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	body fluid secretion Traceable author statement PubMed 14960748. Source: UniProtKB dopamine metabolic process Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of cGMP biosynthetic process Inferred from electronic annotation. Source: Compara 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_component	integral to plasma membrane Inferred by curator PubMed 12547834. Source: UniProtKB
Molecular_function	ATP 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: Compara protein kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32
	Chain	33 – 1061	1029	Atrial natriuretic peptide receptor 1		PRO_0000012360
Regions
	Topological domain	33 – 473	441	Extracellular Potential
	Transmembrane	474 – 494	21	Helical; Potential
	Topological domain	495 – 1061	567	Cytoplasmic Potential
	Domain	528 – 805	278	Protein kinase
	Domain	876 – 1006	131	Guanylate cyclase
Sites
	Binding site	85	1	Chloride By similarity
	Binding site	117	1	Chloride; via amide nitrogen By similarity
	Binding site	118	1	Chloride; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	519	1	Phosphoserine Ref.11
	Modified residue	529	1	Phosphoserine Ref.11
	Modified residue	532	1	Phosphothreonine Ref.11
	Modified residue	534	1	Phosphoserine Ref.11
	Modified residue	538	1	Phosphoserine Ref.11
	Modified residue	542	1	Phosphoserine By similarity
	Modified residue	545	1	Phosphothreonine By similarity
	Glycosylation	34	1	N-linked (GlcNAc...) Potential
	Glycosylation	45	1	N-linked (GlcNAc...) Potential
	Glycosylation	212	1	N-linked (GlcNAc...) Potential
	Glycosylation	338	1	N-linked (GlcNAc...) Potential
	Glycosylation	379	1	N-linked (GlcNAc...) Potential
	Glycosylation	386	1	N-linked (GlcNAc...) Potential
	Glycosylation	427	1	N-linked (GlcNAc...) Potential
	Disulfide bond	92 ↔ 118		By similarity
	Disulfide bond	196 ↔ 245		By similarity
	Disulfide bond	455 ↔ 464		By similarity
Natural variations
	Natural variant	182	1	A → V. Ref.12		VAR_042214
	Natural variant	270	1	F → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.12		VAR_042215
	Natural variant	755	1	V → M. Ref.12		VAR_042216
	Natural variant	939	1	R → Q. Ref.12 Corresponds to variant rs35240348 [ dbSNP | Ensembl ].		VAR_042217
	Natural variant	967	1	E → K. Ref.12 Corresponds to variant rs35479618 [ dbSNP | Ensembl ].		VAR_042218
Experimental info
	Sequence conflict	344	1	G → V in AAH63304. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P16066 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: E6B5BD0FCA32F70D	FASTA	1,061	118,919
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00027200.
PIR	OYHUAR. S04459.
RefSeq	NP_000897.3. NM_000906.3.
UniGene	Hs.490330.
3D structure databases
ProteinModelPortal	P16066.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-46246N.
IntAct	P16066. 2 interactions.
MINT	MINT-1192002.
STRING	9606.ENSP00000357669.
PTM databases
PhosphoSite	P16066.
Polymorphism databases
DMDM	113912.
Proteomic databases
PaxDb	P16066.
PRIDE	P16066.
Protocols and materials databases
DNASU	4881.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368680; ENSP00000357669; ENSG00000169418.
GeneID	4881.
KEGG	hsa:4881.
UCSC	uc001fcs.4. human.
Organism-specific databases
CTD	4881.
GeneCards	GC01P153651.
HGNC	HGNC:7943. NPR1.
HPA	HPA031087.
MIM	108960. gene.
neXtProt	NX_P16066.
PharmGKB	PA31736.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000293307.
HOVERGEN	HBG051862.
InParanoid	P16066.
KO	K12323.
OMA	CFFLVEG.
OrthoDB	EOG4XSKP4.
Enzyme and pathway databases
SignaLink	P16066.
Gene expression databases
ArrayExpress	P16066.
Bgee	P16066.
CleanEx	HS_NPR1.
Genevestigator	P16066.
GermOnline	ENSG00000169418. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.1230. 1 hit.
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_cat_dom. [Graphical view]
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
BindingDB	P16066.
ChEMBL	CHEMBL1988.
DrugBank	DB01613. Erythrityl Tetranitrate. DB00883. Isosorbide Dinitrate. DB01020. Isosorbide Mononitrate. DB04899. Nesiritide. DB00435. Nitric Oxide. DB00727. Nitroglycerin. DB00325. Nitroprusside.
GenomeRNAi	4881.
NextBio	18788.
SOURCE	Search...

Entry information

Entry name

ANPRA_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.