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Protein

Atrial natriuretic peptide receptor 1

Gene

NPR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei85ChlorideBy similarity1
Binding sitei117Chloride; via amide nitrogenBy similarity1
Binding sitei118Chloride; via amide nitrogenBy similarity1

GO - Molecular functioni

  • ATP binding Source: InterPro
  • G-protein coupled peptide receptor activity Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • guanylate cyclase activity Source: UniProtKB
  • hormone binding Source: UniProtKB
  • natriuretic peptide receptor activity Source: UniProtKB
  • peptide hormone binding Source: Ensembl
  • protein kinase activity Source: InterPro
  • protein kinase binding Source: Ensembl

GO - Biological processi

  • body fluid secretion Source: UniProtKB
  • cell surface receptor signaling pathway Source: UniProtKB
  • cGMP biosynthetic process Source: UniProtKB
  • dopamine metabolic process Source: Ensembl
  • intracellular signal transduction Source: Ensembl
  • negative regulation of angiogenesis Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of cGMP biosynthetic process Source: Ensembl
  • positive regulation of renal sodium excretion Source: UniProtKB
  • positive regulation of urine volume Source: UniProtKB
  • receptor guanylyl cyclase signaling pathway Source: UniProtKB
  • regulation of blood pressure Source: UniProtKB
  • regulation of blood vessel diameter Source: UniProtKB
  • regulation of cardiac conduction Source: Reactome
  • regulation of vascular permeability Source: UniProtKB

Keywordsi

Molecular functionLyase, Receptor, Vasoactive
Biological processcGMP biosynthesis
LigandChloride, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi4.6.1.2. 2681.
ReactomeiR-HSA-5578768. Physiological factors.
SignaLinkiP16066.
SIGNORiP16066.

Names & Taxonomyi

Protein namesi
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 namesi
Name:NPR1
Synonyms:ANPRA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000169418.9.
HGNCiHGNC:7943. NPR1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 473ExtracellularSequence analysisAdd BLAST441
Transmembranei474 – 494HelicalSequence analysisAdd BLAST21
Topological domaini495 – 1061CytoplasmicSequence analysisAdd BLAST567

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi4881.
OpenTargetsiENSG00000169418.
PharmGKBiPA31736.

Chemistry databases

ChEMBLiCHEMBL1988.
DrugBankiDB01612. Amyl Nitrite.
DB01613. Erythrityl Tetranitrate.
DB00883. Isosorbide Dinitrate.
DB04899. Nesiritide.
DB00727. Nitroglycerin.
DB00325. Nitroprusside.
DB05034. Ularitide.
GuidetoPHARMACOLOGYi1747.

Polymorphism and mutation databases

BioMutaiNPR1.
DMDMi113912.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Add BLAST32
ChainiPRO_000001236033 – 1061Atrial natriuretic peptide receptor 1Add BLAST1029

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi34N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi45N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi92 ↔ 118By similarity
Disulfide bondi196 ↔ 245By similarity
Glycosylationi212N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi338N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi379N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi386N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi427N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi455 ↔ 464By similarity
Modified residuei519Phosphoserine1 Publication1
Modified residuei529Phosphoserine1 Publication1
Modified residuei532Phosphothreonine1 Publication1
Modified residuei534Phosphoserine1 Publication1
Modified residuei538Phosphoserine1 Publication1
Modified residuei542PhosphoserineBy similarity1
Modified residuei545PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylation of the protein kinase-like domain is required for full activation by ANP.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP16066.
MaxQBiP16066.
PaxDbiP16066.
PeptideAtlasiP16066.
PRIDEiP16066.

PTM databases

iPTMnetiP16066.
PhosphoSitePlusiP16066.

Expressioni

Gene expression databases

BgeeiENSG00000169418.
CleanExiHS_NPR1.
ExpressionAtlasiP16066. baseline and differential.
GenevisibleiP16066. HS.

Organism-specific databases

HPAiHPA031087.

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110941. 5 interactors.
DIPiDIP-46246N.
IntActiP16066. 5 interactors.
MINTiMINT-1192002.
STRINGi9606.ENSP00000357669.

Chemistry databases

BindingDBiP16066.

Structurei

3D structure databases

ProteinModelPortaliP16066.
SMRiP16066.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini528 – 805Protein kinasePROSITE-ProRule annotationAdd BLAST278
Domaini876 – 1006Guanylate cyclasePROSITE-ProRule annotationAdd BLAST131

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1023. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000293307.
HOVERGENiHBG051862.
InParanoidiP16066.
KOiK12323.
OMAiREDPSML.
OrthoDBiEOG091G02QS.
PhylomeDBiP16066.
TreeFamiTF106338.

Family and domain databases

Gene3Di3.30.70.1230. 1 hit.
InterProiView protein in InterPro
IPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR001828. ANF_lig-bd_rcpt.
IPR001170. ANPR/GUC.
IPR011009. Kinase-like_dom.
IPR029787. Nucleotide_cyclase.
IPR028082. Peripla_BP_I.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
PfamiView protein in Pfam
PF01094. ANF_receptor. 1 hit.
PF00211. Guanylate_cyc. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PRINTSiPR00255. NATPEPTIDER.
SMARTiView protein in SMART
SM00044. CYCc. 1 hit.
SUPFAMiSSF53822. SSF53822. 1 hit.
SSF55073. SSF55073. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00458. ANF_RECEPTORS. 1 hit.
PS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16066-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGPRRPAGS RLRLLLLLLL PPLLLLLRGS HAGNLTVAVV LPLANTSYPW
60 70 80 90 100
SWARVGPAVE LALAQVKARP DLLPGWTVRT VLGSSENALG VCSDTAAPLA
110 120 130 140 150
AVDLKWEHNP AVFLGPGCVY AAAPVGRFTA HWRVPLLTAG APALGFGVKD
160 170 180 190 200
EYALTTRAGP SYAKLGDFVA ALHRRLGWER QALMLYAYRP GDEEHCFFLV
210 220 230 240 250
EGLFMRVRDR LNITVDHLEF AEDDLSHYTR LLRTMPRKGR VIYICSSPDA
260 270 280 290 300
FRTLMLLALE AGLCGEDYVF FHLDIFGQSL QGGQGPAPRR PWERGDGQDV
310 320 330 340 350
SARQAFQAAK IITYKDPDNP EYLEFLKQLK HLAYEQFNFT MEDGLVNTIP
360 370 380 390 400
ASFHDGLLLY IQAVTETLAH GGTVTDGENI TQRMWNRSFQ GVTGYLKIDS
410 420 430 440 450
SGDRETDFSL WDMDPENGAF RVVLNYNGTS QELVAVSGRK LNWPLGYPPP
460 470 480 490 500
DIPKCGFDNE DPACNQDHLS TLEVLALVGS LSLLGILIVS FFIYRKMQLE
510 520 530 540 550
KELASELWRV RWEDVEPSSL ERHLRSAGSR LTLSGRGSNY GSLLTTEGQF
560 570 580 590 600
QVFAKTAYYK GNLVAVKRVN RKRIELTRKV LFELKHMRDV QNEHLTRFVG
610 620 630 640 650
ACTDPPNICI LTEYCPRGSL QDILENESIT LDWMFRYSLT NDIVKGMLFL
660 670 680 690 700
HNGAICSHGN LKSSNCVVDG RFVLKITDYG LESFRDLDPE QGHTVYAKKL
710 720 730 740 750
WTAPELLRMA SPPVRGSQAG DVYSFGIILQ EIALRSGVFH VEGLDLSPKE
760 770 780 790 800
IIERVTRGEQ PPFRPSLALQ SHLEELGLLM QRCWAEDPQE RPPFQQIRLT
810 820 830 840 850
LRKFNRENSS NILDNLLSRM EQYANNLEEL VEERTQAYLE EKRKAEALLY
860 870 880 890 900
QILPHSVAEQ LKRGETVQAE AFDSVTIYFS DIVGFTALSA ESTPMQVVTL
910 920 930 940 950
LNDLYTCFDA VIDNFDVYKV ETIGDAYMVV SGLPVRNGRL HACEVARMAL
960 970 980 990 1000
ALLDAVRSFR IRHRPQEQLR LRIGIHTGPV CAGVVGLKMP RYCLFGDTVN
1010 1020 1030 1040 1050
TASRMESNGE ALKIHLSSET KAVLEEFGGF ELELRGDVEM KGKGKVRTYW
1060
LLGERGSSTR G
Length:1,061
Mass (Da):118,919
Last modified:April 1, 1990 - v1
Checksum:iE6B5BD0FCA32F70D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti344G → V in AAH63304 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042214182A → V1 PublicationCorresponds to variant dbSNP:rs56019647Ensembl.1
Natural variantiVAR_042215270F → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042216755V → M1 PublicationCorresponds to variant dbSNP:rs55837780Ensembl.1
Natural variantiVAR_042217939R → Q1 PublicationCorresponds to variant dbSNP:rs35240348Ensembl.1
Natural variantiVAR_042218967E → K1 PublicationCorresponds to variant dbSNP:rs35479618Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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. No translation available.
CH471121 Genomic DNA. Translation: EAW53284.1.
BC063304 mRNA. Translation: AAH63304.1.
S72628 mRNA. Translation: AAD14112.1.
CCDSiCCDS1051.1.
PIRiS04459. OYHUAR.
RefSeqiNP_000897.3. NM_000906.3.
UniGeneiHs.490330.

Genome annotation databases

EnsembliENST00000368680; ENSP00000357669; ENSG00000169418.
GeneIDi4881.
KEGGihsa:4881.
UCSCiuc001fcs.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANPRA_HUMAN
AccessioniPrimary (citable) accession number: P16066
Secondary accession number(s): B0ZBF0, Q5SR08, Q6P4Q3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 25, 2017
This is version 191 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families