NPR1

Protein identityUniProt · HPA

UniProt accession

P16066

Gene

NPR1

Ensembl

ENSG00000169418

Chromosome

1

Canonical length

1061 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Nucleoli,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

Guanylyl cyclases, catalyzing the production of cGMP from GTP, are classified as soluble and membrane forms (Garbers and Lowe, 1994 [PubMed 7982997]). The membrane guanylyl cyclases, often termed guanylyl cyclases A through F, form a family of cell-surface receptors with a similar topographic structure: an extracellular ligand-binding domain, a single membrane-spanning domain, and an intracellular region that contains a protein kinase-like domain and a cyclase catalytic domain. GC-A and GC-B function as receptors for natriuretic peptides; they are also referred to as atrial natriuretic peptide receptor A (NPR1) and type B (NPR2; MIM 108961). Also see NPR3 (MIM 108962), which encodes a protein with only the ligand-binding transmembrane and 37-amino acid cytoplasmic domains. NPR1 is a membrane-bound guanylate cyclase that serves as the receptor for both atrial and brain natriuretic peptides (ANP (MIM 108780) and BNP (MIM 600295), respectively).[supplied by OMIM, May 2009]

Canonical amino-acid sequenceUniProt

1061 residues, UniProt reviewed canonical sequence.

>P16066|NPR1
     1  MPGPRRPAGS RLRLLLLLLL PPLLLLLRGS HAGNLTVAVV LPLANTSYPW SWARVGPAVE
    61  LALAQVKARP DLLPGWTVRT VLGSSENALG VCSDTAAPLA AVDLKWEHNP AVFLGPGCVY
   121  AAAPVGRFTA HWRVPLLTAG APALGFGVKD EYALTTRAGP SYAKLGDFVA ALHRRLGWER
   181  QALMLYAYRP GDEEHCFFLV EGLFMRVRDR LNITVDHLEF AEDDLSHYTR LLRTMPRKGR
   241  VIYICSSPDA FRTLMLLALE AGLCGEDYVF FHLDIFGQSL QGGQGPAPRR PWERGDGQDV
   301  SARQAFQAAK IITYKDPDNP EYLEFLKQLK HLAYEQFNFT MEDGLVNTIP ASFHDGLLLY
   361  IQAVTETLAH GGTVTDGENI TQRMWNRSFQ GVTGYLKIDS SGDRETDFSL WDMDPENGAF
   421  RVVLNYNGTS QELVAVSGRK LNWPLGYPPP DIPKCGFDNE DPACNQDHLS TLEVLALVGS
   481  LSLLGILIVS FFIYRKMQLE KELASELWRV RWEDVEPSSL ERHLRSAGSR LTLSGRGSNY
   541  GSLLTTEGQF QVFAKTAYYK GNLVAVKRVN RKRIELTRKV LFELKHMRDV QNEHLTRFVG
   601  ACTDPPNICI LTEYCPRGSL QDILENESIT LDWMFRYSLT NDIVKGMLFL HNGAICSHGN
   661  LKSSNCVVDG RFVLKITDYG LESFRDLDPE QGHTVYAKKL WTAPELLRMA SPPVRGSQAG
   721  DVYSFGIILQ EIALRSGVFH VEGLDLSPKE IIERVTRGEQ PPFRPSLALQ SHLEELGLLM
   781  QRCWAEDPQE RPPFQQIRLT LRKFNRENSS NILDNLLSRM EQYANNLEEL VEERTQAYLE
   841  EKRKAEALLY QILPHSVAEQ LKRGETVQAE AFDSVTIYFS DIVGFTALSA ESTPMQVVTL
   901  LNDLYTCFDA VIDNFDVYKV ETIGDAYMVV SGLPVRNGRL HACEVARMAL ALLDAVRSFR
   961  IRHRPQEQLR LRIGIHTGPV CAGVVGLKMP RYCLFGDTVN TASRMESNGE ALKIHLSSET
  1021  KAVLEEFGGF ELELRGDVEM KGKGKVRTYW LLGERGSSTR G

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NPR1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

127 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.48

gnomAD pLI

0

gnomAD missense Z

2.82

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood vessel diameter maintenance
• body fluid secretion
• cell surface receptor signaling pathway
• cGMP biosynthetic process
• cGMP-mediated signaling
• dopamine metabolic process
• negative regulation of angiogenesis
• negative regulation of cell growth
• negative regulation of smooth muscle cell proliferation
• positive regulation of cGMP-mediated signaling
• positive regulation of renal sodium excretion
• positive regulation of urine volume
• receptor guanylyl cyclase signaling pathway
• regulation of blood pressure
• regulation of vascular permeability

Molecular functions

• ATP binding
• G protein-coupled peptide receptor activity
• GTP binding
• guanylate cyclase activity
• hormone binding
• natriuretic peptide receptor activity
• peptide hormone binding
• peptide receptor activity
• protein kinase activity

Cellular components

• plasma membrane
• receptor complex
• ANPR-A receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Adenylyl cyclase class-3/4/guanylyl cyclase
• Adenylyl cyclase class-4/guanylyl cyclase
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Receptor, ligand binding region
• Protein kinase-like domain superfamily
• Adenylyl cyclase class-4/guanylyl cyclase, conserved site
• Periplasmic binding protein-like I
• Nucleotide cyclase
• Cyclic nucleotide synthase
• Adenylate and Guanylate cyclase catalytic domain
• Receptor family ligand binding region
• Protein tyrosine and serine/threonine kinase

KeywordsUniProt

• cGMP biosynthesis
• Chloride
• Disulfide bond
• Glycoprotein
• GTP-binding
• Lyase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Signal
• Transmembrane
• Transmembrane helix
• Vasoactive