ANPRB_RAT
ID ANPRB_RAT Reviewed; 1047 AA.
AC P16067;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Atrial natriuretic peptide receptor 2;
DE EC=4.6.1.2 {ECO:0000250|UniProtKB:P20594};
DE AltName: Full=Atrial natriuretic peptide receptor type B;
DE Short=ANP-B;
DE Short=ANPR-B;
DE Short=NPR-B;
DE AltName: Full=Guanylate cyclase B;
DE Short=GC-B;
DE Flags: Precursor;
GN Name=Npr2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2570641; DOI=10.1016/0092-8674(89)90513-8;
RA Schulz S., Singh S., Bellet R.A., Singh G., Tubb D.J., Chin H.,
RA Garbers D.L.;
RT "The primary structure of a plasma membrane guanylate cyclase demonstrates
RT diversity within this new receptor family.";
RL Cell 58:1155-1162(1989).
RN [2]
RP PHOSPHORYLATION AT SER-513; THR-516; SER-518; SER-523 AND SER-526, AND
RP MUTAGENESIS OF SER-513; THR-516; SER-518; GLY-521; SER-522; SER-523;
RP SER-526 AND THR-529.
RX PubMed=9624142; DOI=10.1074/jbc.273.25.15533;
RA Potter L.R., Hunter T.;
RT "Identification and characterization of the major phosphorylation sites of
RT the B-type natriuretic peptide receptor.";
RL J. Biol. Chem. 273:15533-15539(1998).
RN [3]
RP PHOSPHORYLATION AT SER-513; THR-516; SER-518; SER-523; SER-526 AND THR-529.
RX PubMed=20977274; DOI=10.1021/bi101700e;
RA Yoder A.R., Stone M.D., Griffin T.J., Potter L.R.;
RT "Mass spectrometric identification of phosphorylation sites in guanylyl
RT cyclase A and B.";
RL Biochemistry 49:10137-10145(2010).
CC -!- FUNCTION: Receptor for the C-type natriuretic peptide NPPC/CNP hormone.
CC Has guanylate cyclase activity upon binding of its ligand. May play a
CC role in the regulation of skeletal growth.
CC {ECO:0000250|UniProtKB:P20594}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000250|UniProtKB:P20594};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P20594};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P20594}.
CC -!- PTM: Phosphorylated. Phosphorylation of the protein kinase-like domain
CC is required for full activation by CNP. {ECO:0000269|PubMed:20977274,
CC ECO:0000269|PubMed:9624142}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P20594}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M26896; AAA41205.1; -; mRNA.
DR PIR; A33300; OYRTBR.
DR RefSeq; NP_446290.1; NM_053838.1.
DR AlphaFoldDB; P16067; -.
DR SMR; P16067; -.
DR STRING; 10116.ENSRNOP00000021802; -.
DR GlyGen; P16067; 7 sites.
DR iPTMnet; P16067; -.
DR PhosphoSitePlus; P16067; -.
DR PaxDb; P16067; -.
DR PRIDE; P16067; -.
DR GeneID; 116564; -.
DR KEGG; rno:116564; -.
DR UCSC; RGD:620851; rat.
DR CTD; 4882; -.
DR RGD; 620851; Npr2.
DR VEuPathDB; HostDB:ENSRNOG00000015991; -.
DR eggNOG; KOG1023; Eukaryota.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; P16067; -.
DR OMA; AAKSEHY; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P16067; -.
DR TreeFam; TF106338; -.
DR BRENDA; 4.6.1.2; 5301.
DR Reactome; R-RNO-5578768; Physiological factors.
DR PRO; PR:P16067; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000015991; Expressed in heart and 20 other tissues.
DR Genevisible; P16067; RN.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; ISO:RGD.
DR GO; GO:0042562; F:hormone binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; ISO:RGD.
DR GO; GO:0017046; F:peptide hormone binding; IMP:RGD.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD.
DR GO; GO:0006182; P:cGMP biosynthetic process; ISO:RGD.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:RGD.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:Ensembl.
DR GO; GO:0051447; P:negative regulation of meiotic cell cycle; ISO:RGD.
DR GO; GO:1900194; P:negative regulation of oocyte maturation; ISO:RGD.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; ISS:UniProtKB.
DR GO; GO:0022414; P:reproductive process; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR001170; ANPR/GUC.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00255; NATPEPTIDER.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00458; ANF_RECEPTORS; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cell membrane; cGMP biosynthesis; Disulfide bond; Glycoprotein;
KW GTP-binding; Lyase; Membrane; Nucleotide-binding; Osteogenesis;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..1047
FT /note="Atrial natriuretic peptide receptor 2"
FT /id="PRO_0000012366"
FT TOPO_DOM 17..458
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..1047
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 513..786
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 861..991
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274,
FT ECO:0000269|PubMed:9624142"
FT MOD_RES 516
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20977274,
FT ECO:0000269|PubMed:9624142"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274,
FT ECO:0000269|PubMed:9624142"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274,
FT ECO:0000269|PubMed:9624142"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274,
FT ECO:0000269|PubMed:9624142"
FT MOD_RES 529
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..101
FT /evidence="ECO:0000250"
FT DISULFID 439
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT DISULFID 448
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT MUTAGEN 513
FT /note="S->A: Reduced phosphorylation, 30% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 516
FT /note="T->A: Reduced phosphorylation, 30% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 518
FT /note="S->A: Reduced phosphorylation, 30% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 521
FT /note="G->A: Reduced phosphorylation, 50% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 522
FT /note="S->A: Reduced phosphorylation, 30% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 523
FT /note="S->A: Markedly reduced phosphorylation, 70% loss of
FT CNP-dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 526
FT /note="S->A: Markedly reduced phosphorylation, 80% loss of
FT CNP-dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
FT MUTAGEN 529
FT /note="T->A: No effect on phosphorylation, 30% loss of CNP-
FT dependent activity."
FT /evidence="ECO:0000269|PubMed:9624142"
SQ SEQUENCE 1047 AA; 117127 MW; 5062C49228CC14A3 CRC64;
MALPSLLLVV AALAGGVRPP GARNLTLAVV LPEHNLSYAW AWPRVGPAVA LAVEALGRAL
PVDLRFVSSE LDGACSEYLA PLRAVDLKLY HDPDLLLGPG CVYPAASVAR FASHWHLPLL
TAGAVASGFA AKNEHYRTLV RTGPSAPKLG EFVVTLHGHF NWTARAALLY LDARTDDRPH
YFTIEGVFEA LQGSNLSVQH QVYTREPGGP EQATHFIRAN GRIVYICGPL EMLHEILLQA
QRENLTNGDY VFFYLDVFGE SLRAGPTRAT GRPWQDNRTQ EQAQALREAF QTVLVITYRE
PPNPEYQEFQ NRLLIRARED FGVELAPSLM NLIAGCFYDG ILLYAQVLNE TIQEGGTRED
GLRIVEKMQG RRYHGVTGLV VMDKNNDRET DFVLWAMGDL ESGDFQPAAH YSGAEKQIWW
TGRPIPWVKG APPLDNPPCA FDLDDPSCDK TPLSTLAIVA LGTGITFIMF GVSSFLIFRK
LMLEKELASM LWRIRWEELQ FGNSDRYHKG AGSRLTLSLR GSSYGSLMTA HGKYQIFANT
GHFKGNVVAI KHVNKKRIEL TRQVLFELKH MRDVQFNHLT RFIGACIDPP NICIVTEYCP
RGSLQDILEN DSINLDWMFR YSLINDLVKG MAFLHNSIIS SHGSLKSSNC VVDSRFVLKI
TDYGLASFRS TAEPDDSHAL YAKKLWTAPE LLSGNPLPTT GMQKADVYSF AIILQEIALR
SGPFYLEGLD LSPKEIVQKV RNGQRPYFRP SIDRTQLNEE LVLLMERCWA QDPTERPDFG
QIKGFIRRFN KEGGTSILDN LLLRMEQYAN NLEKLVEERT QAYLEEKRKA EALLYQILPH
SVAEQLKRGE TVQAEAFDSV TIYFSDIVGF TALSAESTPM QVVTLLNDLY TCFDAIIDNF
DVYKVETIGD AYMVVSGLPG RNGQRHAPEI ARMALALLDA VSSFRIRHRP HDQLRLRIGV
HTGPVCAGVV GLKMPRYCLF GDTVNTASRM ESNGQALKIH VSSTTKDALD ELGCFQLELR
GDVEMKGKGK MRTYWLLGER KGPPGLL
