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   27-MAR-2024, entry version 187.
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   GlyCosmos; P16067; 7 sites, No reported glycans.
DR   GlyGen; P16067; 7 sites.
DR   iPTMnet; P16067; -.
DR   PhosphoSitePlus; P16067; -.
DR   PaxDb; 10116-ENSRNOP00000021802; -.
DR   GeneID; 116564; -.
DR   KEGG; rno:116564; -.
DR   UCSC; RGD:620851; rat.
DR   AGR; RGD:620851; -.
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   OrthoDB; 3683909at2759; -.
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 cell types or tissues.
DR   GO; GO:0005929; C:cilium; ISO:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0043005; C:neuron projection; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0004016; F:adenylate cyclase activity; IBA:GO_Central.
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:0004672; F:protein kinase activity; IEA:InterPro.
DR   GO; GO:0060466; P:activation of meiosis involved in egg activation; ISO:RGD.
DR   GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR   GO; GO:0060385; P:axonogenesis involved in innervation; ISO:RGD.
DR   GO; GO:0008015; P:blood circulation; ISO:RGD.
DR   GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR   GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR   GO; GO:0060348; P:bone development; ISO:RGD.
DR   GO; GO:0098868; P:bone growth; ISO:RGD.
DR   GO; GO:0061939; P:c-di-GMP signaling; ISO:RGD.
DR   GO; GO:0051216; P:cartilage development; ISO:RGD.
DR   GO; GO:0071321; P:cellular response to cGMP; ISO:RGD.
DR   GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD.
DR   GO; GO:1901653; P:cellular response to peptide; ISO:RGD.
DR   GO; GO:0006182; P:cGMP biosynthetic process; ISO:RGD.
DR   GO; GO:0046068; P:cGMP metabolic process; ISO:RGD.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IDA:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0002062; P:chondrocyte differentiation; ISO:RGD.
DR   GO; GO:0035988; P:chondrocyte proliferation; ISO:RGD.
DR   GO; GO:0051276; P:chromosome organization; ISO:RGD.
DR   GO; GO:0048668; P:collateral sprouting; ISO:RGD.
DR   GO; GO:0001549; P:cumulus cell differentiation; ISO:RGD.
DR   GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR   GO; GO:0048546; P:digestive tract morphogenesis; ISO:RGD.
DR   GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD.
DR   GO; GO:0097194; P:execution phase of apoptosis; ISO:RGD.
DR   GO; GO:0030540; P:female genitalia development; ISO:RGD.
DR   GO; GO:0035483; P:gastric emptying; ISO:RGD.
DR   GO; GO:0035112; P:genitalia morphogenesis; ISO:RGD.
DR   GO; GO:0007281; P:germ cell development; ISO:RGD.
DR   GO; GO:0003417; P:growth plate cartilage development; ISO:RGD.
DR   GO; GO:0060173; P:limb development; ISO:RGD.
DR   GO; GO:0035108; P:limb morphogenesis; ISO:RGD.
DR   GO; GO:0001945; P:lymph vessel development; ISO:RGD.
DR   GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR   GO; GO:0051321; P:meiotic cell cycle; ISO:RGD.
DR   GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; ISO:RGD.
DR   GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR   GO; GO:0032504; P:multicellular organism reproduction; ISO:RGD.
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:0021675; P:nerve development; ISO:RGD.
DR   GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR   GO; GO:0019228; P:neuronal action potential; ISO:RGD.
DR   GO; GO:0048599; P:oocyte development; ISO:RGD.
DR   GO; GO:0001541; P:ovarian follicle development; ISO:RGD.
DR   GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IDA:RGD.
DR   GO; GO:0036342; P:post-anal tail morphogenesis; ISO:RGD.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; ISS:UniProtKB.
DR   GO; GO:0022414; P:reproductive process; ISO:RGD.
DR   GO; GO:0071774; P:response to fibroblast growth factor; ISO:RGD.
DR   GO; GO:0009725; P:response to hormone; ISO:RGD.
DR   GO; GO:0034699; P:response to luteinizing hormone; ISO:RGD.
DR   GO; GO:1902074; P:response to salt; ISO:RGD.
DR   GO; GO:0009611; P:response to wounding; ISO:RGD.
DR   GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR   GO; GO:0007338; P:single fertilization; ISO:RGD.
DR   GO; GO:0048745; P:smooth muscle tissue development; ISO:RGD.
DR   GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR   GO; GO:0001964; P:startle response; ISO:RGD.
DR   GO; GO:0007033; P:vacuole organization; ISO:RGD.
DR   GO; GO:0061042; P:vascular wound healing; ISO:RGD.
DR   GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR   GO; GO:0021562; P:vestibulocochlear nerve development; ISO:RGD.
DR   GO; GO:0021647; P:vestibulocochlear nerve maturation; ISO:RGD.
DR   GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
DR   CDD; cd07302; CHD; 1.
DR   CDD; cd06384; PBP1_NPR_B; 1.
DR   CDD; cd14042; PK_GC-A_B; 1.
DR   Gene3D; 3.40.50.2300; -; 3.
DR   Gene3D; 3.30.70.1230; Nucleotide cyclase; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR11920:SF508; ATRIAL NATRIURETIC PEPTIDE RECEPTOR 2; 1.
DR   PANTHER; PTHR11920; GUANYLYL CYCLASE; 1.
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; SSF55073; Nucleotide cyclase; 1.
DR   SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; P16067; RN.
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
FT                   CNP-dependent activity."
FT                   /evidence="ECO:0000269|PubMed:9624142"
FT   MUTAGEN         516
FT                   /note="T->A: Reduced phosphorylation, 30% loss of
FT                   CNP-dependent activity."
FT                   /evidence="ECO:0000269|PubMed:9624142"
FT   MUTAGEN         518
FT                   /note="S->A: Reduced phosphorylation, 30% loss of
FT                   CNP-dependent activity."
FT                   /evidence="ECO:0000269|PubMed:9624142"
FT   MUTAGEN         521
FT                   /note="G->A: Reduced phosphorylation, 50% loss of
FT                   CNP-dependent activity."
FT                   /evidence="ECO:0000269|PubMed:9624142"
FT   MUTAGEN         522
FT                   /note="S->A: Reduced phosphorylation, 30% loss of
FT                   CNP-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
FT                   CNP-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
//