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Receptor activity-modifying protein 3 (Calcitonin-receptor-like receptor activity-modifying protein 3) (CRLR activity-modifying protein 3)

 RAMP3_HUMAN             Reviewed;         148 AA.
O60896; Q7Z2Y1;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-AUG-1998, sequence version 1.
13-FEB-2019, entry version 157.
RecName: Full=Receptor activity-modifying protein 3;
AltName: Full=Calcitonin-receptor-like receptor activity-modifying protein 3;
Short=CRLR activity-modifying protein 3;
Flags: Precursor;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
PubMed=9620797; DOI=10.1038/30666;
McLatchie L.M., Fraser N.J., Main M.J., Wise A., Brown J.,
Thompson N., Solari R., Lee M.G., Foord S.M.;
"RAMPs regulate the transport and ligand specificity of the
calcitonin-receptor-like receptor.";
Nature 393:333-339(1998).
Kopatz S.A., Aronstam R.S., Sharma S.V.;
"cDNA clones of human proteins involved in signal transduction
sequenced by the Guthrie cDNA resource center (";
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
TISSUE=Lung, and PNS;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
PubMed=23674134; DOI=10.1530/JME-13-0021;
Lenhart P.M., Broselid S., Barrick C.J., Leeb-Lundberg L.M.,
Caron K.M.;
"G-protein-coupled receptor 30 interacts with receptor activity-
modifying protein 3 and confers sex-dependent cardioprotection.";
J. Mol. Endocrinol. 51:191-202(2013).
-!- FUNCTION: Plays a role in cardioprotection by reducing cardiac
hypertrophy and perivascular fibrosis in a GPER1-dependent manner.
Transports the calcitonin gene-related peptide type 1 receptor
(CALCRL) and GPER1 to the plasma membrane. Acts as a receptor for
adrenomedullin (AM) together with CALCRL.
{ECO:0000269|PubMed:23674134, ECO:0000269|PubMed:9620797}.
-!- SUBUNIT: Heterodimer of CALCRL and RAMP3 (By similarity).
Interacts with GPER1. {ECO:0000250, ECO:0000269|PubMed:23674134}.
A8MQ03:CYSRT1; NbExp=4; IntAct=EBI-720447, EBI-3867333;
P26371:KRTAP5-9; NbExp=3; IntAct=EBI-720447, EBI-3958099;
Q7Z3S9:NOTCH2NLA; NbExp=5; IntAct=EBI-720447, EBI-945833;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23674134};
Single-pass type I membrane protein {ECO:0000269|PubMed:23674134}.
Membrane {ECO:0000269|PubMed:23674134}; Single-pass type I
membrane protein {ECO:0000269|PubMed:23674134}. Note=Moves from
intracellular puncta to the plasma membrane in a RAMP3-dependent
-!- TISSUE SPECIFICITY: Strongly expressed in lung, breast, immune
system and fetal tissues. {ECO:0000269|PubMed:9620797}.
-!- SIMILARITY: Belongs to the RAMP family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; AJ001016; CAA04474.1; -; mRNA.
EMBL; AY265459; AAP23300.1; -; mRNA.
EMBL; AC004844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC022304; AAH22304.1; -; mRNA.
EMBL; BC053852; AAH53852.1; -; mRNA.
CCDS; CCDS5503.1; -.
RefSeq; NP_005847.1; NM_005856.2.
UniGene; Hs.25691; -.
ProteinModelPortal; O60896; -.
SMR; O60896; -.
BioGrid; 115559; 7.
ComplexPortal; CPX-3148; Adrenomedullin receptor AM2 complex.
ComplexPortal; CPX-3187; Amylin receptor 3 complex.
CORUM; O60896; -.
IntAct; O60896; 9.
STRING; 9606.ENSP00000242249; -.
BindingDB; O60896; -.
ChEMBL; CHEMBL2111191; -.
DrugBank; DB01278; Pramlintide.
GuidetoPHARMACOLOGY; 53; -.
BioMuta; RAMP3; -.
jPOST; O60896; -.
PaxDb; O60896; -.
PeptideAtlas; O60896; -.
PRIDE; O60896; -.
ProteomicsDB; 49659; -.
DNASU; 10268; -.
Ensembl; ENST00000242249; ENSP00000242249; ENSG00000122679.
Ensembl; ENST00000481345; ENSP00000419012; ENSG00000122679.
GeneID; 10268; -.
KEGG; hsa:10268; -.
UCSC; uc003tnb.4; human.
CTD; 10268; -.
DisGeNET; 10268; -.
EuPathDB; HostDB:ENSG00000122679.8; -.
GeneCards; RAMP3; -.
MIM; 605155; gene.
neXtProt; NX_O60896; -.
OpenTargets; ENSG00000122679; -.
PharmGKB; PA34204; -.
eggNOG; ENOG410IXGF; Eukaryota.
eggNOG; ENOG4111U8C; LUCA.
GeneTree; ENSGT00940000161026; -.
HOGENOM; HOG000253018; -.
HOVERGEN; HBG061268; -.
InParanoid; O60896; -.
KO; K08449; -.
OrthoDB; 1432933at2759; -.
PhylomeDB; O60896; -.
TreeFam; TF333286; -.
Reactome; R-HSA-418555; G alpha (s) signalling events.
Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
ChiTaRS; RAMP3; human.
GeneWiki; RAMP3; -.
GenomeRNAi; 10268; -.
PRO; PR:O60896; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000122679; Expressed in 165 organ(s), highest expression level in right lung.
ExpressionAtlas; O60896; baseline and differential.
Genevisible; O60896; HS.
GO; GO:1903143; C:adrenomedullin receptor complex; IDA:UniProtKB.
GO; GO:0150058; C:amylin receptor complex 3; IDA:ARUK-UCL.
GO; GO:0005623; C:cell; IDA:ARUK-UCL.
GO; GO:0009986; C:cell surface; IDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0005764; C:lysosome; TAS:ProtInc.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0043235; C:receptor complex; IDA:UniProtKB.
GO; GO:0001605; F:adrenomedullin receptor activity; IPI:UniProtKB.
GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
GO; GO:0008565; F:protein transporter activity; IDA:UniProtKB.
GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
GO; GO:1990410; P:adrenomedullin receptor signaling pathway; IPI:UniProtKB.
GO; GO:0097647; P:amylin receptor signaling pathway; IGI:ARUK-UCL.
GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central.
GO; GO:0038041; P:cross-receptor inhibition within G protein-coupled receptor heterodimer; IPI:UniProtKB.
GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
GO; GO:0086103; P:G protein-coupled receptor signaling pathway involved in heart process; ISS:UniProtKB.
GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IGI:ARUK-UCL.
GO; GO:0010942; P:positive regulation of cell death; IGI:ARUK-UCL.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:ARUK-UCL.
GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:ARUK-UCL.
GO; GO:0010739; P:positive regulation of protein kinase A signaling; IGI:ARUK-UCL.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:ARUK-UCL.
GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:UniProtKB.
GO; GO:0001921; P:positive regulation of receptor recycling; IDA:UniProtKB.
GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
GO; GO:0015031; P:protein transport; IDA:UniProtKB.
GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
GO; GO:1904645; P:response to amyloid-beta; IGI:ARUK-UCL.
Gene3D;; -; 1.
InterPro; IPR006985; RAMP.
InterPro; IPR038126; RAMP_sf.
PANTHER; PTHR14076; PTHR14076; 1.
Pfam; PF04901; RAMP; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
Membrane; Polymorphism; Receptor; Reference proteome; Signal;
Transmembrane; Transmembrane helix; Transport.
SIGNAL 1 23 {ECO:0000255}.
CHAIN 24 148 Receptor activity-modifying protein 3.
TOPO_DOM 24 118 Extracellular. {ECO:0000255}.
TRANSMEM 119 138 Helical. {ECO:0000255}.
TOPO_DOM 139 148 Cytoplasmic. {ECO:0000255}.
CARBOHYD 29 29 N-linked (GlcNAc...) asparagine.
CARBOHYD 58 58 N-linked (GlcNAc...) asparagine.
CARBOHYD 71 71 N-linked (GlcNAc...) asparagine.
CARBOHYD 103 103 N-linked (GlcNAc...) asparagine.
DISULFID 40 72 {ECO:0000250}.
DISULFID 57 104 {ECO:0000250}.
VARIANT 26 26 G -> D (in dbSNP:rs10272187).
VARIANT 33 33 M -> L (in dbSNP:rs11550711).
VARIANT 56 56 W -> R (in dbSNP:rs2074654).
SEQUENCE 148 AA; 16518 MW; EEEE312496EF513C CRC64;

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Pathways :
WP2272: Pathogenic Escherichia coli infection
WP2292: Chemokine signaling pathway
WP2197: Endothelin
WP1004: Kit Receptor Signaling Pathway
WP1011: T Cell Receptor Signaling Pathway
WP1014: Androgen receptor signaling pathway
WP1025: B Cell Receptor Signaling Pathway
WP1045: TGF-beta Receptor Signaling Pathway
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1049: G Protein Signaling Pathways
WP1067: Toll-like receptor signaling pathway
WP1112: EPO Receptor Signaling
WP1121: Kit Receptor Signaling Pathway
WP1130: T Cell Receptor Signaling Pathway
WP1133: Androgen receptor signaling pathway
WP1144: B Cell Receptor Signaling Pathway
WP1161: TGF-beta Receptor Signaling Pathway
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1165: G Protein Signaling Pathways
WP1183: Toll-like receptor signaling pathway
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP1249: EPO Receptor Signaling
WP1271: Toll-like receptor signaling pathway
WP1284: EPO Receptor Signaling

Related Genes :
[Calcrl Crlr] Calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor) (Calcitonin receptor-like receptor)
[CALCRL CGRPR] Calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor) (Calcitonin receptor-like receptor)
[CALCRL CGRPR] Calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor) (Calcitonin receptor-like receptor)
[Tas1r3 Sac T1r3 Tr3] Taste receptor type 1 member 3 (Saccharin preference protein) (Sweet taste receptor T1R3)
[Calcrl Cgrpr] Calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor) (Calcitonin receptor-like receptor)
[PELP1 HMX3 MNAR] Proline-, glutamic acid- and leucine-rich protein 1 (Modulator of non-genomic activity of estrogen receptor) (Transcription factor HMX3)
[Itpr3] Inositol 1,4,5-trisphosphate receptor type 3 (IP3 receptor isoform 3) (IP3R 3) (InsP3R3) (Type 3 inositol 1,4,5-trisphosphate receptor) (Type 3 InsP3 receptor)
[GPER1 CEPR CMKRL2 DRY12 GPER GPR30] G-protein coupled estrogen receptor 1 (Chemoattractant receptor-like 2) (Flow-induced endothelial G-protein coupled receptor 1) (FEG-1) (G protein-coupled estrogen receptor 1) (G-protein coupled receptor 30) (GPCR-Br) (IL8-related receptor DRY12) (Lymphocyte-derived G-protein coupled receptor) (LYGPR) (Membrane estrogen receptor) (mER)
[AHK4 CRE1 RAW1 WOL At2g01830 T23K3.2] Histidine kinase 4 (EC (Arabidopsis histidine kinase 4) (AtHK4) (Cytokinin receptor CYTOKININ RESPONSE 1) (AtCRE1) (Cytokinin receptor CRE1) (Phosphoprotein phosphatase AHK4) (EC (Protein AUTHENTIC HIS-KINASE 4) (Protein ROOT AS IN WOL 1) (Protein WOODEN LEG)
[Arc] Activity-regulated cytoskeleton-associated protein (mArc) (Activity-regulated gene 3.1 protein) (ARC/ARG3.1) (Arg3.1)
[Arc] Activity-regulated cytoskeleton-associated protein (Activity-regulated gene 3.1 protein) (ARC/ARG3.1) (Arg3.1)
[Gper1 Cmkrl2 Gper Gpr30] G-protein coupled estrogen receptor 1 (Chemoattractant receptor-like 2) (G protein-coupled estrogen receptor 1) (G-protein coupled receptor 30) (Membrane estrogen receptor) (mER)
[Casp3 Cpp32] Caspase-3 (CASP-3) (EC (Apopain) (Cysteine protease CPP32) (CPP-32) (LICE) (Protein Yama) (SREBP cleavage activity 1) (SCA-1) [Cleaved into: Caspase-3 subunit p17; Caspase-3 subunit p12]
[CRMB G2R G4R] Cytokine response-modifying protein B (CrmB) (Viral tumor necrosis factor receptor II) (vTNFR)
[Ackr3 Cmkor1 Cxcr7 Rdc1] Atypical chemokine receptor 3 (C-X-C chemokine receptor type 7) (CXC-R7) (CXCR-7) (Chemokine orphan receptor 1) (G-protein coupled receptor RDC1 homolog) (RDC-1)
[Tlr4 Lps] Toll-like receptor 4 (CD antigen CD284)
[NCOA3 AIB1 BHLHE42 RAC3 TRAM1] Nuclear receptor coactivator 3 (NCoA-3) (EC (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1)
[PRNP PRN-P] Major prion protein homolog (65-21 protein) (Acetylcholine receptor-inducing activity) (ARIA) (PR-LP)
[ARC KIAA0278] Activity-regulated cytoskeleton-associated protein (hArc) (Activity-regulated gene 3.1 protein homolog) (ARC/ARG3.1) (Arg3.1)
[NRG1 GGF HGL HRGA NDF SMDF] Pro-neuregulin-1, membrane-bound isoform (Pro-NRG1) [Cleaved into: Neuregulin-1 (Acetylcholine receptor-inducing activity) (ARIA) (Breast cancer cell differentiation factor p45) (Glial growth factor) (Heregulin) (HRG) (Neu differentiation factor) (Sensory and motor neuron-derived factor)]
[BAK1 ELG SERK3 At4g33430 F17M5.190] BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (AtBAK1) (BRI1-associated receptor kinase 1) (EC (EC (Protein ELONGATED) (Somatic embryogenesis receptor kinase 3) (AtSERK3) (Somatic embryogenesis receptor-like kinase 3)
[CXCR4] C-X-C chemokine receptor type 4 (CXC-R4) (CXCR-4) (FB22) (Fusin) (HM89) (LCR1) (Leukocyte-derived seven transmembrane domain receptor) (LESTR) (Lipopolysaccharide-associated protein 3) (LAP-3) (LPS-associated protein 3) (NPYRL) (Stromal cell-derived factor 1 receptor) (SDF-1 receptor) (CD antigen CD184)
[SUMF1 PSEC0152 UNQ3037/PRO9852] Formylglycine-generating enzyme (FGE) (EC (C-alpha-formylglycine-generating enzyme 1) (Sulfatase-modifying factor 1)
[CXCR3 GPR9] C-X-C chemokine receptor type 3 (CXC-R3) (CXCR-3) (CKR-L2) (G protein-coupled receptor 9) (Interferon-inducible protein 10 receptor) (IP-10 receptor) (CD antigen CD183)
[Ephb2 Epth3 Nuk Sek3] Ephrin type-B receptor 2 (EC (Neural kinase) (Nuk receptor tyrosine kinase) (Tyrosine-protein kinase receptor EPH-3) (Tyrosine-protein kinase receptor SEK-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2]
[ACKR3 CMKOR1 CXCR7 GPR159 RDC1] Atypical chemokine receptor 3 (C-X-C chemokine receptor type 7) (CXC-R7) (CXCR-7) (Chemokine orphan receptor 1) (G-protein coupled receptor 159) (G-protein coupled receptor RDC1 homolog) (RDC-1)
[BMPR1A ACVRLK3 ALK3] Bone morphogenetic protein receptor type-1A (BMP type-1A receptor) (BMPR-1A) (EC (Activin receptor-like kinase 3) (ALK-3) (Serine/threonine-protein kinase receptor R5) (SKR5) (CD antigen CD292)
[Flt3 Flk-2 Flt-3] Receptor-type tyrosine-protein kinase FLT3 (EC (FL cytokine receptor) (Fetal liver kinase 2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Tyrosine-protein kinase receptor flk-2) (CD antigen CD135)
[carC car3 DDB_G0277829] Cyclic AMP receptor 3 (cAMP receptor 3)
[FCRL3 FCRH3 IFGP3 IRTA3 SPAP2] Fc receptor-like protein 3 (FcR-like protein 3) (FcRL3) (Fc receptor homolog 3) (FcRH3) (IFGP family protein 3) (hIFGP3) (Immune receptor translocation-associated protein 3) (SH2 domain-containing phosphatase anchor protein 2) (CD antigen CD307c)

Bibliography :
[27583470] Adrenomedullin2 (ADM2)/Intermedin (IMD): A Potential Role in the Pathophysiology of Preeclampsia.
[27108271] Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.
[26927337] Hypercholesterolemia Up-Regulates the Expression of Intermedin and Its Receptor Components in the Aorta of Rats via Inducing the Oxidative Stress.
[26259851] Role of cerebellar adrenomedullin in blood pressure regulation.
[26014968] Intermedin is upregulated and attenuates renal fibrosis by inhibition of oxidative stress in rats with unilateral ureteral obstruction.
[25140812] Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle.
[24218431] Intermedin in paraventricular nucleus attenuates sympathetic activity and blood pressure via nitric oxide in hypertensive rats.
[24169318] Adrenomedullin expression in the developing human fetal lung.
[23849271] Temporo-spatial expression of adrenomedullin and its receptors in the bovine placenta.
[23520487] An angiogenic role for adrenomedullin in choroidal neovascularization.