ID   RAMP3_HUMAN             Reviewed;         148 AA.
AC   O60896; Q7Z2Y1;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   13-FEB-2019, entry version 157.
DE   RecName: Full=Receptor activity-modifying protein 3;
DE   AltName: Full=Calcitonin-receptor-like receptor activity-modifying protein 3;
DE            Short=CRLR activity-modifying protein 3;
DE   Flags: Precursor;
GN   Name=RAMP3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=9620797; DOI=10.1038/30666;
RA   McLatchie L.M., Fraser N.J., Main M.J., Wise A., Brown J.,
RA   Thompson N., Solari R., Lee M.G., Foord S.M.;
RT   "RAMPs regulate the transport and ligand specificity of the
RT   calcitonin-receptor-like receptor.";
RL   Nature 393:333-339(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT   "cDNA clones of human proteins involved in signal transduction
RT   sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-33.
RC   TISSUE=Lung, and PNS;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   FUNCTION, INTERACTION WITH GPER1, AND SUBCELLULAR LOCATION.
RX   PubMed=23674134; DOI=10.1530/JME-13-0021;
RA   Lenhart P.M., Broselid S., Barrick C.J., Leeb-Lundberg L.M.,
RA   Caron K.M.;
RT   "G-protein-coupled receptor 30 interacts with receptor activity-
RT   modifying protein 3 and confers sex-dependent cardioprotection.";
RL   J. Mol. Endocrinol. 51:191-202(2013).
CC   -!- FUNCTION: Plays a role in cardioprotection by reducing cardiac
CC       hypertrophy and perivascular fibrosis in a GPER1-dependent manner.
CC       Transports the calcitonin gene-related peptide type 1 receptor
CC       (CALCRL) and GPER1 to the plasma membrane. Acts as a receptor for
CC       adrenomedullin (AM) together with CALCRL.
CC       {ECO:0000269|PubMed:23674134, ECO:0000269|PubMed:9620797}.
CC   -!- SUBUNIT: Heterodimer of CALCRL and RAMP3 (By similarity).
CC       Interacts with GPER1. {ECO:0000250, ECO:0000269|PubMed:23674134}.
CC   -!- INTERACTION:
CC       A8MQ03:CYSRT1; NbExp=4; IntAct=EBI-720447, EBI-3867333;
CC       P26371:KRTAP5-9; NbExp=3; IntAct=EBI-720447, EBI-3958099;
CC       Q7Z3S9:NOTCH2NLA; NbExp=5; IntAct=EBI-720447, EBI-945833;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23674134};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:23674134}.
CC       Membrane {ECO:0000269|PubMed:23674134}; Single-pass type I
CC       membrane protein {ECO:0000269|PubMed:23674134}. Note=Moves from
CC       intracellular puncta to the plasma membrane in a RAMP3-dependent
CC       manner.
CC   -!- TISSUE SPECIFICITY: Strongly expressed in lung, breast, immune
CC       system and fetal tissues. {ECO:0000269|PubMed:9620797}.
CC   -!- SIMILARITY: Belongs to the RAMP family. {ECO:0000305}.
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DR   EMBL; AJ001016; CAA04474.1; -; mRNA.
DR   EMBL; AY265459; AAP23300.1; -; mRNA.
DR   EMBL; AC004844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC022304; AAH22304.1; -; mRNA.
DR   EMBL; BC053852; AAH53852.1; -; mRNA.
DR   CCDS; CCDS5503.1; -.
DR   RefSeq; NP_005847.1; NM_005856.2.
DR   UniGene; Hs.25691; -.
DR   ProteinModelPortal; O60896; -.
DR   SMR; O60896; -.
DR   BioGrid; 115559; 7.
DR   ComplexPortal; CPX-3148; Adrenomedullin receptor AM2 complex.
DR   ComplexPortal; CPX-3187; Amylin receptor 3 complex.
DR   CORUM; O60896; -.
DR   IntAct; O60896; 9.
DR   STRING; 9606.ENSP00000242249; -.
DR   BindingDB; O60896; -.
DR   ChEMBL; CHEMBL2111191; -.
DR   DrugBank; DB01278; Pramlintide.
DR   GuidetoPHARMACOLOGY; 53; -.
DR   BioMuta; RAMP3; -.
DR   jPOST; O60896; -.
DR   PaxDb; O60896; -.
DR   PeptideAtlas; O60896; -.
DR   PRIDE; O60896; -.
DR   ProteomicsDB; 49659; -.
DR   DNASU; 10268; -.
DR   Ensembl; ENST00000242249; ENSP00000242249; ENSG00000122679.
DR   Ensembl; ENST00000481345; ENSP00000419012; ENSG00000122679.
DR   GeneID; 10268; -.
DR   KEGG; hsa:10268; -.
DR   UCSC; uc003tnb.4; human.
DR   CTD; 10268; -.
DR   DisGeNET; 10268; -.
DR   EuPathDB; HostDB:ENSG00000122679.8; -.
DR   GeneCards; RAMP3; -.
DR   HGNC; HGNC:9845; RAMP3.
DR   MIM; 605155; gene.
DR   neXtProt; NX_O60896; -.
DR   OpenTargets; ENSG00000122679; -.
DR   PharmGKB; PA34204; -.
DR   eggNOG; ENOG410IXGF; Eukaryota.
DR   eggNOG; ENOG4111U8C; LUCA.
DR   GeneTree; ENSGT00940000161026; -.
DR   HOGENOM; HOG000253018; -.
DR   HOVERGEN; HBG061268; -.
DR   InParanoid; O60896; -.
DR   KO; K08449; -.
DR   OrthoDB; 1432933at2759; -.
DR   PhylomeDB; O60896; -.
DR   TreeFam; TF333286; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR   ChiTaRS; RAMP3; human.
DR   GeneWiki; RAMP3; -.
DR   GenomeRNAi; 10268; -.
DR   PRO; PR:O60896; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000122679; Expressed in 165 organ(s), highest expression level in right lung.
DR   ExpressionAtlas; O60896; baseline and differential.
DR   Genevisible; O60896; HS.
DR   GO; GO:1903143; C:adrenomedullin receptor complex; IDA:UniProtKB.
DR   GO; GO:0150058; C:amylin receptor complex 3; IDA:ARUK-UCL.
DR   GO; GO:0005623; C:cell; IDA:ARUK-UCL.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0043235; C:receptor complex; IDA:UniProtKB.
DR   GO; GO:0001605; F:adrenomedullin receptor activity; IPI:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR   GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
DR   GO; GO:0008565; F:protein transporter activity; IDA:UniProtKB.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
DR   GO; GO:1990410; P:adrenomedullin receptor signaling pathway; IPI:UniProtKB.
DR   GO; GO:0097647; P:amylin receptor signaling pathway; IGI:ARUK-UCL.
DR   GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR   GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
DR   GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central.
DR   GO; GO:0038041; P:cross-receptor inhibition within G protein-coupled receptor heterodimer; IPI:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0086103; P:G protein-coupled receptor signaling pathway involved in heart process; ISS:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IGI:ARUK-UCL.
DR   GO; GO:0010942; P:positive regulation of cell death; IGI:ARUK-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:ARUK-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:ARUK-UCL.
DR   GO; GO:0010739; P:positive regulation of protein kinase A signaling; IGI:ARUK-UCL.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:ARUK-UCL.
DR   GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:UniProtKB.
DR   GO; GO:0001921; P:positive regulation of receptor recycling; IDA:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR   GO; GO:0015031; P:protein transport; IDA:UniProtKB.
DR   GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR   GO; GO:1904645; P:response to amyloid-beta; IGI:ARUK-UCL.
DR   Gene3D; 1.10.150.510; -; 1.
DR   InterPro; IPR006985; RAMP.
DR   InterPro; IPR038126; RAMP_sf.
DR   PANTHER; PTHR14076; PTHR14076; 1.
DR   Pfam; PF04901; RAMP; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
KW   Membrane; Polymorphism; Receptor; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    148       Receptor activity-modifying protein 3.
FT                                /FTId=PRO_0000030176.
FT   TOPO_DOM     24    118       Extracellular. {ECO:0000255}.
FT   TRANSMEM    119    138       Helical. {ECO:0000255}.
FT   TOPO_DOM    139    148       Cytoplasmic. {ECO:0000255}.
FT   CARBOHYD     29     29       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     58     58       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     71     71       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    103    103       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     40     72       {ECO:0000250}.
FT   DISULFID     57    104       {ECO:0000250}.
FT   VARIANT      26     26       G -> D (in dbSNP:rs10272187).
FT                                /FTId=VAR_034437.
FT   VARIANT      33     33       M -> L (in dbSNP:rs11550711).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_053628.
FT   VARIANT      56     56       W -> R (in dbSNP:rs2074654).
FT                                /FTId=VAR_024602.
SQ   SEQUENCE   148 AA;  16518 MW;  EEEE312496EF513C CRC64;
     METGALRRPQ LLPLLLLLCG GCPRAGGCNE TGMLERLPLC GKAFADMMGK VDVWKWCNLS
     EFIVYYESFT NCTEMEANVV GCYWPNPLAQ GFITGIHRQF FSNCTVDRVH LEDPPDEVLI
     PLIVIPVVLT VAMAGLVVWR SKRTDTLL
//