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 27-MAR-2024, entry version 184.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Thompson N.,
RA Solari R., Lee M.G., Foord S.M.;
RT "RAMPs regulate the transport and ligand specificity of the calcitonin-
RT 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 sequenced by
RT 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., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., 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., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA 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 project:
RT 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., Caron K.M.;
RT "G-protein-coupled receptor 30 interacts with receptor activity-modifying
RT 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 (CALCRL)
CC and GPER1 to the plasma membrane. Acts as a receptor for adrenomedullin
CC (AM) together with CALCRL. {ECO:0000269|PubMed:23674134,
CC ECO:0000269|PubMed:9620797}.
CC -!- SUBUNIT: Heterodimer of CALCRL and RAMP3 (By similarity). Interacts
CC with GPER1. {ECO:0000250, ECO:0000269|PubMed:23674134}.
CC -!- INTERACTION:
CC O60896; A8MQ03: CYSRT1; NbExp=6; IntAct=EBI-720447, EBI-3867333;
CC O60896; Q6L8H2: KRTAP5-3; NbExp=3; IntAct=EBI-720447, EBI-11974251;
CC O60896; Q6L8G8: KRTAP5-7; NbExp=3; IntAct=EBI-720447, EBI-11987425;
CC O60896; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-720447, EBI-3958099;
CC O60896; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-720447, EBI-1043191;
CC O60896; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-720447, EBI-945833;
CC O60896; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-720447, EBI-22310682;
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 membrane
CC protein {ECO:0000269|PubMed:23674134}. Note=Moves from intracellular
CC puncta to the plasma membrane in a RAMP3-dependent manner.
CC -!- TISSUE SPECIFICITY: Strongly expressed in lung, breast, immune system
CC 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 PDB; 6UUS; EM; 2.40 A; E=24-148.
DR PDB; 6UVA; EM; 2.30 A; E=24-148.
DR PDB; 7TZF; EM; 2.40 A; E=24-148.
DR PDB; 8F0K; EM; 1.90 A; E=24-148.
DR PDB; 8F2A; EM; 2.20 A; E=24-148.
DR PDB; 8F2B; EM; 2.00 A; E=24-148.
DR PDBsum; 6UUS; -.
DR PDBsum; 6UVA; -.
DR PDBsum; 7TZF; -.
DR PDBsum; 8F0K; -.
DR PDBsum; 8F2A; -.
DR PDBsum; 8F2B; -.
DR AlphaFoldDB; O60896; -.
DR EMDB; EMD-20901; -.
DR EMDB; EMD-20906; -.
DR EMDB; EMD-26208; -.
DR EMDB; EMD-28759; -.
DR EMDB; EMD-28810; -.
DR EMDB; EMD-28812; -.
DR SMR; O60896; -.
DR BioGRID; 115559; 203.
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; CHEMBL2111190; -.
DR ChEMBL; CHEMBL2111191; -.
DR DrugBank; DB01278; Pramlintide.
DR DrugCentral; O60896; -.
DR GuidetoPHARMACOLOGY; 53; -.
DR TCDB; 8.A.127.1.3; the receptor activity-modifying protein (ramp) family.
DR GlyCosmos; O60896; 4 sites, No reported glycans.
DR GlyGen; O60896; 4 sites.
DR PhosphoSitePlus; O60896; -.
DR BioMuta; RAMP3; -.
DR jPOST; O60896; -.
DR MassIVE; O60896; -.
DR PaxDb; 9606-ENSP00000242249; -.
DR PeptideAtlas; O60896; -.
DR ProteomicsDB; 49659; -.
DR Antibodypedia; 27450; 229 antibodies from 32 providers.
DR DNASU; 10268; -.
DR Ensembl; ENST00000242249.8; ENSP00000242249.4; ENSG00000122679.8.
DR Ensembl; ENST00000481345.1; ENSP00000419012.1; ENSG00000122679.8.
DR GeneID; 10268; -.
DR KEGG; hsa:10268; -.
DR MANE-Select; ENST00000242249.8; ENSP00000242249.4; NM_005856.3; NP_005847.1.
DR UCSC; uc003tnb.4; human.
DR AGR; HGNC:9845; -.
DR CTD; 10268; -.
DR DisGeNET; 10268; -.
DR GeneCards; RAMP3; -.
DR HGNC; HGNC:9845; RAMP3.
DR HPA; ENSG00000122679; Low tissue specificity.
DR MIM; 605155; gene.
DR neXtProt; NX_O60896; -.
DR OpenTargets; ENSG00000122679; -.
DR PharmGKB; PA34204; -.
DR VEuPathDB; HostDB:ENSG00000122679; -.
DR eggNOG; ENOG502S3C2; Eukaryota.
DR GeneTree; ENSGT00940000161026; -.
DR InParanoid; O60896; -.
DR OMA; VAVWKWC; -.
DR OrthoDB; 5359286at2759; -.
DR PhylomeDB; O60896; -.
DR TreeFam; TF333286; -.
DR PathwayCommons; O60896; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR SignaLink; O60896; -.
DR BioGRID-ORCS; 10268; 4 hits in 1154 CRISPR screens.
DR ChiTaRS; RAMP3; human.
DR GeneWiki; RAMP3; -.
DR GenomeRNAi; 10268; -.
DR Pharos; O60896; Tclin.
DR PRO; PR:O60896; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O60896; Protein.
DR Bgee; ENSG00000122679; Expressed in right lung and 141 other cell types or tissues.
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:0009986; C:cell surface; IDA:UniProtKB.
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:0097643; F:amylin receptor activity; IGI:ARUK-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
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: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:0050850; P:positive regulation of calcium-mediated signaling; IGI:ARUK-UCL.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA: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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IGI:ARUK-UCL.
DR GO; GO:0010739; P:positive regulation of protein kinase A 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; Receptor activity modifying family; 1.
DR InterPro; IPR006985; RAMP.
DR InterPro; IPR038126; RAMP_sf.
DR PANTHER; PTHR14076; RECEPTOR ACTIVITY MODIFYING PROTEIN RAMP; 1.
DR PANTHER; PTHR14076:SF2; RECEPTOR ACTIVITY-MODIFYING PROTEIN 3; 1.
DR Pfam; PF04901; RAMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Membrane;
KW Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..148
FT /note="Receptor activity-modifying protein 3"
FT /id="PRO_0000030176"
FT TOPO_DOM 24..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..72
FT /evidence="ECO:0000250"
FT DISULFID 57..104
FT /evidence="ECO:0000250"
FT VARIANT 26
FT /note="G -> D (in dbSNP:rs10272187)"
FT /id="VAR_034437"
FT VARIANT 33
FT /note="M -> L (in dbSNP:rs11550711)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053628"
FT VARIANT 56
FT /note="W -> R (in dbSNP:rs2074654)"
FT /id="VAR_024602"
FT HELIX 30..47
FT /evidence="ECO:0007829|PDB:8F0K"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:8F0K"
FT HELIX 59..79
FT /evidence="ECO:0007829|PDB:8F0K"
FT HELIX 87..100
FT /evidence="ECO:0007829|PDB:8F0K"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:8F0K"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:8F0K"
FT HELIX 121..140
FT /evidence="ECO:0007829|PDB:8F0K"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:8F2B"
SQ SEQUENCE 148 AA; 16518 MW; EEEE312496EF513C CRC64;
METGALRRPQ LLPLLLLLCG GCPRAGGCNE TGMLERLPLC GKAFADMMGK VDVWKWCNLS
EFIVYYESFT NCTEMEANVV GCYWPNPLAQ GFITGIHRQF FSNCTVDRVH LEDPPDEVLI
PLIVIPVVLT VAMAGLVVWR SKRTDTLL
//
