RAMP3_HUMAN
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 03-AUG-2022, entry version 175.
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 PDBsum; 6UUS; -.
DR PDBsum; 6UVA; -.
DR PDBsum; 7TZF; -.
DR AlphaFoldDB; O60896; -.
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 GlyGen; O60896; 4 sites.
DR PhosphoSitePlus; O60896; -.
DR BioMuta; RAMP3; -.
DR jPOST; O60896; -.
DR MassIVE; O60896; -.
DR PaxDb; O60896; -.
DR PeptideAtlas; O60896; -.
DR PRIDE; O60896; -.
DR ProteomicsDB; 49659; -.
DR Antibodypedia; 27450; 210 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 CTD; 10268; -.
DR DisGeNET; 10268; -.
DR GeneCards; RAMP3; -.
DR HGNC; HGNC:9845; RAMP3.
DR HPA; ENSG00000122679; Tissue enhanced (lung).
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; FTNCTEE; -.
DR OrthoDB; 1432933at2759; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; O60896; -.
DR BioGRID-ORCS; 10268; 4 hits in 1068 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 139 other 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: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: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: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 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 TURN 34..36
FT /evidence="ECO:0007829|PDB:6UUS"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:6UVA"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:6UVA"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:6UVA"
FT HELIX 63..75
FT /evidence="ECO:0007829|PDB:6UVA"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:6UVA"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:6UVA"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:6UVA"
FT HELIX 121..141
FT /evidence="ECO:0007829|PDB:6UVA"
SQ SEQUENCE 148 AA; 16518 MW; EEEE312496EF513C CRC64;
METGALRRPQ LLPLLLLLCG GCPRAGGCNE TGMLERLPLC GKAFADMMGK VDVWKWCNLS
EFIVYYESFT NCTEMEANVV GCYWPNPLAQ GFITGIHRQF FSNCTVDRVH LEDPPDEVLI
PLIVIPVVLT VAMAGLVVWR SKRTDTLL