ID RAMP2_HUMAN Reviewed; 175 AA. AC O60895; A7L9S6; K7EMD3; Q8N1F2; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 10-JAN-2003, sequence version 2. DT 24-JAN-2024, entry version 191. DE RecName: Full=Receptor activity-modifying protein 2; DE AltName: Full=Calcitonin-receptor-like receptor activity-modifying protein 2; DE Short=CRLR activity-modifying protein 2; DE Flags: Precursor; GN Name=RAMP2; 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] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Neuroblastoma; 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 [MRNA] (ISOFORM 2). RA Rorabaugh B.R., Witt K.M., Smith D.D., Abel P.W., Scofield M.A.; RT "Characterization of adrenomedullin receptors and identification of a RT receptor activity modifying protein 2 (RAMP2) variant in SV40LT-SMC RT cells."; RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Heart; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; 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 [6] RP INTERACTION WITH CALCRL. RX PubMed=30115739; DOI=10.1084/jem.20180528; RA Mackie D.I., Al Mutairi F., Davis R.B., Kechele D.O., Nielsen N.R., RA Snyder J.C., Caron M.G., Kliman H.J., Berg J.S., Simms J., Poyner D.R., RA Caron K.M.; RT "hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with RT lymphatic dysplasia."; RL J. Exp. Med. 215:2339-2353(2018). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 48-139, AND DISULFIDE BONDS. RG Structural genomics consortium (SGC); RT "Structure of the extracellular domain of human RAMP2."; RL Submitted (DEC-2010) to the PDB data bank. RN [8] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-139 IN COMPLEX WITH CALCRL, RP FUNCTION, AND DISULFIDE BONDS. RX PubMed=22102369; DOI=10.1002/pro.2003; RA Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., RA Shirouzu M., Shindo T., Yokoyama S.; RT "Structural basis for extracellular interactions between calcitonin RT receptor-like receptor and receptor activity-modifying protein 2 for RT adrenomedullin-specific binding."; RL Protein Sci. 21:199-210(2012). CC -!- FUNCTION: Transports the calcitonin gene-related peptide type 1 CC receptor (CALCRL) to the plasma membrane. Acts as a receptor for CC adrenomedullin (AM) together with CALCRL. {ECO:0000269|PubMed:22102369, CC ECO:0000269|PubMed:9620797}. CC -!- SUBUNIT: Heterodimer of CALCRL and RAMP2. CC {ECO:0000269|PubMed:30115739}. CC -!- INTERACTION: CC O60895; Q16602: CALCRL; NbExp=6; IntAct=EBI-9009040, EBI-962878; CC O60895; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-9009040, EBI-7062247; CC O60895; P80188: LCN2; NbExp=3; IntAct=EBI-9009040, EBI-11911016; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60895-1; Sequence=Displayed; CC Name=2; CC IsoId=O60895-2; Sequence=VSP_055838; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ001015; CAA04473.1; -; mRNA. DR EMBL; EF687002; ABS28868.1; -; mRNA. DR EMBL; AY265458; AAP23299.1; -; mRNA. DR EMBL; AC100793; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027975; AAH27975.1; -; mRNA. DR CCDS; CCDS11437.1; -. [O60895-1] DR RefSeq; NP_005845.2; NM_005854.2. [O60895-1] DR PDB; 2XVT; X-ray; 2.05 A; A/B/C/D/E/F=48-139. DR PDB; 3AQE; X-ray; 2.00 A; A/B/C/D/E/F=56-139. DR PDB; 3AQF; X-ray; 2.60 A; A=56-139. DR PDB; 4RWF; X-ray; 1.76 A; A=55-138. DR PDB; 6UUN; EM; 3.00 A; E=44-175. DR PDB; 6V2E; X-ray; 1.83 A; A=55-140. DR PDB; 7TYH; EM; 3.30 A; E=44-175. DR PDB; 7TYX; EM; 2.55 A; E=44-175. DR PDB; 7TYY; EM; 3.00 A; E=44-175. DR PDBsum; 2XVT; -. DR PDBsum; 3AQE; -. DR PDBsum; 3AQF; -. DR PDBsum; 4RWF; -. DR PDBsum; 6UUN; -. DR PDBsum; 6V2E; -. DR PDBsum; 7TYH; -. DR PDBsum; 7TYX; -. DR PDBsum; 7TYY; -. DR AlphaFoldDB; O60895; -. DR EMDB; EMD-20883; -. DR EMDB; EMD-26179; -. DR EMDB; EMD-26197; -. DR EMDB; EMD-26199; -. DR SMR; O60895; -. DR BioGRID; 115557; 107. DR ComplexPortal; CPX-2191; Adrenomedullin receptor AM1 complex. DR ComplexPortal; CPX-3186; Amylin receptor 2 complex. DR CORUM; O60895; -. DR IntAct; O60895; 3. DR STRING; 9606.ENSP00000253796; -. DR BindingDB; O60895; -. DR ChEMBL; CHEMBL2109232; -. DR ChEMBL; CHEMBL2364173; -. DR DrugBank; DB01278; Pramlintide. DR DrugCentral; O60895; -. DR GuidetoPHARMACOLOGY; 52; -. DR TCDB; 8.A.127.1.2; the receptor activity-modifying protein (ramp) family. DR GlyCosmos; O60895; 1 site, No reported glycans. DR GlyGen; O60895; 1 site. DR PhosphoSitePlus; O60895; -. DR BioMuta; RAMP2; -. DR EPD; O60895; -. DR MassIVE; O60895; -. DR PaxDb; 9606-ENSP00000253796; -. DR PeptideAtlas; O60895; -. DR ProteomicsDB; 49658; -. [O60895-1] DR Antibodypedia; 29403; 312 antibodies from 32 providers. DR DNASU; 10266; -. DR Ensembl; ENST00000253796.10; ENSP00000253796.3; ENSG00000131477.11. [O60895-1] DR Ensembl; ENST00000587142.5; ENSP00000466455.1; ENSG00000131477.11. [O60895-2] DR GeneID; 10266; -. DR KEGG; hsa:10266; -. DR MANE-Select; ENST00000253796.10; ENSP00000253796.3; NM_005854.3; NP_005845.2. DR UCSC; uc002ibg.5; human. [O60895-1] DR AGR; HGNC:9844; -. DR CTD; 10266; -. DR DisGeNET; 10266; -. DR GeneCards; RAMP2; -. DR HGNC; HGNC:9844; RAMP2. DR HPA; ENSG00000131477; Low tissue specificity. DR MIM; 605154; gene. DR neXtProt; NX_O60895; -. DR OpenTargets; ENSG00000131477; -. DR PharmGKB; PA34203; -. DR VEuPathDB; HostDB:ENSG00000131477; -. DR eggNOG; ENOG502S5WC; Eukaryota. DR GeneTree; ENSGT00940000160264; -. DR InParanoid; O60895; -. DR OMA; WCDWAVI; -. DR OrthoDB; 5323652at2759; -. DR PhylomeDB; O60895; -. DR TreeFam; TF333286; -. DR PathwayCommons; O60895; -. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors. DR SignaLink; O60895; -. DR BioGRID-ORCS; 10266; 17 hits in 1157 CRISPR screens. DR ChiTaRS; RAMP2; human. DR GeneWiki; RAMP2; -. DR GenomeRNAi; 10266; -. DR Pharos; O60895; Tclin. DR PRO; PR:O60895; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O60895; Protein. DR Bgee; ENSG00000131477; Expressed in right lung and 138 other cell types or tissues. DR ExpressionAtlas; O60895; baseline and differential. DR GO; GO:1903143; C:adrenomedullin receptor complex; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005905; C:clathrin-coated pit; TAS:ProtInc. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IDA:UniProtKB. DR GO; GO:1990409; F:adrenomedullin binding; IPI:UniProtKB. DR GO; GO:0001605; F:adrenomedullin receptor activity; IPI:UniProtKB. DR GO; GO:0015026; F:coreceptor activity; ISS:UniProtKB. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IPI:UniProtKB. DR GO; GO:0034333; P:adherens junction assembly; IDA:UniProtKB. DR GO; GO:1990410; P:adrenomedullin receptor signaling pathway; IPI:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB. DR GO; GO:0070831; P:basement membrane assembly; ISS:UniProtKB. DR GO; GO:0070830; P:bicellular tight junction assembly; IDA:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB. DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:0043116; P:negative regulation of vascular permeability; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:2001214; P:positive regulation of vasculogenesis; IEA:Ensembl. 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:0008217; P:regulation of blood pressure; ISS:UniProtKB. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IEA:InterPro. DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0097084; P:vascular associated smooth muscle cell development; ISS:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB. 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:SF9; RECEPTOR ACTIVITY-MODIFYING PROTEIN 2; 1. DR Pfam; PF04901; RAMP; 1. DR Genevisible; O60895; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein; Membrane; KW Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix; KW Transport. FT SIGNAL 1..42 FT /evidence="ECO:0000255" FT CHAIN 43..175 FT /note="Receptor activity-modifying protein 2" FT /id="PRO_0000030172" FT TOPO_DOM 43..145 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 146..166 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 167..175 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 68..99 FT DISULFID 84..131 FT VAR_SEQ 54 FT /note="E -> EASVPT (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_055838" FT CONFLICT 13 FT /note="R -> C (in Ref. 2; ABS28868)" FT /evidence="ECO:0000305" FT CONFLICT 25 FT /note="L -> V (in Ref. 1; CAA04473)" FT /evidence="ECO:0000305" FT HELIX 49..54 FT /evidence="ECO:0007829|PDB:4RWF" FT HELIX 61..76 FT /evidence="ECO:0007829|PDB:4RWF" FT HELIX 77..82 FT /evidence="ECO:0007829|PDB:4RWF" FT HELIX 86..106 FT /evidence="ECO:0007829|PDB:4RWF" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:7TYY" FT HELIX 114..126 FT /evidence="ECO:0007829|PDB:4RWF" FT TURN 127..130 FT /evidence="ECO:0007829|PDB:3AQE" FT HELIX 143..166 FT /evidence="ECO:0007829|PDB:7TYX" SQ SEQUENCE 175 AA; 19608 MW; AF69A9A461EFFCA3 CRC64; MASLRVERAG GPRLPRTRVG RPAALRLLLL LGAVLNPHEA LAQPLPTTGT PGSEGGTVKN YETAVQFCWN HYKDQMDPIE KDWCDWAMIS RPYSTLRDCL EHFAELFDLG FPNPLAERII FETHQIHFAN CSLVQPTFSD PPEDVLLAMI IAPICLIPFL ITLVVWRSKD SEAQA //