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 13-FEB-2019, entry version 163. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE RP 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., 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 [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 RT sequenced by 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., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA 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 RT the 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] 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 [7] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-139 IN COMPLEX WITH RP CALCRL, FUNCTION, AND DISULFIDE BONDS. RX PubMed=22102369; DOI=10.1002/pro.2003; RA Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., RA Sakamoto K., 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. CC {ECO:0000269|PubMed:22102369, ECO:0000269|PubMed:9620797}. CC -!- SUBUNIT: Heterodimer of CALCRL and RAMP2. {ECO:0000250}. CC -!- INTERACTION: CC Q16602:CALCRL; NbExp=6; IntAct=EBI-9009040, EBI-962878; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC 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 CC system 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 UniGene; Hs.514193; -. 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 PDBsum; 2XVT; -. DR PDBsum; 3AQE; -. DR PDBsum; 3AQF; -. DR PDBsum; 4RWF; -. DR ProteinModelPortal; O60895; -. DR SMR; O60895; -. DR BioGrid; 115557; 1. 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; CHEMBL2364173; -. DR DrugBank; DB01278; Pramlintide. DR GuidetoPHARMACOLOGY; 52; -. DR PhosphoSitePlus; O60895; -. DR BioMuta; RAMP2; -. DR EPD; O60895; -. DR jPOST; O60895; -. DR PaxDb; O60895; -. DR PeptideAtlas; O60895; -. DR PRIDE; O60895; -. DR ProteomicsDB; 49658; -. DR DNASU; 10266; -. DR Ensembl; ENST00000253796; ENSP00000253796; ENSG00000131477. [O60895-1] DR Ensembl; ENST00000587142; ENSP00000466455; ENSG00000131477. [O60895-2] DR GeneID; 10266; -. DR KEGG; hsa:10266; -. DR UCSC; uc002ibg.5; human. [O60895-1] DR CTD; 10266; -. DR DisGeNET; 10266; -. DR EuPathDB; HostDB:ENSG00000131477.10; -. DR GeneCards; RAMP2; -. DR HGNC; HGNC:9844; RAMP2. DR HPA; HPA052020; -. DR MIM; 605154; gene. DR neXtProt; NX_O60895; -. DR OpenTargets; ENSG00000131477; -. DR PharmGKB; PA34203; -. DR eggNOG; ENOG410IYPR; Eukaryota. DR eggNOG; ENOG4112A9G; LUCA. DR GeneTree; ENSGT00940000160264; -. DR HOGENOM; HOG000230963; -. DR HOVERGEN; HBG067366; -. DR InParanoid; O60895; -. DR KO; K08448; -. DR OMA; GAVLKPH; -. DR OrthoDB; 1482534at2759; -. DR PhylomeDB; O60895; -. DR TreeFam; TF333286; -. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors. DR ChiTaRS; RAMP2; human. DR GeneWiki; RAMP2; -. DR GenomeRNAi; 10266; -. DR PRO; PR:O60895; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000131477; Expressed in 167 organ(s), highest expression level in right lung. DR ExpressionAtlas; O60895; baseline and differential. DR Genevisible; O60895; HS. DR GO; GO:1903143; C:adrenomedullin receptor complex; IDA:UniProtKB. DR GO; GO:0150057; C:amylin receptor complex 2; IDA:ARUK-UCL. DR GO; GO:0005623; C:cell; IDA:ARUK-UCL. 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:0005887; C:integral component of plasma membrane; TAS:ProtInc. 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: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:0034333; P:adherens junction assembly; IDA:UniProtKB. 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; 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:0007565; P:female pregnancy; IEA:Ensembl. 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:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl. DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0097084; P:vascular smooth muscle cell development; ISS:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB. 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; Alternative splicing; Complete proteome; Disulfide bond; KW Glycoprotein; Membrane; Receptor; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1 42 {ECO:0000255}. FT CHAIN 43 175 Receptor activity-modifying protein 2. FT /FTId=PRO_0000030172. FT TOPO_DOM 43 145 Extracellular. {ECO:0000255}. FT TRANSMEM 146 166 Helical. {ECO:0000255}. FT TOPO_DOM 167 175 Cytoplasmic. {ECO:0000255}. FT CARBOHYD 130 130 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 68 99 FT DISULFID 84 131 FT VAR_SEQ 54 54 E -> EASVPT (in isoform 2). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055838. FT CONFLICT 13 13 R -> C (in Ref. 2; ABS28868). FT {ECO:0000305}. FT CONFLICT 25 25 L -> V (in Ref. 1; CAA04473). FT {ECO:0000305}. FT HELIX 49 54 {ECO:0000244|PDB:4RWF}. FT HELIX 61 76 {ECO:0000244|PDB:4RWF}. FT HELIX 77 82 {ECO:0000244|PDB:4RWF}. FT HELIX 86 106 {ECO:0000244|PDB:4RWF}. FT HELIX 114 126 {ECO:0000244|PDB:4RWF}. FT TURN 127 130 {ECO:0000244|PDB:3AQE}. 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 //