RAMP2_HUMAN
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 03-AUG-2022, entry version 183.
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}.
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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 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 GlyGen; O60895; 1 site.
DR PhosphoSitePlus; O60895; -.
DR BioMuta; RAMP2; -.
DR EPD; O60895; -.
DR MassIVE; O60895; -.
DR PaxDb; O60895; -.
DR PeptideAtlas; O60895; -.
DR PRIDE; O60895; -.
DR ProteomicsDB; 49658; -. [O60895-1]
DR Antibodypedia; 29403; 298 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 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; CDWAVIS; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; O60895; -.
DR BioGRID-ORCS; 10266; 17 hits in 1073 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 136 other tissues.
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: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: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: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; -; 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; 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 HELIX 114..126
FT /evidence="ECO:0007829|PDB:4RWF"
FT TURN 127..130
FT /evidence="ECO:0007829|PDB:3AQE"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:6UUN"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:6UUN"
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
