IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column predetermined predetermined participant predetermined Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. crosslink cross-linking study crosslink western blot western blot Immuno blot Immuno blot Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. crosslinking agent: 365 nm light yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro electrophoresis electrophoretic mobility-based method electrophoresis weight by comassie molecular weight estimation by coomasie staining weight by comassie Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. (0961-8368) 2012 imex curation Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp 12-Nov-2014: Contacted by IntAct-Help. Only protein-protein interactions human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. yokoyama@riken.jp,yokoyama@biochem.s.u-tokyo.ac.jp Accepted 2014-NOV-03 by MGT Protein Sci. (0961-8368) 2012 Only protein-protein interactions imex curation p06881-pro_0000004054 Calcitonin gene-related peptide 1 CALCA CALC1 Alpha-type CGRP Calcitonin gene-related peptide I peptide peptide polypeptide oligopeptide oligopeptide polypeptide human Homo sapiens Human ACDTATCVTHRLAGLLSRSGGVVKNNFVPTNVGSKAF 83 119 F5DDEDA3C7A5F427 calrl_human Calcitonin gene-related peptide type 1 receptor CALCRL CGRPR Calcitonin receptor-like receptor protein protein human Homo sapiens Human MEKKCTLNFLVLLPFFMILVTAELEESPEDSIQLGVTRNKIMTAQYECYQKIMQDPIQQAEGVYCNRTWDGWLCWNDVAAGTESMQLCPDYFQDFDPSEKVTKICDQDGNWFRHPASNRTWTNYTQCNVNTHEKVKTALNLFYLTIIGHGLSIASLLISLGIFFYFKSLSCQRITLHKNLFFSFVCNSVVTIIHLTAVANNQALVATNPVSCKVSQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYFLGWGFPLIPACIHAIARSLYYNDNCWISSDTHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLIPWRPEGKIAEEVYDYIMHILMHFQGLLVSTIFCFFNGEVQAILRRNWNQYKIQFGNSFSNSEALRSASYTVSTISDGPGYSHDCPSEHLNGKSIHDIENVLLKPENLYN DIP protein Q16602 original sequence version: 94 AF98E55E5454767C ramp2_human Receptor activity-modifying protein 2 RAMP2 Calcitonin-receptor-like receptor activity-modifying protein 2 protein protein human Homo sapiens Human MASLRVERAGGPRLPRTRVGRPAALRLLLLLGAVLNPHEALAQPLPTTGTPGSEGGTVKNYETAVQFCWNHYKDQMDPIEKDWCDWAMISRPYSTLRDCLEHFAELFDLGFPNPLAERIIFETHQIHFANCSLVQPTFSDPPEDVLLAMIIAPICLIPFLITLVVWRSKDSEAQA AF69A9A461EFFCA3 o60895-pro_0000030172 Receptor activity-modifying protein 2 RAMP2 Calcitonin-receptor-like receptor activity-modifying protein 2 protein protein human Homo sapiens Human QPLPTTGTPGSEGGTVKNYETAVQFCWNHYKDQMDPIEKDWCDWAMISRPYSTLRDCLEHFAELFDLGFPNPLAERIIFETHQIHFANCSLVQPTFSDPPEDVLLAMIIAPICLIPFLITLVVWRSKDSEAQA 43 175 9AA7F5AE7E0263B8 o60894-pro_0000030168 Receptor activity-modifying protein 1 RAMP1 Calcitonin-receptor-like receptor activity-modifying protein 1 protein protein human Homo sapiens Human CQEANYGALLRELCLTQFQVDMEAVGETLWCDWGRTIRSYRELADCTWHMAEKLGCFWPNAEVDRFFLAVHGRYFRSCPISGRAVRDPPGSILYPFIVVPITVTLLVTALVVWQSKRTEGIV 27 148 20B59276F16D37B9 p35318-pro_0000000963 Adrenomedullin ADM AM protein protein human Homo sapiens Human YRQSMNNFQGLRSFGCRFGTCTVQKLAHQIYQFTDKDKDNVAPRSKISPQGY 95 146 628F36B17E17DC88 calcrl-ramp2-1 4 9 unspecified role unspecified role neutral component neutral component gpcr, family 2, extracellular hormone receptor domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region se(s)met L-selenomethionine Delta:S(-1)Se(1) Se(S)Met Selenium replaces sulphur semetm undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) 10 unspecified role unspecified role neutral component neutral component extracellular domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region se(s)met L-selenomethionine Delta:S(-1)Se(1) Se(S)Met Selenium replaces sulphur semetm undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) 16 19 direct interaction direct interaction Rwork = 0.22, Rfree = 0.28 2.6 A Fig.s 1b-d, 3, Table 1 ramp2-1 4 10 unspecified role unspecified role neutral component neutral component extracellular domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region se(s)met L-selenomethionine Delta:S(-1)Se(1) Se(S)Met Selenium replaces sulphur semetm undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) direct interaction direct interaction R = 0.23, Rwork = 0.23, Rfree = 0.28 2.0 A Fig. 2c, Table S1 calcrl-ramp2-2 3 9 unspecified role unspecified role neutral component neutral component c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 10 unspecified role unspecified role neutral component neutral component undefined mutation mutation mutation certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:40 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'ser94p-benzoyl-l-phenylalanine' c-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range undefined mutation mutation mutation certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:39 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'arg97p-benzoyl-l-phenylalanine' undefined mutation mutation mutation certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:40 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'phe121p-benzoyl-l-phenylalanine' undefined mutation mutation mutation certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:37 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'glu117p-benzoyl-l-phenylalanine' undefined mutation mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:38 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'tyr93p-benzoyl-l-phenylalanine' undefined mutation mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:36 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'ile120p-benzoyl-l-phenylalanine' undefined mutation mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:31:36 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'his124p-benzoyl-l-phenylalanine' undefined mutation mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:32:02 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'phe128p-benzoyl-l-phenylalanine' physical association physical association Fig. 4b arg97 and glu117 mutations to p-benzoyl-L-phenylalanine were much weaker than such mutants at ser94 and phe121. calcrl_ramp2-adm-1 2 13 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 41 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) physical association physical association The complex participants have the following lengths: CALCRL: 23-136 aa, and RAMP2: 56-139. Mutations decreasing: CALCRL WT / RAMP2 Glu101Ala, CALCRL WT / RAMP2 Phe111Ala, CALCRL Trp72Ala / RAMP2 WT, CALCRL Phe92Ala / RAMP2 WT, CALCRL Trp121Ala / RAMP2 WT, CALCRL WT / RAMP2 Ser94Arg/Arg97Ala/Glu101Trp/Phe111Trp When xml3 is out, the chain lengths needs to be added as feature at the participant level. and all mutants need adding to features at complex participant level Fig.s 5a, 5e, 6c, Table II calcrl-ramp2-4 1 9 unspecified role unspecified role neutral component neutral component gpcr, family 2, extracellular hormone receptor domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 10 unspecified role unspecified role neutral component neutral component extracellular domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) direct interaction direct interaction Fig.s S1A, S1C calcrl-ramp2-5 1 9 unspecified role unspecified role neutral component neutral component gpcr, family 2, extracellular hormone receptor domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 10 unspecified role unspecified role neutral component neutral component extracellular domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) direct interaction direct interaction Fig.s S1A, S1C calcrl-ramp2-6 6 9 unspecified role unspecified role neutral component neutral component gpcr, family 2, extracellular hormone receptor domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 10 unspecified role unspecified role neutral component neutral component extracellular domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 54 56 direct interaction direct interaction Fig.s S1D calcrl-adm 2 13 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 9 unspecified role unspecified role bait bait gpcr, family 2, extracellular hormone receptor domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region se(s)met L-selenomethionine Delta:S(-1)Se(1) Se(S)Met Selenium replaces sulphur semetm undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) direct interaction direct interaction Fig. 5a, Table II calcrl_ramp2-cgrp 2 41 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) 8 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association The complex participants have the following lengths: CALCRL: 23-136 aa, and RAMP2: 56-139. Mutations decreasing: CALCRL WT / RAMP2 Glu101Ala, CALCRL WT / RAMP2 Phe111Ala, CALCRL Trp72Ala / RAMP2 WT, CALCRL Phe92Ala / RAMP2 WT, CALCRL Trp121Ala / RAMP2 WT, Mutation increasing: CALCRL WT / RAMP2 Ser94Arg/Arg97Ala/Glu101Trp/Phe111Trp When xml3 is out, the chain lengths needs to be added as feature at the participant level. and all mutants need adding to features at complex participant level Table II, Fig. 6d calcrl_ramp1-adm 2 67 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) 13 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) physical association physical association The complex participants have the following lengths: CALCRL: 23-136 aa, and RAMP1: 27–112. When xml3 is out, the chain lengths needs to be added as feature at the participant level. Table II, Fig. 6d calcrl_ramp1-cgrp 2 8 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) 67 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) physical association physical association The complex participants have the following lengths: CALCRL: 23-136 aa, and RAMP1: 27–112. When xml3 is out, the chain lengths needs to be added as feature at the participant level. Table II, Fig. 6d calcrl-ramp2-3 7 9 unspecified role unspecified role neutral component neutral component c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. 10 unspecified role unspecified role neutral component neutral component c-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. physical association physical association Fig. 4b cgrp-receptor_human calcitonin-gene-related peptide receptor, CALCRL/RAMP1 CGRP receptor complex CGRP-R complex calrl-ramp1 complex CALCRL:RAMP1 calcitonin-gene-related polypeptide receptor complex calcitonin-gene-related peptide receptor complex 12 unspecified role unspecified role carlcrl binding region direct binding direct binding region direct binding undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 9 unspecified role unspecified role ramp1 binding region direct binding direct binding region direct binding undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 78 80 direct interaction direct interaction human Homo sapiens Human stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction A transmembrane, G-protein-coupled signalling receptor complex that serves as receptor for calcitonin gene-related peptides (CGRP). CGRPs are produced in both peripheral and central neurons and are one of the most potent peptide vasodilators known. Expressed at trigeminal nerve endings that innervate cerebral blood vessels. RAMP1 is responsible for transporting CALCRL to the plasma membrane. Heterodimer Consisting of the calcitonin receptor-like receptor (CALCRL), a class B G-protein-coupled receptor, and RAMP1, a receptor activity-modifying protein. The ligand binding site resides in the dimerization-interface of the extracellular domains. Buried surface: 1010 A^2 Complex may also exist with CALCRL as dimer. Calcitonin gene-related peptide 1 (CGRP1, CALCA, alpha-type CGRP) (P06881- PRO_0000004045) Calcitonin gene-related peptide 2 (CGRP2, CALCB, beta-type CGRP) (P10092-PRO_0000004087) Trigeminal nerve ending location, vasodilatory effect, and other evidence suggest a direct role of CGRPs in migraine. created with intact-jami-dbscripts am1-receptor_human Adrenomedullin receptor AM1 complex AM1 complex CALRL-RAMP2 complex CALCRL:RAMP2 ADM1 receptor Adrenomedullin receptor AM1; CALCRL/RAMP2 11 unspecified role unspecified role calcrl binding region direct binding direct binding region direct binding undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 9 unspecified role unspecified role ramp2 binding region direct binding direct binding region direct binding undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 84 82 direct interaction direct interaction human Homo sapiens Human stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction A transmembrane, G-protein-coupled signalling receptor complex that serves as the adrenomedullin (AM) receptor to control neovascularization and the stabilization of vascular integrity. AM, a polypeptide, belongs to the calcitonin family of peptides. It is produced by vascular smooth muscle cells and endothelial cells and has strong hypotensive and vasodilation activity. RAMP2 is responsible for transporting CALCRL to the plasma membrane. Consisting of the calcitonin receptor-like receptor (CALCRL), a class B G-protein-coupled receptor, and RAMP2, a receptor activity-modifying protein. The ligand binding site resides in the dimerization-interface of the extracellular domains. MW ~80 kD buried surface: 924 A^2 Complex may also exist with CALCRL as dimer. Heterodimer Adrenomedullin (AM, ADM) (P35318, PRO_0000000963) created with intact-jami-dbscripts