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Protein

Receptor activity-modifying protein 2

Gene

RAMP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for adrenomedullin (AM) together with CALCRL.2 Publications

GO - Molecular functioni

  • coreceptor activity Source: UniProtKB
  • protein transporter activity Source: UniProtKB

GO - Biological processi

  • adherens junction assembly Source: UniProtKB
  • angiogenesis Source: UniProtKB
  • basement membrane assembly Source: UniProtKB
  • bicellular tight junction assembly Source: UniProtKB
  • calcium ion transport Source: UniProtKB
  • cAMP biosynthetic process Source: UniProtKB
  • cellular response to hormone stimulus Source: Ensembl
  • cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  • female pregnancy Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: Ensembl
  • heart development Source: UniProtKB
  • intracellular protein transport Source: InterPro
  • negative regulation of endothelial cell apoptotic process Source: UniProtKB
  • negative regulation of vascular permeability Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of vasculogenesis Source: Ensembl
  • protein localization to plasma membrane Source: UniProtKB
  • protein transport Source: UniProtKB
  • receptor internalization Source: UniProtKB
  • regulation of blood pressure Source: UniProtKB
  • regulation of G-protein coupled receptor protein signaling pathway Source: InterPro
  • response to estradiol Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to progesterone Source: Ensembl
  • sprouting angiogenesis Source: UniProtKB
  • vascular smooth muscle cell development Source: UniProtKB
  • vasculogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiREACT_18290. Calcitonin-like ligand receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor activity-modifying protein 2
Alternative name(s):
Calcitonin-receptor-like receptor activity-modifying protein 2
Short name:
CRLR activity-modifying protein 2
Gene namesi
Name:RAMP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:9844. RAMP2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini43 – 145103ExtracellularSequence AnalysisAdd
BLAST
Transmembranei146 – 16621HelicalSequence AnalysisAdd
BLAST
Topological domaini167 – 1759CytoplasmicSequence Analysis

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • coated pit Source: ProtInc
  • cytoplasm Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • lysosome Source: ProtInc
  • plasma membrane Source: Reactome
  • receptor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA34203.

Chemistry

DrugBankiDB01278. Pramlintide.

Polymorphism and mutation databases

BioMutaiRAMP2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4242Sequence AnalysisAdd
BLAST
Chaini43 – 175133Receptor activity-modifying protein 2PRO_0000030172Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi68 ↔ 99
Disulfide bondi84 ↔ 131
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO60895.
PRIDEiO60895.

PTM databases

PhosphoSiteiO60895.

Expressioni

Tissue specificityi

Strongly expressed in lung, breast, immune system and fetal tissues.1 Publication

Gene expression databases

BgeeiO60895.
CleanExiHS_RAMP2.
ExpressionAtlasiO60895. baseline and differential.
GenevisibleiO60895. HS.

Interactioni

Subunit structurei

Heterodimer of CALCRL and RAMP2.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CALCRLQ166026EBI-9009040,EBI-962878

Protein-protein interaction databases

BioGridi115557. 1 interaction.
IntActiO60895. 1 interaction.
STRINGi9606.ENSP00000253796.

Structurei

Secondary structure

1
175
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi61 – 7616Combined sources
Helixi77 – 826Combined sources
Helixi86 – 10621Combined sources
Helixi114 – 12613Combined sources
Turni127 – 1304Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2XVTX-ray2.05A/B/C/D/E/F48-139[»]
3AQEX-ray2.00A/B/C/D/E/F56-139[»]
3AQFX-ray2.60A56-139[»]
4RWFX-ray1.76A55-138[»]
ProteinModelPortaliO60895.
SMRiO60895. Positions 60-135.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the RAMP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42995.
GeneTreeiENSGT00390000016200.
HOGENOMiHOG000230963.
HOVERGENiHBG067366.
InParanoidiO60895.
KOiK08448.
OMAiDWCDWAM.
PhylomeDBiO60895.
TreeFamiTF333286.

Family and domain databases

InterProiIPR006985. RAMP.
[Graphical view]
PANTHERiPTHR14076. PTHR14076. 1 hit.
PfamiPF04901. RAMP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60895-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASLRVERAG GPRLPRTRVG RPAALRLLLL LGAVLNPHEA LAQPLPTTGT
60 70 80 90 100
PGSEGGTVKN YETAVQFCWN HYKDQMDPIE KDWCDWAMIS RPYSTLRDCL
110 120 130 140 150
EHFAELFDLG FPNPLAERII FETHQIHFAN CSLVQPTFSD PPEDVLLAMI
160 170
IAPICLIPFL ITLVVWRSKD SEAQA
Length:175
Mass (Da):19,608
Last modified:January 10, 2003 - v2
Checksum:iAF69A9A461EFFCA3
GO
Isoform 2 (identifier: O60895-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     54-54: E → EASVPT

Show »
Length:180
Mass (Da):20,063
Checksum:i17FEBC82A10A0E2F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131R → C in ABS28868 (Ref. 2) Curated
Sequence conflicti25 – 251L → V in CAA04473 (PubMed:9620797).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei54 – 541E → EASVPT in isoform 2. 1 PublicationVSP_055838

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001015 mRNA. Translation: CAA04473.1.
EF687002 mRNA. Translation: ABS28868.1.
AY265458 mRNA. Translation: AAP23299.1.
AC100793 Genomic DNA. No translation available.
BC027975 mRNA. Translation: AAH27975.1.
CCDSiCCDS11437.1. [O60895-1]
RefSeqiNP_005845.2. NM_005854.2. [O60895-1]
UniGeneiHs.514193.

Genome annotation databases

EnsembliENST00000253796; ENSP00000253796; ENSG00000131477.
ENST00000587142; ENSP00000466455; ENSG00000131477. [O60895-2]
GeneIDi10266.
KEGGihsa:10266.
UCSCiuc002ibg.3. human. [O60895-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001015 mRNA. Translation: CAA04473.1.
EF687002 mRNA. Translation: ABS28868.1.
AY265458 mRNA. Translation: AAP23299.1.
AC100793 Genomic DNA. No translation available.
BC027975 mRNA. Translation: AAH27975.1.
CCDSiCCDS11437.1. [O60895-1]
RefSeqiNP_005845.2. NM_005854.2. [O60895-1]
UniGeneiHs.514193.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2XVTX-ray2.05A/B/C/D/E/F48-139[»]
3AQEX-ray2.00A/B/C/D/E/F56-139[»]
3AQFX-ray2.60A56-139[»]
4RWFX-ray1.76A55-138[»]
ProteinModelPortaliO60895.
SMRiO60895. Positions 60-135.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115557. 1 interaction.
IntActiO60895. 1 interaction.
STRINGi9606.ENSP00000253796.

Chemistry

BindingDBiO60895.
ChEMBLiCHEMBL2109232.
DrugBankiDB01278. Pramlintide.

PTM databases

PhosphoSiteiO60895.

Polymorphism and mutation databases

BioMutaiRAMP2.

Proteomic databases

PaxDbiO60895.
PRIDEiO60895.

Protocols and materials databases

DNASUi10266.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253796; ENSP00000253796; ENSG00000131477.
ENST00000587142; ENSP00000466455; ENSG00000131477. [O60895-2]
GeneIDi10266.
KEGGihsa:10266.
UCSCiuc002ibg.3. human. [O60895-1]

Organism-specific databases

CTDi10266.
GeneCardsiGC17P040913.
HGNCiHGNC:9844. RAMP2.
MIMi605154. gene.
neXtProtiNX_O60895.
PharmGKBiPA34203.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42995.
GeneTreeiENSGT00390000016200.
HOGENOMiHOG000230963.
HOVERGENiHBG067366.
InParanoidiO60895.
KOiK08448.
OMAiDWCDWAM.
PhylomeDBiO60895.
TreeFamiTF333286.

Enzyme and pathway databases

ReactomeiREACT_18290. Calcitonin-like ligand receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

ChiTaRSiRAMP2. human.
GeneWikiiRAMP2.
GenomeRNAii10266.
NextBioi35463350.
PROiO60895.
SOURCEiSearch...

Gene expression databases

BgeeiO60895.
CleanExiHS_RAMP2.
ExpressionAtlasiO60895. baseline and differential.
GenevisibleiO60895. HS.

Family and domain databases

InterProiIPR006985. RAMP.
[Graphical view]
PANTHERiPTHR14076. PTHR14076. 1 hit.
PfamiPF04901. RAMP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor."
    McLatchie L.M., Fraser N.J., Main M.J., Wise A., Brown J., Thompson N., Solari R., Lee M.G., Foord S.M.
    Nature 393:333-339(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
    Tissue: Neuroblastoma.
  2. "Characterization of adrenomedullin receptors and identification of a receptor activity modifying protein 2 (RAMP2) variant in SV40LT-SMC cells."
    Rorabaugh B.R., Witt K.M., Smith D.D., Abel P.W., Scofield M.A.
    Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Heart.
  4. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Pancreas.
  6. "Structure of the extracellular domain of human RAMP2."
    Structural genomics consortium (SGC)
    Submitted (DEC-2010) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 48-139, DISULFIDE BONDS.
  7. "Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding."
    Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S.
    Protein Sci. 21:199-210(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 52-139 IN COMPLEX WITH CALCRL, FUNCTION, DISULFIDE BONDS.

Entry informationi

Entry nameiRAMP2_HUMAN
AccessioniPrimary (citable) accession number: O60895
Secondary accession number(s): A7L9S6, K7EMD3, Q8N1F2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 10, 2003
Last modified: July 22, 2015
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.