MRAP2_MOUSE
ID MRAP2_MOUSE Reviewed; 207 AA.
AC D3Z1Q2; D3YVA7; D3YZ75; D3Z746;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Melanocortin-2 receptor accessory protein 2;
GN Name=Mrap2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION.
RX PubMed=20371771; DOI=10.1126/scisignal.2000593;
RA Sebag J.A., Hinkle P.M.;
RT "Regulation of G protein-coupled receptor signaling: specific dominant-
RT negative effects of melanocortin 2 receptor accessory protein 2.";
RL Sci. Signal. 3:RA28-RA28(2010).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH MC4R, AND TISSUE
RP SPECIFICITY.
RX PubMed=23869016; DOI=10.1126/science.1233000;
RA Asai M., Ramachandrappa S., Joachim M., Shen Y., Zhang R., Nuthalapati N.,
RA Ramanathan V., Strochlic D.E., Ferket P., Linhart K., Ho C.,
RA Novoselova T.V., Garg S., Ridderstrale M., Marcus C., Hirschhorn J.N.,
RA Keogh J.M., O'Rahilly S., Chan L.F., Clark A.J., Farooqi I.S.,
RA Majzoub J.A.;
RT "Loss of function of the melanocortin 2 receptor accessory protein 2 is
RT associated with mammalian obesity.";
RL Science 341:275-278(2013).
CC -!- FUNCTION: Modulator of melanocortin receptor 4 (MC4R), a receptor
CC involved in energy homeostasis. Plays a central role in the control of
CC energy homeostasis and body weight regulation by increasing ligand-
CC sensitivity of MC4R and MC4R-mediated generation of cAMP. May also act
CC as a negative regulator of MC2R: competes with MRAP for binding to MC2R
CC and impairs the binding of corticotropin (ACTH) to MC2R. May also
CC regulate activity of other melanocortin receptors (MC1R, MC3R and
CC MC5R); however, additional evidence is required in vivo.
CC {ECO:0000269|PubMed:20371771, ECO:0000269|PubMed:23869016}.
CC -!- SUBUNIT: Homodimer and heterodimer. Forms antiparallel homodimers and
CC heterodimers with MRAP. Interacts with MC1R, MC2R, MC3R and MC5R (By
CC similarity). Interacts with MC4R. {ECO:0000250,
CC ECO:0000269|PubMed:23869016}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass membrane
CC protein {ECO:0000250}. Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass membrane protein {ECO:0000250}. Note=The formation of
CC antiparallel homo- and heterodimers suggest that N- and C-terminus can
CC both localize in the cytoplasmic and extracellular parts, depending on
CC the context. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the brain, mainly in the
CC pons and cerebellum but also in regions involved in energy homeostasis,
CC such as the hypothalamus and brainstem. {ECO:0000269|PubMed:23869016}.
CC -!- DISRUPTION PHENOTYPE: Obesity. Mice are normal at birth, with normal
CC weight gain and post-weaning food intake during early life, although
CC young males trend toward greater weight and food intake with advancing
CC age. Mice of both genders gradually become extremely obese on a diet of
CC regular chow ad libitum. {ECO:0000269|PubMed:23869016}.
CC -!- SIMILARITY: Belongs to the MRAP family. {ECO:0000305}.
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DR EMBL; AC125370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC168882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52878.1; -.
DR RefSeq; NP_001094952.2; NM_001101482.2.
DR RefSeq; NP_001171202.1; NM_001177731.1.
DR RefSeq; XP_006511237.1; XM_006511174.2.
DR RefSeq; XP_006511238.1; XM_006511175.2.
DR RefSeq; XP_006511239.1; XM_006511176.2.
DR RefSeq; XP_006511240.1; XM_006511177.3.
DR RefSeq; XP_006511241.1; XM_006511178.3.
DR RefSeq; XP_006511242.1; XM_006511179.2.
DR RefSeq; XP_006511243.1; XM_006511180.3.
DR AlphaFoldDB; D3Z1Q2; -.
DR STRING; 10090.ENSMUSP00000135904; -.
DR GlyGen; D3Z1Q2; 1 site.
DR PhosphoSitePlus; D3Z1Q2; -.
DR PaxDb; D3Z1Q2; -.
DR PRIDE; D3Z1Q2; -.
DR ProteomicsDB; 291398; -.
DR Antibodypedia; 2456; 116 antibodies from 20 providers.
DR Ensembl; ENSMUST00000049457; ENSMUSP00000046271; ENSMUSG00000042761.
DR Ensembl; ENSMUST00000113149; ENSMUSP00000108774; ENSMUSG00000042761.
DR Ensembl; ENSMUST00000179313; ENSMUSP00000135904; ENSMUSG00000042761.
DR GeneID; 244958; -.
DR KEGG; mmu:244958; -.
DR UCSC; uc012gxw.1; mouse.
DR CTD; 112609; -.
DR MGI; MGI:3609239; Mrap2.
DR VEuPathDB; HostDB:ENSMUSG00000042761; -.
DR eggNOG; ENOG502RYQM; Eukaryota.
DR GeneTree; ENSGT00650000093438; -.
DR HOGENOM; CLU_110753_0_0_1; -.
DR InParanoid; D3Z1Q2; -.
DR OMA; ADYEWHY; -.
DR OrthoDB; 1318662at2759; -.
DR PhylomeDB; D3Z1Q2; -.
DR TreeFam; TF338691; -.
DR BioGRID-ORCS; 244958; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Mrap2; mouse.
DR PRO; PR:D3Z1Q2; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; D3Z1Q2; protein.
DR Bgee; ENSMUSG00000042761; Expressed in pontine nuclear group and 69 other tissues.
DR Genevisible; D3Z1Q2; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031780; F:corticotropin hormone receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030545; F:signaling receptor regulator activity; IMP:UniProtKB.
DR GO; GO:0070996; F:type 1 melanocortin receptor binding; ISO:MGI.
DR GO; GO:0031781; F:type 3 melanocortin receptor binding; ISO:MGI.
DR GO; GO:0031782; F:type 4 melanocortin receptor binding; IDA:UniProtKB.
DR GO; GO:0031783; F:type 5 melanocortin receptor binding; ISO:MGI.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0006112; P:energy reserve metabolic process; IMP:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; IMP:UniProtKB.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0106071; P:positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0106070; P:regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR InterPro; IPR028111; MRAP.
DR PANTHER; PTHR28675; PTHR28675; 1.
DR Pfam; PF15183; MRAP; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..207
FT /note="Melanocortin-2 receptor accessory protein 2"
FT /id="PRO_0000424027"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96G30"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 207 AA; 23678 MW; BDCFE5947A30E85E CRC64;
MEMSAQRLAS NRTSPQSPSN SDYTWEYEYY EIGPVSFEGL KAHKYSIVIG FWVGLAVFVI
FMFFVLTLLT KTGAPHQDNA ESSERRFRMN SFVSDFGKPL ESDKVFSRQG NEESRSLFHC
YINEVEHLDR VKVCHQTTAI DSDVHLQEAS RSSGRPEEEL ARFMKFDIPN FVNTEQSSFG
EDDLLISEAP VLLENKPVSQ TSRIDLD
