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    MRAP melanocortin 2 receptor accessory protein [ Homo sapiens (human) ]

    Gene ID: 56246, updated on 5-Mar-2024

    Summary

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    Official Symbol
    MRAPprovided by HGNC
    Official Full Name
    melanocortin 2 receptor accessory proteinprovided by HGNC
    Primary source
    HGNC:HGNC:1304
    See related
    Ensembl:ENSG00000170262 MIM:609196; AllianceGenome:HGNC:1304
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    B27; FALP; FGD2; GCCD2; MRAP1; C21orf61
    Summary
    This gene encodes a melanocortin receptor-interacting protein. The encoded protein regulates trafficking and function of the melanocortin 2 receptor in the adrenal gland. The encoded protein can also modulate signaling of other melanocortin receptors. Mutations in this gene have been associated with familial glucocorticoid deficiency type 2. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]
    Expression
    Broad expression in fat (RPKM 19.3), adrenal (RPKM 18.8) and 20 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    21q22.11
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (32291813..32314784)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (30661493..30684541)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (33664124..33687095)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene MIS18 kinetochore protein A Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:33650609-33651110 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:33651111-33651610 Neighboring gene MIS18A antisense RNA 1 Neighboring gene uncharacterized LOC124905009 Neighboring gene Sharpr-MPRA regulatory region 333 Neighboring gene MRAP antisense RNA 1 Neighboring gene NANOG hESC enhancer GRCh37_chr21:33702964-33703556 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:33706649-33707848 Neighboring gene URB1 ribosome biogenesis homolog Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18361 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:33754437-33755636 Neighboring gene H3K27ac hESC enhancers GRCh37_chr21:33764587-33765369 and GRCh37_chr21:33765370-33766151 Neighboring gene small nucleolar RNA, H/ACA box 80A Neighboring gene URB1 antisense RNA 1 (head to head)

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients. Mehde AA, et al. Int J Biol Macromol, 2017 Dec. PMID 28760704
    2. H295R expression of melanocortin 2 receptor accessory protein results in ACTH responsiveness. Nanba K, et al. J Mol Endocrinol, 2016 Feb. PMID 26576642
    3. Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane. Malik S, et al. J Biol Chem, 2015 Nov 13. PMID 26424796, Free PMC Article
    4. Neonatal presentation of familial glucocorticoid deficiency resulting from a novel splice mutation in the melanocortin 2 receptor accessory protein. Jain V, et al. Eur J Endocrinol, 2011 Dec. PMID 21951701, Free PMC Article
    5. Missense mutations in the melanocortin 2 receptor accessory protein that lead to late onset familial glucocorticoid deficiency type 2. Hughes CR, et al. J Clin Endocrinol Metab, 2010 Jul. PMID 20427498

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. allele of the 5 insertion/deletion polymorphism in the Alpha-2-MRAP gene is related with an increase of oxidative stress in nephrolithiasis patients
      Title: Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients.
    2. Data (including data from studies in transgenic mice) suggest that MRAP plays critical role in (1) regulation of lipolysis in adipose tissue, (2) regulation of enzyme expression in adipose tissue, and (3) whole-body energy balance.
      Title: Regulation of Lipolytic Response and Energy Balance by Melanocortin 2 Receptor Accessory Protein (MRAP) in Adipocytes.
    3. MRAP expression in human cell line results in an ACTH responsive phenotype.
      Title: H295R expression of melanocortin 2 receptor accessory protein results in ACTH responsiveness.
    4. Data show that co-expression with MRAPalpha, but not MRAP2, enhances MC4R constitutive activity. MRAPalpha-enhanced MC4R constitutive activity is not dependent on MC4R complex glycosylation but may result from MRAPalpha-induced changes in MC4R conformational states.
      Title: hMRAPα, but Not hMRAP2, Enhances hMC4R Constitutive Activity in HEK293 Cells and This Is Not Dependent on hMRAPα Induced Changes in hMC4R Complex N-linked Glycosylation.
    5. The results firmly establish that only the copy of MRAP oriented with the amino terminus on the extracellular side of the receptor is essential for Adrenocorticotropic Hormone signal transduction.
      Title: Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.
    6. Data suggest that MRAP regulates expression of melanocortin receptors (MC1R-MC5R); MRAP is highly expressed in both zona fasciculata and undifferentiated zone of adrenal gland, sites of MC2R-mediated adrenal steroidogenesis. [REVIEW]
      Title: Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.
    7. The data suggest that MRAPalpha is involved in MC2R targeting to the plasma membrane, while MRAPbeta may enhance ACTH-MC2R coupling to cAMP production.
      Title: The C-terminal domains of melanocortin-2 receptor (MC2R) accessory proteins (MRAP1) influence their localization and ACTH-induced cAMP production.
    8. MRAP is positively regulated by ACTH and AngII in human adrenocortical tissues.
      Title: Melanocortin 2 receptor-associated protein (MRAP) and MRAP2 in human adrenocortical tissues: regulation of expression and association with ACTH responsiveness.
    9. A novel MRAP mutation is identified in a neonate where disruption of intron 3 splice-site results in a prematurely terminated translation product causing complete lack of adrenocorticotrophic (ADTH) hormone receptor response.
      Title: Neonatal presentation of familial glucocorticoid deficiency resulting from a novel splice mutation in the melanocortin 2 receptor accessory protein.
    10. The MRAP promoter is activated by serum depletion according to promoter reporter assays in HEK 293 cells.
      Title: Functional analysis and identification of cis-regulatory elements of human chromosome 21 gene promoters.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Glucocorticoid deficiency 2
    MedGen: C4049714 OMIM: 607398 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables corticotropin hormone receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables corticotropin hormone receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables type 1 melanocortin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables type 1 melanocortin receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables type 3 melanocortin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables type 3 melanocortin receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables type 4 melanocortin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables type 4 melanocortin receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables type 5 melanocortin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables type 5 melanocortin receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of protein localization to plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein localization to plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    melanocortin-2 receptor accessory protein
    Names
    fat cell-specific low molecular weight protein
    fat tissue-specific low MW protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016234.1 RefSeqGene

      Range
      12043..25478
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001285394.2 → NP_001272323.1  melanocortin-2 receptor accessory protein isoform c

      See identical proteins and their annotated locations for NP_001272323.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a coding exon compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform alpha.
      Source sequence(s)
      AP000266
      UniProtKB/Swiss-Prot
      Q8TCY5
      Related
      ENST00000497833.1
      Conserved Domains (1) summary
      pfam15183
      Location:1 → 30
      MRAP; Melanocortin-2 receptor accessory protein family

    2. NM_001379228.1 → NP_001366157.1  melanocortin-2 receptor accessory protein isoform alpha

      Status: REVIEWED

      Source sequence(s)
      AP000266
      Consensus CDS
      CCDS13613.1
      UniProtKB/Swiss-Prot
      Q5EBR3, Q8TCY5, Q8TDB7, Q8WXC1, Q8WXC2
      Related
      ENSP00000306697.5, ENST00000303645.10
      Conserved Domains (1) summary
      pfam15183
      Location:1 → 89
      MRAP; Melanocortin-2 receptor accessory protein family

    3. NM_178817.4 → NP_848932.1  melanocortin-2 receptor accessory protein isoform alpha

      See identical proteins and their annotated locations for NP_848932.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (alpha).
      Source sequence(s)
      AP000266
      Consensus CDS
      CCDS13613.1
      UniProtKB/Swiss-Prot
      Q5EBR3, Q8TCY5, Q8TDB7, Q8WXC1, Q8WXC2
      Related
      ENSP00000382684.2, ENST00000399784.6
      Conserved Domains (1) summary
      pfam15183
      Location:1 → 89
      MRAP; Melanocortin-2 receptor accessory protein family

    4. NM_206898.2 → NP_996781.1  melanocortin-2 receptor accessory protein isoform beta

      See identical proteins and their annotated locations for NP_996781.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR and coding region compared to variant 1. The resulting isoform (beta) is shorter and has a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AF454915, AF483549
      Consensus CDS
      CCDS13612.1
      UniProtKB/Swiss-Prot
      Q8TCY5
      Related
      ENSP00000343661.4, ENST00000339944.4
      Conserved Domains (1) summary
      pfam15183
      Location:1 → 72
      MRAP; Melanocortin-2 receptor accessory protein family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      32291813..32314784
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      30661493..30684541
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TCY5.2 GenPept UniProtKB/Swiss-Prot:Q8TCY5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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