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

Summary

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

Location:: 21q22.11

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	21	NC_000021.9 (32291813..32314784)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	21	NC_060945.1 (30661493..30684541)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (33664124..33687095)

Chromosome 21 - NC_000021.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-87585 (e-PCR)
- UniSTS:71756

SHGC-6834 (e-PCR)
- UniSTS:85582

D21S404 (e-PCR)
- UniSTS:147873

SHGC-170086 (e-PCR)
- UniSTS:173732

D21S313 (e-PCR)
- UniSTS:147697

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

NG_016234.1 RefSeqGene

Range

12043..25478

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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