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FLASH GENE

Symbol

MRAP2

contributors: mct/npt - updated : 07-07-2020

HGNC name	melanocortin 2 receptor accessory protein 2
HGNC id	21232

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	113.66 kb     4 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_138409 4 - 2137 NP_612418 23.5 205 - 2019 30951854 NM_001346542 5 - 2381 NP_001333471 - 205 - 2019 30951854 NM_001346543 5 - 2231 NP_001333472 - 150 - 2019 30951854 NM_001346541 3 - 2037 NP_001333470 - 119 - 2019 30951854 NM_001346544 4 - 2160 NP_001333473 - 205 - 2019 30951854

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland cortex     lowly Homo sapiens Nervous brain diencephalon hypothalamus   predominantly Homo sapiens Reproductive female system uterus       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular     Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

lacks amino acids 18LDYI21 of MRAP (Sebag 2009)

HOMOLOGY

intraspecies

paralog to MRAP

Homologene

FAMILY

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus

basic FUNCTION	having ability to facilitate trafficking of the MC2R to the plasma membrane and to enable the receptor to signal in response to its unique ligand, ACTH (Chan 2009)
	having 2 separate MC2R accessory roles: first in trafficking of the receptor, and second in enabling receptor responsiveness to ACTH (Chan 2009)
	like MRAP(18-21A), allows MC2 receptor trafficking but not signaling (Sebag 2009)
	transports the MC2R to the cell surface but might prevent activation
	role for MRAP2 in regulating melanocortin receptor activity and in the development of obesity
	regulates Ghrelin Receptor signaling and hunger sensing
	MRAP2 regulates endometrial receptivity and function

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	can homodimerize and form heterodimers with MRAP (Chan 2009)
	complex MC4R-MRAP2 throws light on the action of ACTH and, by extension, on the relay of stress-related information to additional biological systems

INTERACTION

DNA

RNA

small molecule

protein	interaction with MRAP (interaction results in MC2R surface expression and signaling) (Chan 2009)
	modulates MC2R activity
	MRAP2 interaction with the melanocortin-4-receptor (MC4R) affects receptor signaling
	MRAP2 interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PROKR1)
	role of MRAP2 in the regulation of the orexin receptor 1 (HCRTR1)
	is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling
	MRAP2 altered GHSR signaling by inhibiting its constitutive activity, as well as by enhancing its G protein-dependent signaling and blocking the recruitment and signaling of ARRB in response to ghrelin

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   lower in adrenocortical carcinomas (ACC) than in other adrenal tissues

Susceptibility

to hyperphagic obesity, hyperglycemia and hypertension

Variant & Polymorphism other	loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Mrap2 complete knockout (KO) mice have increased body weight without detectable changes to food intake or energy expenditure