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Q8TCY5 (MRAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Melanocortin-2 receptor accessory protein
Alternative name(s):
B27
Fat cell-specific low molecular weight protein
Fat tissue-specific low MW protein
Gene names
Name:MRAP
Synonyms:C21orf61, FALP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length172 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Modulator of melanocortin receptors (MC1R, MC2R, MC3R, MC4R and MC5R). Acts by increasing ligand-sensitivity of melanocortin receptors and enhancing generation of cAMP by the receptors. Required both for MC2R trafficking to the cell surface of adrenal cells and for signaling in response to corticotropin (ACTH). May be involved in the intracellular trafficking pathways in adipocyte cells. Ref.4 Ref.5 Ref.6

Subunit structure

Homodimer and heterodimer. Forms antiparallel homodimers and heterodimers with MRAP2. Interacts with MC1R, MC2R, MC3R, MC4R and MC5R. Ref.4 Ref.5 Ref.6

Subcellular location

Cell membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. Note: The formation of antiparallel homo- and heterodimers suggest that N- and C-terminus can both localize in the cytoplasmic and extracellular parts, depending on the context (Ref.5). Upon insulin stimulation, it is redistributed into spotty structures throughout the cytoplasm. Ref.6

Tissue specificity

Expressed in adrenal cortex, testis, breast, thyroid, lymph node, ovary and fat. Expressed in adipose tissues. Ref.6

Involvement in disease

Glucocorticoid deficiency 2 (GCCD2) [MIM:607398]: A rare, potentially lethal, autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the MRAP family.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 4 (identifier: Q8TCY5-4)

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.
Isoform 1 (identifier: Q8TCY5-1)

Also known as: Alpha; MRAP-alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     68-68: M → MR
Isoform 2 (identifier: Q8TCY5-2)

Also known as: Beta; MRAP-beta;

The sequence of this isoform differs from the canonical sequence as follows:
     69-101: RNSPKHHQTCPWSHGLNLHLCIQKCLPCHREPL → SFNTDESLLHSEVLPQTRAISCDELQAPREEGAA
     102-172: Missing.
Isoform 3 (identifier: Q8TCY5-3)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 172172Melanocortin-2 receptor accessory protein
PRO_0000096570

Regions

Transmembrane38 – 5821Helical; Potential

Natural variations

Alternative sequence1 – 5959Missing in isoform 3.
VSP_003862
Alternative sequence681M → MR in isoform 1.
VSP_021020
Alternative sequence69 – 10133RNSPK…HREPL → SFNTDESLLHSEVLPQTRAI SCDELQAPREEGAA in isoform 2.
VSP_003863
Alternative sequence102 – 17271Missing in isoform 2.
VSP_003864

Sequences

Sequence LengthMass (Da)Tools
Isoform 4 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 9F93F39B40FAAFEA

FASTA17219,136
        10         20         30         40         50         60 
MANGTNASAP YYSYEYYLDY LDLIPVDEKK LKAHKHSIVI AFWVSLAAFV VLLFLILLYM 

        70         80         90        100        110        120 
SWSASPQMRN SPKHHQTCPW SHGLNLHLCI QKCLPCHREP LATSQAQASS VEPGSRTGPD 

       130        140        150        160        170 
QPLRQESSST LPLGGFQTHP TLLWELTLNG GPLVRSKPSE PPPGDRTSQL QS 

« Hide

Isoform 1 (Alpha) (MRAP-alpha) [UniParc].

Checksum: 7F6A2A3D99045107
Show »

FASTA17319,292
Isoform 2 (Beta) (MRAP-beta) [UniParc].

Checksum: 7FA8FCF335B43DA3
Show »

FASTA10211,519
Isoform 3 (Short) [UniParc].

Checksum: 968FDEF0D68ECCCA
Show »

FASTA11312,338

References

« Hide 'large scale' references
[1]"Identification of novel putative membrane proteins selectively expressed during adipose conversion of 3T3-L1 cells."
Xu A., Choi K.-L., Wang Y., Permana P.A., Xu L.Y., Bogardus C., Cooper G.J.S.
Biochem. Biophys. Res. Commun. 293:1161-1167(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Adipocyte.
[2]"Annotation of human chromosome 21 for relevance to Down syndrome: gene structure and expression analysis."
Gardiner K., Slavov D., Bechtel L., Davisson M.
Genomics 79:833-843(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
Tissue: Brain.
[3]"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 4).
Tissue: Thyroid.
[4]"MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family."
Chan L.F., Webb T.R., Chung T.T., Meimaridou E., Cooray S.N., Guasti L., Chapple J.P., Egertova M., Elphick M.R., Cheetham M.E., Metherell L.A., Clark A.J.
Proc. Natl. Acad. Sci. U.S.A. 106:6146-6151(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH MC1R; MC2R; MC3R; MC4R; MC5R AND MRAP2.
[5]"Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2."
Sebag J.A., Hinkle P.M.
Sci. Signal. 3:RA28-RA28(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, TOPOLOGY, INTERACTION WITH MC2R AND MRAP2.
[6]"Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2."
Metherell L.A., Chapple J.P., Cooray S., David A., Becker C., Rueschendorf F., Naville D., Begeot M., Khoo B., Nuernberg P., Huebner A., Cheetham M.E., Clark A.J.L.
Nat. Genet. 37:166-170(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN GCCD2, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MC2R.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF483549 mRNA. Translation: AAL86908.1.
AY079152 mRNA. Translation: AAL80042.1.
AF454915 mRNA. Translation: AAL51048.1.
AF454916 mRNA. Translation: AAL51049.1.
BC062721 mRNA. Translation: AAH62721.1.
CCDSCCDS13612.1. [Q8TCY5-2]
CCDS13613.1. [Q8TCY5-4]
RefSeqNP_001272323.1. NM_001285394.1. [Q8TCY5-3]
NP_848932.1. NM_178817.3. [Q8TCY5-4]
NP_996781.1. NM_206898.1. [Q8TCY5-2]
XP_006724091.1. XM_006724028.1. [Q8TCY5-4]
UniGeneHs.584940.

3D structure databases

ProteinModelPortalQ8TCY5.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121114. 2 interactions.
DIPDIP-29948N.
STRING9606.ENSP00000306697.

PTM databases

PhosphoSiteQ8TCY5.

Polymorphism databases

DMDM116242634.

Proteomic databases

PRIDEQ8TCY5.

Protocols and materials databases

DNASU56246.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303645; ENSP00000306697; ENSG00000170262. [Q8TCY5-4]
ENST00000339944; ENSP00000343661; ENSG00000170262. [Q8TCY5-2]
ENST00000399784; ENSP00000382684; ENSG00000170262. [Q8TCY5-4]
ENST00000399786; ENSP00000382686; ENSG00000170262. [Q8TCY5-2]
GeneID56246.
KEGGhsa:56246.
UCSCuc002ypj.3. human. [Q8TCY5-4]
uc002ypk.3. human. [Q8TCY5-2]

Organism-specific databases

CTD56246.
GeneCardsGC21P033664.
HGNCHGNC:1304. MRAP.
HPAHPA011024.
HPA011093.
MIM607398. phenotype.
609196. gene.
neXtProtNX_Q8TCY5.
Orphanet361. Familial glucocorticoid deficiency.
PharmGKBPA25856.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG28578.
HOGENOMHOG000113646.
HOVERGENHBG052507.
InParanoidQ8TCY5.
OMAPWSHSLN.
OrthoDBEOG7VMP86.
PhylomeDBQ8TCY5.
TreeFamTF338691.

Gene expression databases

BgeeQ8TCY5.
CleanExHS_MRAP.
GenevestigatorQ8TCY5.

Family and domain databases

InterProIPR028111. MRAP.
[Graphical view]
PfamPF15183. MRAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi56246.
NextBio61872.
PROQ8TCY5.
SOURCESearch...

Entry information

Entry nameMRAP_HUMAN
AccessionPrimary (citable) accession number: Q8TCY5
Secondary accession number(s): Q5EBR3 expand/collapse secondary AC list , Q8TDB7, Q8WXC1, Q8WXC2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM