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Reviewed, UniProtKB/Swiss-Prot Q01718 (ACTHR_HUMAN)

Last modified November 4, 2008. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Adrenocorticotropic hormone receptor
      Short name=ACTH receptor
      Short name=ACTH-R
      Short name=Adrenocorticotropin receptor
Alternative name(s):
    Melanocortin receptor 2
    MC2-R
Gene names
Name: MC2R
Synonyms: ACTHR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length297 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor for ACTH. This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase.

Subunit structure

Interacts with FALP/MRAP.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Melanocytes and corticoadrenal tissue.

Involvement in disease

Defects in MC2R are the cause of glucocorticoid deficiency type 1 (GCCD1) [MIM:202200]; also known as familial glucocorticoid deficiency type 1 (FGD1). GCCD1 is an autosomal recessive disorder due to congenital insensitivity or resistance to adrenocorticotropin (ACTH). It is characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords

   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMGlycoprotein
Lipoprotein
Palmitate
Phosphoprotein

Gene Ontology (GO)

   Biological processG-protein signaling, coupled to cyclic nucleotide second messenger

Traceable author statement. Source: ProtInc

   Cellular componentintegral to plasma membrane

Traceable author statement. Source: ProtInc

   Molecular functionadrenocorticotropin receptor activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 297297Adrenocorticotropic hormone receptor
PRO_0000069054

Regions

Topological domain1 – 2323Extracellular Potential
Transmembrane24 – 49261 Potential
Topological domain50 – 589Cytoplasmic Potential
Transmembrane59 – 79212 Potential
Topological domain80 – 10425Extracellular Potential
Transmembrane105 – 126223 Potential
Topological domain127 – 14721Cytoplasmic Potential
Transmembrane148 – 168214 Potential
Topological domain169 – 18012Extracellular Potential
Transmembrane181 – 199195 Potential
Topological domain200 – 21718Cytoplasmic Potential
Transmembrane218 – 244276 Potential
Topological domain245 – 25612Extracellular Potential
Transmembrane257 – 278227 Potential
Topological domain279 – 29719Cytoplasmic Potential

Amino acid modifications

Lipidation2931S-palmitoyl cysteine Potential
Glycosylation121N-linked (GlcNAc...) Potential
Glycosylation171N-linked (GlcNAc...) Potential

Natural variations

Natural variant271P → R
VAR_003509
Natural variant741S → I in GCCD1; complete loss of activity.
VAR_003510
Natural variant1031D → N in GCCD1.
VAR_010702
Natural variant1071D → N in GCCD1.
VAR_015095
Natural variant1201S → R in GCCD1.
VAR_003511
Natural variant1281R → C in GCCD1.
VAR_003512
Natural variant1371R → W in GCCD1; partial loss of ACTIVITY.
VAR_010703
Natural variant1461R → H in GCCD1.
VAR_003513
Natural variant2511C → F in GCCD1.
VAR_015096
Natural variant2541Y → C in GCCD1; complete loss of activity.
VAR_015295

Sequences

Sequence LengthMass (Da)Tools
Q01718-1 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 66EE31961ABB8773

FASTA29733,927
        10         20         30         40         50         60 
MKHIINSYEN INNTARNNSD CPRVVLPEEI FFTISIVGVL ENLIVLLAVF KNKNLQAPMY 

        70         80         90        100        110        120 
FFICSLAISD MLGSLYKILE NILIILRNMG YLKPRGSFET TADDIIDSLF VLSLLGSIFS 

       130        140        150        160        170        180 
LSVIAADRYI TIFHALRYHS IVTMRRTVVV LTVIWTFCTG TGITMVIFSH HVPTVITFTS 

       190        200        210        220        230        240 
LFPLMLVFIL CLYVHMFLLA RSHTRKISTL PRANMKGAIT LTILLGVFIF CWAPFVLHVL 

       250        260        270        280        290 
LMTFCPSNPY CACYMSLFQV NGMLIMCNAV IDPFIYAFRS PELRDAFKKM IFCSRYW 

« Hide

References

« Hide 'large scale' references
[1]"The cloning of a family of genes that encode the melanocortin receptors."
Mountjoy K.G., Robbins L.S., Mortrud M., Cone R.D.
Science 257:1248-1251(1992) [PubMed: 1325670] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Skin.
[2]"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Molecular cloning of a novel melanocortin receptor."
Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G., Watson S.J., Delvalle J., Yamada T.
J. Biol. Chem. 268:8246-8250(1993) [PubMed: 8463333] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-293.
[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: 15654338] [Abstract]
Cited for: INTERACTION WITH FALP.
[7]"Molecular insights into inherited ACTH resistance syndromes."
Clark A.J.L., Weber A.
Trends Endocrinol. Metab. 5:209-214(1994)
Cited for: REVIEW ON GCCD1 VARIANTS.
[8]"Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor."
Clark A.J.L., McLoughlin L., Grossman A.
Lancet 341:461-462(1993) [PubMed: 8094489] [Abstract]
Cited for: VARIANT GCCD1 ILE-74.
[9]"Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene."
Tsigos C., Arai K., Hung W., Chrousos G.P.
J. Clin. Invest. 92:2458-2461(1993) [PubMed: 8227361] [Abstract]
Cited for: VARIANT GCCD1 ARG-120.
[10]"Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency."
Naville D., Barjhoux L., Jaillard C., Faury D., Despert F., Esteva B., Durand P., Saez J.M., Begeot M.
J. Clin. Endocrinol. Metab. 81:1442-1448(1996) [PubMed: 8636348] [Abstract]
Cited for: VARIANTS GCCD1 ASN-107 AND PHE-251.
[11]"Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH."
Ishii T., Ogata T., Sasaki G., Sato S., Kinoshita E.I., Matsuo N.
Clin. Endocrinol. (Oxf.) 53:389-392(2000) [PubMed: 10971458] [Abstract]
Cited for: VARIANTS GCCD1 ASN-103 AND TRP-137.
[12]"Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay."
Fluck C.E., Martens J.W.M., Conte F.A., Miller W.L.
J. Clin. Endocrinol. Metab. 87:4318-4323(2002) [PubMed: 12213892] [Abstract]
Cited for: VARIANTS GCCD1 ILE-74; TRP-137 AND CYS-254.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

X65633 Genomic DNA. Translation: CAA46587.1.
AB065915 Genomic DNA. Translation: BAC06130.1.
BC069074 mRNA. Translation: AAH69074.1.
BC094710 mRNA. Translation: AAH94710.1.
BC104169 mRNA. Translation: AAI04170.1.
BC104170 mRNA. Translation: AAI04171.1.
AY225229 Genomic DNA. Translation: AAO67714.1.
PIRC43265.
RefSeqNP_000520.1.
UniGeneHs.248144

3D structure databases

ModBaseSearch...

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ01718.

Genome annotation databases

EnsemblENSG00000185231. Homo sapiens. [Contig view]
GeneID4158.
KEGGhsa:4158.

Organism-specific databases

H-InvDBHIX0039742.
HGNCHGNC:6930. MC2R.
MIM202200. phenotype.
607397. gene.
Orphanet361. Glucocorticoid deficiency, familial.
PharmGKBPA30674.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ01718.
HOVERGENQ01718.

Gene expression databases

ArrayExpressQ01718.
CleanExHS_MC2R.
GermOnlineENSG00000185231. Homo sapiens.

Family and domain databases

InterProIPR001168. ACTH_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_supfam.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERPTHR22750:SF3. ACTH_rcpt. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00520. ACTROPHINR.
PR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01285. Corticotropin.
DB01284. Cosyntropin.
NextBio16382.
SOURCESearch...

Entry information

Entry nameACTHR_HUMAN
AccessionPrimary (citable) accession number: Q01718
Secondary accession number(s): Q3MI45, Q504X6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 4, 2008
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents