Q01718 (ACTHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adrenocorticotropic hormone receptor
Short name=ACTH receptor
Short name=ACTH-R

Alternative name(s):
Adrenocorticotropin receptor
Melanocortin receptor 2
Short name=MC2-R

Gene names

Name:	MC2R
Synonyms:	ACTHR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	297 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.6
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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cyclic nucleotide second messenger Traceable author statement. Source: ProtInc positive regulation of cAMP biosynthetic process Inferred from direct assay. Source: BHF-UCL
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	corticotropin receptor activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 297	297	Adrenocorticotropic hormone receptor		PRO_0000069054
Regions
	Topological domain	1 – 23	23	Extracellular By similarity
	Transmembrane	24 – 49	26	Helical; Name=1; By similarity
	Topological domain	50 – 58	9	Cytoplasmic By similarity
	Transmembrane	59 – 79	21	Helical; Name=2; By similarity
	Topological domain	80 – 104	25	Extracellular By similarity
	Transmembrane	105 – 126	22	Helical; Name=3; By similarity
	Topological domain	127 – 147	21	Cytoplasmic By similarity
	Transmembrane	148 – 168	21	Helical; Name=4; By similarity
	Topological domain	169 – 180	12	Extracellular By similarity
	Transmembrane	181 – 199	19	Helical; Name=5; By similarity
	Topological domain	200 – 217	18	Cytoplasmic By similarity
	Transmembrane	218 – 244	27	Helical; Name=6; By similarity
	Topological domain	245 – 256	12	Extracellular By similarity
	Transmembrane	257 – 278	22	Helical; Name=7; By similarity
	Topological domain	279 – 297	19	Cytoplasmic By similarity
Amino acid modifications
	Lipidation	293	1	S-palmitoyl cysteine Potential
	Glycosylation	12	1	N-linked (GlcNAc...) Potential
	Glycosylation	17	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	27	1	P → R. Corresponds to variant rs28926178 [ dbSNP | Ensembl ].		VAR_003509
	Natural variant	74	1	S → I in GCCD1; complete loss of activity. Ref.8 Ref.12		VAR_003510
	Natural variant	103	1	D → N in GCCD1. Ref.11		VAR_010702
	Natural variant	107	1	D → N in GCCD1. Ref.10		VAR_015095
	Natural variant	120	1	S → R in GCCD1. Ref.9		VAR_003511
	Natural variant	128	1	R → C in GCCD1.		VAR_003512
	Natural variant	137	1	R → P Found in a glucocorticoid deficiency patient carrying also mutation I-74. Ref.13		VAR_064986
	Natural variant	137	1	R → W in GCCD1; partial loss of ACTIVITY. Ref.11 Ref.12		VAR_010703
	Natural variant	146	1	R → H in GCCD1.		VAR_003513
	Natural variant	251	1	C → F in GCCD1. Ref.10		VAR_015096
	Natural variant	254	1	Y → C in GCCD1; complete loss of activity. Ref.12 Corresponds to variant rs28940892 [ dbSNP | Ensembl ].		VAR_015295
	Natural variant	278	1	F → C. Corresponds to variant rs28926182 [ dbSNP | Ensembl ].		VAR_049369

Sequences

	Sequence		Length	Mass (Da)
	Q01718 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 66EE31961ABB8773	FASTA	297	33,927
	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

References

	« Hide 'large scale' referencesShow '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.
[13]	"Novel human pathological mutations. Gene symbol: MC2R. Disease: Glucocorticoid deficiency." Mueller O.T., Coovadia A. Hum. Genet. 127:112-112(2010) [PubMed: 20108423] [Abstract] Cited for: VARIANT PRO-137.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00009312.
PIR	C43265.
RefSeq	NP_000520.1. NM_000529.2.
UniGene	Hs.248144.
3D structure databases
ProteinModelPortal	Q01718.
SMR	Q01718. Positions 25-295.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29949N.
STRING	Q01718.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q01718.
Polymorphism databases
DMDM	399002.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000327606; ENSP00000333821; ENSG00000185231. ENST00000399821; ENSP00000382718; ENSG00000185231.
GeneID	4158.
KEGG	hsa:4158.
UCSC	uc002ksp.1. human.
Organism-specific databases
CTD	4158.
GeneCards	GC18M013874.
H-InvDB	HIX0039742.
HGNC	HGNC:6930. MC2R.
MIM	202200. phenotype. 607397. gene.
neXtProt	NX_Q01718.
Orphanet	361. Familial glucocorticoid deficiency.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16349.
GeneTree	ENSGT00600000084156.
HOGENOM	HBG717691.
HOVERGEN	HBG108148.
InParanoid	Q01718.
OMA	ARNNSDC.
OrthoDB	EOG4CNQRP.
PhylomeDB	Q01718.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q01718.
Bgee	Q01718.
CleanEx	HS_MC2R.
Genevestigator	Q01718.
GermOnline	ENSG00000185231. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR001168. ACTH_rcpt. IPR017452. GPCR_Rhodpsn_supfam. IPR001671. Melcrt_ACTH_rcpt. [Graphical view]
KO	K04200.
PANTHER	PTHR22750:SF3. ACTH_rcpt. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00520. ACTROPHINR. PR00237. GPCRRHODOPSN. PR00534. MCRFAMILY.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB01285. Corticotropin. DB01284. Cosyntropin.
NextBio	16382.
SOURCE	Search...

Entry information

Entry name

ACTHR_HUMAN

Accession

Primary (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:	December 14, 2011
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.