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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.8
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Melanocytes and corticoadrenal tissue.
Involvement in disease	Glucocorticoid deficiency 1 (GCCD1) [MIM:202200]: 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.10 Ref.11 Ref.12 Ref.13 Ref.14
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement PubMed 9175632. Source: ProtInc positive regulation of cAMP biosynthetic process Inferred from direct assay PubMed 19329486. Source: BHF-UCL
Cellular_component	integral to plasma membrane Traceable author statement PubMed 9175632. Source: ProtInc
Molecular_function	corticotropin receptor activity Traceable author statement PubMed 9175632. Source: ProtInc
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.10 Ref.14		VAR_003510
	Natural variant	103	1	D → N in GCCD1. Ref.13		VAR_010702
	Natural variant	107	1	D → N in GCCD1. Ref.12		VAR_015095
	Natural variant	120	1	S → R in GCCD1. Ref.11		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.15		VAR_064986
	Natural variant	137	1	R → W in GCCD1; partial loss of ACTIVITY. Ref.13 Ref.14		VAR_010703
	Natural variant	146	1	R → H in GCCD1.		VAR_003513
	Natural variant	251	1	C → F in GCCD1. Ref.12		VAR_015096
	Natural variant	254	1	Y → C in GCCD1; complete loss of activity. Ref.14 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] [Europe PMC] [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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Adrenal gland.
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-293.
[8]	"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: INTERACTION WITH FALP.
[9]	"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.
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANT GCCD1 ILE-74.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT GCCD1 ARG-120.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GCCD1 ASN-107 AND PHE-251.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GCCD1 ASN-103 AND TRP-137.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GCCD1 ILE-74; TRP-137 AND CYS-254.
[15]	"Novel human pathological mutations. Gene symbol: MC2R. Disease: Glucocorticoid deficiency." Mueller O.T., Coovadia A. Hum. Genet. 127:112-112(2010) [PubMed] [Europe PMC] [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. AK289381 mRNA. Translation: BAF82070.1. AK315319 mRNA. Translation: BAG37722.1. CH471113 Genomic DNA. Translation: EAX01503.1. 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.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29949N.
STRING	9606.ENSP00000333821.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q01718.
Polymorphism databases
DMDM	399002.
Proteomic databases
PRIDE	Q01718.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000327606; ENSP00000333821; ENSG00000185231.
GeneID	4158.
KEGG	hsa:4158.
UCSC	uc002ksp.1. human.
Organism-specific databases
CTD	4158.
GeneCards	GC18M013874.
HGNC	HGNC:6930. MC2R.
MIM	202200. phenotype. 607397. gene.
neXtProt	NX_Q01718.
Orphanet	361. Familial glucocorticoid deficiency.
PharmGKB	PA30674.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG331926.
HOGENOM	HOG000246927.
HOVERGEN	HBG108148.
InParanoid	Q01718.
KO	K04200.
OMA	HARKIST.
OrthoDB	EOG4CNQRP.
PhylomeDB	Q01718.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q01718.
CleanEx	HS_MC2R.
Genevestigator	Q01718.
GermOnline	ENSG00000185231. Homo sapiens.
Family and domain databases
InterPro	IPR001168. ACTH_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR001671. Melcrt_ACTH_rcpt. [Graphical view]
PANTHER	PTHR22750:SF3. PTHR22750:SF3. 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
BindingDB	Q01718.
ChEMBL	CHEMBL1965.
DrugBank	DB01285. Corticotropin. DB01284. Cosyntropin.
GenomeRNAi	4158.
NextBio	16382.
SOURCE	Search...

Entry information

Entry name

ACTHR_HUMAN

Accession

Primary (citable) accession number: Q01718
Secondary accession number(s): A8K016, Q3MI45, Q504X6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	May 1, 2013
This is version 126 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.