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Q01718 (ACTHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length297 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP). Ref.9 Ref.10

Subunit structure

Interacts with MRAP; increasing ligand-sensitivity and generation of cAMP. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of corticotropin (ACTH). Ref.8 Ref.9 Ref.10

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.12 Ref.13 Ref.14 Ref.15 Ref.16

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 297297Adrenocorticotropic hormone receptor
PRO_0000069054

Regions

Topological domain1 – 2323Extracellular By similarity
Transmembrane24 – 4926Helical; Name=1; By similarity
Topological domain50 – 589Cytoplasmic By similarity
Transmembrane59 – 7921Helical; Name=2; By similarity
Topological domain80 – 10425Extracellular By similarity
Transmembrane105 – 12622Helical; Name=3; By similarity
Topological domain127 – 14721Cytoplasmic By similarity
Transmembrane148 – 16821Helical; Name=4; By similarity
Topological domain169 – 18012Extracellular By similarity
Transmembrane181 – 19919Helical; Name=5; By similarity
Topological domain200 – 21718Cytoplasmic By similarity
Transmembrane218 – 24427Helical; Name=6; By similarity
Topological domain245 – 25612Extracellular By similarity
Transmembrane257 – 27822Helical; Name=7; By similarity
Topological domain279 – 29719Cytoplasmic By similarity

Amino acid modifications

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

Natural variations

Natural variant271P → R.
Corresponds to variant rs28926178 [ dbSNP | Ensembl ].
VAR_003509
Natural variant741S → I in GCCD1; complete loss of activity. Ref.12 Ref.16
VAR_003510
Natural variant1031D → N in GCCD1. Ref.15
VAR_010702
Natural variant1071D → N in GCCD1. Ref.14
VAR_015095
Natural variant1201S → R in GCCD1. Ref.13
VAR_003511
Natural variant1281R → C in GCCD1.
VAR_003512
Natural variant1371R → P Found in a glucocorticoid deficiency patient carrying also mutation I-74. Ref.17
VAR_064986
Natural variant1371R → W in GCCD1; partial loss of ACTIVITY. Ref.15 Ref.16
VAR_010703
Natural variant1461R → H in GCCD1.
VAR_003513
Natural variant2511C → F in GCCD1. Ref.14
VAR_015096
Natural variant2541Y → C in GCCD1; complete loss of activity. Ref.16
Corresponds to variant rs28940892 [ dbSNP | Ensembl ].
VAR_015295
Natural variant2781F → C.
Corresponds to variant rs28926182 [ dbSNP | Ensembl ].
VAR_049369

Sequences

Sequence LengthMass (Da)Tools
Q01718 [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] [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. expand/collapse author list , 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. expand/collapse author list , 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 MRAP.
[9]"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, INTERACTION WITH MRAP AND MRAP2.
[10]"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, INTERACTION WITH MRAP AND MRAP2.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.

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.
CCDSCCDS11869.1.
PIRC43265.
RefSeqNP_000520.1. NM_000529.2.
NP_001278840.1. NM_001291911.1.
UniGeneHs.248144.

3D structure databases

ProteinModelPortalQ01718.
SMRQ01718. Positions 32-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110328. 3 interactions.
DIPDIP-29949N.
STRING9606.ENSP00000333821.

Chemistry

BindingDBQ01718.
ChEMBLCHEMBL1965.
DrugBankDB01285. Corticotropin.
DB01284. Cosyntropin.
GuidetoPHARMACOLOGY283.

Protein family/group databases

TCDB9.A.14.2.4. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteQ01718.

Polymorphism databases

DMDM399002.

Proteomic databases

PRIDEQ01718.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327606; ENSP00000333821; ENSG00000185231.
GeneID4158.
KEGGhsa:4158.
UCSCuc002ksp.1. human.

Organism-specific databases

CTD4158.
GeneCardsGC18M013874.
HGNCHGNC:6930. MC2R.
MIM202200. phenotype.
607397. gene.
neXtProtNX_Q01718.
Orphanet361. Familial glucocorticoid deficiency.
PharmGKBPA30674.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG331926.
HOGENOMHOG000246927.
HOVERGENHBG108148.
InParanoidQ01718.
KOK04200.
OMAKPRGNFE.
OrthoDBEOG7327PD.
PhylomeDBQ01718.
TreeFamTF332646.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ01718.
CleanExHS_MC2R.
GenevestigatorQ01718.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR001168. ACTH_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERPTHR22750:SF3. PTHR22750:SF3. 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

GeneWikiACTH_receptor.
GenomeRNAi4158.
NextBio16382.
PROQ01718.
SOURCESearch...

Entry information

Entry nameACTHR_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 137 of the entry and version 1 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries