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Protein

Adrenocorticotropic hormone receptor

Gene

MC2R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP).2 Publications

GO - Molecular functioni

  • corticotropin receptor activity Source: ProtInc
  • melanocortin receptor activity Source: ProtInc

GO - Biological processi

  • G-protein coupled receptor signaling pathway Source: ProtInc
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  • placenta development Source: Ensembl
  • positive regulation of cAMP biosynthetic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:G66-31213-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-5579031. Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD).

Protein family/group databases

TCDBi9.A.14.2.4. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MC2R
Synonyms:ACTHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:6930. MC2R.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23ExtracellularBy similarityAdd BLAST23
Transmembranei24 – 49Helical; Name=1By similarityAdd BLAST26
Topological domaini50 – 58CytoplasmicBy similarity9
Transmembranei59 – 79Helical; Name=2By similarityAdd BLAST21
Topological domaini80 – 104ExtracellularBy similarityAdd BLAST25
Transmembranei105 – 126Helical; Name=3By similarityAdd BLAST22
Topological domaini127 – 147CytoplasmicBy similarityAdd BLAST21
Transmembranei148 – 168Helical; Name=4By similarityAdd BLAST21
Topological domaini169 – 180ExtracellularBy similarityAdd BLAST12
Transmembranei181 – 199Helical; Name=5By similarityAdd BLAST19
Topological domaini200 – 217CytoplasmicBy similarityAdd BLAST18
Transmembranei218 – 244Helical; Name=6By similarityAdd BLAST27
Topological domaini245 – 256ExtracellularBy similarityAdd BLAST12
Transmembranei257 – 278Helical; Name=7By similarityAdd BLAST22
Topological domaini279 – 297CytoplasmicBy similarityAdd BLAST19

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Glucocorticoid deficiency 1 (GCCD1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:202200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00351074S → I in GCCD1; complete loss of activity. 2 PublicationsCorresponds to variant rs104894658dbSNPEnsembl.1
Natural variantiVAR_010702103D → N in GCCD1. 1 PublicationCorresponds to variant rs768093045dbSNPEnsembl.1
Natural variantiVAR_015095107D → N in GCCD1. 1 PublicationCorresponds to variant rs104894661dbSNPEnsembl.1
Natural variantiVAR_003511120S → R in GCCD1. 1 PublicationCorresponds to variant rs104894656dbSNPEnsembl.1
Natural variantiVAR_003512128R → C in GCCD1. Corresponds to variant rs104894657dbSNPEnsembl.1
Natural variantiVAR_010703137R → W in GCCD1; partial loss of ACTIVITY. 2 PublicationsCorresponds to variant rs104894660dbSNPEnsembl.1
Natural variantiVAR_003513146R → H in GCCD1. Corresponds to variant rs758709668dbSNPEnsembl.1
Natural variantiVAR_015096251C → F in GCCD1. 1 PublicationCorresponds to variant rs104894662dbSNPEnsembl.1
Natural variantiVAR_015295254Y → C in GCCD1; complete loss of activity. 1 PublicationCorresponds to variant rs28940892dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4158.
MalaCardsiMC2R.
MIMi202200. phenotype.
OpenTargetsiENSG00000185231.
Orphaneti361. Familial glucocorticoid deficiency.
PharmGKBiPA30674.

Chemistry databases

ChEMBLiCHEMBL1965.
DrugBankiDB01285. Corticotropin.
DB01284. Cosyntropin.
GuidetoPHARMACOLOGYi283.

Polymorphism and mutation databases

BioMutaiMC2R.
DMDMi399002.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000690541 – 297Adrenocorticotropic hormone receptorAdd BLAST297

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi12N-linked (GlcNAc...)Sequence analysis1
Glycosylationi17N-linked (GlcNAc...)Sequence analysis1
Lipidationi293S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ01718.
PeptideAtlasiQ01718.
PRIDEiQ01718.

PTM databases

iPTMnetiQ01718.
PhosphoSitePlusiQ01718.

Expressioni

Tissue specificityi

Melanocytes and corticoadrenal tissue.

Gene expression databases

BgeeiENSG00000185231.
CleanExiHS_MC2R.
ExpressionAtlasiQ01718. baseline and differential.
GenevisibleiQ01718. HS.

Organism-specific databases

HPAiCAB000130.

Interactioni

Subunit structurei

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).3 Publications

Protein-protein interaction databases

BioGridi110328. 2 interactors.
DIPiDIP-29949N.
IntActiQ01718. 1 interactor.
STRINGi9606.ENSP00000333821.

Chemistry databases

BindingDBiQ01718.

Structurei

3D structure databases

ProteinModelPortaliQ01718.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiQ01718.
KOiK04200.
OMAiAVIWTFC.
OrthoDBiEOG091G0BVW.
PhylomeDBiQ01718.
TreeFamiTF332646.

Family and domain databases

InterProiIPR001168. ACTH_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF3. PTHR22750:SF3. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00520. ACTROPHINR.
PR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q01718-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKHIINSYEN INNTARNNSD CPRVVLPEEI FFTISIVGVL ENLIVLLAVF
60 70 80 90 100
KNKNLQAPMY FFICSLAISD MLGSLYKILE NILIILRNMG YLKPRGSFET
110 120 130 140 150
TADDIIDSLF VLSLLGSIFS LSVIAADRYI TIFHALRYHS IVTMRRTVVV
160 170 180 190 200
LTVIWTFCTG TGITMVIFSH HVPTVITFTS LFPLMLVFIL CLYVHMFLLA
210 220 230 240 250
RSHTRKISTL PRANMKGAIT LTILLGVFIF CWAPFVLHVL LMTFCPSNPY
260 270 280 290
CACYMSLFQV NGMLIMCNAV IDPFIYAFRS PELRDAFKKM IFCSRYW
Length:297
Mass (Da):33,927
Last modified:July 1, 1993 - v1
Checksum:i66EE31961ABB8773
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00350927P → R.Corresponds to variant rs28926178dbSNPEnsembl.1
Natural variantiVAR_00351074S → I in GCCD1; complete loss of activity. 2 PublicationsCorresponds to variant rs104894658dbSNPEnsembl.1
Natural variantiVAR_010702103D → N in GCCD1. 1 PublicationCorresponds to variant rs768093045dbSNPEnsembl.1
Natural variantiVAR_015095107D → N in GCCD1. 1 PublicationCorresponds to variant rs104894661dbSNPEnsembl.1
Natural variantiVAR_003511120S → R in GCCD1. 1 PublicationCorresponds to variant rs104894656dbSNPEnsembl.1
Natural variantiVAR_003512128R → C in GCCD1. Corresponds to variant rs104894657dbSNPEnsembl.1
Natural variantiVAR_064986137R → P Found in a glucocorticoid deficiency patient carrying also mutation I-74. 1 Publication1
Natural variantiVAR_010703137R → W in GCCD1; partial loss of ACTIVITY. 2 PublicationsCorresponds to variant rs104894660dbSNPEnsembl.1
Natural variantiVAR_003513146R → H in GCCD1. Corresponds to variant rs758709668dbSNPEnsembl.1
Natural variantiVAR_015096251C → F in GCCD1. 1 PublicationCorresponds to variant rs104894662dbSNPEnsembl.1
Natural variantiVAR_015295254Y → C in GCCD1; complete loss of activity. 1 PublicationCorresponds to variant rs28940892dbSNPEnsembl.1
Natural variantiVAR_049369278F → C.Corresponds to variant rs28926182dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11869.1.
PIRiC43265.
RefSeqiNP_000520.1. NM_000529.2.
NP_001278840.1. NM_001291911.1.
XP_016881270.1. XM_017025781.1.
UniGeneiHs.248144.

Genome annotation databases

EnsembliENST00000327606; ENSP00000333821; ENSG00000185231.
GeneIDi4158.
KEGGihsa:4158.
UCSCiuc002ksp.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11869.1.
PIRiC43265.
RefSeqiNP_000520.1. NM_000529.2.
NP_001278840.1. NM_001291911.1.
XP_016881270.1. XM_017025781.1.
UniGeneiHs.248144.

3D structure databases

ProteinModelPortaliQ01718.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110328. 2 interactors.
DIPiDIP-29949N.
IntActiQ01718. 1 interactor.
STRINGi9606.ENSP00000333821.

Chemistry databases

BindingDBiQ01718.
ChEMBLiCHEMBL1965.
DrugBankiDB01285. Corticotropin.
DB01284. Cosyntropin.
GuidetoPHARMACOLOGYi283.

Protein family/group databases

TCDBi9.A.14.2.4. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiQ01718.
PhosphoSitePlusiQ01718.

Polymorphism and mutation databases

BioMutaiMC2R.
DMDMi399002.

Proteomic databases

PaxDbiQ01718.
PeptideAtlasiQ01718.
PRIDEiQ01718.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327606; ENSP00000333821; ENSG00000185231.
GeneIDi4158.
KEGGihsa:4158.
UCSCiuc002ksp.2. human.

Organism-specific databases

CTDi4158.
DisGeNETi4158.
GeneCardsiMC2R.
HGNCiHGNC:6930. MC2R.
HPAiCAB000130.
MalaCardsiMC2R.
MIMi202200. phenotype.
607397. gene.
neXtProtiNX_Q01718.
OpenTargetsiENSG00000185231.
Orphaneti361. Familial glucocorticoid deficiency.
PharmGKBiPA30674.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiQ01718.
KOiK04200.
OMAiAVIWTFC.
OrthoDBiEOG091G0BVW.
PhylomeDBiQ01718.
TreeFamiTF332646.

Enzyme and pathway databases

BioCyciZFISH:G66-31213-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-5579031. Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD).

Miscellaneous databases

GeneWikiiACTH_receptor.
GenomeRNAii4158.
PROiQ01718.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185231.
CleanExiHS_MC2R.
ExpressionAtlasiQ01718. baseline and differential.
GenevisibleiQ01718. HS.

Family and domain databases

InterProiIPR001168. ACTH_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF3. PTHR22750:SF3. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00520. ACTROPHINR.
PR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACTHR_HUMAN
AccessioniPrimary (citable) accession number: Q01718
Secondary accession number(s): A8K016, Q3MI45, Q504X6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.