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Protein

Adrenocorticotropic hormone receptor

Gene

MC2R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

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)
SIGNORiQ01718

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

EuPathDBiHostDB:ENSG00000185231.4
HGNCiHGNC:6930 MC2R
MIMi607397 gene
neXtProtiNX_Q01718

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 form of glucocorticoid deficiency, a rare 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 dbSNP:rs104894658EnsemblClinVar.1
Natural variantiVAR_010702103D → N in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs768093045Ensembl.1
Natural variantiVAR_015095107D → N in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894661EnsemblClinVar.1
Natural variantiVAR_003511120S → R in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894656EnsemblClinVar.1
Natural variantiVAR_003512128R → C in GCCD1. Corresponds to variant dbSNP:rs104894657EnsemblClinVar.1
Natural variantiVAR_010703137R → W in GCCD1; partial loss of ACTIVITY. 2 PublicationsCorresponds to variant dbSNP:rs104894660EnsemblClinVar.1
Natural variantiVAR_003513146R → H in GCCD1. Corresponds to variant dbSNP:rs758709668Ensembl.1
Natural variantiVAR_015096251C → F in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894662EnsemblClinVar.1
Natural variantiVAR_015295254Y → C in GCCD1; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs28940892EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4158
MalaCardsiMC2R
MIMi202200 phenotype
OpenTargetsiENSG00000185231
Orphaneti361 Familial glucocorticoid deficiency
PharmGKBiPA30674

Chemistry databases

ChEMBLiCHEMBL1965
DrugBankiDB01285 Corticotropin
DB01284 Tetracosactide
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...) asparagineSequence analysis1
Glycosylationi17N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi293S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ01718
PeptideAtlasiQ01718
PRIDEiQ01718
ProteomicsDBi57983

PTM databases

iPTMnetiQ01718
PhosphoSitePlusiQ01718

Expressioni

Tissue specificityi

Melanocytes and corticoadrenal tissue.

Gene expression databases

BgeeiENSG00000185231 Expressed in 31 organ(s), highest expression level in adrenal tissue
CleanExiHS_MC2R
ExpressionAtlasiQ01718 baseline and differential
GenevisibleiQ01718 HS

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

Binary interactionsi

WithEntry#Exp.IntActNotes
MRAPQ8TCY52EBI-9537171,EBI-9538727

Protein-protein interaction databases

BioGridi110328, 2 interactors
DIPiDIP-29949N
IntActiQ01718, 2 interactors
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
OMAiYCECYRS
OrthoDBiEOG091G0BVW
PhylomeDBiQ01718
TreeFamiTF332646

Family and domain databases

InterProiView protein in InterPro
IPR001168 ACTH_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001671 Melcrt_ACTH_rcpt
PANTHERiPTHR22750:SF3 PTHR22750:SF3, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00520 ACTROPHINR
PR00237 GPCRRHODOPSN
PR00534 MCRFAMILY
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
R4GMM0R4GMM0_HUMAN
Adrenocorticotropic hormone recepto...
MC2R
123Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00350927P → R. Corresponds to variant dbSNP:rs28926178EnsemblClinVar.1
Natural variantiVAR_00351074S → I in GCCD1; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs104894658EnsemblClinVar.1
Natural variantiVAR_010702103D → N in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs768093045Ensembl.1
Natural variantiVAR_015095107D → N in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894661EnsemblClinVar.1
Natural variantiVAR_003511120S → R in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894656EnsemblClinVar.1
Natural variantiVAR_003512128R → C in GCCD1. Corresponds to variant dbSNP:rs104894657EnsemblClinVar.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 dbSNP:rs104894660EnsemblClinVar.1
Natural variantiVAR_003513146R → H in GCCD1. Corresponds to variant dbSNP:rs758709668Ensembl.1
Natural variantiVAR_015096251C → F in GCCD1. 1 PublicationCorresponds to variant dbSNP:rs104894662EnsemblClinVar.1
Natural variantiVAR_015295254Y → C in GCCD1; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs28940892EnsemblClinVar.1
Natural variantiVAR_049369278F → C. Corresponds to variant dbSNP:rs28926182EnsemblClinVar.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

Similar proteinsi

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, 2 interactors
STRINGi9606.ENSP00000333821

Chemistry databases

BindingDBiQ01718
ChEMBLiCHEMBL1965
DrugBankiDB01285 Corticotropin
DB01284 Tetracosactide
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
ProteomicsDBi57983

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4158
DisGeNETi4158
EuPathDBiHostDB:ENSG00000185231.4
GeneCardsiMC2R
HGNCiHGNC:6930 MC2R
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
OMAiYCECYRS
OrthoDBiEOG091G0BVW
PhylomeDBiQ01718
TreeFamiTF332646

Enzyme and pathway databases

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)
SIGNORiQ01718

Miscellaneous databases

GeneWikiiACTH_receptor
GenomeRNAii4158
PROiPR:Q01718
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185231 Expressed in 31 organ(s), highest expression level in adrenal tissue
CleanExiHS_MC2R
ExpressionAtlasiQ01718 baseline and differential
GenevisibleiQ01718 HS

Family and domain databases

InterProiView protein in InterPro
IPR001168 ACTH_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001671 Melcrt_ACTH_rcpt
PANTHERiPTHR22750:SF3 PTHR22750:SF3, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00520 ACTROPHINR
PR00237 GPCRRHODOPSN
PR00534 MCRFAMILY
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACTHR_HUMAN
AccessioniPrimary (citable) accession number: Q01718
Secondary accession number(s): A8K016, Q3MI45, Q504X6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 7, 2018
This is version 171 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  6. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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Main funding by: National Institutes of Health

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