ADRA2C

Protein identityUniProt · HPA

UniProt accession

P18825

Gene

ADRA2C

Ensembl

ENSG00000184160

Chromosome

4

Canonical length

462 aa

Protein class

FDA approved drug targets, G-protein coupled receptors, Predicted membrane proteins

OverviewNCBI Gene

Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. They include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. The mouse studies revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. The alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity. This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

462 residues, UniProt reviewed canonical sequence.

>P18825|ADRA2C
     1  MASPALAAAL AVAAAAGPNA SGAGERGSGG VANASGASWG PPRGQYSAGA VAGLAAVVGF
    61  LIVFTVVGNV LVVIAVLTSR ALRAPQNLFL VSLASADILV ATLVMPFSLA NELMAYWYFG
   121  QVWCGVYLAL DVLFCTSSIV HLCAISLDRY WSVTQAVEYN LKRTPRRVKA TIVAVWLISA
   181  VISFPPLVSL YRQPDGAAYP QCGLNDETWY ILSSCIGSFF APCLIMGLVY ARIYRVAKLR
   241  TRTLSEKRAP VGPDGASPTT ENGLGAAAGA GENGHCAPPP ADVEPDESSA AAERRRRRGA
   301  LRRGGRRRAG AEGGAGGADG QGAGPGAAES GALTASRSPG PGGRLSRASS RSVEFFLSRR
   361  RRARSSVCRR KVAQAREKRF TFVLAVVMGV FVLCWFPFFF SYSLYGICRE ACQVPGPLFK
   421  FFFWIGYCNS SLNPVIYTVF NQDFRRSFKH ILFRRRRRGF RQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADRA2C can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

102 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.61

gnomAD pLI

0.5

gnomAD missense Z

1.64

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting adrenergic receptor signaling pathway
• adrenergic receptor signaling pathway
• cell-cell signaling
• epidermal growth factor receptor signaling pathway
• G protein-coupled receptor signaling pathway
• negative regulation of epinephrine secretion
• negative regulation of insulin secretion
• negative regulation of norepinephrine secretion
• platelet activation
• positive regulation of MAPK cascade
• positive regulation of neuron differentiation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• regulation of smooth muscle contraction
• regulation of vasoconstriction

Molecular functions

• alpha-2A adrenergic receptor binding
• alpha2-adrenergic receptor activity
• epinephrine binding
• protein heterodimerization activity
• protein homodimerization activity

Cellular components

• cytoplasm
• endosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Adrenoceptor family
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Alpha 2C adrenoceptor

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Receptor
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ADRA2C in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PPP1R9B