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HTR2A Membrane Protein Introduction

Introduction of HTR2A

5-hydroxytryptamine receptor 2A, alternatively known as serotonin receptor 2A, is one of the subtypes for serotonin receptor (5-HT receptor) which in human is encoded by HTR2A gene. HTR2A is expressed postsynaptically to serotonergic neurons, and are particularly concentrated in the frontal cortex. It is also found in high density in the claustrum, a region which is connected to the visual cortex, in parts of the limbic system (i.e. amygdala and hippocampus), and in the basal ganglia. The high level of HTR2A expression throughout the cortex suggests that this 5-HT receptor subtype may be involved in higher cognitive or integrative functions.

Basic Information of HTR2A
Protein Name 5-hydroxytryptamine receptor 2A
Gene Name HTR2A
Aliases 5-HT-2A, 5-HT2A
Organism Homo sapiens (Human)
UniProt ID P28223
Transmembrane Times 7
Length (aa) 471
Sequence MDILCEENTSLSSTTNSLMQLNDDTRLYSNDFNSGEANTSDAFNWTVDSENRTNLSCEGCLSPSCLSLLHL
QEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILYGYRWP
LPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNPIHHSRFNSRTKAFLKIIAVWTISVGISMPIPVF
GLQDDSKVFKEGSCLLADDNFVLIGSFVSFFIPLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFL
PQSSLSSEKLFQRSIHREPGSYTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNE
DVIGALLNVFVWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKKPLQLILVNTIPALAYKSSQLQM
GQKKNSKQDAKTTDNDCSMVALGKQHSEEASKDNSDGVNEKVSCV

Function of HTR2A Membrane Protein

HTR2A or 5-HT2A belongs to a beta-arrestin family and acts as a receptor for the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). It inhibits the signaling via G proteins and mediates activation of alternative signaling pathways. When binding with its ligand, 5-HT2A causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Activation of 5-HT2A in the central nervous system leads to an increase in body temperature (hyperthermia) and increased secretion of ACTH. In the periphery, 5-HT2A mediates the contractile responses of vascular smooth muscle, and a component of the contractile response of smooth muscle in the gut, to 5-HT. And it may also play a role in arterial vasoconstriction. 5-HT2A signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that regulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca2+ ions from intracellular stores. It also has an impact on neural activity, perception, cognition, and mood, and thus can function as a receptor for various drugs and psychoactive substances.

Structure of 5-HT2A membrane protein. Fig.1 Structure of 5-HT2A membrane protein.

Application of HTR2A Membrane Protein in Literature

  1. Berthoux C., et al. Sustained activation of postsynaptic 5-HT2A receptors gates plasticity at prefrontal cortex synapses. Cereb Cortex. 2018. PubMed ID: 29917056

    The results showed that 5-HT2A receptor activation promoted phosphorylation of GluA2 AMPA receptor subunit at Ser880 and AMPA receptor internalization, indicating common mechanisms with electrically induced LTD (long-term depression).

  2. Zimering M. B. Circulating neurotoxic 5-HT2A receptor agonist autoantibodies in adult type 2 Diabetes with Parkinson's disease. J Endocrinol Diabetes. 2018, 5(2). PubMed ID: 29888323

    This study found that increased autoantibodies in older adult diabetes with Parkinson's disease or dementia caused accelerated neuron loss via the 5-hydroxytryptamine 2 receptor coupled to inositol triphosphate receptor-mediated cytosolic Ca2+ release.

  3. Ibarra-Lecue I., et al. Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway. Neuropsychopharmacology. 2018. PubMed ID: 29748632

    Authors in the study observed supersensitive coupling of 5-HT2AR toward inhibitory Gαi1-, Gαi3-, Gαo-, and Gαz-proteins after chronic THC exposure, without changes in the canonical Gαq/11-protein pathway.

  4. Gao X., et al. Relationship between job stress and 5-HT2A receptor polymorphisms on self-reported sleep quality in physicians in urumqi (Xinjiang, China): A Cross-Sectional Study. Int J Environ Res Public Health. 2018, 15(5). PubMed ID: 29883419

    The findings of this study indicated that job stress and 5-HTR2A receptor gene polymorphisms were associated with sleep quality in physicians.

  5. Li C., et al. Chronic fluoxetine treatment accelerates kindling epileptogenesis in mice independently of 5-HT2A receptors. Epilepsia. 2018. PubMed ID: 29858497

    Authors of this study concluded that treatment with fluoxetine promoted epileptogenesis in mice, but this effect was not mediated by 5-HT2A receptors.

HTR2A Preparation Options

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