Halothane (T3D3001)

General Function:

Toxic substance binding

Specific Function:

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.

Gene Name:

ALB

Uniprot ID:

P02768

Molecular Weight:

69365.94 Da

References

1. Chan K, Meng QC, Johansson JS, Eckenhoff RG: Low-affinity analytical chromatography for measuring inhaled anesthetic binding to isolated proteins. Anal Biochem. 2002 Feb 15;301(2):308-13. [11814301 ]
2. Solt K, Johansson JS: Binding of the active metabolite of chloral hydrate, 2,2,2-trichloroethanol, to serum albumin demonstrated using tryptophan fluorescence quenching. Pharmacology. 2002;64(3):152-9. [11834892 ]
3. Liu R, Pidikiti R, Ha CE, Petersen CE, Bhagavan NV, Eckenhoff RG: The role of electrostatic interactions in human serum albumin binding and stabilization by halothane. J Biol Chem. 2002 Sep 27;277(39):36373-9. Epub 2002 Jul 12. [12118010 ]
4. Liu R, Meng Q, Xi J, Yang J, Ha CE, Bhagavan NV, Eckenhoff RG: Comparative binding character of two general anaesthetics for sites on human serum albumin. Biochem J. 2004 May 15;380(Pt 1):147-52. [14759223 ]
5. Streiff JH, Juranic NO, Macura SI, Warner DO, Jones KA, Perkins WJ: Saturation transfer difference nuclear magnetic resonance spectroscopy as a method for screening proteins for anesthetic binding. Mol Pharmacol. 2004 Oct;66(4):929-35. [15385643 ]
6. Eckenhoff RG, Knoll FJ, Greenblatt EP, Dailey WP: Halogenated diazirines as photolabel mimics of the inhaled haloalkane anesthetics. J Med Chem. 2002 Apr 25;45(9):1879-86. [11960499 ]

General Function:

Signal transducer activity

Specific Function:

Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity).

Gene Name:

GNG2

Uniprot ID:

P59768

Molecular Weight:

7850.03 Da

References

1. Ishizawa Y, Sharp R, Liebman PA, Eckenhoff RG: Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling. Biochemistry. 2000 Jul 25;39(29):8497-502. [10913255 ]
2. Milovic S, Steinecker-Frohnwieser B, Schreibmayer W, Weigl LG: The sensitivity of G protein-activated K+ channels toward halothane is essentially determined by the C terminus. J Biol Chem. 2004 Aug 13;279(33):34240-9. Epub 2004 Jun 2. [15175324 ]
3. Zang WJ, Yu XJ, Zang YM: [Effect of halothane on the muscarinic potassium current of the heart]. Sheng Li Xue Bao. 2000 Apr;52(2):175-8. [11961592 ]
4. Yoshimura H, Jones KA, Perkins WJ, Warner DO: Dual effects of hexanol and halothane on the regulation of calcium sensitivity in airway smooth muscle. Anesthesiology. 2003 Apr;98(4):871-80. [12657848 ]
5. Streiff J, Jones K, Perkins WJ, Warner DO, Jones KA: Effect of halothane on the guanosine 5' triphosphate binding activity of G-protein alphai subunits. Anesthesiology. 2003 Jul;99(1):105-11. [12826849 ]

General Function:

G-protein activated inward rectifier potassium channel activity

Specific Function:

This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat.

Gene Name:

KCNJ3

Uniprot ID:

P48549

Molecular Weight:

56602.84 Da

References

1. Milovic S, Steinecker-Frohnwieser B, Schreibmayer W, Weigl LG: The sensitivity of G protein-activated K+ channels toward halothane is essentially determined by the C terminus. J Biol Chem. 2004 Aug 13;279(33):34240-9. Epub 2004 Jun 2. [15175324 ]
2. Weigl LG, Schreibmayer W: G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics. Mol Pharmacol. 2001 Aug;60(2):282-9. [11455015 ]
3. Yamakura T, Lewohl JM, Harris RA: Differential effects of general anesthetics on G protein-coupled inwardly rectifying and other potassium channels. Anesthesiology. 2001 Jul;95(1):144-53. [11465552 ]

General Function:

Vasopressin receptor activity

Specific Function:

G-protein coupled receptor for neuropeptide S (NPS) (PubMed:16790440). Promotes mobilization of intracellular Ca(2+) stores (PubMed:16790440). Inhibits cell growth in response to NPS binding (PubMed:15947423). Involved in pathogenesis of asthma and other IgE-mediated diseases.

Gene Name:

NPSR1

Uniprot ID:

Q6W5P4

Molecular Weight:

42686.28 Da

References

1. Ishizawa Y, Sharp R, Liebman PA, Eckenhoff RG: Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling. Biochemistry. 2000 Jul 25;39(29):8497-502. [10913255 ]
2. Streiff J, Jones K, Perkins WJ, Warner DO, Jones KA: Effect of halothane on the guanosine 5' triphosphate binding activity of G-protein alphai subunits. Anesthesiology. 2003 Jul;99(1):105-11. [12826849 ]
3. Ishizawa Y, Pidikiti R, Liebman PA, Eckenhoff RG: G protein-coupled receptors as direct targets of inhaled anesthetics. Mol Pharmacol. 2002 May;61(5):945-52. [11961111 ]

General Function:

Transporter activity

Specific Function:

Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.

Gene Name:

ATP5D

Uniprot ID:

P30049

Molecular Weight:

17489.755 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Voltage-gated potassium channel activity

Specific Function:

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).

Gene Name:

KCNMA1

Uniprot ID:

Q12791

Molecular Weight:

137558.115 Da

References

1. Namba T, Ishii TM, Ikeda M, Hisano T, Itoh T, Hirota K, Adelman JP, Fukuda K: Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics. Eur J Pharmacol. 2000 Apr 28;395(2):95-101. [10794813 ]
2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Signal transducer activity

Specific Function:

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.

Gene Name:

ATP2C1

Uniprot ID:

P98194

Molecular Weight:

100576.42 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Inward rectifier potassium channel activity

Specific Function:

This potassium channel may be involved in the regulation of insulin secretion by glucose and/or neurotransmitters acting through G-protein-coupled receptors. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.

Gene Name:

KCNJ6

Uniprot ID:

P48051

Molecular Weight:

48450.96 Da

References

1. Milovic S, Steinecker-Frohnwieser B, Schreibmayer W, Weigl LG: The sensitivity of G protein-activated K+ channels toward halothane is essentially determined by the C terminus. J Biol Chem. 2004 Aug 13;279(33):34240-9. Epub 2004 Jun 2. [15175324 ]
2. Hara K, Yamakura T, Sata T, Harris RA: The effects of anesthetics and ethanol on alpha2 adrenoceptor subtypes expressed with G protein-coupled inwardly rectifying potassium channels in Xenopus oocytes. Anesth Analg. 2005 Nov;101(5):1381-8. [16243998 ]

General Function:

Inhibitory extracellular ligand-gated ion channel activity

Specific Function:

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).

Gene Name:

GABRA1

Uniprot ID:

P14867

Molecular Weight:

51801.395 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Transmitter-gated ion channel activity

Specific Function:

The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).

Gene Name:

GLRA1

Uniprot ID:

P23415

Molecular Weight:

52623.35 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Protein phosphatase binding

Specific Function:

Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).

Gene Name:

KCNN4

Uniprot ID:

O15554

Molecular Weight:

47695.12 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Nadh dehydrogenase (ubiquinone) activity

Specific Function:

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).

Gene Name:

MT-ND1

Uniprot ID:

P03886

Molecular Weight:

35660.055 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

S100 protein binding

Specific Function:

pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward.

Gene Name:

KCNK3

Uniprot ID:

O14649

Molecular Weight:

43517.665 Da

References

1. Lazarenko RM, Willcox SC, Shu S, Berg AP, Jevtovic-Todorovic V, Talley EM, Chen X, Bayliss DA: Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J Neurosci. 2010 Jun 2;30(22):7691-704. doi: 10.1523/JNEUROSCI.1655-10.2010. [20519544 ]
2. Pandit JJ, Buckler KJ: Halothane and sevoflurane exert different degrees of inhibition on carotid body glomus cell intracellular Ca2+ response to hypoxia. Adv Exp Med Biol. 2010;669:201-4. doi: 10.1007/978-1-4419-5692-7_40. [20217349 ]

General Function:

Voltage-gated potassium channel activity

Specific Function:

pH-dependent, voltage-insensitive, background potassium channel protein.

Gene Name:

KCNK9

Uniprot ID:

Q9NPC2

Molecular Weight:

42263.485 Da

References

1. Lazarenko RM, Willcox SC, Shu S, Berg AP, Jevtovic-Todorovic V, Talley EM, Chen X, Bayliss DA: Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J Neurosci. 2010 Jun 2;30(22):7691-704. doi: 10.1523/JNEUROSCI.1655-10.2010. [20519544 ]
2. Pandit JJ, Buckler KJ: Halothane and sevoflurane exert different degrees of inhibition on carotid body glomus cell intracellular Ca2+ response to hypoxia. Adv Exp Med Biol. 2010;669:201-4. doi: 10.1007/978-1-4419-5692-7_40. [20217349 ]

General Function:

Photoreceptor activity

Specific Function:

Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal.

Gene Name:

RHO

Uniprot ID:

P08100

Molecular Weight:

38892.335 Da

References

1. Ishizawa Y, Sharp R, Liebman PA, Eckenhoff RG: Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling. Biochemistry. 2000 Jul 25;39(29):8497-502. [10913255 ]
2. Keller C, Grimm C, Wenzel A, Hafezi F, Reme C: Protective effect of halothane anesthesia on retinal light damage: inhibition of metabolic rhodopsin regeneration. Invest Ophthalmol Vis Sci. 2001 Feb;42(2):476-80. [11157886 ]

General Function:

Not Available

Specific Function:

Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.

Gene Name:

FBF1

Uniprot ID:

Q8TES7

Molecular Weight:

125445.19 Da

References

1. Bertaccini EJ, Trudell JR, Franks NP: The common chemical motifs within anesthetic binding sites. Anesth Analg. 2007 Feb;104(2):318-24. [17242087 ]

General Function:

Pdz domain binding

Specific Function:

Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.

Gene Name:

GRIA1

Uniprot ID:

P42261

Molecular Weight:

101505.245 Da

References

1. Plested AJ, Wildman SS, Lieb WR, Franks NP: Determinants of the sensitivity of AMPA receptors to xenon. Anesthesiology. 2004 Feb;100(2):347-58. [14739810 ]

General Function:

Zinc ion binding

Specific Function:

NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.

Gene Name:

GRIN2A

Uniprot ID:

Q12879

Molecular Weight:

165281.215 Da

References

1. Perouansky M, Kirson ED, Yaari Y: Halothane blocks synaptic excitation of inhibitory interneurons. Anesthesiology. 1996 Dec;85(6):1431-8; discussion 29A. [8968191 ]

General Function:

Protein phosphatase 2a binding

Specific Function:

NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity).

Gene Name:

GRIN3A

Uniprot ID:

Q8TCU5

Molecular Weight:

125464.07 Da

References

1. Perouansky M, Kirson ED, Yaari Y: Halothane blocks synaptic excitation of inhibitory interneurons. Anesthesiology. 1996 Dec;85(6):1431-8; discussion 29A. [8968191 ]

General Function:

Nmda glutamate receptor activity

Specific Function:

NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.

Gene Name:

GRIN3B

Uniprot ID:

O60391

Molecular Weight:

112990.98 Da

References

1. Perouansky M, Kirson ED, Yaari Y: Halothane blocks synaptic excitation of inhibitory interneurons. Anesthesiology. 1996 Dec;85(6):1431-8; discussion 29A. [8968191 ]

General Function:

Voltage-gated potassium channel activity

Specific Function:

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).

Gene Name:

KCNMA1

Uniprot ID:

Q12791

Molecular Weight:

137558.115 Da

References

1. Namba T, Ishii TM, Ikeda M, Hisano T, Itoh T, Hirota K, Adelman JP, Fukuda K: Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics. Eur J Pharmacol. 2000 Apr 28;395(2):95-101. [10794813 ]

General Function:

Inhibitory extracellular ligand-gated ion channel activity

Specific Function:

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).

Included Proteins:

P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88