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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:28
Primary Accession Number DB01151
Secondary Accession Number
  • APRD00022
Name Desipramine
Drug Type
  • Approved
  • Small Molecule
Description A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. [PubChem]
Synonyms
  1. DMI
  2. Demethylimipramine
  3. Desimipramine
  4. Desimpramine
  5. Desipramin
  6. Desipramine Hcl
  7. Desmethylimipramine
  8. Dezipramine
  9. Dimethylimipramine
  10. Methylaminopropyliminodibenzyl
  11. Monodemethylimipramine
  12. Norimipramine
  13. Norpramine
Brand Names
  1. Pentofran
  2. Pertofran
  3. Pertrofane
  4. Sertofran
Brand Mixtures Not Available
Chemical IUPAC Name 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methylpropan-1-amine
Chemical Formula C18H22N2
Chemical Structure Structure
CAS Registry Number 50-47-5
InChI Identifier InChI=1/C18H22N2/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20/h2-5,7-10,19H,6,11-14H2,1H3
InChI Key HCYAFALTSJYZDH-UHFFFAOYAV
KEGG Drug Not Available
KEGG Compound C06943 Link Image
PubChem Compound 2995 Link Image
PubChem Substance 148551 Link Image
ChEBI ID Not Available
PharmGKB ID PA449233 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02216272 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/desipram.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Desipramine Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 266.3807
Monoisotopic Molecular Weight 266.1783
State Solid
Melting Point 214-218 oC
Experimental Water Solubility 0.0586 mg/mL at 24 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] Source: PhysProp
Predicted Water Solubility 3.96e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.7 Source: PhysProp
Predicted LogP 4.02 Calculated using ALOGPS
Experimental LogS -3.66 [ADME Research, USCD]
Predicted LogS -3.83 Calculated using ALOGPS
Experimental Caco2 Permeability -4.67 [ADME Research, USCD]
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12
Canonical SMILES CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12
Drug Category
  • Adrenergic Uptake Inhibitors
  • Antidepressants
  • Antidepressive Agents, Tricyclic
  • Enzyme Inhibitors
  • Norepinephrine-Reuptake Inhibitors
ATC Codes
AHFS Codes
  • 28:16.04.28
Indication For relief of symptoms in various depressive syndromes, especially endogenous depression.
Pharmacology Desipramine, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. Desipramine is used to treat depression, pain of neuropathic origin, attention_deficit hyperactivity disorder, functional enuresis in children, panic and phobic disorder, and to manage some eating disorders. Desipramine inhibits the re-uptake of noradrenaline at the noradrenergic nerve endings and the re-uptake of serotonin (5-hydroxy tryptamine) at the serotoninergic nerve endings in the central nervous system. These two effects are considered to be the likely base of the antidepressant effect of Desipramine. The drug also has a strong anticholinergic effect and serves as an antagonist on a1 and H1 receptors.
Mechanism of Action Desipramine is a tricyclic antidepressant that selectively blocks reuptake of norepinephrine (noradrenaline) from the neural synapse. It also appears to impair serotonin transport. Desipramine also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Evidence also suggests that Desiprmaine binds to and down regulates histamine and beta adrenergic receptors. Tricyclic drugs are believed to act by restoring normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system.
Absorption Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. 90.5% (range 73-92%) of desipramine binds to plasma proteins.
Toxicity Male mice: LD50 = 290 mg/kg, female rats: LD50 = 320 mg/kg
Protein Binding 15%
Biotransformation Desipramine is extensively metabolized in the liver and is cleared mainly by 2-hydroxylation and glucuronidation, whereas 10-hydroxylation is of minor importance. The 2-hydroxylation metabolic pathway of desipramine is under genetic control.
Half Life 21-23 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Altretamine Risk of severe hypotension
Atazanavir Atazanavir increases the effect and toxicity of tricyclics
Carbamazepine The tricyclic increases the effect of carbamazepine
Cimetidine Cimetidine increases the effect of tricyclic agent
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricyclic decreases the effect of clonidine
Dihydroquinidine barbiturate Quinidine increases the effect of tricyclic agent
Dobutamine The tricyclic increases the sympathomimetic effect
Donepezil Possible antagonism of action
Dopamine The tricyclic increases the sympathomimetic effect
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Ephedra The tricyclic increases the sympathomimetic effect
Ephedrine The tricyclic increases the sympathomimetic effect
Epinephrine The tricyclic increases the sympathomimetic effect
Fenoterol The tricyclic increases the sympathomimetic effect
Fluoxetine Fluoxetine increases the effect and toxicity of tricyclics
Fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclic decreases the effect of guanethidine
Isocarboxazid Possibility of severe adverse effects
Isoproterenol The tricyclic increases the sympathomimetic effect
Mephentermine The tricyclic increases the sympathomimetic effect
Metaraminol The tricyclic increases the sympathomimetic effect
Methoxamine The tricyclic increases the sympathomimetic effect
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic increases the sympathomimetic effect
Orciprenaline The tricyclic increases the sympathomimetic effect
Phenelzine Possibility of severe adverse effects
Phenylephrine The tricyclic increases the sympathomimetic effect
Phenylpropanolamine The tricyclic increases the sympathomimetic effect
Pirbuterol The tricyclic increases the sympathomimetic effect
Procaterol The tricyclic increases the sympathomimetic effect
Pseudoephedrine The tricyclic increases the sympathomimetic effect
Quinidine Quinidine increases the effect of tricyclic agent
Quinidine barbiturate Quinidine increases the effect of tricyclic agent
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin decreases the effect of tricyclics
Rifampin The rifamycin decreases the effect of tricyclics
Ritonavir Ritonavir increases the effect and toxicity of tricyclics
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic increases the sympathomimetic effect
Sibutramine Increased risk of CNS adverse effects
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Terbinafine Terbinafine increases the effect and toxicity of the tricyclic
Terbutaline The tricyclic increases the sympathomimetic effect
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine Possibility of severe adverse effects
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation, limit caffeine intake.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C19 (CYP2C19)
  2. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Muscarinic acetylcholine receptor M1
  2. Beta-1 adrenergic receptor
  3. Histamine H1 receptor
  4. Sodium-dependent noradrenaline transporter
  5. Muscarinic acetylcholine receptor M2
  6. Beta-2 adrenergic receptor
  7. Sodium-dependent serotonin transporter
  8. Sphingomyelin phosphodiesterase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C19 (CYP2C19)
Enzyme 1 Gene Name CYP2C19
Enzyme 1 SwissProt ID P33261 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80) 
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 2 Gene Name CYP2D6
Enzyme 2 SwissProt ID P10635 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 103
Target 1 Name Muscarinic acetylcholine receptor M1
Target 1 Synonyms Not Available
Target 1 Gene Name CHRM1
Target 1 Protein Sequence >Muscarinic acetylcholine receptor M1 
MNTSAPPAVSPNITVLAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVN
NYFLLSLACADLIIGTFSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLIS
FDRYFSVTRPLSYRAKRTPRRAALMIGLAWLVSFVLWAPAILFWQYLVGERTVLAGQCYI
QFLSQPIITFGTAMAAFYLPVTVMCTLYWRIYRETENRARELAALQGSETPGKGGGSSSS
SERSQPGAEGSPETPPGRCCRCCRAPRLLQAYSWKEEEEEDEGSMESLTSSEGEEPGSEV
VIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLAKRKTFSLVKE
KKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL
CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGSVHRTPSRQC
Target 1 Number of Residues 467
Target 1 Molecular Weight 51421
Target 1 Theoretical pI 9.67
Target 1 GO Classification
Function
amine receptor activity
muscarinic acetylcholine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in rhodopsin-like receptor activity
Target 1 Specific Function The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 25-47
  • 62-82
  • 100-121
  • 142-164
  • 187-209
  • 367-387
  • 402-421
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 34451 Link Image
Target 1 UniProtKB/Swiss-Prot ID P11229 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ACM1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1383 bp 
ATGAACACTTCAGCCCCACCTGCTGTCAGCCCCAACATCACCGTCCTGGCACCAGGAAAG
GGTCCCTGGCAAGTGGCCTTCATTGGGATCACCACGGGCCTCCTGTCGCTAGCCACAGTG
ACAGGCAACCTGCTGGTACTCATCTCTTTCAAGGTCAACACGGAGCTCAAGACAGTCAAT
AACTACTTCCTGCTGAGCCTGGCCTGTGCTGACCTCATCATCGGTACCTTCTCCATGAAC
CTCTATACCACGTACCTGCTCATGGGCCACTGGGCTCTGGGCACGCTGGCTTGTGACCTC
TGGCTGGCCCTGGACTATGTGGCCAGCAATGCCTCCGTCATGAATCTGCTGCTCATCAGC
TTTGACCGCTACTTCTCCGTGACTCGGCCCCTGAGCTACCGTGCCAAGCGCACACCCCGC
CGGGCAGCTCTGATGATCGGCCTGGCCTGGCTGGTTTCCTTTGTGCTCTGGGCCCCAGCC
ATCCTCTTCTGGCAGTACCTGGTAGGGGAGCGGACAGTGCTAGCTGGGCAGTGCTACATC
CAGTTCCTCTCCCAGCCCATCATCACCTTTGGCACAGCCATGGCTGCCTTCTACCTCCCT
GTCACAGTCATGTGCACGCTCTACTGGCGCATCTACCGGGAGACAGAGAACCGAGCACGG
GAGCTGGCAGCCCTTCAGGGCTCCGAGACGCCAGGCAAAGGGGGTGGCAGCAGCAGCAGC
TCAGAGAGGTCTCAGCCAGGGGCTGAGGGCTCACCAGAGACTCCTCCAGGCCGCTGCTGT
CGCTGCTGCCGGGCCCCCAGGCTGCTGCAGGCCTACAGCTGGAAGGAAGAAGAGGAAGAG
GACGAAGGCTCCATGGAGTCCCTCACATCCTCAGAGGGAGAGGAGCCTGGCTCCGAAGTG
GTGATCAAGATGCCAATGGTGGACCCCGAGGCACAGGCCCCCACCAAGCAGCCCCCACGG
AGCTCCCCAAATACAGTCAAGAGGCCGACTAAGAAAGGGCGTGATCGAGCTGGCAAGGGC
CAGAAGCCCCGTGGAAAGGAGCAGCTGGCCAAGCGGAAGACCTTCTCGCTGGTCAAGGAG
AAGAAGGCGGCTCGGACCCTGAGTGCCATCCTCCTGGCCTTCATCCTCACCTGGACACCG
TACAACATCATGGTGCTGGTGTCCACCTTCTGCAAGGACTGTGTTCCCGAGACCCTGTGG
GAGCTGGGCTACTGGCTGTGCTACGTCAACAGCACCATCAACCCCATGTGCTACGCACTC
TGCAACAAAGCCTTCCGGGACACCTTTCGCCTGCTGCTGCTTTGCCGCTGGGACAAGAGA
CGCTGGCGCAAGATCCCCAAGCGCCCTGGCTCCGTGCACCGCACTCCCTCCCGCCAATGC
TGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID CHRM1 Link Image
Target 1 GenAtlas ID CHRM1 Link Image
Target 1 HGNC ID HGNC:1950 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11q13
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Arden JR, Nagata O, Shockley MS, Philip M, Lameh J, Sadee W: Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1111-5. [PubMed Link Image]
  2. Chapman CG, Browne MJ: Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. Nucleic Acids Res. 1990 Apr 25;18(8):2191. [PubMed Link Image]
  3. Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9. [PubMed Link Image]
  4. Allard WJ, Sigal IS, Dixon RA: Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. Nucleic Acids Res. 1987 Dec 23;15(24):10604. [PubMed Link Image]
Target 1 Drug References
  1. 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. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 193
Target 2 Name Beta-1 adrenergic receptor
Target 2 Synonyms
  1. Beta-1 adrenoceptor
  2. Beta-1 adrenoreceptor
Target 2 Gene Name ADRB1
Target 2 Protein Sequence >Beta-1 adrenergic receptor 
MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAG
MGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVV
WGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVC
TVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIM
AFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAP
LANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFV
FFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGP
PPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
Target 2 Number of Residues 484
Target 2 Molecular Weight 51323
Target 2 Theoretical pI 9.03
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
beta-adrenergic receptor activity
beta1-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in beta1-adrenergic receptor activity
Target 2 Specific Function Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 60-83
  • 97-120
  • 132-155
  • 176-199
  • 222-245
  • 326-349
  • 357-380
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 178200 Link Image
Target 2 UniProtKB/Swiss-Prot ID P08588 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ADRB1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Cell membrane
  • multi-pass membrane protein. Localized at the plasma membrane. Found in the Golgi upo
Target 2 Gene Sequence >1434 bp 
ATGGGCGCGGGGGTGCTCGTCCTGGGCGCCTCCGAGCCCGGTAACCTGTCGTCGGCCGCA
CCGCTCCCCGACGGCGCGGCCACCGCGGCGCGGCTGCTGGTGCCCGCGTCGCCGCCCGCC
TCGTTGCTGCCTCCCGCCAGCGAAAGCCCCGAGCCGCTGTCTCAGCAGTGGACAGCGGGC
ATGGGTCTGCTGATGGCGCTCATCGTGCTGCTCATCGTGGCGGGCAATGTGCTGGTGATC
GTGGCCATCGCCAAGACGCCGCGGCTGCAGACGCTCACCAACCTCTTCATCATGTCCCTG
GCCAGCGCCGACCTGGTCATGGGGCTGCTGGTGGTGCCGTTCGGGGCCACCATCGTGGTG
TGGGGCCGCTGGGAGTACGGCTCCTTCTTCTGCGAGCTGTGGACCTCAGTGGACGTGCTG
TGCGTGACGGCCAGCATCGAGACCCTGTGTGTCATTGCCCTGGACCGCTACCTCGCCATC
ACCTCGCCCTTCCGCTACCAGAGCCTGCTGACGCGCGCGCGGGCGCGGGGCCTCGTGTGC
ACCGTGTGGGCCATCTCGGCCCTGGTGTCCTTCCTGCCCATCCTCATGCACTGGTGGCGG
GCGGAGAGCGACGAGGCGCGCCGCTGCTACAACGACCCCAAGTGCTGCGACTTCGTCACC
AACCGGGCCTACGCCATCGCCTCGTCCGTAGTCTCCTTCTACGTGCCCCTGTGCATCATG
GCCTTCGTGTACCTGCGGGTGTTCCGCGAGGCCCAGAAGCAGGTGAAGAAGATCGACAGC
TGCGAGCGCCGTTTCCTCGGCGGCCCAGCGCGGCCGCCCTCGCCCTCGCCCTCGCCCGTC
CCCGCGCCCGCGCCGCCGCCCGGACCCCCGCGCCCCGCCGCCGCCGCCGCCACCGCCCCG
CTGGCCAACGGGCGTGCGGGTAAGCGGCGGCCCTCGCGCCTCGTGGCCCTACGCGAGCAG
AAGGCGCTCAAGACGCTGGGCATCATCATGGGCGTCTTCACGCTCTGCTGGCTGCCCTTC
TTCCTGGCCAACGTGGTGAAGGCCTTCCACCGCGAGCTGGTGCCCGACCGCCTCTTCGTC
TTCTTCAACTGGCTGGGCTACGCCAACTCGGCCTTCAACCCCATCATCTACTGCCGCAGC
CCCGACTTCCGCAAGGCCTTCCAGGGACTGCTCTGCTGCGCGCGCAGGGCTGCCCGCCGG
CGCCACGCGACCCACGGAGACCGGCCGCGCGCCTCGGGCTGTCTGGCCCGGCCCGGACCC
CCGCCATCGCCCGGGGCCGCCTCGGACGACGACGACGACGATGTCGTCGGGGCCACGCCG
CCCGCGCGCCTGCTGGAGCCCTGGGCCGGCTGCAACGGCGGGGCGGCGGCGGACAGCGAC
TCGAGCCTGGACGAGCCGTGCCGCCCCGGCTTCGCCTCGGAATCCAAGGTGTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID ADRB1 Link Image
Target 2 GenAtlas ID ADRB1 Link Image
Target 2 HGNC ID HGNC:285 Link Image
Target 2 Chromosome Location 10
Target 2 Locus 10q24-q26
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Mason DA, Moore JD, Green SA, Liggett SB: A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. [PubMed Link Image]
  2. Moore JD, Mason DA, Green SA, Hsu J, Liggett SB: Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999 Sep 19;14(3):271. [PubMed Link Image]
  3. Borjesson M, Magnusson Y, Hjalmarson A, Andersson B: A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J. 2000 Nov;21(22):1853-8. [PubMed Link Image]
  4. Ranade K, Jorgenson E, Sheu WH, Pei D, Hsiung CA, Chiang FT, Chen YD, Pratt R, Olshen RA, Curb D, Cox DR, Botstein D, Risch N: A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002 Apr;70(4):935-42. Epub 2002 Feb 18. [PubMed Link Image]
  5. Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK: Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920-4. [PubMed Link Image]
Target 2 Drug References
  1. Burgi S, Baltensperger K, Honegger UE: Antidepressant-induced switch of beta 1-adrenoceptor trafficking as a mechanism for drug action. J Biol Chem. 2003 Jan 10;278(2):1044-52. Epub 2002 Oct 21. [PubMed Link Image]
  2. Samnick S, Scheuer C, Munks S, El-Gibaly AM, Menger MD, Kirsch CM: Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4-(2-mercapto-2-met hylpropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats. Nucl Med Biol. 2004 May;31(4):511-22. [PubMed Link Image]
  3. Matsumoto K, Ojima K, Ohta H, Watanabe H: Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice. Pharmacol Biochem Behav. 1994 Sep;49(1):13-8. [PubMed Link Image]
  4. Mudunkotuwa NT, Horton RW: Desipramine administration in the olfactory bulbectomized rat: changes in brain beta-adrenoceptor and 5-HT2A binding sites and their relationship to behaviour. Br J Pharmacol. 1996 Apr;117(7):1481-6. [PubMed Link Image]
  5. Sapena R, Morin D, Zini R, Morin C, Tillement JP: Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes. Eur J Pharmacol. 1996 Apr 4;300(1-2):159-62. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 492
Target 3 Name Histamine H1 receptor
Target 3 Synonyms Not Available
Target 3 Gene Name HRH1
Target 3 Protein Sequence >Histamine H1 receptor 
MSLPNSSCLLEDKMCEGNKTTMASPQLMPLVVVLSTICLVTVGLNLLVLYAVRSERKLHT
VGNLYIVSLSVADLIVGAVVMPMNILYLLMSKWSLGRPLCLFWLSMDYVASTASIFSVFI
LCIDRYRSVQQPLRYLKYRTKTRASATILGAWFLSFLWVIPILGWNHFMQQTSVRREDKC
ETDFYDVTWFKVMTAIINFYLPTLLMLWFYAKIYKAVRQHCQHRELINRSLPSFSEIKLR
PENPKGDAKKPGKESPWEVLKRKPKDAGGGSVLKSPSQTPKEMKSPVVFSQEDDREVDKL
YCFPLDIVHMQAAAEGSSRDYVAVNRSHGQLKTDEQGLNTHGASEISEDQMLGDSQSFSR
TDSDTTTETAPGKGKLRSGSNTGLDYIKFTWKRLRSHSRQYVSGLHMNRERKAAKQLGFI
MAAFILCWIPYFIFFMVIAFCKNCCNEHLHMFTIWLGYINSTLNPLIYPLCNENFKKTFK
RILHIRS
Target 3 Number of Residues 495
Target 3 Molecular Weight 55785
Target 3 Theoretical pI 9.58
Target 3 GO Classification
Function
amine receptor activity
histamine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Involved in rhodopsin-like receptor activity
Target 3 Specific Function In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 30-49
  • 64-83
  • 102-123
  • 146-165
  • 190-210
  • 419-438
  • 451-470
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 510296 Link Image
Target 3 UniProtKB/Swiss-Prot ID P35367 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name HRH1_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1464 bp 
ATGAGCCTCCCCAATTCCTCCTGCCTCTTAGAAGACAAGATGTGTGAGGGCAACAAGACC
ACTATGGCCAGCCCCCAGCTGATGCCCCTGGTGGTGGTCCTGAGCACTATCTGCTTGGTC
ACAGTAGGGCTCAACCTGCTGGTGCTGTATGCCGTACGGAGTGAGCGGAAGCTCCACACT
GTGGGGAACCTGTACATCGTCAGCCTCTCGGTGGCGGACTTGATCGTGGGTGCCGTCGTC
ATGCCTATGAACATCCTCTACCTGCTCATGTCCAAGTGGTCACTGGGCCGTCCTCTCTGC
CTCTTTTGGCTTTCCATGGACTATGTGGCCAGCACAGCGTCCATTTTCAGTGTCTTCATC
CTGTGCATTGATCGCTACCGCTCTGTCCAGCAGCCCCTCAGGTACCTTAAGTATCGTACC
AAGACCCGAGCCTCGGCCACCATTCTGGGGGCCTGGTTTCTCTCTTTTCTGTGGGTTATT
CCCATTCTAGGCTGGAATCACTTCATGCAGCAGACCTCGGTGCGCCGAGAGGACAAGTGT
GAGACAGACTTCTATGATGTCACCTGGTTCAAGGTCATGACTGCCATCATCAACTTCTAC
CTGCCCACCTTGCTCATGCTCTGGTTCTATGCCAAGATCTACAAGGCCGTACGACAACAC
TGCCAGCACCGGGAGCTCATCAATAGGTCCCTCCCTTCCTTCTCAGAAATTAAGCTGAGG
CCAGAGAACCCCAAGGGGGATGCCAAGAAACCAGGGAAGGAGTCTCCCTGGGAGGTTCTG
AAAAGGAAGCCAAAAGATGCTGGTGGTGGATCTGTCTTGAAGTCACCATCCCAAACCCCC
AAGGAGATGAAATCCCCAGTTGTCTTCAGCCAAGAGGATGATAGAGAAGTAGACAAACTC
TACTGCTTTCCACTTGATATTGTGCACATGCAGGCTGCGGCAGAGGGGAGTAGCAGGGAC
TATGTAGCCGTCAACCGGAGCCATGGCCAGCTCAAGACAGATGAGCAGGGCCTGAACACA
CATGGGGCCAGCGAGATATCAGAGGATCAGATGTTAGGTGATAGCCAATCCTTCTCTCGA
ACGGACTCAGATACCACCACAGAGACAGCACCAGGCAAAGGCAAATTGAGGAGTGGGTCT
AACACAGGCCTGGATTACATCAAGTTTACTTGGAAGAGGCTCCGCTCGCATTCAAGACAG
TATGTATCTGGGTTGCACATGAACCGCGAAAGGAAGGCCGCCAAACAGTTGGGTTTTATC
ATGGCAGCCTTCATCCTCTGCTGGATCCCTTATTTCATCTTCTTCATGGTCATTGCCTTC
TGCAAGAACTGTTGCAATGAACATTTGCACATGTTCACCATCTGGCTGGGCTACATCAAC
TCCACACTGAACCCCCTCATCTACCCCTTGTGCAATGAGAACTTCAAGAAGACATTCAAG
AGAATTCTGCATATTCGCTCCTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID HRH1 Link Image
Target 3 GenAtlas ID HRH1 Link Image
Target 3 HGNC ID HGNC:5182 Link Image
Target 3 Chromosome Location 3
Target 3 Locus 3p25
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K, Horio Y, Takai S, Yamada K, Ito S: Molecular cloning of the human histamine H1 receptor gene. Biochem Biophys Res Commun. 1994 Jun 15;201(2):894-901. [PubMed Link Image]
  2. De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH: Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1601-8. [PubMed Link Image]
Target 3 Drug References
  1. Sawynok J, Esser MJ, Reid AR: Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain. 1999 Aug;82(2):149-58. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 540
Target 4 Name Sodium-dependent noradrenaline transporter
Target 4 Synonyms
  1. NET
  2. Norepinephrine transporter
Target 4 Gene Name SLC6A2
Target 4 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 4 Number of Residues 627
Target 4 Molecular Weight 69333
Target 4 Theoretical pI 7.53
Target 4 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 4 General Function Involved in neurotransmitter:sodium symporter activity
Target 4 Specific Function Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 65-85
  • 93-112
  • 136-156
  • 235-253
  • 262-279
  • 315-332
  • 344-365
  • 398-417
  • 444-462
  • 478-498
  • 519-538
  • 557-575
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 189258 Link Image
Target 4 UniProtKB/Swiss-Prot ID P23975 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name SC6A2_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 Gene Sequence >1854 bp 
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID SLC6A2 Link Image
Target 4 GenAtlas ID SLC6A2 Link Image
Target 4 HGNC ID HGNC:11048 Link Image
Target 4 Chromosome Location 16
Target 4 Locus 16q12.2
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000 Feb 24;342(8):541-9. [PubMed Link Image]
  2. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed Link Image]
  3. Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350-4. [PubMed Link Image]
  4. Porzgen P, Bonisch H, Bruss M: Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1145-50. [PubMed Link Image]
Target 4 Drug References
  1. Zavosh A, Schaefer J, Ferrel A, Figlewicz DP: Desipramine treatment decreases 3H-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells. Brain Res Bull. 1999 Jul 1;49(4):291-5. [PubMed Link Image]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  3. Weinshenker D, White SS, Javors MA, Palmiter RD, Szot P: Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo. Brain Res. 2002 Aug 16;946(2):239-46. [PubMed Link Image]
  4. Bryan-Lluka LJ, Bonisch H, Lewis RJ: chi-Conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter. J Biol Chem. 2003 Oct 10;278(41):40324-9. Epub 2003 Jul 1. [PubMed Link Image]
  5. Zhu MY, Kyle PB, Hume AS, Ordway GA: The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function. Neurochem Res. 2004 Feb;29(2):419-27. [PubMed Link Image]
  6. Ordway GA, Jia W, Li J, Zhu MY, Mandela P, Pan J: Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation. J Neurosci Methods. 2005 Apr 30;143(2):217-25. Epub 2004 Dec 30. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 617
Target 5 Name Muscarinic acetylcholine receptor M2
Target 5 Synonyms Not Available
Target 5 Gene Name CHRM2
Target 5 Protein Sequence >Muscarinic acetylcholine receptor M2 
MNNSTNSSNNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNY
FLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLLIISFD
RYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGECYIQF
FSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSPSLVQGRI
VKPNNNNMPSSDDGLEHNKIQNGKAPRDPVTENCVQGEEKESSNDSTSVSAVASNMRDDE
ITQDENTVSTSLGHSKDENSKQTCIRIGTKTPKSDSCTPTNTTVEVVGSSGQNGDEKQNI
VARKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNT
VWTIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATR
Target 5 Number of Residues 473
Target 5 Molecular Weight 51716
Target 5 Theoretical pI 9.08
Target 5 GO Classification
Function
amine receptor activity
muscarinic acetylcholine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 5 General Function Involved in rhodopsin-like receptor activity
Target 5 Specific Function The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • 23-45
  • 60-80
  • 98-119
  • 140-162
  • 185-207
  • 389-409
  • 424-443
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 177990 Link Image
Target 5 UniProtKB/Swiss-Prot ID P08172 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name ACM2_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 5 Gene Sequence >1401 bp 
ATGAATAACTCAACAAACTCCTCTAACAATAGCCTGGCTCTTACAAGTCCTTATAAGACA
TTTGAAGTGGTGTTTATTGTCCTGGTGGCTGGATCCCTCAGTTTGGTGACCATTATCGGG
AACATCCTAGTCATGGTTTCCATTAAAGTCAACCGCCACCTCCAGACCGTCAACAATTAC
TTTTTATTCAGCTTGGCCTGTGCTGACCTTATCATAGGTGTTTTCTCCATGAACTTGTAC
ACCCTCTACACTGTGATTGGTTACTGGCCTTTGGGACCTGTGGTGTGTGACCTTTGGCTA
GCCCTGGACTATGTGGTCAGCAATGCCTCAGTTATGAATCTGCTCATCATCAGCTTTGAC
AGGTACTTCTGTGTCACAAAACCTCTGACCTACCCAGTCAAGCGGACCACAAAAATGGCA
GGTATGATGATTGCAGCTGCCTGGGTCCTCTCTTTCATCCTCTGGGCTCCAGCCATTCTC
TTCTGGCAGTTCATTGTAGGGGTGAGAACTGTGGAGGATGGGGAGTGCTACATTCAGTTT
TTTTCCAATGCTGCTGTCACCTTTGGTACGGCTATTGCAGCCTTCTATTTGCCAGTGATC
ATCATGACTGTGCTATATTGGCACATATCCCGAGCCAGCAAGAGCAGGATAAAGAAGGAC
AAGAAGGAGCCTGTTGCCAACCAAGACCCCGTTTCTCCAAGTCTGGTACAAGGAAGGATA
GTGAAGCCAAACAATAACAACATGCCCAGCAGTGACGATGGCCTGGAGCACAACAAAATC
CAGAATGGCAAAGCCCCCAGGGATCCTGTGACTGAAAACTGTGTTCAGGGAGAGGAGAAG
GAGAGCTCCAATGACTCCACCTCAGTCAGTGCTGTTGCCTCTAATATGAGAGATGATGAA
ATAACCCAGGATGAAAACACAGTTTCCACTTCCCTGGGCCATTCCAAAGATGAGAACTCT
AAGCAAACATGCATCAGAATTGGCACCAAGACCCCAAAAAGTGACTCATGTACCCCAACT
AATACCACCGTGGAGGTAGTGGGGTCTTCAGGTCAGAATGGAGATGAAAAGCAGAATATT
GTAGCCCGCAAGATTGTGAAGATGACTAAGCAGCCTGCAAAAAAGAAGCCTCCTCCTTCC
CGGGAAAAGAAAGTCACCAGGACAATCTTGGCTATTCTGTTGGCTTTCATCATCACTTGG
GCCCCATACAATGTCATGGTGCTCATTAACACCTTTTGTGCACCTTGCATCCCCAACACT
GTGTGGACAATTGGTTACTGGCTTTGTTACATCAACAGCACTATCAACCCTGCCTGCTAT
GCACTTTGCAATGCCACCTTCAAGAAGACCTTTAAACACCTTCTCATGTGTCATTATAAG
AACATAGGCGCTACAAGGTAA
Target 5 GenBank Gene ID
Target 5 GeneCard ID CHRM2 Link Image
Target 5 GenAtlas ID CHRM2 Link Image
Target 5 HGNC ID HGNC:1951 Link Image
Target 5 Chromosome Location 7
Target 5 Locus 7q31-q35
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Bonner TI, Buckley NJ, Young AC, Brann MR: Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987 Jul 31;237(4814):527-32. [PubMed Link Image]
  2. Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9. [PubMed Link Image]
Target 5 Drug References
  1. 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. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 766
Target 6 Name Beta-2 adrenergic receptor
Target 6 Synonyms
  1. Beta-2 adrenoceptor
  2. Beta-2 adrenoreceptor
Target 6 Gene Name ADRB2
Target 6 Protein Sequence >Beta-2 adrenergic receptor 
MGQPGNGSAFLLAPNRSHAPDHDVTQQRDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
Target 6 Number of Residues 419
Target 6 Molecular Weight 46557
Target 6 Theoretical pI 7.44
Target 6 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
beta-adrenergic receptor activity
beta2-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 6 General Function Involved in beta2-adrenergic receptor activity
Target 6 Specific Function Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Pfam Domain Function
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • 35-58
  • 72-95
  • 107-129
  • 151-174
  • 197-220
  • 275-298
  • 306-329
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 29371 Link Image
Target 6 UniProtKB/Swiss-Prot ID P07550 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name ADRB2_HUMAN Link Image
Target 6 PDB ID Not Available
Target 6 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 6 Gene Sequence >1242 bp 
ATGGGGCAACCCGGGAACGGCAGCGCCTTCTTGCTGGCACCCAATAGAAGCCATGCGCCG
GACCACGACGTCACGCAGCAAAGGGACGAGGTGTGGGTGGTGGGCATGGGCATCGTCATG
TCTCTCATCGTCCTGGCCATCGTGTTTGGCAATGTGCTGGTCATCACAGCCATTGCCAAG
TTCGAGCGTCTGCAGACGGTCACCAACTACTTCATCACTTCACTGGCCTGTGCTGATCTG
GTCATGGGCCTGGCAGTGGTGCCCTTTGGGGCCGCCCATATTCTTATGAAAATGTGGACT
TTTGGCAACTTCTGGTGCGAGTTTTGGACTTCCATTGATGTGCTGTGCGTCACGGCCAGC
ATTGAGACCCTGTGCGTGATCGCAGTGGATCGCTACTTTGCCATTACTTCACCTTTCAAG
TACCAGAGCCTGCTGACCAAGAATAAGGCCCGGGTGATCATTCTGATGGTGTGGATTGTG
TCAGGCCTTACCTCCTTCTTGCCCATTCAGATGCACTGGTACCGGGCCACCCACCAGGAA
GCCATCAACTGCTATGCCAATGAGACCTGCTGTGACTTCTTCACGAACCAAGCCTATGCC
ATTGCCTCTTCCATCGTGTCCTTCTACGTTCCCCTGGTGATCATGGTCTTCGTCTACTCC
AGGGTCTTTCAGGAGGCCAAAAGGCAGCTCCAGAAGATTGACAAATCTGAGGGCCGCTTC
CATGTCCAGAACCTTAGCCAGGTGGAGCAGGATGGGCGGACGGGGCATGGACTCCGCAGA
TCTTCCAAGTTCTGCTTGAAGGAGCACAAAGCCCTCAAGACGTTAGGCATCATCATGGGC
ACTTTCACCCTCTGCTGGCTGCCCTTCTTCATCGTTAACATTGTGCATGTGATCCAGGAT
AACCTCATCCGTAAGGAAGTTTACATCCTCCTAAATTGGATAGGCTATGTCAATTCTGGT
TTCAATCCCCTTATCTACTGCCGGAGCCCAGATTTCAGGATTGCCTTCCAGGAGCTTCTG
TGCCTGCGCAGGTCTTCTTTGAAGGCCTATGGGAATGGCTACTCCAGCAACGGCAACACA
GGGGAGCAGAGTGGATATCACGTGGAACAGGAGAAAGAAAATAAACTGCTGTGTGAAGAC
CTCCCAGGCACGGAAGACTTTGTGGGCCATCAAGGTACTGTGCCTAGCGATAACATTGAT
TCACAAGGGAGGAATTGTAGTACAAATGACTCACTGCTGTAA
Target 6 GenBank Gene ID
Target 6 GeneCard ID ADRB2 Link Image
Target 6 GenAtlas ID ADRB2 Link Image
Target 6 HGNC ID HGNC:286 Link Image
Target 6 Chromosome Location 5
Target 6 Locus 5q31-q32
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M: A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. [PubMed Link Image]
  2. Moffett S, Rousseau G, Lagace M, Bouvier M: The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization. J Neurochem. 2001 Jan;76(1):269-79. [PubMed Link Image]
  3. O'Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M: Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem. 1989 May 5;264(13):7564-9. [PubMed Link Image]
  4. Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD: Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):6995-9. [PubMed Link Image]
  5. Chung FZ, Wang CD, Potter PC, Venter JC, Fraser CM: Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. J Biol Chem. 1988 Mar 25;263(9):4052-5. [PubMed Link Image]
  6. Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ: cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci U S A. 1987 Jan;84(1):46-50. [PubMed Link Image]
  7. Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC: Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. FEBS Lett. 1987 Jan 26;211(2):200-6. [PubMed Link Image]
  8. Schofield PR, Rhee LM, Peralta EG: Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res. 1987 Apr 24;15(8):3636. [PubMed Link Image]
  9. Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RA, Keller P, Caron MG, Lefkowitz RJ: Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. J Biol Chem. 1987 May 25;262(15):7321-7. [PubMed Link Image]
  10. Turki J, Pak J, Green SA, Martin RJ, Liggett SB: Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest. 1995 Apr;95(4):1635-41. [PubMed Link Image]
  11. 7915137 Green SA, Turki J, Innis M, Liggett SB: Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994 Aug 16;33(32):9414-9.
  12. 8383511 Reihsaus E, Innis M, MacIntyre N, Liggett SB: Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol. 1993 Mar;8(3):334-9.
Target 6 Drug References
  1. Prenner L, Sieben A, Zeller K, Weiser D, Haberlein H: Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy. Biochemistry. 2007 May 1;46(17):5106-13. Epub 2007 Apr 7. [PubMed Link Image]
  2. Osadchii OE, Woodiwiss AJ, Deftereos D, Norton GR: Temporal changes in myocardial adrenergic regulation with the progression to pump dysfunction after chronic beta-adrenoreceptor activation in rats. Pflugers Arch. 2007 Nov;455(2):251-60. Epub 2007 Jun 9. [PubMed Link Image]
  3. Matsumoto K, Ojima K, Ohta H, Watanabe H: Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice. Pharmacol Biochem Behav. 1994 Sep;49(1):13-8. [PubMed Link Image]
  4. Sapena R, Morin D, Zini R, Morin C, Tillement JP: Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes. Eur J Pharmacol. 1996 Apr 4;300(1-2):159-62. [PubMed Link Image]
  5. Abadie C, Foucart S, Page P, Nadeau R: Modulation of noradrenaline release from isolated human atrial appendages. J Auton Nerv Syst. 1996 Dec 14;61(3):269-76. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 824
Target 7 Name Sodium-dependent serotonin transporter
Target 7 Synonyms
  1. 5HT transporter
  2. 5HTT
Target 7 Gene Name SLC6A4
Target 7 Protein Sequence >Sodium-dependent serotonin transporter 
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
Target 7 Number of Residues 640
Target 7 Molecular Weight 70325
Target 7 Theoretical pI 6.17
Target 7 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 7 General Function Involved in serotonin:sodium symporter activity
Target 7 Specific Function Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 7 Pathways Not Available
Target 7 Reactions Not Available
Target 7 Pfam Domain Function
Target 7 Signals
  • None
Target 7 Transmembrane Regions
  • 88-108
  • 116-135
  • 160-180
  • 253-271
  • 280-297
  • 333-350
  • 362-383
  • 417-436
  • 464-482
  • 498-518
  • 539-558
  • 577-595
Target 7 Essentiality Non-Essential
Target 7 GenBank ID Protein 36433 Link Image
Target 7 UniProtKB/Swiss-Prot ID P31645 Link Image
Target 7 UniProtKB/Swiss-Prot Entry Name SC6A4_HUMAN Link Image
Target 7 PDB ID Not Available
Target 7 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 7 Gene Sequence >1893 bp 
ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT
TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC
GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG
CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG
ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC
AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC
TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA
CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG
ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG
GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC
AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG
ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC
CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG
CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG
GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC
ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC
CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC
TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT
GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC
ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC
GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC
ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT
GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG
CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC
CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA
GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG
TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC
TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG
CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC
ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
Target 7 GenBank Gene ID
Target 7 GeneCard ID SLC6A4 Link Image
Target 7 GenAtlas ID SLC6A4 Link Image
Target 7 HGNC ID HGNC:11050 Link Image
Target 7 Chromosome Location 17
Target 7 Locus 17q11.1-q12
Target 7 SNPs SNPJam Report Link Image
Target 7 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9. [PubMed Link Image]
  3. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD: Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542-6. [PubMed Link Image]
  4. Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993 Jun;60(6):2319-22. [PubMed Link Image]
  5. Lesch KP, Wolozin BL, Estler HC, Murphy DL, Riederer P: Isolation of a cDNA encoding the human brain serotonin transporter. J Neural Transm Gen Sect. 1993;91(1):67-72. [PubMed Link Image]
Target 7 Drug References
  1. Holmes A, Yang RJ, Murphy DL, Crawley JN: Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology. 2002 Dec;27(6):914-23. [PubMed Link Image]
  2. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [PubMed Link Image]
  3. Zhou L, Huang KX, Kecojevic A, Welsh AM, Koliatsos VE: Evidence that serotonin reuptake modulators increase the density of serotonin innervation in the forebrain. J Neurochem. 2006 Jan;96(2):396-406. Epub 2005 Nov 21. [PubMed Link Image]
  4. Hoffman AF, Gerhardt GA: In vivo electrochemical studies of dopamine clearance in the rat substantia nigra: effects of locally applied uptake inhibitors and unilateral 6-hydroxydopamine lesions. J Neurochem. 1998 Jan;70(1):179-89. [PubMed Link Image]
Drug Target 8 [top]
Target 8 ID 1360
Target 8 Name Sphingomyelin phosphodiesterase
Target 8 Synonyms
  1. Acid sphingomyelinase
  2. EC 3.1.4.12
  3. Sphingomyelin phosphodiesterase precursor
  4. aSMase
Target 8 Gene Name SMPD1
Target 8 Protein Sequence >Sphingomyelin phosphodiesterase precursor 
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALSDSRVLWAPAEAH
PLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIKLC
NLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLPT
VPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPG
AGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTTVT
ALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALRT
LRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKV
HIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAF
LAPSATTYIGLNPGYRVYQIDGNYSRSSHVVLDHETYILNLTQANIPGAIPHWQLLYRAR
ETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSAR
ADSPALCRHLMPDGSLPEAQSLWPRPLFC
Target 8 Number of Residues 639
Target 8 Molecular Weight 69852
Target 8 Theoretical pI 7.42
Target 8 GO Classification
Function
hydrolase activity, acting on ester bonds
phosphoric ester hydrolase activity
phosphoric diester hydrolase activity
sphingomyelin phosphodiesterase activity
catalytic activity
hydrolase activity
Process
physiological process
metabolism
primary metabolism
lipid metabolism
cellular lipid metabolism
membrane lipid metabolism
phospholipid metabolism
sphingomyelin metabolism
sphingomyelin catabolism
Component
Not Available
Target 8 General Function Involved in hydrolase activity
Target 8 Specific Function Converts sphingomyelin to ceramide. aSM also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol
Target 8 Pathways
Name SMPDB Link KEGG Link
Glycosphingolipid metabolism map00600 Link Image
Target 8 Reactions
  • sphingomyelin + H2O = N-acylsphingosine + choline phosphate
Target 8 Pfam Domain Function
Target 8 Signals
  • 1-46
Target 8 Transmembrane Regions
  • None
Target 8 Essentiality Non-Essential
Target 8 GenBank ID Protein 179095 Link Image
Target 8 UniProtKB/Swiss-Prot ID P17405 Link Image
Target 8 UniProtKB/Swiss-Prot Entry Name ASM_HUMAN Link Image
Target 8 PDB ID Not Available
Target 8 Cellular Location
  • Lysosome
Target 8 Gene Sequence >1890 bp 
ATGCCCCGCTACGGAGCGTCACTCCGCCAGAGCTGCCCCAGGTCCGGCCGGGAGCAGGGA
CAAGACGGGACCGCCGGAGCCCCCGGACTCCTTTGGATGGGCCTGGTGCTGGCGCTGGCG
CTGGCGCTGGCGCTGGCTCTGTCTGACTCTCGGGTTCTCTGGGCTCCGGCAGAGGCTCAC
CCTCTTTCTCCCCAAGGCCATCCTGCCAGGTTACATCGCATAGTGCCCCGGCTCCGAGAT
GTCTTTGGGTGGGGGAACCTCACCTGCCCAATCTGCAAAGGTCTATTCACCGCCATCAAC
CTCGGGCTGAAGAAGGAACCCAATGTGGCTCGCGTGGGCTCCGTGGCCATCAAGCTGTGC
AATCTGCTGAAGATAGCACCACCTGCCGTGTGCCAATCCATTGTCCACCTCTTTGAGGAT
GACATGGTGGAGGTGTGGAGACGCTCAGTGCTGAGCCCATCTGAGGCCTGTGGCCTGCTC
CTGGGCTCCACCTGTGGGCACTGGGACATTTTCTCATCTTGGAACATCTCTTTGCCTACT
GTGCCGAAGCCGCCCCCCAAACCCCCTAGCCCCCCAGCCCCAGGTGCCCCTGTCAGCCGC
ATCCTCTTCCTCACTGACCTGCACTGGGATCATGACTACCTGGAGGGCACGGACCCTGAC
TGTGCAGACCCACTGTGCTGCCGCCGGGGTTCTGGCCTGCCGCCCGCATCCCGGCCAGGT
GCCGGATACTGGGGCGAATACAGCAAGTGTGACCTGCCCCTGAGGACCCTGGAGAGCCTG
TTGAGTGGGCTGGGCCCAGCCGGCCCTTTTGATATGGTGTACTGGACAGGAGACATCCCC
GCACATGATGTCTGGCACCAGACTCGTCAGGACCAACTGCGGGCCCTGACCACCGTCACA
GCACTTGTGAGGAAGTTCCTGGGGCCAGTGCCAGTGTACCCTGCTGTGGGTAACCATGAA
AGCATACCTGTCAATAGCTTCCCTCCCCCCTTCATTGAGGGCAACCACTCCTCCCGCTGG
CTCTATGAAGCGATGGCCAAGGCTTGGGAGCCCTGGCTGCCTGCCGAAGCCCTGCGCACC
CTCAGAATTGGGGGGTTCTATGCTCTTTCCCCATACCCCGGTCTCCGCCTCATCTCTCTC
AATATGAATTTTTGTTCCCGTGAGAACTTCTGGCTCTTGATCAACTCCACGGATCCCGCA
GGACAGCTCCAGTGGCTGGTGGGGGAGCTTCAGGCTGCTGAGGATCGAGGAGACAAAGTG
CATATAATTGGCCACATTCCCCCAGGGCACTGTCTGAAGAGCTGGAGCTGGAATTATTAC
CGAATTGTAGCCAGGTATGAGAACACCCTGGCTGCTCAGTTCTTTGGCCACACTCATGTG
GATGAATTTGAGGTCTTCTATGATGAAGAGACTCTGAGCCGGCCGCTGGCTGTAGCCTTC
CTGGCACCCAGTGCAACTACCTACATCGGCCTTAATCCTGGTTACCGTGTGTACCAAATA
GATGGAAACTACTCCAGGAGCTCTCACGTGGTCCTGGACCATGAGACCTACATCCTGAAT
CTGACCCAGGCAAACATACCGGGAGCCATACCGCACTGGCAGCTTCTCTACAGGGCTCGA
GAAACCTATGGGCTGCCCAACACACTGCCTACCGCCTGGCACAACCTGGTATATCGCATG
CGGGGCGACATGCAACTTTTCCAGACCTTCTGGTTTCTCTACCATAAGGGCCACCCACCC
TCGGAGCCCTGTGGCACGCCCTGCCGTCTGGCTACTCTTTGTGCCCAGCTCTCTGCCCGT
GCTGACAGCCCTGCTCTGTGCCGCCACCTGATGCCAGATGGGAGCCTCCCAGAGGCCCAG
AGCCTGTGGCCAAGGCCACTGTTTTGCTAG
Target 8 GenBank Gene ID
Target 8 GeneCard ID SMPD1 Link Image
Target 8 GenAtlas ID SMPD1 Link Image
Target 8 HGNC ID HGNC:11120 Link Image
Target 8 Chromosome Location 11
Target 8 Locus 11p15.4-p15.1
Target 8 SNPs SNPJam Report Link Image
Target 8 General References
  1. Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH: The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations. Am J Hum Genet. 2002 Dec;71(6):1413-9. Epub 2002 Oct 4. [PubMed Link Image]
  2. Sikora J, Pavlu-Pereira H, Elleder M, Roelofs H, Wevers RA: Seven novel acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients. Ann Hum Genet. 2003 Jan;67(Pt 1):63-70. [PubMed Link Image]
  3. Lansmann S, Schuette CG, Bartelsen O, Hoernschemeyer J, Linke T, Weisgerber J, Sandhoff K: Human acid sphingomyelinase. Eur J Biochem. 2003 Mar;270(6):1076-88. [PubMed Link Image]
  4. Newrzella D, Stoffel W: Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene. Biol Chem Hoppe Seyler. 1992 Dec;373(12):1233-8. [PubMed Link Image]
  5. Takahashi T, Desnick RJ, Takada G, Schuchman EH: Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease. Hum Mutat. 1992;1(1):70-1. [PubMed Link Image]
  6. Levran O, Desnick RJ, Schuchman EH: Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients. Blood. 1992 Oct 15;80(8):2081-7. [PubMed Link Image]
  7. Takahashi T, Suchi M, Desnick RJ, Takada G, Schuchman EH: Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms. J Biol Chem. 1992 Jun 25;267(18):12552-8. [PubMed Link Image]
  8. Ferlinz K, Hurwitz R, Sandhoff K: Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1187-91. [PubMed Link Image]
  9. Schuchman EH, Levran O, Pereira LV, Desnick RJ: Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1). Genomics. 1992 Feb;12(2):197-205. [PubMed Link Image]
  10. Schuchman EH, Suchi M, Takahashi T, Sandhoff K, Desnick RJ: Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs. J Biol Chem. 1991 May 5;266(13):8531-9. [PubMed Link Image]
  11. 1885770 Levran O, Desnick RJ, Schuchman EH: Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. J Clin Invest. 1991 Sep;88(3):806-10.
  12. 2023926 Levran O, Desnick RJ, Schuchman EH: Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3748-52.
  13. 2555181 Quintern LE, Schuchman EH, Levran O, Suchi M, Ferlinz K, Reinke H, Sandhoff K, Desnick RJ: Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts. EMBO J. 1989 Sep;8(9):2469-73.
  14. 8051942 Sperl W, Bart G, Vanier MT, Christomanou H, Baldissera I, Steichen-Gersdorf E, Paschke E: A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate. J Inherit Metab Dis. 1994;17(1):93-103.
  15. 8407868 Ida H, Rennert OM, Eto Y, Chan WY: Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive. J Biochem (Tokyo). 1993 Jul;114(1):15-20.
  16. 8664904 Ida H, Rennert OM, Maekawa K, Eto Y: Identification of three novel mutations in the acid sphinogomyelinase gene of Japanese patients with Niemann-Pick disease type A and B. Hum Mutat. 1996;7(1):65-7.
  17. 8680412 Schuchman EH: Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X. Hum Mutat. 1995;6(4):352-4.
  18. 8693491 Takahashi T, Suchi M, Sato W, Ten SB, Sakuragawa N, Desnick RJ, Schuchman EH, Takada G: Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease. Tohoku J Exp Med. 1995 Oct;177(2):117-23.
  19. 9030779 Ferlinz K, Hurwitz R, Moczall H, Lansmann S, Schuchman EH, Sandhoff K: Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis. Eur J Biochem. 1997 Jan 15;243(1-2):511-7.
Target 8 Drug References
  1. Testai FD, Landek MA, Dawson G: Regulation of sphingomyelinases in cells of the oligodendrocyte lineage. J Neurosci Res. 2004 Jan 1;75(1):66-74. [PubMed Link Image]
  2. Kolzer M, Werth N, Sandhoff K: Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine. FEBS Lett. 2004 Feb 13;559(1-3):96-8. [PubMed Link Image]
  3. Erdreich-Epstein A, Tran LB, Cox OT, Huang EY, Laug WE, Shimada H, Millard M: Endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 involves ceramide metabolic pathways. Blood. 2005 Jun 1;105(11):4353-61. Epub 2005 Feb 10. [PubMed Link Image]
  4. Zeidan YH, Pettus BJ, Elojeimy S, Taha T, Obeid LM, Kawamori T, Norris JS, Hannun YA: Acid ceramidase but not acid sphingomyelinase is required for tumor necrosis factor-{alpha}-induced PGE2 production. J Biol Chem. 2006 Aug 25;281(34):24695-703. Epub 2006 Jun 27. [PubMed Link Image]
  5. Hurwitz R, Ferlinz K, Sandhoff K: The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts. Biol Chem Hoppe Seyler. 1994 Jul;375(7):447-50. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.