|
Drug Target 1
[top]
|
| Target 1 ID |
193 |
| Target 1 Name |
Beta-1 adrenergic receptor |
| Target 1 Synonyms |
- Beta-1 adrenoceptor
- Beta-1 adrenoreceptor
|
| Target 1 Gene Name |
ADRB1 |
| Target 1 Protein Sequence |
>Beta-1 adrenergic receptor
MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAG
MGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVV
WGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVC
TVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIM
AFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAP
LANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFV
FFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGP
PPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
|
| Target 1 Number of Residues |
484 |
| Target 1 Molecular Weight |
51323 |
| Target 1 Theoretical pI |
9.03 |
| Target 1 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 1 General Function |
Involved in beta1-adrenergic receptor activity |
| Target 1 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 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 60-83
- 97-120
- 132-155
- 176-199
- 222-245
- 326-349
- 357-380
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
178200  |
| Target 1 UniProtKB/Swiss-Prot ID |
P08588  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
ADRB1_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Cell membrane
- multi-pass membrane protein. Localized at the plasma membrane. Found in the Golgi upo
|
| Target 1 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 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
ADRB1  |
| Target 1 GenAtlas ID |
ADRB1  |
| Target 1 HGNC ID |
HGNC:285  |
| Target 1 Chromosome Location |
10 |
| Target 1 Locus |
10q24-q26 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 1 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
- Sato M, Gong H, Terracciano CM, Ranu H, Harding SE: Loss of beta-adrenoceptor response in myocytes overexpressing the Na+/Ca(2+)-exchanger. J Mol Cell Cardiol. 2004 Jan;36(1):43-8. [PubMed
]
- Jurgens CW, Rau KE, Knudson CA, King JD, Carr PA, Porter JE, Doze VA: Beta1 adrenergic receptor-mediated enhancement of hippocampal CA3 network activity. J Pharmacol Exp Ther. 2005 Aug;314(2):552-60. Epub 2005 May 20. [PubMed
]
- Kobayashi H, Narita Y, Nishida M, Kurose H: Beta-arrestin2 enhances beta2-adrenergic receptor-mediated nuclear translocation of ERK. Cell Signal. 2005 Oct;17(10):1248-53. Epub 2005 Feb 12. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
766 |
| Target 2 Name |
Beta-2 adrenergic receptor |
| Target 2 Synonyms |
- Beta-2 adrenoceptor
- Beta-2 adrenoreceptor
|
| Target 2 Gene Name |
ADRB2 |
| Target 2 Protein Sequence |
>Beta-2 adrenergic receptor
MGQPGNGSAFLLAPNRSHAPDHDVTQQRDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
|
| Target 2 Number of Residues |
419 |
| Target 2 Molecular Weight |
46557 |
| Target 2 Theoretical pI |
7.44 |
| 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
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 2 General Function |
Involved in beta2-adrenergic receptor activity |
| Target 2 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 2 Pathways |
Not Available
|
| Target 2 Reactions |
Not Available |
| Target 2 Pfam Domain Function |
|
| Target 2 Signals |
|
| Target 2 Transmembrane Regions |
- 35-58
- 72-95
- 107-129
- 151-174
- 197-220
- 275-298
- 306-329
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
29371  |
| Target 2 UniProtKB/Swiss-Prot ID |
P07550  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
ADRB2_HUMAN  |
| Target 2 PDB ID |
Not Available |
| Target 2 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 2 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 2 GenBank Gene ID |
|
| Target 2 GeneCard ID |
ADRB2  |
| Target 2 GenAtlas ID |
ADRB2  |
| Target 2 HGNC ID |
HGNC:286  |
| Target 2 Chromosome Location |
5 |
| Target 2 Locus |
5q31-q32 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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.
- 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 2 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
- Abraham G, Kottke C, Dhein S, Ungemach FR: Pharmacological and biochemical characterization of the beta-adrenergic signal transduction pathway in different segments of the respiratory tract. Biochem Pharmacol. 2003 Sep 15;66(6):1067-81. [PubMed
]
- Jones SM, Hiller FC, Jacobi SE, Foreman SK, Pittman LM, Cornett LE: Enhanced beta2-adrenergic receptor (beta2AR) signaling by adeno-associated viral (AAV)-mediated gene transfer. BMC Pharmacol. 2003 Dec 4;3:15. [PubMed
]
- Teixeira CE, Baracat JS, Zanesco A, Antunes E, De Nucci G: Atypical beta-adrenoceptor subtypes mediate relaxations of rabbit corpus cavernosum. J Pharmacol Exp Ther. 2004 May;309(2):587-93. Epub 2004 Jan 29. [PubMed
]
- Odley A, Hahn HS, Lynch RA, Marreez Y, Osinska H, Robbins J, Dorn GW 2nd: Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling. Proc Natl Acad Sci U S A. 2004 May 4;101(18):7082-7. Epub 2004 Apr 22. [PubMed
]
- Uezono Y, Kaibara M, Murasaki O, Taniyama K: Involvement of G protein betagamma-subunits in diverse signaling induced by G(i/o)-coupled receptors: study using the Xenopus oocyte expression system. Am J Physiol Cell Physiol. 2004 Oct;287(4):C885-94. Epub 2004 May 19. [PubMed
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
1281 |
| Target 3 Name |
Phosphatidylinositol 3-kinase regulatory subunit alpha |
| Target 3 Synonyms |
- PI3-kinase p85-subunit alpha
- PI3K
- PtdIns-3-kinase p85-alpha
|
| Target 3 Gene Name |
PIK3R1 |
| Target 3 Protein Sequence |
>Phosphatidylinositol 3-kinase regulatory subunit alpha
MSAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYN
ETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGSSKTEADVEQQALTLPDLAE
QFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVH
VLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTL
QYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILISTEWNE
RQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDA
STKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKL
DVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMK
RTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIID
SRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGN
ENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACS
VVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYA
QQRR
|
| Target 3 Number of Residues |
736 |
| Target 3 Molecular Weight |
83599 |
| Target 3 Theoretical pI |
6.06 |
| Target 3 GO Classification |
|
Function
|
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
lipid kinase activity
phosphoinositide 3-kinase activity
phosphatidylinositol 3-kinase activity
binding
nucleotide binding
purine nucleotide binding
guanyl nucleotide binding
GTP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
GTPase activity |
|
Process
|
cellular process
cell communication
signal transduction
intracellular signaling cascade
response to stimulus
response to biotic stimulus
defense response
immune response |
|
Component
|
protein complex
phosphoinositide 3-kinase complex |
|
| Target 3 General Function |
Replication, recombination and repair |
| Target 3 Specific Function |
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues |
| Target 3 Pathways |
Not Available
|
| Target 3 Reactions |
Not Available |
| Target 3 Pfam Domain Function |
|
| Target 3 Signals |
|
| Target 3 Transmembrane Regions |
|
| Target 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
Not Available |
| Target 3 UniProtKB/Swiss-Prot ID |
P27986  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
P85A_HUMAN  |
| Target 3 PDB ID |
1PBW  |
| Target 3 PDB File |
Show |
| Target 3 3D Structure |
|
| Target 3 Cellular Location |
|
| Target 3 Gene Sequence |
Not Available |
| Target 3 GenBank Gene ID |
|
| Target 3 GeneCard ID |
PIK3R1  |
| Target 3 GenAtlas ID |
PIK3R1  |
| Target 3 HGNC ID |
HGNC:8979  |
| Target 3 Chromosome Location |
5 |
| Target 3 Locus |
5q13.1 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- Baynes KC, Beeton CA, Panayotou G, Stein R, Soos M, Hansen T, Simpson H, O'Rahilly S, Shepherd PR, Whitehead JP: Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity. Diabetologia. 2000 Mar;43(3):321-31. [PubMed
]
- Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN: NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1397-404. Epub 2001 Sep 21. [PubMed
]
- Linnemann T, Zheng YH, Mandic R, Peterlin BM: Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV. Virology. 2002 Mar 15;294(2):246-55. [PubMed
]
- Zhu M, Janssen E, Leung K, Zhang W: Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. J Biol Chem. 2002 Nov 29;277(48):46151-8. Epub 2002 Sep 30. [PubMed
]
- Skolnik EY, Margolis B, Mohammadi M, Lowenstein E, Fischer R, Drepps A, Ullrich A, Schlessinger J: Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83-90. [PubMed
]
- Craparo A, O'Neill TJ, Gustafson TA: Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995 Jun 30;270(26):15639-43. [PubMed
]
- Koyama S, Yu H, Dalgarno DC, Shin TB, Zydowsky LD, Schreiber SL: Structure of the PI3K SH3 domain and analysis of the SH3 family. Cell. 1993 Mar 26;72(6):945-52. [PubMed
]
- Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC: Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat Struct Biol. 1996 Apr;3(4):364-74. [PubMed
]
- Antonetti DA, Algenstaedt P, Kahn CR: Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol. 1996 May;16(5):2195-203. [PubMed
]
- Liang J, Chen JK, Schreiber ST, Clardy J: Crystal structure of P13K SH3 domain at 20 angstroms resolution. J Mol Biol. 1996 Apr 5;257(3):632-43. [PubMed
]
- 8670861 Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA: Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase. EMBO J. 1996 Jul 15;15(14):3579-89.
- 8961927 Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE: Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry. 1996 Dec 10;35(49):15646-53.
- 8962058 Musacchio A, Cantley LC, Harrison SC: Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14373-8.
- 9032108 Hansen T, Andersen CB, Echwald SM, Urhammer SA, Clausen JO, Vestergaard H, Owens D, Hansen L, Pedersen O: Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. Diabetes. 1997 Mar;46(3):494-501.
- 9489702 Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998 Jan 9;92(1):83-92.
- 9687533 Bruyns E, Marie-Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, Autschbach F, Bensussan A, Meuer S, Schraven B: T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane. J Exp Med. 1998 Aug 3;188(3):561-75.
|
| Target 3 Drug References |
- Slomiany BL, Slomiany A: Salivary phospholipid secretion in response to beta-adrenergic stimulation is mediated by Src kinase-dependent epidermal growth factor receptor transactivation. Biochem Biophys Res Commun. 2004 May 21;318(1):247-52. [PubMed
]
- Slomiany BL, Slomiany A: Secretion of gastric mucus phospholipids in response to beta-adrenergic G protein-coupled receptor activation is mediated by SRC kinase-dependent epidermal growth factor receptor transactivation. J Physiol Pharmacol. 2004 Sep;55(3):627-38. [PubMed
]
- Slomiany BL, Slomiany A: Src-kinase-dependent epidermal growth factor receptor transactivation in salivary mucin secretion in response to beta-adrenergic G-protein-coupled receptor activation. Inflammopharmacology. 2004;12(3):233-45. [PubMed
]
- Machida K, Inoue H, Matsumoto K, Tsuda M, Fukuyama S, Koto H, Aizawa H, Kureishi Y, Hara N, Nakanishi Y: Activation of PI3K-Akt pathway mediates antiapoptotic effects of beta-adrenergic agonist in airway eosinophils. Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L860-7. Epub 2004 Dec 23. [PubMed
]
- Slomiany BL, Slomiany A: Gastric mucin secretion in response to beta-adrenergic G protein-coupled receptor activation is mediated by SRC kinase-dependent epidermal growth factor receptor transactivation. J Physiol Pharmacol. 2005 Jun;56(2):247-58. [PubMed
]
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Drug Target 4
[top]
|
| Target 4 ID |
1714 |
| Target 4 Name |
Mitogen-activated protein kinase 3 |
| Target 4 Synonyms |
- EC 2.7.11.24
- ERK-1
- ERT2
- Extracellular signal-regulated kinase 1
- Insulin-stimulated MAP2 kinase
- MAP kinase 1
- MAPK 1
- Microtubule- associated protein 2 kinase
- p44-ERK1
- p44-MAPK
|
| Target 4 Gene Name |
MAPK3 |
| Target 4 Protein Sequence |
>Mitogen-activated protein kinase 3
MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAY
DHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYI
VQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL
KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLS
NRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSD
SKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL
KELIFQETARFQPGVLEAP
|
| Target 4 Number of Residues |
385 |
| Target 4 Molecular Weight |
43136 |
| Target 4 Theoretical pI |
6.74 |
| Target 4 GO Classification |
|
Function
|
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
protein serine/threonine kinase activity
receptor signaling protein serine/threonine kinase activity
MAP kinase activity |
|
Process
|
physiological process
metabolism
macromolecule metabolism
biopolymer metabolism
biopolymer modification
protein modification
protein amino acid phosphorylation |
|
Component
|
| Not Available |
|
| Target 4 General Function |
Involved in MAP kinase activity |
| Target 4 Specific Function |
Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 |
| Target 4 Pathways |
Not Available
|
| Target 4 Reactions |
- ATP + a protein = ADP + a phosphoprotein
|
| Target 4 Pfam Domain Function |
|
| Target 4 Signals |
|
| Target 4 Transmembrane Regions |
|
| Target 4 Essentiality |
Non-Essential |
| Target 4 GenBank ID Protein |
31221  |
| Target 4 UniProtKB/Swiss-Prot ID |
P27361  |
| Target 4 UniProtKB/Swiss-Prot Entry Name |
MK03_HUMAN  |
| Target 4 PDB ID |
Not Available |
| Target 4 Cellular Location |
Not Available |
| Target 4 Gene Sequence |
>1140 bp
ATGGCGGCGGCGGCGGCTCAGGGGGGCGGGGGCGGGGAGCCCCGTAGAACCGAGGGGGTC
GGCCCGGGGGTCCCGGGGGAGGTGGAGATGGTGAAGGGGCAGCCGTTCGACGTGGGCCCG
CGCTACACGCAGTTGCAGTACATCGGCGAGGGCGCGTACGGCATGGTCAGCTCGGCCTAT
GACCACGTGCGCAAGACTCGCGTGGCCATCAAGAAGATCAGCCCCTTCGAACATCAGACC
TACTGCCAGCGCACGCTCCGGGAGATCCAGATCCTGCTGCGCTTCCGCCATGAGAATGTC
ATCGGCATCCGAGACATTCTGCGGGCGTCCACCCTGGAAGCCATGAGAGATGTCTACATT
GTGCAGGACCTGATGGAGACTGACCTGTACAAGTTGCTGAAAAGCCAGCAGCTGAGCAAT
GACCATATCTGCTACTTCCTCTACCAGATCCTGCGGGGCCTCAAGTACATCCACTCCGCC
AACGTGCTCCACCGAGATCTAAAGCCCTCCAACCTGCTCAGCAACACCACCTGCGACCTT
AAGATTTGTGATTTCGGCCTGGCCCGGATTGCCGATCCTGAGCATGACCACACCGGCTTC
CTGACGGAGTATGTGGCTACGCGCTGGTACCGGGCCCCAGAGATCATGCTGAACTCCAAG
GGCTATACCAAGTCCATCGACATCTGGTCTGTGGGCTGCATTCTGGCTGAGATGCTCTCT
AACCGGCCCATCTTCCCTGGCAAGCACTACCTGGATCAGCTCAACCACATTCTGGGCATC
CTGGGCTCCCCATCCCAGGAGGACCTGAATTGTATCATCAACATGAAGGCCCGAAACTAC
CTACAGTCTCTGCCCTCCAAGACCAAGGTGGCTTGGGCCAAGCTTTTCCCCAAGTCAGAC
TCCAAAGCCCTTGACCTGCTGGACCGGATGTTAACCTTTAACCCCAATAAACGGATCACA
GTGGAGGAAGCGCTGGCTCACCCCTACCTGGAGCAGTACTATGACCCGACGGATGAGCCA
GTGGCCGAGGAGCCCTTCACCTTCGCCATGGAGCTGGATGACCTACCTAAGGAGCGGCTG
AAGGAGCTCATCTTCCAGGAGACAGCACGCTTCCAGCCCGGAGTGCTGGAGGCCCCCTAG
|
| Target 4 GenBank Gene ID |
|
| Target 4 GeneCard ID |
MAPK3  |
| Target 4 GenAtlas ID |
MAPK3  |
| Target 4 HGNC ID |
HGNC:6877  |
| Target 4 Chromosome Location |
16 |
| Target 4 Locus |
16p11.2 |
| Target 4 SNPs |
SNPJam Report  |
| Target 4 General References |
- Gonzalez FA, Raden DL, Rigby MR, Davis RJ: Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 1992 Jun 15;304(2-3):170-8. [PubMed
]
- Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD: Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1416-22. [PubMed
]
- Charest DL, Mordret G, Harder KW, Jirik F, Pelech SL: Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1. Mol Cell Biol. 1993 Aug;13(8):4679-90. [PubMed
]
- Greenway A, Azad A, Mills J, McPhee D: Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. J Virol. 1996 Oct;70(10):6701-8. [PubMed
]
|
| Target 4 Drug References |
- Oudit GY, Crackower MA, Eriksson U, Sarao R, Kozieradzki I, Sasaki T, Irie-Sasaki J, Gidrewicz D, Rybin VO, Wada T, Steinberg SF, Backx PH, Penninger JM: Phosphoinositide 3-kinase gamma-deficient mice are protected from isoproterenol-induced heart failure. Circulation. 2003 Oct 28;108(17):2147-52. Epub 2003 Sep 8. [PubMed
]
- Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, Pineyro G: Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11406-11. Epub 2003 Sep 17. [PubMed
]
- Adissu HA, Schuller HM: Antagonistic growth regulation of cell lines derived from human lung adenocarcinomas of Clara cell and aveolar type II cell lineage: Implications for chemoprevention. Int J Oncol. 2004 Jun;24(6):1467-72. [PubMed
]
- Dubey RK, Jackson EK, Gillespie DG, Zacharia LC, Imthurn B: Catecholamines block the antimitogenic effect of estradiol on human coronary artery smooth muscle cells. J Clin Endocrinol Metab. 2004 Aug;89(8):3922-31. [PubMed
]
- Yeh CK, Ghosh PM, Dang H, Liu Q, Lin AL, Zhang BX, Katz MS: beta-Adrenergic-responsive activation of extracellular signal-regulated protein kinases in salivary cells: role of epidermal growth factor receptor and cAMP. Am J Physiol Cell Physiol. 2005 Jun;288(6):C1357-66. Epub 2005 Feb 2. [PubMed
]
|