|
Drug Target 1
[top]
|
| Target 1 ID |
631 |
| Target 1 Name |
3-hydroxy-3-methylglutaryl-coenzyme A reductase |
| Target 1 Synonyms |
- EC 1.1.1.34
- HMG-CoA reductase
|
| Target 1 Gene Name |
HMGCR |
| Target 1 Protein Sequence |
>3-hydroxy-3-methylglutaryl-coenzyme A reductase
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
|
| Target 1 Number of Residues |
902 |
| Target 1 Molecular Weight |
97477 |
| Target 1 Theoretical pI |
6.72 |
| Target 1 GO Classification |
|
Function
|
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase (NADPH) activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
hydroxymethylglutaryl-CoA reductase (NADPH) activity |
|
Process
|
primary metabolism
lipid metabolism
physiological process
metabolism
biosynthesis |
|
Component
|
organelle membrane
endoplasmic reticulum membrane
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 1 General Function |
Lipid transport and metabolism |
| Target 1 Specific Function |
This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Biosynthesis of steroids |
|
map00100  |
|
| Target 1 Reactions |
- (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 10-39
- 57-78
- 90-114
- 124-149
- 160-187
- 192-220
- 315-339
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
306865  |
| Target 1 UniProtKB/Swiss-Prot ID |
P04035  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
HMDH_HUMAN  |
| Target 1 PDB ID |
1HWL  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
- Endoplasmic reticulum
- endoplasmic reticulum membrane
- multi-pass membrane protein. Peroxisome
- pero
|
| Target 1 Gene Sequence |
>2667 bp
ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC
ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC
AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT
GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC
CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT
TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC
TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA
GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA
ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA
GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA
GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA
GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA
GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG
TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA
AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA
ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT
GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA
CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA
CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG
AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA
AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC
TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG
GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA
TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG
TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC
AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC
TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG
GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT
TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC
AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT
GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG
GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA
CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT
TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT
CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG
GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA
TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT
GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC
TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA
ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA
GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG
CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA
ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA
CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA
GGAGCTTGCACCAAGAAGACAGCCTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
HMGCR  |
| Target 1 GenAtlas ID |
HMGCR  |
| Target 1 HGNC ID |
HGNC:5006  |
| Target 1 Chromosome Location |
5 |
| Target 1 Locus |
5q13.3-q14 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [PubMed
]
- Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [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
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
1490 |
| Target 2 Name |
Solute carrier organic anion transporter family member 1B1 |
| Target 2 Synonyms |
- LST-1
- Liver-specific organic anion transporter 1
- OATP 2
- OATP-C
- Sodium-independent organic anion- transporting polypeptide 2
- Solute carrier family 21 member 6
|
| Target 2 Gene Name |
SLCO1B1 |
| Target 2 Protein Sequence |
>Solute carrier organic anion transporter family member 1B1
MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFE
ISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGY
YRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNML
RGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYV
DLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLE
TNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVF
KYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLS
FYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGIT
YISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAI
QVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCI
KWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASE
NGSVMDEANLESLNKNKHFVPSAGADSETHC
|
| Target 2 Number of Residues |
702 |
| Target 2 Molecular Weight |
76450 |
| Target 2 Theoretical pI |
8.68 |
| Target 2 GO Classification |
|
Function
|
| transporter activity |
|
Process
|
physiological process
cellular physiological process
transport |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 2 General Function |
Carbohydrate transport and metabolism |
| Target 2 Specific Function |
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver |
| Target 2 Pathways |
Not Available
|
| Target 2 Reactions |
Not Available |
| Target 2 Pfam Domain Function |
|
| Target 2 Signals |
|
| Target 2 Transmembrane Regions |
- 97-117
- 207-227
- 259-279
- 336-356
- 376-396
- 410-430
- 575-595
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
5051630  |
| Target 2 UniProtKB/Swiss-Prot ID |
Q9Y6L6  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
SO1B1_HUMAN  |
| Target 2 PDB ID |
Not Available |
| Target 2 Cellular Location |
- Cell membrane
- basolateral cell membrane
- multi-pass membrane protein. Note=Detected in basolateral
|
| Target 2 Gene Sequence |
>2076 bp
ATGGACCAAAATCAACATTTGAATAAAACAGCAGAGGCACAACCTTCAGAGAATAAGAAA
ACAAGATACTGCAATGGATTGAAGATGTTCTTGGCAGCTCTGTCACTCAGCTTTATTGCT
AAGACACTAGGTGCAATTATTATGAAAAGTTCCATCATTCATATAGAACGGAGATTTGAG
ATATCCTCTTCTCTTGTTGGTTTTATTGACGGAAGCTTTGAAATTGGAAATTTGCTTGTG
ATTGTATTTGTGAGTTACTTTGGATCCAAACTACATAGACCAAAGTTAATTGGAATCGGT
TGTTTCATTATGGGAATTGGAGGTGTTTTGACTGCTTTGCCACATTTCTTCATGGGATAT
TACAGGTATTCTAAAGAAACTAATATCAATTCATCAGAAAATTCAACATCGACCTTATCC
ACTTGTTTAATTAATCAAATTTTATCACTCAATAAAGCATCACCTGAGATAGTGGGAAAA
GGTTGTTTAAAGGAATCTGGGTCATACATGTGGATATATGTGTTCATGGGTAATATGCTT
CGTGGAATAGGGGAGACTCCCATAGTACCACTGGGGCTTTCTTACATTGATGATTTCGCT
AAAGAAGGACATTCTTCTTTGTATTTAGGTATATTGAATGCAATAGCAATGATTGGTCCA
ATCATTGGCTTTACCCTGGGATCTCTGTTTTCTAAAATGTACGTGGATATTGGATATGTT
AATCTAAGCACTATCAGGATAACTCCTACTGATTCTCGATGGGTTGGAGCTTGGTGGCTT
AATTTCCTTGTGTCTGGACTATTCTCCATTATTTCTTCCATACCATTCTTTTTCTTGCCC
CAAACTCCAAATAAACCACAAAAAGAAAGAAAAGCTTCACTGTCTTTGCATGTGCTGGAA
ACAAATGATGAAAAGGATCAAACAGCTAATTTGACCAATCAAGGAAAAAATATTACCAAA
AATGTGACTGGTTTTTTCCAGTCTTTTAAAAGCATCCTTACTAATCCCCTGTATGTTATG
TTTGTGCTTTTGACGTTGTTACAAGTAAGCAGCTATATTGGTGCTTTTACTTATGTCTTC
AAATACGTAGAGCAACAGTATGGTCAGCCTTCATCTAAGGCTAACATCTTATTGGGAGTC
ATAACCATACCTATTTTTGCAAGTGGAATGTTTTTAGGAGGATATATCATTAAAAAATTC
AAACTGAACACCGTTGGAATTGCCAAATTCTCATGTTTTACTGCTGTGATGTCATTGTCC
TTTTACCTATTATATTTTTTCATACTCTGTGAAAACAAATCAGTTGCCGGACTAACCATG
ACCTATGATGGAAATAATCCAGTGACATCTCATAGAGATGTACCACTTTCTTATTGCAAC
TCAGACTGCAATTGTGATGAAAGTCAATGGGAACCAGTCTGTGGAAACAATGGAATAACT
TACATCTCACCCTGTCTAGCAGGTTGCAAATCTTCAAGTGGCAATAAAAAGCCTATAGTG
TTTTACAACTGCAGTTGTTTGGAAGTAACTGGTCTCCAGAACAGAAATTACTCAGCCCAT
TTGGGTGAATGCCCAAGAGATGATGCTTGTACAAGGAAATTTTACTTTTTTGTTGCAATA
CAAGTCTTGAATTTATTTTTCTCTGCACTTGGAGGCACCTCACATGTCATGCTGATTGTT
AAAATTGTTCAACCTGAATTGAAATCACTTGCACTGGGTTTCCACTCAATGGTTATACGA
GCACTAGGAGGAATTCTAGCTCCTATATATTTTGGGGCTCTGATTGATACAACGTGTATA
AAGTGGTCCACCAACAACTGTGGCACACGTGGGTCATGTAGGACATATAATTCCACATCA
TTTTCAAGGGTCTACTTGGGCTTGTCTTCAATGTTAAGAGTCTCATCACTTGTTTTATAT
ATTATATTAATTTATGCCATGAAGAAAAAATATCAAGAGAAAGATATCAATGCATCAGAA
AATGGAAGTGTCATGGATGAAGCAAACTTAGAATCCTTAAATAAAAATAAACATTTTGTC
CCTTCTGCTGGGGCAGATAGTGAAACACATTGTTAA
|
| Target 2 GenBank Gene ID |
|
| Target 2 GeneCard ID |
SLCO1B1  |
| Target 2 GenAtlas ID |
SLCO1B1  |
| Target 2 HGNC ID |
HGNC:10959  |
| Target 2 Chromosome Location |
12 |
| Target 2 Locus |
12p |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D, Nomura H, Unno M, Suzuki M, Naitoh T, Matsuno S, Yawo H: Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63. [PubMed
]
- Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. [PubMed
]
- Konig J, Cui Y, Nies AT, Keppler D: A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol. 2000 Jan;278(1):G156-64. [PubMed
]
- Konig J, Cui Y, Nies AT, Keppler D: Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J Biol Chem. 2000 Jul 28;275(30):23161-8. [PubMed
]
- Tirona RG, Leake BF, Merino G, Kim RB: Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem. 2001 Sep 21;276(38):35669-75. Epub 2001 Jul 26. [PubMed
]
- Nozawa T, Nakajima M, Tamai I, Noda K, Nezu J, Sai Y, Tsuji A, Yokoi T: Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. J Pharmacol Exp Ther. 2002 Aug;302(2):804-13. [PubMed
]
- Michalski C, Cui Y, Nies AT, Nuessler AK, Neuhaus P, Zanger UM, Klein K, Eichelbaum M, Keppler D, Konig J: A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. J Biol Chem. 2002 Nov 8;277(45):43058-63. Epub 2002 Aug 23. [PubMed
]
|
| Target 2 Drug References |
- Izar MC: [Hypolipidemic treatment under special conditions: posttransplant and/or immunosuppressive therapy] Arq Bras Cardiol. 2005 Oct;85 Suppl 5:50-7. Epub 2006 Jan 2. [PubMed
]
- Rohrbacher M, Kirchhof A, Skarke C, Geisslinger G, Lotsch J: Rapid identification of three functionally relevant polymorphisms in the OATP1B1 transporter gene using Pyrosequencing. Pharmacogenomics. 2006 Mar;7(2):167-76. [PubMed
]
- Hedman M, Antikainen M, Holmberg C, Neuvonen M, Eichelbaum M, Kivisto KT, Neuvonen PJ, Niemi M: Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes. Br J Clin Pharmacol. 2006 Jun;61(6):706-15. [PubMed
]
- Niemi M, Pasanen MK, Neuvonen PJ: SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006 Oct;80(4):356-66. [PubMed
]
- Kivisto KT, Niemi M: Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans. Pharm Res. 2007 Feb;24(2):239-47. Epub 2006 Dec 20. [PubMed
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
1735 |
| Target 3 Name |
Canalicular multispecific organic anion transporter 1 |
| Target 3 Synonyms |
- ATP-binding cassette sub-family C member 2
- Canalicular multidrug resistance protein
- Multidrug resistance-associated protein 2
|
| Target 3 Gene Name |
ABCC2 |
| Target 3 Protein Sequence |
>Canalicular multispecific organic anion transporter 1
MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGFLWLLAPWQLLHVYKSRTKRSS
TTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYS
RQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILI
FSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVS
KFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSG
TKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIG
YLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGET
VNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAIL
STKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFS
QLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMI
SSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLD
IMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNIL
FGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLD
IYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIV
EKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAAS
ITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETG
KVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQR
DMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRI
VNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMF
YVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSW
ITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTS
EIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGI
TCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTII
PQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIG
QRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMD
SDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF
|
| Target 3 Number of Residues |
1570 |
| Target 3 Molecular Weight |
174194 |
| Target 3 Theoretical pI |
8.46 |
| Target 3 GO Classification |
|
Function
|
transporter activity
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP 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
binding
nucleotide binding |
|
Process
|
physiological process
cellular physiological process
transport |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 3 General Function |
Defense mechanisms and drug export |
| Target 3 Specific Function |
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter |
| Target 3 Pathways |
Not Available
|
| Target 3 Reactions |
Not Available |
| Target 3 Pfam Domain Function |
|
| Target 3 Signals |
|
| Target 3 Transmembrane Regions |
- 28-48
- 69-89
- 94-114
- 127-147
- 166-186
- 314-334
- 361-381
- 438-458
- 462-482
- 545-565
- 588-608
- 972-992
- 1034-1054
- 1098-1118
- 1120-1140
- 1212-1232
- 1235-1255
|
| Target 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
1764162  |
| Target 3 UniProtKB/Swiss-Prot ID |
Q92887  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
MRP2_HUMAN  |
| Target 3 PDB ID |
Not Available |
| Target 3 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 3 Gene Sequence |
>4638 bp
ATGCTGGAGAAGTTCTGCAACTCTACTTTTTGGAATTCCTCATTCCTGGACAGTCCGGAG
GCAGACCTGCCACTTTGTTTTGAGCAAACTGTTCTGGTGTGGATTCCCTTGGGCTTCCTA
TGGCTCCTGGCCCCCTGGCAGCTTCTCCACGTGTATAAATCCAGGACCAAGAGATCCTCT
ACCACCAAACTCTATCTTGCTAAGCAGGTATTCGTTGGTTTTCTTCTTATTCTAGCAGCC
ATAGAGCTGGCCCTTGTACTCACAGAAGACTCTGGACAAGCCACAGTCCCTGCTGTTCGA
TATACCAATCCAAGCCTCTACCTAGGCACATGGCTCCTGGTTTTGCTGATCCAATACAGC
AGACAATGGTGTGTACAGAAAAACTCCTGGTTCCTGTCCCTATTCTGGATTCTCTCGATA
CTCTGTGGCACTTTCCAATTTCAGACTCTGATCCGGACACTCTTACAGGGTGACAATTCT
AATCTAGCCTACTCCTGCCTGTTCTTCATCTCCTACGGATTCCAGATCCTGATCCTGATC
TTTTCAGCATTTTCAGAAAATAATGAGTCATCAAATAATCCATCATCCATAGCTTCATTC
CTGAGTAGCATTACCTACAGCTGGTATGACAGCATCATTCTGAAAGGCTACAAGCGTCCT
CTGACACTCGAGGATGTCTGGGAAGTTGATGAAGAGATGAAAACCAAGACATTAGTGAGC
AAGTTTGAAACGCACATGAAGAGAGAGCTGCAGAAAGCCAGGCGGGCACTCCAGAGACGG
CAGGAGAAGAGCTCCCAGCAGAACTCTGGAGCCAGGCTGCCTGGCTTGAACAAGAATCAG
AGTCAAAGCCAAGATGCCCTTGTCCTGGAAGATGTTGAAAAGAAAAAAAAGAAGTCTGGG
ACCAAAAAAGATGTTCCAAAATCCTGGTTGATGAAGGCTCTGTTCAAAACTTTCTACATG
GTGCTCCTGAAATCATTCCTACTGAAGCTAGTGAATGACATCTTCACGTTTGTGAGTCCT
CAGCTGCTGAAATTGCTGATCTCCTTTGCAAGTGACCGTGACACATATTTGTGGATTGGA
TATCTCTGTGCAATCCTCTTATTCACTGCGGCTCTCATTCAGTCTTTCTGCCTTCAGTGT
TATTTCCAACTGTGCTTCAAGCTGGGTGTAAAAGTACGGACAGCTATCATGGCTTCTGTA
TATAAGAAGGCATTGACCCTATCCAACTTGGCCAGGAAGGAGTACACCGTTGGAGAAACA
GTGAACCTGATGTCTGTGGATGCCCAGAAGCTCATGGATGTGACCAACTTCATGCACATG
CTGTGGTCAAGTGTTCTACAGATTGTCTTATCTATCTTCTTCCTATGGAGAGAGTTGGGA
CCCTCAGTCTTAGCAGGTGTTGGGGTGATGGTGCTTGTAATCCCAATTAATGCGATACTG
TCCACCAAGAGTAAGACCATTCAGGTCAAAAATATGAAGAATAAAGACAAACGTTTAAAG
ATCATGAATGAGATTCTTAGTGGAATCAAGATCCTGAAATATTTTGCCTGGGAACCTTCA
TTCAGAGACCAAGTACAAAACCTCCGGAAGAAAGAGCTCAAGAACCTGCTGGCCTTTAGT
CAACTACAGTGTGTAGTAATATTCGTCTTCCAGTTAACTCCAGTCCTGGTATCTGTGGTC
ACATTTTCTGTTTATGTCCTGGTGGATAGCAACAATATTTTGGATGCACAAAAGGCCTTC
ACCTCCATTACCCTCTTCAATATCCTGCGCTTTCCCCTGAGCATGCTTCCCATGATGATC
TCCTCCATGCTCCAGGCCAGTGTTTCCACAGAGCGGCTAGAGAAGTACTTGGGAGGGGAT
GACTTGGACACATCTGCCATTCGACATGACTGCAATTTTGACAAAGCCATGCAGTTTTCT
GAGGCCTCCTTTACCTGGGAACATGATTCGGAAGCCACAGTCCGAGATGTGAACCTGGAC
ATTATGGCAGGCCAACTTGTGGCTGTGATAGGCCCTGTCGGCTCTGGGAAATCCTCCTTG
ATATCAGCCATGCTGGGAGAAATGGAAAATGTCCACGGGCACATCACCATCAAGGGCACC
ACTGCCTATGTCCCACAGCAGTCCTGGATTCAGAATGGCACCATAAAGGACAACATCCTT
TTTGGAACAGAGTTTAATGAAAAGAGGTACCAGCAAGTACTGGAGGCCTGTGCTCTCCTC
CCAGACTTGGAAATGCTGCCTGGAGGAGATTTGGCTGAGATTGGAGAGAAGGGTATAAAT
CTTAGTGGGGGTCAGAAGCAGCGGATCAGCCTGGCCAGAGCTACCTACCAAAATTTAGAC
ATCTATCTTCTAGATGACCCCCTGTCTGCAGTGGATGCTCATGTAGGAAAACATATTTTT
AATAAGGTCTTGGGCCCCAATGGCCTGTTGAAAGGCAAGACTCGACTCTTGGTTACACAT
AGCATGCACTTTCTTCCTCAAGTGGATGAGATTGTAGTTCTGGGGAATGGAACAATTGTA
GAGAAAGGATCCTACAGTGCTCTCCTGGCCAAAAAAGGAGAGTTTGCTAAGAATCTGAAG
ACATTTCTAAGACATACAGGCCCTGAAGAGGAAGCCACAGTCCATGATGGCAGTGAAGAA
GAAGACGATGACTATGGGCTGATATCCAGTGTGGAAGAGATCCCCGAAGATGCAGCCTCC
ATAACCATGAGAAGAGAGAACAGCTTTCGTCGAACACTTAGCCGCAGTTCTAGGTCCAAT
GGCAGGCATCTGAAGTCCCTGAGAAACTCCTTGAAAACTCGGAATGTGAATAGCCTGAAG
GAAGACGAAGAACTAGTGAAAGGACAAAAACTAATTAAGAAGGAATTCATAGAAACTGGA
AAGGTGAAGTTCTCCATCTACCTGGAGTACCTACAAGCAATAGGATTGTTTTCGATATTC
TTCATCATCCTTGCGTTTGTGATGAATTCTGTGGCTTTTATTGGATCCAACCTCTGGCTC
AGTGCTTGGACCAGTGACTCTAAAATCTTCAATAGCACCGACTATCCAGCATCTCAGAGG
GACATGAGAGTTGGAGTCTACGGAGCTCTGGGATTAGCCCAAGGTATATTTGTGTTCATA
GCACATTTCTGGAGTGCCTTTGGTTTCGTCCATGCATCAAATATCTTGCACAAGCAACTG
CTGAACAATATCCTTCGAGCACCTATGAGATTTTTTGACACAACACCCACAGGCCGGATT
GTGAACAGGTTTGCCGGCGATATTTCCACAGTGGATGACACCCTGCCTCAGTCCTTGCGC
AGCTGGATTACATGCTTCCTGGGGATAATCAGCACCCTTGTCATGATCTGCATGGCCACT
CCTGTCTTCACCATCATCGTCATTCCTCTTGGCATTATTTATGTATCTGTTCAGATGTTT
TATGTGTCTACCTCCCGCCAGCTGAGGCGTCTGGACTCTGTCACCAGGTCCCCAATCTAC
TCTCACTTCAGCGAGACCGTATCAGGTTTGCCAGTTATCCGTGCCTTTGAGCACCAGCAG
CGATTTCTGAAACACAATGAGGTGAGGATTGACACCAACCAGAAATGTGTCTTTTCCTGG
ATCACCTCCAACAGGTGGCTTGCAATTCGCCTGGAGCTGGTTGGGAACCTGACTGTCTTC
TTTTCAGCCTTGATGATGGTTATTTATAGAGATACCCTAAGTGGGGACACTGTTGGCTTT
GTTCTGTCCAATGCACTCAATATCACACAAACCCTGAACTGGCTGGTGAGGATGACATCA
GAAATAGAGACCAACATTGTGGCTGTTGAGCGAATAACTGAGTACACAAAAGTGGAAAAT
GAGGCACCCTGGGTGACTGATAAGAGGCCTCCGCCAGATTGGCCCAGCAAAGGCAAGATC
CAGTTTAACAACTACCAAGTGCGGTACCGACCTGAGCTGGATCTGGTCCTCAGAGGGATC
ACTTGTGACATCGGTAGCATGGAGAAGATTGGTGTGGTGGGCAGGACAGGAGCTGGAAAG
TCATCCCTCACAAACTGCCTCTTCAGAATCTTAGAGGCTGCCGGTGGTCAGATTATCATT
GATGGAGTAGATATTGCTTCCATTGGGCTCCACGACCTCCGAGAGAAGCTGACCATCATC
CCCCAGGACCCCATCCTGTTCTCTGGAAGCCTGAGGATGAATCTCGACCCTTTCAACAAC
TACTCAGATGAGGAGATTTGGAAGGCCTTGGAGCTGGCTCACCTCAAGTCTTTTGTGGCC
AGCCTGCAACTTGGGTTATCCCACGAAGTGACAGAGGCTGGTGGCAACCTGAGCATAGGC
CAGAGGCAGCTGCTGTGCCTGGGCAGGGCTCTGCTTCGGAAATCCAAGATCCTGGTCCTG
GATGAGGCCACTGCTGCGGTGGATCTAGAGACAGACAACCTCATTCAGACGACCATCCAA
AACGAGTTCGCCCACTGCACAGTGATCACCATCGCCCACAGGCTGCACACCATCATGGAC
AGTGACAAGGTAATGGTCCTAGACAACGGGAAGATTATAGAGTGCGGCAGCCCTGAAGAA
CTGCTACAAATCCCTGGACCCTTTTACTTTATGGCTAAGGAAGCTGGCATTGAGAATGTG
AACAGCACAAAATTCTAG
|
| Target 3 GenBank Gene ID |
|
| Target 3 GeneCard ID |
ABCC2  |
| Target 3 GenAtlas ID |
ABCC2  |
| Target 3 HGNC ID |
HGNC:53  |
| Target 3 Chromosome Location |
10 |
| Target 3 Locus |
10q24 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- Toh S, Wada M, Uchiumi T, Inokuchi A, Makino Y, Horie Y, Adachi Y, Sakisaka S, Kuwano M: Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am J Hum Genet. 1999 Mar;64(3):739-46. [PubMed
]
- Tsujii H, Konig J, Rost D, Stockel B, Leuschner U, Keppler D: Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Gastroenterology. 1999 Sep;117(3):653-60. [PubMed
]
- Keppler D, Konig J: Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis. 2000;20(3):265-72. [PubMed
]
- Keitel V, Kartenbeck J, Nies AT, Spring H, Brom M, Keppler D: Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome. Hepatology. 2000 Dec;32(6):1317-28. [PubMed
]
- Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K: Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics. 2001 Mar;11(2):175-84. [PubMed
]
- Mor-Cohen R, Zivelin A, Rosenberg N, Shani M, Muallem S, Seligsohn U: Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome. J Biol Chem. 2001 Oct 5;276(40):36923-30. Epub 2001 Jul 26. [PubMed
]
- Ito K, Oleschuk CJ, Westlake C, Vasa MZ, Deeley RG, Cole SP: Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity. J Biol Chem. 2001 Oct 12;276(41):38108-14. Epub 2001 Aug 10. [PubMed
]
- Buchler M, Konig J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D: cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem. 1996 Jun 21;271(25):15091-8. [PubMed
]
- Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M: A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996 Sep 15;56(18):4124-9. [PubMed
]
- Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K, Yoshida I, Kimura A, Sakisaka S, Adachi Y, Kuwano M: Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. Hum Mol Genet. 1998 Feb;7(2):203-7. [PubMed
]
|
| Target 3 Drug References |
- Niemi M, Arnold KA, Backman JT, Pasanen MK, Godtel-Armbrust U, Wojnowski L, Zanger UM, Neuvonen PJ, Eichelbaum M, Kivisto KT, Lang T: Association of genetic polymorphism in ABCC2 with hepatic multidrug resistance-associated protein 2 expression and pravastatin pharmacokinetics. Pharmacogenet Genomics. 2006 Nov;16(11):801-8. [PubMed
]
- Kivisto KT, Niemi M: Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans. Pharm Res. 2007 Feb;24(2):239-47. Epub 2006 Dec 20. [PubMed
]
- Nakagomi-Hagihara R, Nakai D, Tokui T, Abe T, Ikeda T: Gemfibrozil and its glucuronide inhibit the hepatic uptake of pravastatin mediated by OATP1B1. Xenobiotica. 2007 May;37(5):474-86. [PubMed
]
|
|
Drug Target 4
[top]
|
| Target 4 ID |
1882 |
| Target 4 Name |
Ras-related C3 botulinum toxin substrate 1 |
| Target 4 Synonyms |
- Cell migration-inducing gene 5 protein
- Ras- like protein TC25
- Ras-related C3 botulinum toxin substrate 1 precursor
- p21-Rac1
|
| Target 4 Gene Name |
RAC1 |
| Target 4 Protein Sequence |
>Ras-related C3 botulinum toxin substrate 1 precursor
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAG
QEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR
DDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPP
PVKKRKRKCLLL
|
| Target 4 Number of Residues |
195 |
| Target 4 Molecular Weight |
21450 |
| Target 4 Theoretical pI |
8.65 |
| Target 4 GO Classification |
|
Function
|
binding
nucleotide binding
purine nucleotide binding
guanyl nucleotide binding
GTP binding |
|
Process
|
cellular process
cell communication
signal transduction
intracellular signaling cascade
small GTPase mediated signal transduction |
|
Component
|
| Not Available |
|
| Target 4 General Function |
Involved in GTP binding |
| Target 4 Specific Function |
Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP- dependent manner, suggesting that the insertion does not completely abolish effector interaction |
| Target 4 Pathways |
Not Available
|
| Target 4 Reactions |
Not Available |
| Target 4 Pfam Domain Function |
|
| Target 4 Signals |
|
| Target 4 Transmembrane Regions |
|
| Target 4 Essentiality |
Non-Essential |
| Target 4 GenBank ID Protein |
190824  |
| Target 4 UniProtKB/Swiss-Prot ID |
P63000  |
| Target 4 UniProtKB/Swiss-Prot Entry Name |
RAC1_HUMAN  |
| Target 4 PDB ID |
1I4L  |
| Target 4 PDB File |
Show |
| Target 4 3D Structure |
|
| Target 4 Cellular Location |
- Cell membrane
- cytoplasmic side. Melanosome. Note=Inner surface of plasma membrane pos
- lipid-anchor
|
| Target 4 Gene Sequence |
>579 bp
ATGCAGGCCATCAAGTGTGTGGTGGTGGGAGACGGAGCTGTAGGTAAAACTTGCCTACTG
ATCAGTTACACAACCAATGCATTTCCTGGAGAATATATCCCTACTGTCTTTGACAATTAT
TCTGCCAATGTTATGGTAGATGGAAAACCGGTGAATCTGGGCTTATGGGATACAGCTGGA
CAAGAAGATTATGACAGATTACGCCCCCTATCCTATCCGCAAACAGATGTGTTCTTAATT
TGCTTTTCCCTTGTGAGTCCTGCATCATTTGAAAATGTCCGTGCAAAGTGGTATCCTGAG
GTGCGGCACCACTGTCCCAACACTCCCATCATCCTAGTGGGAACTAAACTTGATCTTAGG
GATGATAAAGACACGATCGAGAAACTGAAGGAGAAGAAGCTGACTCCCATCACCTATCCG
CAGGGTCTAGCCATGGCTAAGGAGATTGGTGCTGTAAAATACCTGGAGTGCTCGGCGCTC
ACACAGCGAGGCCTCAAGACAGTGTTTGACGAAGCGATCCGAGCAGTCCTCTGCCCGCCT
CCCGTGAAGAAGAGGAAGAGAAAATGCCTGCTGTTGTAA
|
| Target 4 GenBank Gene ID |
|
| Target 4 GeneCard ID |
RAC1  |
| Target 4 GenAtlas ID |
RAC1  |
| Target 4 HGNC ID |
HGNC:9801  |
| Target 4 Chromosome Location |
7 |
| Target 4 Locus |
7p22 |
| Target 4 SNPs |
SNPJam Report  |
| Target 4 General References |
- Nishihara H, Kobayashi S, Hashimoto Y, Ohba F, Mochizuki N, Kurata T, Nagashima K, Matsuda M: Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim Biophys Acta. 1999 Nov 11;1452(2):179-87. [PubMed
]
- Jordan P, Brazao R, Boavida MG, Gespach C, Chastre E: Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene. 1999 Nov 18;18(48):6835-9. [PubMed
]
- Johansson A, Driessens M, Aspenstrom P: The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J Cell Sci. 2000 Sep;113 ( Pt 18):3267-75. [PubMed
]
- Vikis HG, Li W, He Z, Guan KL: The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12457-62. [PubMed
]
- Matos P, Skaug J, Marques B, Beck S, Verissimo F, Gespach C, Boavida MG, Scherer SW, Jordan P: Small GTPase Rac1: structure, localization, and expression of the human gene. Biochem Biophys Res Commun. 2000 Nov 2;277(3):741-51. [PubMed
]
- Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K: Structure of the TPR domain of p67phox in complex with Rac.GTP. Mol Cell. 2000 Oct;6(4):899-907. [PubMed
]
- Worthylake DK, Rossman KL, Sondek J: Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature. 2000 Dec 7;408(6813):682-8. [PubMed
]
- Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A: How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol. 2001 Jan;8(1):23-6. [PubMed
]
- Stebbins CE, Galan JE: Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell. 2000 Dec;6(6):1449-60. [PubMed
]
- Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H: Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. Genes Cells. 2001 Feb;6(2):107-19. [PubMed
]
- 11346801 Tarricone C, Xiao B, Justin N, Walker PA, Rittinger K, Gamblin SJ, Smerdon SJ: The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways. Nature. 2001 May 10;411(6834):215-9.
- 11513578 Grizot S, Faure J, Fieschi F, Vignais PV, Dagher MC, Pebay-Peyroula E: Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation. Biochemistry. 2001 Aug 28;40(34):10007-13.
- 11955434 Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, Stephens LR: P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell. 2002 Mar 22;108(6):809-21.
- 12134158 Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS: Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol. 2002 Aug;4(8):574-82.
- 12853948 Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64.
- 1903399 Kinsella BT, Erdman RA, Maltese WA: Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA. J Biol Chem. 1991 May 25;266(15):9786-94.
- 2108320 Drivas GT, Shih A, Coutavas E, Rush MG, D'Eustachio P: Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990 Apr;10(4):1793-8.
- 2674130 Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R: rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem. 1989 Oct 5;264(28):16378-82.
- 7673236 Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G, Camonis JH: Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7.
- 9033596 Hirshberg M, Stockley RW, Dodson G, Webb MR: The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat Struct Biol. 1997 Feb;4(2):147-52.
|
| Target 4 Drug References |
- Liang SL, Liu H, Zhou A: Lovastatin-induced apoptosis in macrophages through the Rac1/Cdc42/JNK pathway. J Immunol. 2006 Jul 1;177(1):651-6. [PubMed
]
- Ceolotto G, Papparella I, Lenzini L, Sartori M, Mazzoni M, Iori E, Franco L, Gallo A, de Kreutzenberg SV, Tiengo A, Pessina AC, Avogaro A, Semplicini A: Insulin generates free radicals in human fibroblasts ex vivo by a protein kinase C-dependent mechanism, which is inhibited by pravastatin. Free Radic Biol Med. 2006 Aug 1;41(3):473-83. Epub 2006 Apr 30. [PubMed
]
- Lin SJ, Chen YH, Lin FY, Hsieh LY, Wang SH, Lin CY, Wang YC, Ku HH, Chen JW, Chen YL: Pravastatin induces thrombomodulin expression in TNFalpha-treated human aortic endothelial cells by inhibiting Rac1 and Cdc42 translocation and activity. J Cell Biochem. 2007 Jun 1;101(3):642-53. [PubMed
]
|
|
Drug Target 5
[top]
|
| Target 5 ID |
1994 |
| Target 5 Name |
Geranylgeranyl transferase type-1 subunit beta |
| Target 5 Synonyms |
- EC 2.5.1.59
- GGTase-I-beta
- Geranylgeranyl transferase type I subunit beta
- Type I protein geranyl-geranyltransferase subunit beta
|
| Target 5 Gene Name |
PGGT1B |
| Target 5 Protein Sequence |
>Geranylgeranyl transferase type-1 subunit beta
MVATEDERLAGSGEGERLDFLRDRHVRFFQRCLQVLPERYSSLETSRLTIAFFALSGLDM
LDSLDVVNKDDIIEWIYSLQVLPTEDRSNLNRCGFRGSSYLGIPFNPSKAPGTAHPYDSG
HIAMTYTGLSCLVILGDDLSRVNKEACLAGLRALQLEDGSFCAVPEGSENDMRFVYCASC
ICYMLNNWSGMDMKKAITYIRRSMSYDNGLAQGAGLESHGGSTFCGIASLCLMGKLEEVF
SEKELNRIKRWCIMRQQNGYHGRPNKPVDTCYSFWVGATLKLLKIFQYTNFEKNRNYILS
TQDRLVGGFAKWPDSHPDALHAYFGICGLSLMEESGICKVHPALNVSTRTSERLLDLHQS
WKTKDSKQCSENVHIST
|
| Target 5 Number of Residues |
383 |
| Target 5 Molecular Weight |
42397 |
| Target 5 Theoretical pI |
6.82 |
| Target 5 GO Classification |
|
Function
|
| catalytic activity |
|
Process
|
| Not Available |
|
Component
|
| Not Available |
|
| Target 5 General Function |
Involved in geranyl-geranyl transferase activity |
| Target 5 Specific Function |
Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Acts on the Rac1, Rac2, Rap1A and Rap1B proteins. The beta subunit is responsible for peptide-binding |
| Target 5 Pathways |
Not Available
|
| Target 5 Reactions |
- geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate
|
| Target 5 Pfam Domain Function |
|
| Target 5 Signals |
|
| Target 5 Transmembrane Regions |
|
| Target 5 Essentiality |
Non-Essential |
| Target 5 GenBank ID Protein |
466491  |
| Target 5 UniProtKB/Swiss-Prot ID |
P53609  |
| Target 5 UniProtKB/Swiss-Prot Entry Name |
PGT1_HUMAN  |
| Target 5 PDB ID |
1S64  |
| Target 5 PDB File |
Show |
| Target 5 3D Structure |
|
| Target 5 Cellular Location |
Not Available |
| Target 5 Gene Sequence |
>1134 bp
ATGGTGGCCACTGAGGATGAGAGGCTAGCAGGGAGCGGTGAGGGAGAGCGGCTGGATTTC
TTACGGGATCGGCACGTGCGATTTTTCCAGCGCTGCCTCCAGGTTTTGCCGGAGCGCTAT
TCTTCACTCGAGACAAGCAGGTTGACAATTGCATTTTTTGCACTCTCCGGGCTGGATATG
TTGGATTCCTTAGATGTGGTGAACAAAGATGATATAATAGAGTGGATTTATTCCCTGCAG
GTCCTTCCCACAGAAGACAGATCAAATCTAAATCGCTGTGGTTTCCGAGGCTCTTCATAC
CTGGGTATTCCGTTCAATCCATCAAAGGCTCCTGGAACAGCTCATCCTTATGATAGTGGC
CACATTGCAATGACCTACACTGGCCTCTCATGCTTAGTTATTCTTGGAGACGACTTAAGC
CGAGTAAATAAAGAAGCTTGCTTAGCGGGCTTGAGAGCCCTTCAGCTGGAAGATGGGAGT
TTTTGTGCAGTACCTGAAGGCAGTGAAAATGACATGCGATTTGTGTACTGTGCTTCCTGT
ATTTGCTATATGCTCAACAACTGGTCAGGCATGGATATGAAAAAAGCCATCACCTATATT
AGAAGGAGTATGTCCTATGACAATGGACTGGCACAGGGAGCTGGACTTGAATCTCATGGA
GGATCAACTTTTTGTGGCATTGCCTCACTATGTCTGATGGGTAAACTAGAAGAAGTTTTT
TCAGAAAAAGAATTGAACAGGATAAAGAGGTGGTGTATAATGAGGCAACAAAATGGTTAT
CATGGAAGACCTAATAAGCCTGTAGACACCTGTTATTCTTTTTGGGTGGGAGCAACTCTG
AAGCTTCTAAAAATTTTCCAATACACTAACTTTGAGAAAAATAGAAATTACATCTTATCA
ACTCAAGATCGCCTTGTAGGGGGATTTGCCAAGTGGCCAGACAGTCATCCAGATGCTTTG
CATGCATACTTTGGGATCTGTGGCCTGTCACTAATGGAGGAAAGTGGAATTTGTAAAGTT
CATCCTGCTCTGAATGTAAGCACACGGACTTCTGAACGCCTTCTAGATCTCCATCAAAGC
TGGAAAACCAAGGACTCTAAACAATGCTCAGAGAATGTACATATCTCCACATGA
|
| Target 5 GenBank Gene ID |
|
| Target 5 GeneCard ID |
PGGT1B  |
| Target 5 GenAtlas ID |
PGGT1B  |
| Target 5 HGNC ID |
HGNC:8895  |
| Target 5 Chromosome Location |
5 |
| Target 5 Locus |
5q22.3 |
| Target 5 SNPs |
SNPJam Report  |
| Target 5 General References |
- Zhang FL, Diehl RE, Kohl NE, Gibbs JB, Giros B, Casey PJ, Omer CA: cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I. J Biol Chem. 1994 Feb 4;269(5):3175-80. [PubMed
]
|
| Target 5 Drug References |
- Efuet ET, Keyomarsi K: Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting the proteasome. Cancer Res. 2006 Jan 15;66(2):1040-51. [PubMed
]
- Dunford JE, Rogers MJ, Ebetino FH, Phipps RJ, Coxon FP: Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. J Bone Miner Res. 2006 May;21(5):684-94. [PubMed
]
- Khwaja A, Sharpe CC, Noor M, Hendry BM: The role of geranylgeranylated proteins in human mesangial cell proliferation. Kidney Int. 2006 Oct;70(7):1296-304. Epub 2006 Aug 23. [PubMed
]
|
|
Drug Target 6
[top]
|
| Target 6 ID |
4093 |
| Target 6 Name |
HERV-K_1p13.3 provirus ancestral Env polyprotein |
| Target 6 Synonyms |
- Envelope polyprotein
|
| Target 6 Gene Name |
Not Available |
| Target 6 Protein Sequence |
>HERV-K_1p13.3 provirus ancestral Env polyprotein
MPGAIDDHCPAQPGEEGTAFNVTMGYKYPPLCLGHATRCIHLETQVWAAYLLERLATGKW
GHLVSGLSLCPLRQMKRGVIGDTPYFQYKPVGKLCPKNFEGPSKTLIWGDCVNSHAVVLK
NDSYALVIDWAPKGYLKNTCSSGGGEFLEATYFISYWEDEDHHPTLHRWFGSFFTLKWED
KDITLHPQGLV
|
| Target 6 Number of Residues |
194 |
| Target 6 Molecular Weight |
21462 |
| Target 6 Theoretical pI |
6.78 |
| Target 6 GO Classification |
Not Available |
| Target 6 General Function |
Not Available |
| Target 6 Specific Function |
Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution |
| Target 6 Pathways |
Not Available
|
| Target 6 Reactions |
Not Available |
| Target 6 Pfam Domain Function |
Not Available |
| Target 6 Signals |
|
| Target 6 Transmembrane Regions |
|
| Target 6 Essentiality |
Non Essential |
| Target 6 GenBank ID Protein |
34533179  |
| Target 6 UniProtKB/Swiss-Prot ID |
P61568  |
| Target 6 UniProtKB/Swiss-Prot Entry Name |
ENK13_HUMAN  |
| Target 6 PDB ID |
Not Available |
| Target 6 Cellular Location |
Not Available |
| Target 6 Gene Sequence |
>576 bp
ATGCCTGGAGCTATAGATGACCATTGCCCTGCTCAACCAGGAGAAGAAGGCACTGCATTT
AATGTTACTATGGGTTATAGATACCCTCCTCTGTGCCTCAGGCATGCAACTCGTTGTATC
CATCTAGAAACTCAAGTCTGGGCTGCTTATCTTCTGGAGAGATTAGCTACAGGAAAATGG
GGACATTTGGTCTCCGGCCTCTCCCTTTGTCCTTTAAGACAAATGAAAAGGGGAGTAATA
GGAGATACCCCATACTTTCAATATAAACCTGTAGGAAAACTATGTCCTAAAAATTTTGAG
GGCCCATCTAAAACTTTAATTTGGGGAGATTGTGTTAACTCACATGCAGTAGTATTAAAA
AATGACTCATATGCTTTAGTAATAGACTGGGCACCAAAGGGCTATTTAAAAAACACTTGC
TCCTCTGGGGGAGGGGAATTCCTGGAGGCTACTTATTTTATTTCTTATTGGGAGGACGAG
GATCATCATCCTACTTTGCATAGGTGGTTCGGCTCATTCTTTACCTTAAAATGGGAAGAT
AAGGACATTACCCTCCACCCCCAAGGCCTTGTATGA
|
| Target 6 GenBank Gene ID |
|
| Target 6 GeneCard ID |
Not Available |
| Target 6 GenAtlas ID |
Not Available |
| Target 6 HGNC ID |
Not Available |
| Target 6 Chromosome Location |
Not Available |
| Target 6 Locus |
Not Available |
| Target 6 SNPs |
Not Available |
| Target 6 General References |
Not Available |
| Target 6 Drug References |
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|