RegulonDB

Gene
Name:	alkB
Synonym(s):	ECK2204, EG10037, aidD, b2212
Genome position(nucleotides):	2308691 <-- 2309341
Strand:	reverse
Sequence:	Get nucleotide sequence FastaFormat
GC content %:	52.69
External database links:

ASAP:	ABE-0007308
CGSC:	18544
ECHOBASE:	EB0036
ECOLIHUB:	alkB
OU-MICROARRAY:	b2212
STRING:	511145.b2212
COLOMBOS:	alkB

Gene

Name:

alkB

Synonym(s):

ECK2204, EG10037, aidD, b2212

Genome position(nucleotides):

2308691 <-- 2309341

Strand:

reverse

Sequence:

Get nucleotide sequence FastaFormat

GC content %:

52.69

External database links:

ASAP:

CGSC:

ECHOBASE:

ECOLIHUB:

OU-MICROARRAY:

STRING:

COLOMBOS:

Product

Name:

DNA oxidative demethylase

Synonym(s):

alpha;-ketoglutarate-dependent dioxygenase, AidD, AlkB, alkyladenine-DNA dioxygenase

Sequence:

Get amino acid sequence Fasta Format

Cellular location:

cytosol

Molecular weight:

24.076

Isoelectric point:

7.995

Motif(s):

Type	Positions	Sequence	Comment
	20 -> 210	VILRRFAFNAAEQLIRDINDVASQSPFRQMVTPGGYTMSVAMTNCGHLGWTTHRQGYLYSPIDPQTNKPWPAMPQSFHNLCQRAATAAGYPDFQPDACLINRYAPGAKLSLHQDKDEPDLRAPIVSVSLGLPAIFQFGGLKRNDPLKRLLLEHGDVVVWGGESRLFYHGIQPLKAGFHPLTIDCRYNLTFR
	51 -> 51	T	UniProt: Slighly reduced activity towards single-stranded DNA containing 1-methyladenine. Reduces affinity for undamaged DNA..
	69 -> 69	W	UniProt: Abolishes activity towards single-stranded DNA containing 1-methyladenine..
	76 -> 78	YLY	UniProt: Substrate binding; Sequence Annotation Type: region of interest.
	113 -> 213	QPDACLINRYAPGAKLSLHQDKDEPDLRAPIVSVSLGLPAIFQFGGLKRNDPLKRLLLEHGDVVVWGGESRLFYHGIQPLKAGFHPLTIDCRYNLTFRQAG	UniProt: Fe2OG dioxygenase.

Classification:

Multifun Terms (GenProtEC)
Multifun Terms (GenProtEC)		2 - information transfer --> 2.1 - DNA related --> 2.1.4 - DNA repair
Gene Ontology Terms (GO)
	cellular_component	GO:0005737 - cytoplasm GO:0005829 - cytosol
	molecular_function	GO:0035516 - oxidative DNA demethylase activity GO:0005515 - protein binding GO:0046872 - metal ion binding GO:0016491 - oxidoreductase activity GO:0008198 - ferrous iron binding GO:0051213 - dioxygenase activity GO:0035515 - oxidative RNA demethylase activity GO:0043734 - DNA-N1-methyladenine dioxygenase activity
	biological_process	GO:0072702 - response to methyl methanesulfonate GO:0006281 - DNA repair GO:0006974 - cellular response to DNA damage stimulus GO:0042245 - RNA repair GO:0006307 - DNA dealkylation involved in DNA repair GO:0070989 - oxidative demethylation GO:0035513 - oxidative RNA demethylation GO:0035552 - oxidative single-stranded DNA demethylation GO:0035553 - oxidative single-stranded RNA demethylation GO:0080111 - DNA demethylation

Note(s):

Note(s): ...[more].

Reference(s):

[1] Aravind L., et al., 2001
[2] Baldwin MR., et al., 2020
[3] Berger MB., et al., 2021
[4] Bian K., et al., 2019
[5] Bleijlevens B., et al., 2012
[6] Chang SC., et al., 2015
[7] Chen BJ., et al., 1994
[8] Chen F., et al., 2017
[9] Cozen AE., et al., 2015
[10] Dai Q., et al., 2017
[11] Dylewska M., et al., 2017
[12] Ergel B., et al., 2014
[13] Henshaw TF., et al., 2004
[14] Hrabeta-Robinson E., et al., 2017
[15] Kanazhevskaya LY., et al., 2019
[16] Kondo H., et al., 1986
[17] Lenz SAP., et al., 2020
[18] Li D., et al., 2010
[19] Li D., et al., 2013
[20] Li Q., et al., 2016
[21] Li X., et al., 2016
[22] Liu H., et al., 2009
[23] Mielecki D., et al., 2016
[24] Mishina Y., et al., 2003
[25] Mishina Y., et al., 2004
[26] Mohan M., et al., 2018
[27] Nieminuszczy J., et al., 2006
[28] Nigam R., et al., 2018
[29] Nigam R., et al., 2018
[30] Quesne MG., et al., 2014
[31] Rebeck GW., et al., 1988
[32] Sedgwick B., et al., 2006
[33] Shivarattan T., et al., 2005
[34] Shrivastav N., et al., 2014
[35] Sikora A., et al., 2015
[36] Sikora A., et al., 2010
[37] Sundheim O., et al., 2008
[38] Waheed SO., et al., 2020
[39] Wang G., et al., 1995
[40] Wang Y., et al., 2021
[41] Watanabe K., et al., 1990
[42] Welford RW., et al., 2005
[43] Wrzesinski M., et al., 2010
[44] van den Born E., et al., 2009

External database links:

ALPHAFOLD:

DIP:

ECOCYC:

ECOLIWIKI:

INTERPRO:

INTERPRO:

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INTERPRO:

PANTHER:

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PROSITE:

REFSEQ:

SMR:

SWISSMODEL:

UNIPROT:

Transcriptional Regulation
	Display Regulation
Activated by:	Ada
Repressed by:	Ada

Transcriptional Regulation

Display Regulation

Activated by:

Ada

Repressed by:

Ada

Reference(s)
[1] Aravind L., Koonin EV., 2001, The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases., Genome Biol 2(3):RESEARCH0007
[2] Baldwin MR., Admiraal SJ., O'Brien PJ., 2020, Transient kinetic analysis of oxidative dealkylation by the direct reversal DNA repair enzyme AlkB., J Biol Chem 295(21):7317-7326
[3] Berger MB., Walker AR., Vazquez-Montelongo EA., Cisneros GA., 2021, Computational investigations of selected enzymes from two iron and α-ketoglutarate-dependent families., Phys Chem Chem Phys 23(39):22227-22240
[4] Bian K., Lenz SAP., Tang Q., Chen F., Qi R., Jost M., Drennan CL., Essigmann JM., Wetmore SD., Li D., 2019, DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro., Nucleic Acids Res 47(11):5522-5529
[5] Bleijlevens B., Shivarattan T., van den Boom KS., de Haan A., van der Zwan G., Simpson PJ., Matthews SJ., 2012, Changes in protein dynamics of the DNA repair dioxygenase AlkB upon binding of Fe(2+) and 2-oxoglutarate., Biochemistry 51(16):3334-41
[6] Chang SC., Fedeles BI., Wu J., Delaney JC., Li D., Zhao L., Christov PP., Yau E., Singh V., Jost M., Drennan CL., Marnett LJ., Rizzo CJ., Levine SS., Guengerich FP., Essigmann JM., 2015, Next-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo., Nucleic Acids Res 43(11):5489-500
[7] Chen BJ., Carroll P., Samson L., 1994, The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity., J Bacteriol 176(20):6255-61
[8] Chen F., Bian K., Tang Q., Fedeles BI., Singh V., Humulock ZT., Essigmann JM., Li D., 2017, Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions., Chem Res Toxicol 30(4):1102-1110
[9] Cozen AE., Quartley E., Holmes AD., Hrabeta-Robinson E., Phizicky EM., Lowe TM., 2015, ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments., Nat Methods 12(9):879-84
[10] Dai Q., Zheng G., Schwartz MH., Clark WC., Pan T., 2017, Selective Enzymatic Demethylation of N(2) ,N(2) -Dimethylguanosine in RNA and Its Application in High-Throughput tRNA Sequencing., Angew Chem Int Ed Engl 56(18):5017-5020
[11] Dylewska M., Kusmierek JT., Pilzys T., Poznanski J., Maciejewska AM., 2017, 1,N(6)-α-hydroxypropanoadenine, the acrolein adduct to adenine, is a substrate for AlkB dioxygenase., Biochem J 474(11):1837-1852
[12] Ergel B., Gill ML., Brown L., Yu B., Palmer AG., Hunt JF., 2014, Protein dynamics control the progression and efficiency of the catalytic reaction cycle of the Escherichia coli DNA-repair enzyme AlkB., J Biol Chem 289(43):29584-601
[13] Henshaw TF., Feig M., Hausinger RP., 2004, Aberrant activity of the DNA repair enzyme AlkB., J Inorg Biochem 98(5):856-61
[14] Hrabeta-Robinson E., Marcus E., Cozen AE., Phizicky EM., Lowe TM., 2017, High-Throughput Small RNA Sequencing Enhanced by AlkB-Facilitated RNA de-Methylation (ARM-Seq)., Methods Mol Biol 1562:231-243
[15] Kanazhevskaya LY., Alekseeva IV., Fedorova OS., 2019, A Single-Turnover Kinetic Study of DNA Demethylation Catalyzed by Fe(II)/α-Ketoglutarate-Dependent Dioxygenase AlkB., Molecules 24(24)
[16] Kondo H., Nakabeppu Y., Kataoka H., Kuhara S., Kawabata S., Sekiguchi M., 1986, Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA., J Biol Chem 261(33):15772-7
[17] Lenz SAP., Li D., Wetmore SD., 2020, Insights into the Direct Oxidative Repair of Etheno Lesions: MD and QM/MM Study on the Substrate Scope of ALKBH2 and AlkB., DNA Repair (Amst) 96:102944
[18] Li D., Delaney JC., Page CM., Chen AS., Wong C., Drennan CL., Essigmann JM., 2010, Repair of DNA Alkylation Damage by the Escherichia coli Adaptive Response Protein AlkB as Studied by ESI-TOF Mass Spectrometry., J Nucleic Acids 369434
[19] Li D., Fedeles BI., Shrivastav N., Delaney JC., Yang X., Wong C., Drennan CL., Essigmann JM., 2013, Removal of N-alkyl modifications from N(2)-alkylguanine and N(4)-alkylcytosine in DNA by the adaptive response protein AlkB., Chem Res Toxicol 26(8):1182-7
[20] Li Q., Huang Y., Liu X., Gan J., Chen H., Yang CG., 2016, Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage., J Biol Chem 291(21):11083-93
[21] Li X., Xiong X., Wang K., Wang L., Shu X., Ma S., Yi C., 2016, Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome., Nat Chem Biol 12(5):311-6
[22] Liu H., Llano J., Gauld JW., 2009, A DFT study of nucleobase dealkylation by the DNA repair enzyme AlkB., J Phys Chem B 113(14):4887-98
[23] Mielecki D., Sikora A., Wrzesinski M., Nieminuszczy J., Detman A., Zuchniewicz K., Gromadka R., Grzesiuk E., 2016, Evaluation of the Escherichia coli HK82 and BS87 strains as tools for AlkB studies., DNA Repair (Amst) 39:34-40
[24] Mishina Y., He C., 2003, Probing the structure and function of the Escherichia coli DNA alkylation repair AlkB protein through chemical cross-linking., J Am Chem Soc 125(29):8730-1
[25] Mishina Y., Lee CH., He C., 2004, Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies., Nucleic Acids Res 32(4):1548-54
[26] Mohan M., Pandya V., Anindya R., 2018, Escherichia coli AlkB and single-stranded DNA binding protein SSB interaction explored by Molecular Dynamics Simulation., J Mol Graph Model 84:29-35
[27] Nieminuszczy J., Sikora A., Wrzesinski M., Janion C., Grzesiuk E., 2006, AlkB dioxygenase in preventing MMS-induced mutagenesis in Escherichia coli: effect of Pol V and AlkA proteins., DNA Repair (Amst) 5(2):181-8
[28] Nigam R., Anindya R., 2018, Escherichia coli single-stranded DNA binding protein SSB promotes AlkB-mediated DNA dealkylation repair., Biochem Biophys Res Commun 496(2):274-279
[29] Nigam R., Mohan M., Shivange G., Dewangan PK., Anindya R., 2018, Escherichia coli AlkB interacts with single-stranded DNA binding protein SSB by an intrinsically disordered region of SSB., Mol Biol Rep 45(5):865-870
[30] Quesne MG., Latifi R., Gonzalez-Ovalle LE., Kumar D., de Visser SP., 2014, Quantum mechanics/molecular mechanics study on the oxygen binding and substrate hydroxylation step in AlkB repair enzymes., Chemistry 20(2):435-46
[31] Rebeck GW., Coons S., Carroll P., Samson L., 1988, A second DNA methyltransferase repair enzyme in Escherichia coli., Proc Natl Acad Sci U S A 85(9):3039-43
[32] Sedgwick B., Robins P., Lindahl T., 2006, Direct removal of alkylation damage from DNA by AlkB and related DNA dioxygenases., Methods Enzymol 408:108-20
[33] Shivarattan T., Chen HA., Simpson P., Sedgwick B., Matthews S., 2005, Resonance assignments of Escherichia coli AlkB: a key 2-oxoglutarate and Fe(II) dependent dioxygenase of the adaptive DNA-repair response., J Biomol NMR 33(2):138
[34] Shrivastav N., Fedeles BI., Li D., Delaney JC., Frick LE., Foti JJ., Walker GC., Essigmann JM., 2014, A chemical genetics analysis of the roles of bypass polymerase DinB and DNA repair protein AlkB in processing N2-alkylguanine lesions in vivo., PLoS One 9(4):e94716
[35] Sikora A., Maciejewska AM., Poznanski J., Pilzys T., Marcinkowski M., Dylewska M., Piwowarski J., Jakubczak W., Pawlak K., Grzesiuk E., 2015, Effects of changes in intracellular iron pool on AlkB-dependent and AlkB-independent mechanisms protecting E.coli cells against mutagenic action of alkylating agent., Mutat Res 778:52-60
[36] Sikora A., Mielecki D., Chojnacka A., Nieminuszczy J., Wrzesinski M., Grzesiuk E., 2010, Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair., Mutagenesis 25(2):139-47
[37] Sundheim O., Talstad VA., Vagbo CB., Slupphaug G., Krokan HE., 2008, AlkB demethylases flip out in different ways., DNA Repair (Amst) 7(11):1916-23
[38] Waheed SO., Ramanan R., Chaturvedi SS., Lehnert N., Schofield CJ., Christov CZ., Karabencheva-Christova TG., 2020, Role of Structural Dynamics in Selectivity and Mechanism of Non-heme Fe(II) and 2-Oxoglutarate-Dependent Oxygenases Involved in DNA Repair., ACS Cent Sci 6(5):795-814
[39] Wang G., Palejwala VA., Dunman PM., Aviv DH., Murphy HS., Rahman MS., Humayun MZ., 1995, Alkylating agents induce UVM, a recA-independent inducible mutagenic phenomenon in Escherichia coli., Genetics 141(3):813-23
[40] Wang Y., Katanski CD., Watkins C., Pan JN., Dai Q., Jiang Z., Pan T., 2021, A high-throughput screening method for evolving a demethylase enzyme with improved and new functionalities., Nucleic Acids Res 49(5):e30
[41] Watanabe K., Ohta T., Watanabe M., Kato T., Shirasu Y., 1990, Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B., Mutat Res 243(4):273-80
[42] Welford RW., Kirkpatrick JM., McNeill LA., Puri M., Oldham NJ., Schofield CJ., 2005, Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans., FEBS Lett 579(23):5170-4
[43] Wrzesinski M., Nieminuszczy J., Sikora A., Mielecki D., Chojnacka A., Kozlowski M., Krwawicz J., Grzesiuk E., 2010, Contribution of transcription-coupled DNA repair to MMS-induced mutagenesis in E. coli strains deficient in functional AlkB protein., Mutat Res 688(1-2):19-27
[44] van den Born E., Bekkelund A., Moen MN., Omelchenko MV., Klungland A., Falnes PO., 2009, Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria., Nucleic Acids Res 37(21):7124-36

Reference(s)

[1] Aravind L., Koonin EV., 2001, The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases., Genome Biol 2(3):RESEARCH0007