Q10630 (ALKA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable bifunctional transcriptional activator/DNA repair enzyme AlkA

Alternative name(s):
Regulatory protein AlkA

Including the following 2 domains:

1. Methylphosphotriester-DNA--protein-cysteine S-methyltransferase
   EC=2.1.1.n11
   Alternative name(s):
   Methylphosphotriester-DNA methyltransferase
2. DNA-3-methyladenine glycosylase
   EC=3.2.2.21
   Alternative name(s):
   DNA-3-methyladenine glycosidase

Gene names

Name:	alkA
Synonyms:	ada
Ordered Locus Names:	Rv1317c, MT1358
ORF Names:	MTCY130.02c

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	496 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs the Sp diastereomer of DNA methylphosphotriester lesions by a direct and irreversible transfer of the methyl group to one of its own cysteine residues. Also catalyzes the hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions By similarity. The methylation of Alka by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene and other alkylation resistance genes By similarity.
Catalytic activity	DNA (containing Sp-methylphosphotriester) + protein L-cysteine = DNA (without Sp-methylphosphotriester) + protein S-methyl-L-cysteine. Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine and 7-methyladenine.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Miscellaneous	This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocytalyst that acts repeatedly and over many reaction cycles.
Sequence similarities	In the C-terminal section; belongs to the alkylbase DNA glycosidase AlkA family. Contains 1 HTH araC/xylS-type DNA-binding domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transcription Transcription regulation
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Hydrolase Methyltransferase Transferase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	DNA dealkylation involved in DNA repair Inferred from direct assay. Source: MTBBASE base-excision repair Inferred from electronic annotation. Source: InterPro response to nitrosative stress Inferred from direct assay. Source: MTBBASE transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cell wall Inferred from direct assay. Source: MTBBASE intracellular Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	DNA-3-methyladenine glycosylase activity Inferred from electronic annotation. Source: EC DNA-3-methylguanine glycosylase activity Inferred from electronic annotation. Source: EC DNA-7-methyladenine glycosylase activity Inferred from electronic annotation. Source: EC DNA-7-methylguanine glycosylase activity Inferred from electronic annotation. Source: EC methyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 496	496	Probable bifunctional transcriptional activator/DNA repair enzyme AlkA		PRO_0000139389
Regions
	Domain	87 – 185	99	HTH araC/xylS-type
	DNA binding	104 – 125	22	H-T-H motif By similarity
	Region	1 – 185	185	Methylphosphotriester-DNA--protein-cysteine methyltransferase
	Region	202 – 354	153	DNA-3-methyladenine glycosylase
	Compositional bias	181 – 197	17	Ala-rich
Sites
	Active site	34	1	Nucleophile; methyl group acceptor from methylphosphotriester By similarity
	Active site	441	1	Proton acceptor; for DNA glycosylase activity By similarity
	Metal binding	34	1	Zinc By similarity
	Metal binding	38	1	Zinc By similarity
	Metal binding	65	1	Zinc By similarity
	Metal binding	68	1	Zinc By similarity
	Binding site	30	1	DNA By similarity
	Binding site	41	1	DNA By similarity
	Binding site	63	1	DNA By similarity
	Site	421	1	Determinant for substrate specificity and/or DNA glycosylase activity By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q10630 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: CA1F52032181268F	FASTA	496	53,743
	10 20 30 40 50 60 MHDDFERCYR AIQSKDARFD GWFVVAVLTT GVYCRPSCPV RPPFARNVRF LPTAAAAQGE 70 80 90 100 110 120 GFRACKRCRP DASPGSPEWN VRSDVVARAM RLIADGTVDR DGVSGLAAQL GYTIRQLERL 130 140 150 160 170 180 LQAVVGAGPL ALARAQRMQT ARVLIETTNL PFGDVAFAAG FSSIRQFNDT VRLACDGTPT 190 200 210 220 230 240 ALRARAAARF ESATASAGTV SLRLPVRAPF AFEGVFGHLA ATAVPGCEEV RDGAYRRTLR 250 260 270 280 290 300 LPWGNGIVSL TPAPDHVRCL LVLDDFRDLM TATARCRRLL DLDADPEAIV EALGADPDLR 310 320 330 340 350 360 AVVGKAPGQR IPRTVDEAEF AVRAVLAQQV STKAASTHAG RLVAAYGRPV HDRHGALTHT 370 380 390 400 410 420 FPSIEQLAEI DPGHLAVPKA RQRTINALVA SLADKSLVLD AGCDWQRARG QLLALPGVGP 430 440 450 460 470 480 WTAEVIAMRG LGDPDAFPAS DLGLRLAAKK LGLPAQRRAL TVHSARWRPW RSYATQHLWT 490 TLEHPVNQWP PQEKIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Mycobacterium tuberculosis 3-methyladenine glycosidase and O6-methylguanine methyltransferase genes." Bourn W.R., Harington A., Wiid I., van Helden P.D. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-496. Strain: ATCC 25618 / H37Rv.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842576 Genomic DNA. Translation: CAA98104.1. U65786 Genomic DNA. Translation: AAB06751.1. AE000516 Genomic DNA. Translation: AAK45620.1.
PIR	A70769.
RefSeq	NP_215833.1. NC_000962.2. NP_335806.1. NC_002755.2.
3D structure databases
ProteinModelPortal	Q10630.
ModBase	Search...
Protein family/group databases
AraC-XylS	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	EBMYCT00000003926; EBMYCP00000003926; EBMYCG00000003924. EBMYCT00000071713; EBMYCP00000069772; EBMYCG00000071708.
GeneID	886916. 924701.
GenomeReviews	Gene locus MT1358 in contig AE000516_GR. Gene locus Rv1317c in contig AL123456_GR.
KEGG	mtc:MT1358. mtu:Rv1317c.
PATRIC	18124756. VBIMycTub22151_1493.
TIGR	MT1358.
Organism-specific databases
TubercuList	Rv1317c.
Phylogenomic databases
GeneTree	EBGT00050000015628.
HOGENOM	HBG510250.
OMA	RCRPDSA.
PhylomeDB	Q10630.
ProtClustDB	CLSK791096.
Family and domain databases
InterPro	IPR004026. Ada_DNA_repair_Zn-bd. IPR010316. AlkA_N. IPR011257. DNA_glycosylase. IPR003265. HhH-GPD_domain. IPR003583. Hlx-hairpin-Hlx_DNA-bd_motif. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. IPR018062. HTH_AraC-typ_sub_2. IPR018060. HTH_AraC_DNA-bd. IPR023170. HTH_base_excis_C. IPR012294. TFIID_C/glycos_N. [Graphical view]
Gene3D	G3DSA:3.40.10.10. Ada_DNA_repair_Zn-bd. 1 hit. G3DSA:3.30.310.20. AlkA_N. 1 hit. G3DSA:1.10.340.30. DNA_glycosylase. 1 hit. G3DSA:1.10.10.60. Homeodomain-rel. 1 hit. G3DSA:1.10.1670.10. HTH_base_excis_C. 1 hit.
KO	K13529.
Pfam	PF02805. Ada_Zn_binding. 1 hit. PF06029. AlkA_N. 1 hit. PF00730. HhH-GPD. 1 hit. [Graphical view]
SMART	SM01009. AlkA_N. 1 hit. SM00478. ENDO3c. 1 hit. SM00278. HhH1. 1 hit. SM00342. HTH_ARAC. 1 hit. [Graphical view]
SUPFAM	SSF57884. Ada_DNA_repair_Zn-bd. 1 hit. SSF48150. DNA_glycsylse. 1 hit. SSF46689. Homeodomain_like. 1 hit. SSF55945. TFIID_C/glycos_N. 1 hit.
PROSITE	PS00041. HTH_ARAC_FAMILY_1. 1 hit. PS01124. HTH_ARAC_FAMILY_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ALKA_MYCTU

Accession

Primary (citable) accession number: Q10630

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program