Rv1638 (uvrA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: UvrABC system protein A
- REFSEQ: excinuclease ABC subunit A
- PATRIC: Excinuclease ABC subunit A
- TUBERCULIST: Probable excinuclease ABC (subunit A - DNA-binding ATPase) UvrA
- NCBI: Probable excinuclease ABC (subunit A-DNA-binding ATPase) UvrA
- updated information (H37Rv4):
  - gene name: uvrA
  - function:
  - reference:
Type: Not Target
Start: 1843741
End: 1846659
Operon:

Trans-membrane region:
Role: II.A.5 - DNA replication, repair, recombination and restriction/modification
GO terms:
- GO:0090305 - nucleic acid phosphodiester bond hydrolysis (Uniprot)
- GO:0060543 - negative regulation of strand invasion (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0016887 - ATPase activity (Uniprot)
- GO:0009432 - SOS response (Uniprot)
- GO:0009381 - excinuclease ABC activity (Uniprot)
- GO:0009380 - excinuclease repair complex (Uniprot)
- GO:0006974 - cellular response to DNA damage stimulus (Uniprot)
- GO:0006289 - nucleotide-excision repair (Uniprot)
- GO:0006281 - DNA repair (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004518 - nuclease activity (Uniprot)
- GO:0003677 - DNA binding (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 3zqj
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
3ZQJ	99%	MYCOBACTERIUM TUBERCULOSIS	Mycobacterium tuberculosis UvrA
3UWX	59%	Geobacillus	Crystal structure of UvrA-UvrB complex
2R6F	59%	Geobacillus stearothermophilus	Crystal Structure of Bacillus stearothermophilus UvrA
3PIH	53%	Thermotoga maritima	T. maritima UvrA in complex with fluorescein-modified DNA
4DFC	50%	Escherichia coli	Core UvrA/TRCF complex
3UX8	46%	Geobacillus	Crystal structure of UvrA
3FPN	44%	Geobacillus stearothermophilus	Crystal structure of UvrA-UvrB interaction domains
6N9L	43%	Thermotoga maritima	Crystal structure of T. maritima UvrA d117-399 with ADP
2VF8	42%	DEINOCOCCUS RADIODURANS	Crystal structure of UvrA2 from Deinococcus radiodurans
2VF7	42%	DEINOCOCCUS RADIODURANS	Crystal structure of UvrA2 from Deinococcus radiodurans

Links to additional information on uvrA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.742 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology
- Mycobrowser
- PATRIC

Amino Acid Sequence

VADRLIVKGAREHNLRSVDLDLPRDALIVFTGLSGSGKSSLAFDTIFAEGQRRYVESLSAYARQFLGQMDKPDVDFIEGLSPAVSIDQKSTNRNPRSTVG
TITEVYDYLRLLYARAGTPHCPTCGERVARQTPQQIVDQVLAMPEGTRFLVLAPVVRTRKGEFADLFDKLNAQGYSRVRVDGVVHPLTDPPKLKKQEKHD
IEVVVDRLTVKAAAKRRLTDSVETALNLADGIVVLEFVDHELGAPHREQRFSEKLACPNGHALAVDDLEPRSFSFNSPYGACPECSGLGIRKEVDPELVV
PDPDRTLAQGAVAPWSNGHTAEYFTRMMAGLGEALGFDVDTPWRKLPAKARKAILEGADEQVHVRYRNRYGRTRSYYADFEGVLAFLQRKMSQTESEQMK
ERYEGFMRDVPCPVCAGTRLKPEILAVTLAGESKGEHGAKSIAEVCELSIADCADFLNALTLGPREQAIAGQVLKEIRSRLGFLLDVGLEYLSLSRAAAT
LSGGEAQRIRLATQIGSGLVGVLYVLDEPSIGLHQRDNRRLIETLTRLRDLGNTLIVVEHDEDTIEHADWIVDIGPGAGEHGGRIVHSGPYDELLRNKDS
ITGAYLSGRESIEIPAIRRSVDPRRQLTVVGAREHNLRGIDVSFPLGVLTSVTGVSGSGKSTLVNDILAAVLANRLNGARQVPGRHTRVTGLDYLDKLVR
VDQSPIGRTPRSNPATYTGVFDKIRTLFAATTEAKVRGYQPGRFSFNVKGGRCEACTGDGTIKIEMNFLPDVYVPCEVCQGARYNRETLEVHYKGKTVSE
VLDMSIEEAAEFFEPIAGVHRYLRTLVDVGLGYVRLGQPAPTLSGGEAQRVKLASELQKRSTGRTVYILDEPTTGLHFDDIRKLLNVINGLVDKGNTVIV
IEHNLDVIKTSDWIIDLGPEGGAGGGTVVAQGTPEDVAAVPASYTGKFLAEVVGGGASAATSRSNRRRNVSA

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.188300; 7 non-insertions in a row out of 39 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.269150; 6 non-insertions in a row out of 39 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.324850; 6 non-insertions in a row out of 39 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 39 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 39 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

Binds To:
- No bindings to other targets were found.
Bound By:

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Direct binding)
- Rv1990c (-) (Direct binding)
- Rv2324 (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv2840c	akvsangli	RCA		authors,L. Cabusora,E. Sutton,A. Fulmer,CV. Forst Differential network expression during drug and stress response. Bioinformatics 2005
Interaction	Activation Rv1633	priyadarshinipriyanka2001	IDA		Spectrophotometric Analysis K. Kurthkoti, P. Kumar et al. Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents. Microbiology (Reading, Engl.) 2008
Citation	Mycobacterium tuberculosis UvrD1 and UvrA Proteins Suppress DNA Strand Exchange Promoted by Cognate and Non-cognate RecA Proteins. P. Singh, KN. Patil et al. Biochemistry 2010	priyadarshinipriyanka2001	IDA	20455546	Spectrophotometric Analysis
Interaction	Activation Rv1633	priyadarshinipriyanka2001	IDA		Spectrophotometric Analysis P. Singh, KN. Patil et al. Mycobacterium tuberculosis UvrD1 and UvrA Proteins Suppress DNA Strand Exchange Promoted by Cognate and Non-cognate RecA Proteins. Biochemistry 2010
Interaction	Activation Rv1633	priyadarshinipriyanka2001	IDA		Spectrophotometric Analysis K. Kurthkoti, P. Kumar et al. Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents. Microbiology (Reading, Engl.) 2008
Citation	Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents. K. Kurthkoti, P. Kumar et al. Microbiology (Reading, Engl.) 2008	priyadarshinipriyanka2001	IDA	18757811	Spectrophotometric Analysis
Interaction	RegulatedBy Rv2720	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv2720	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006
Other	TBPWY:NER and related	vmizrahi			Biochemically and structurally characterized recombinant M. tuberculosis UvrA. Structural investigation reveals an unprecedented conformation of the UvrB-binding domain proposed to be of functional relevance.
Other	TBPWY:NER and related	vmizrahi			Small molecule inhibitor of UvrABC complex identified
Other	TBPWY:NER and related	vmizrahi			Experimental evidence for a physical interaction RecA and UvrA

TB Genome Annotation Portal