Rv3868 (eccA1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ESX-1 secretion system protein EccA1
- REFSEQ: hypothetical protein
- PATRIC: AAA family ATPase ESX-1 secretion system component Rv3868
- TUBERCULIST: ESX conserved component EccA1. ESX-1 type VII secretion system protein.
- NCBI: ESX conserved component EccA1 ESX-1 type VII secretion system protein
- updated information (H37Rv4):
  - gene name: eccA1
  - function:
  - reference:
Type: Conditional
Start: 4343314
End: 4345035
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0044117 - growth of symbiont in host (Uniprot)
- GO:0016887 - ATPase activity (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
- GO:0016042 - lipid catabolic process (FLUTE) (FLUTE Assigned!)
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: 4f3v
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
4F3V	100%	Mycobacterium tuberculosis	Crystal structure of N-terminal domain of EccA1 ATPase from ESX-1 secretion system of Mycobacterium tuberculosis
3ZUH	46%	RHODOBACTER SPHAEROIDES	Negative stain EM Map of the AAA protein CbbX, a red-type Rubisco activase from R. sphaeroides
3SYL	46%	Rhodobacter sphaeroides	Crystal structure of the AAA+ protein CbbX, native structure
3SYK	46%	Rhodobacter sphaeroides	Crystal structure of the AAA+ protein CbbX, selenomethionine structure

Links to additional information on eccA1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.755 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTDRLASLFESAVSMLPMSEARSLDLFTEITNYDESACDAWIGRIRCGDTDRVTLFRAWYSRRNFGQLSGSVQISMSTLNARIAIGGLYGDITYPVTSPL
AITMGFAACEAAQGNYADAMEALEAAPVAGSEHLVAWMKAVVYGAAERWTDVIDQVKSAGKWPDKFLAGAAGVAHGVAAANLALFTEAERRLTEANDSPA
GEACARAIAWYLAMARRSQGNESAAVALLEWLQTTHPEPKVAAALKDPSYRLKTTTAEQIASRADPWDPGSVVTDNSGRERLLAEAQAELDRQIGLTRVK
NQIERYRAATLMARVRAAKGMKVAQPSKHMIFTGPPGTGKTTIARVVANILAGLGVIAEPKLVETSRKDFVAEYEGQSAVKTAKTIDQALGGVLFIDEAY
ALVQERDGRTDPFGQEALDTLLARMENDRDRLVVIIAGYSSDIDRLLETNEGLRSRFATRIEFDTYSPEELLEIANVIAAADDSALTAEAAENFLQAAKQ
LEQRMLRGRRALDVAGNGRYARQLVEASEQCRDMRLAQVLDIDTLDEDRLREINGSDMAEAIAAVHAHLNMRE

(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: 0.609700; 8 non-insertions in a row out of 31 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 31 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 31 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 31 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 31 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 1.8
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:
- Rv3862c (whiB6)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3862c (whiB6)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv3873	shahanup86	IMP		Co-expression (Functional linkage) A. Luthra, A. Mahmood et al. Characterization of Rv3868, an Essential Hypothetical Protein of the ESX-1 Secretion System in Mycobacterium tuberculosis. J. Biol. Chem. 2008
Citation	Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. P. Brodin, L. Majlessi et al. Infect. Immun. 2006	shahanup86	IMP	16368961	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv3874	shahanup86	IMP		Co-expression (Functional linkage) P. Brodin, L. Majlessi et al. Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect. Immun. 2006
Interaction	PhysicalInteraction Rv3873	shahanup86	IMP		Co-expression (Functional linkage) P. Brodin, L. Majlessi et al. Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect. Immun. 2006
Citation	Characterization of Rv3868, an Essential Hypothetical Protein of the ESX-1 Secretion System in Mycobacterium tuberculosis. A. Luthra, A. Mahmood et al. J. Biol. Chem. 2008	shahanup86	IMP	18974091	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv3874	shahanup86	IMP		Co-expression (Functional linkage) A. Luthra, A. Mahmood et al. Characterization of Rv3868, an Essential Hypothetical Protein of the ESX-1 Secretion System in Mycobacterium tuberculosis. J. Biol. Chem. 2008
Citation	A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis. J. Teutschbein, G. Schumann et al. Microbiol. Res. 2007	jlew		17433643	Interacts with Rv3873.. Yeast two-hybrid to examine the interactions between ESX-1 proteins
Citation	Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. P. Brodin, L. Majlessi et al. Infect. Immun. 2006	jlew		16368961	Essential for secretion of ESAT-6 and CFP-10

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