Rv3240c (secA1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: protein translocase subunit secA 1
- REFSEQ: preprotein translocase subunit SecA
- PATRIC: Protein export cytoplasm protein SecA ATPase RNA helicase (TC 3.A.5.1.1)
- TUBERCULIST: Probable preprotein translocase SecA1 1 subunit
- NCBI: Probable preprotein translocase SecA1 1 subunit
- updated information (H37Rv4):
  - gene name: secA1
  - function:
  - reference:
Type: Not Target
Start: 3617682
End: 3620531
Operon:

Trans-membrane region:
Role: III.D - Protein and peptide secretion
GO terms:
- GO:0052059 - evasion or tolerance by symbiont of host-produced reactive oxygen species (Uniprot)
- GO:0043952 - protein transport by the Sec complex (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0031522 - cell envelope Sec protein transport complex (Uniprot)
- GO:0017038 - protein import (Uniprot)
- GO:0016887 - ATPase activity (Uniprot)
- GO:0016020 - membrane (Uniprot)
- GO:0015462 - ATPase-coupled protein transmembrane transporter activity (Uniprot)
- GO:0015031 - protein transport (Uniprot)
- GO:0006886 - intracellular protein transport (Uniprot)
- GO:0006605 - protein targeting (Uniprot)
- GO:0005887 - integral component of plasma membrane (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein 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: 1nl3, 1nkt
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
1NL3	99%	Mycobacterium tuberculosis	CRYSTAL STRUCTURE OF THE SECA PROTEIN TRANSLOCATION ATPASE FROM MYCOBACTERIUM TUBERCULOSIS in APO FORM
1NKT	99%	Mycobacterium tuberculosis	CRYSTAL STRUCTURE OF THE SECA PROTEIN TRANSLOCATION ATPASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEX WITH ADPBS
5K9T	55%	Escherichia coli (strain 55989 / EAEC)	SecA-N68, a C-terminal truncation of the SecA ATPase from E. coli
6GOX	49%	Escherichia coli K-12	SecA
2VDA	49%	ESCHERICHIA COLI	Solution structure of the SecA-signal peptide complex
2FSI	49%	Escherichia coli	Complex SecA:ADP from Escherichia coli
2FSH	49%	Escherichia coli	Complex SecA:AMP-PNP from Escherichia coli
2FSG	49%	Escherichia coli	Complex SecA:ATP from Escherichia coli
2FSF	49%	Escherichia coli	Escherichia coli SecA, the preprotein translocase dimeric ATPase
6S0K	48%	Escherichia coli	Ribosome nascent chain in complex with SecA

Links to additional information on secA1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -10.803 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VLSKLLRLGEGRMVKRLKKVADYVGTLSDDVEKLTDAELRAKTDEFKRRLADQKNPETLDDLLPEAFAVAREAAWRVLDQRPFDVQVMGAAALHLGNVAE
MKTGEGKTLTCVLPAYLNALAGNGVHIVTVNDYLAKRDSEWMGRVHRFLGLQVGVILATMTPDERRVAYNADITYGTNNEFGFDYLRDNMAHSLDDLVQR
GHHYAIVDEVDSILIDEARTPLIISGPADGASNWYTEFARLAPLMEKDVHYEVDLRKRTVGVHEKGVEFVEDQLGIDNLYEAANSPLVSYLNNALKAKEL
FSRDKDYIVRDGEVLIVDEFTGRVLIGRRYNEGMHQAIEAKEHVEIKAENQTLATITLQNYFRLYDKLAGMTGTAQTEAAELHEIYKLGVVSIPTNMPMI
REDQSDLIYKTEEAKYIAVVDDVAERYAKGQPVLIGTTSVERSEYLSRQFTKRRIPHNVLNAKYHEQEATIIAVAGRRGGVTVATNMAGRGTDIVLGGNV
DFLTDQRLRERGLDPVETPEEYEAAWHSELPIVKEEASKEAKEVIEAGGLYVLGTERHESRRIDNQLRGRSGRQGDPGESRFYLSLGDELMRRFNGAALE
TLLTRLNLPDDVPIEAKMVTRAIKSAQTQVEQQNFEVRKNVLKYDEVMNQQRKVIYAERRRILEGENLKDQALDMVRDVITAYVDGATGEGYAEDWDLDA
LWTALKTLYPVGITADSLTRKDHEFERDDLTREELLEALLKDAERAYAAREAELEEIAGEGAMRQLERNVLLNVIDRKWREHLYEMDYLKEGIGLRAMAQ
RDPLVEYQREGYDMFMAMLDGMKEESVGFLFNVTVEAVPAPPVAPAAEPAELAEFAAAAAAAAQQRSAVDGGARERAPSALRAKGVASESPALTYSGPAE
DGSAQVQRNGGGAHKTPAGVPAGASRRERREAARRQGRGAKPPKSVKKR

(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
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 44 non-insertions in a row out of 46 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 43 non-insertions in a row out of 46 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 43 non-insertions in a row out of 46 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 43 non-insertions in a row out of 47 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 43 non-insertions in a row out of 47 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.06
Essential-Domain	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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0678 (-) (Direct binding)
- Rv1990c (-) (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
Citation	Two nonredundant SecA homologues function in mycobacteria. M. Braunstein, AM. Brown et al. J. Bacteriol. 2001	bhupender.srcp	IPI	11717254	Affinity purification(Physical Interaction)
Interaction	PhysicalInteraction Rv1821	bhupender.srcp	IPI		Affinity purification(Physical Interaction) M. Braunstein, AM. Brown et al. Two nonredundant SecA homologues function in mycobacteria. J. Bacteriol. 2001
Citation	ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance for SecA2 function in macrophages. JM. Hou, NG. D'Lima et al. J. Bacteriol. 2008	bhupender.srcp	IPI	18487341	Affinity purification(Physical Interaction)
Interaction	PhysicalInteraction Rv1821	bhupender.srcp	IPI		Affinity purification(Physical Interaction) JM. Hou, NG. D'Lima et al. ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance for SecA2 function in macrophages. J. Bacteriol. 2008
Interaction	PhysicalInteraction Rv1821	atulkatarkar	IMP		Strucural analysis M. Braunstein, AM. Brown et al. Two nonredundant SecA homologues function in mycobacteria. J. Bacteriol. 2001
Interaction	PhysicalInteraction Rv1821	atulkatarkar	IMP		Strucural analysis M. Braunstein, BJ. Espinosa et al. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol. Microbiol. 2003
Interaction	PhysicalInteraction Rv1440	shahanup86	TAS		authors,F. Duong Binding, activation and dissociation of the dimeric SecA ATPase at the dimeric SecYEG translocase. EMBO J. 2003
Interaction	PhysicalInteraction Rv0732	anshula.arora1990	IDA		Structural analysis authors,C. Tziatzios,D. Schubert,M. Lotz,D. Gundogan,H. Betz,H. Schgger,W. Haase,F. Duong,I. Collinson The bacterial protein-translocation complex: SecYEG dimers associate with one or two SecA molecules. J. Mol. Biol. 2004
Interaction	PhysicalInteraction Rv0732	anshula.arora1990	IDA		Structural analysis JM. Hou, NG. D'Lima et al. ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance for SecA2 function in macrophages. J. Bacteriol. 2008

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