Rv1465 (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: NifU family SUF system FeS assembly protein
- REFSEQ: nitrogen fixation related protein
- PATRIC: Putative iron-sulfur cluster assembly scaffold protein for SUF system SufE2
- TUBERCULIST: Possible nitrogen fixation related protein
- NCBI: Possible nitrogen fixation related protein
- updated information (H37Rv4):
  - gene name: sufU/nifU/iscU
  - function: assembly of iron-sulfur clusters
  - reference: (Huet 2005, PMID: 16109955)
Type: Essential
Start: 1652768
End: 1653256
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0097428 - protein maturation by iron-sulfur cluster transfer (Uniprot)
- GO:0051539 - 4 iron, 4 sulfur cluster binding (Uniprot)
- GO:0051537 - 2 iron, 2 sulfur cluster binding (Uniprot)
- GO:0051536 - iron-sulfur cluster binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0036455 - iron-sulfur transferase activity (Uniprot)
- GO:0016226 - iron-sulfur cluster assembly (Uniprot)
- GO:0008198 - ferrous iron binding (Uniprot)
- GO:0006879 - cellular iron ion homeostasis (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005506 - iron ion 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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2QQ4	42%	Thermus thermophilus	Crystal structure of Iron-sulfur cluster biosynthesis protein IscU (TTHA1736) from thermus thermophilus HB8
6JZW	39%	Bacillus subtilis (strain 168)	Crystal structure of SufU from Bacillus subtilis with Cys persulfurated
6JZW	39%	Bacillus subtilis (strain 168)	Crystal structure of SufU from Bacillus subtilis with Cys persulfurated
6JZV	39%	Bacillus subtilis (strain 168)	Crystal structure of SufU from Bacillus subtilis
5XT6	39%	Bacillus subtilis (strain 168)	A sulfur-transferring catalytic intermediate of SufS-SufU complex from Bacillus subtilis
5XT6	39%	Bacillus subtilis (strain 168)	A sulfur-transferring catalytic intermediate of SufS-SufU complex from Bacillus subtilis
5XT5	39%	Bacillus subtilis (strain 168)	SufS-SufU complex from Bacillus subtilis
2AZH	39%	Bacillus subtilis	Solution structure of iron-sulfur cluster assembly protein SUFU from Bacillus subtilis, with zinc bound at the active site. Northeast Structural Genomics Consortium target SR17
1XJS	39%	Bacillus subtilis	Solution structure of Iron-Sulfur cluster assembly protein IscU from Bacillus subtilis, with Zinc bound at the active site. Northeast Structural Genomics Consortium Target SR17
6A6G	38%	Fervidobacterium islandicum	Crystal structure of thermostable FiSufS-SufU complex from thermophilic Fervidobacterium Islandicum AW-1

Links to additional information on Rv1465:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -1.442 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- Photo of spot titer

Amino Acid Sequence

VTLRLEQIYQDVILDHYKHPQHRGLREPFGAQVYHVNPICGDEVTLRVALSEDGTRVTDVSYDGQGCSISQAATSVLTEQVIGQRVPRALNIVDAFTEMV
SSRGTVPGDEDVLGDGVAFAGVAKYPARVKCALLGWMAFKDALAQASEAFEEVTDERNQRTG

(Nucleotide sequence available on KEGG)

Additional Information

sufU or nifU or iscU - assembly of iron-sulfur clusters.

Huet G, Daffé M, Saves I. Identification of the Mycobacterium
tuberculosis SUF machinery as the exclusive mycobacterial system of
[Fe-S] cluster assembly: evidence for its implication in the
pathogen's survival. J Bacteriol. 2005 Sep;187(17):6137-46. doi:
10.1128/JB.187.17.6137-6146.2005. PMID: 16109955; PMCID: PMC1196142.

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	0.65 (0.01)	1.22 (0.42)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv1465/-, gene len: 488 bp, num TA sites: 8

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	uncertain	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=2.29)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=-0.363)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=-1.86)	YM rich vs minimal medium	resampling

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:
- Rv1460 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0691c (-) (Upstream of operon)
- Rv1033c (trcR) (Upstream of operon)
- Rv1460 (-) (Upstream of operon)
- Rv2610c (pimA) (Upstream of operon)

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:
- Rv1460 (-)

Property	Value	Creator	Evidence	PMID	Comment
Citation	GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp. authors,DR. Hill,TJ. Belbin,MV. Thorsteinsson,D. Bassam,S. Brass,A. Ernst,P. Bger,H. Paerl,ME. Mulligan,M. Potts J. Bacteriol. 1996	priti.priety	IEP	8932316	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv1542c	priti.priety	IEP		Co-expression (Functional linkage) authors,DR. Hill,TJ. Belbin,MV. Thorsteinsson,D. Bassam,S. Brass,A. Ernst,P. Bger,H. Paerl,ME. Mulligan,M. Potts GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp. J. Bacteriol. 1996
Citation	GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp. authors,DR. Hill,TJ. Belbin,MV. Thorsteinsson,D. Bassam,S. Brass,A. Ernst,P. Bger,H. Paerl,ME. Mulligan,M. Potts J. Bacteriol. 1996	ashwinigbhat	IEP	8932316	Co-expression (Functional linkage)
Interaction	PhysicalInteraction Rv1542c	ashwinigbhat	IEP		Co-expression (Functional linkage) authors,DR. Hill,TJ. Belbin,MV. Thorsteinsson,D. Bassam,S. Brass,A. Ernst,P. Bger,H. Paerl,ME. Mulligan,M. Potts GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp. J. Bacteriol. 1996
Interaction	RegulatedBy Rv3557c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3416	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv1931c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv1359	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv0818	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv0445c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv0260c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009

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