Rv3545c (cyp125)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: steroid C27-monooxygenase
- REFSEQ: cytochrome P450 125
- PATRIC: Putative cytochrome P450 125 (EC 1.14.-.-); Putative cytochrome P450 IgrA
- TUBERCULIST: Probable cytochrome P450 125 Cyp125
- NCBI: Probable cytochrome P450 125 Cyp125
- updated information (H37Rv4):
  - gene name: cyp125
  - function:
  - reference:
Type: Not Target
Start: 3984144
End: 3985445
Operon:

Trans-membrane region:
Role: IV.F - Cytochrome P450 enzymes
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0044117 - growth of symbiont in host (Uniprot)
- GO:0036199 - cholest-4-en-3-one 26-monooxygenase activity (Uniprot)
- GO:0020037 - heme binding (Uniprot)
- GO:0016705 - oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0016042 - lipid catabolic process (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0008395 - steroid hydroxylase activity (Uniprot)
- GO:0008203 - cholesterol metabolic process (Uniprot)
- GO:0008202 - steroid metabolic process (Uniprot)
- GO:0006707 - cholesterol catabolic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005506 - iron ion binding (Uniprot)
- GO:0004497 - monooxygenase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- CHOLESTENONE[c] -> 3OXOCHOLEST4EN26OATE[c]
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: 2x5l, 2xn8, 3ivy, 2x5w, 2xc3, 3iw2, 3iw0, 3iw1
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3IW2	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP125 in complex with econazole
3IW1	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP125 in complex with androstenedione
3IW0	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP125, C2221 crystal form
3IVY	99%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP125, p212121 crystal form
2X5W	99%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of Mycobacterium tuberculosis cytochrome P450 CYP125 in complex with substrate cholest-4-en-3-one
2XN8	99%	MYCOBACTERIUM TUBERCULOSIS	X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125
2XC3	99%	MYCOBACTERIUM TUBERCULOSIS	X-ray structure of Mycobacterium tuberculosis cyp125 bound to the reverse type I inhibitor
2X5L	99%	MYCOBACTERIUM TUBERCULOSIS	X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125, ALTERNATIVE CRYSTAL FORM
5DQN	75%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Polyethylene 600-bound form of P450 CYP125A3 mutant from Myobacterium Smegmatis - W83Y
4APY	75%	Mycobacterium smegmatis str. MC2 155	Ethylene glycol-bound form of P450 CYP125A3 from Mycobacterium smegmatis

Links to additional information on cyp125:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.641 (from Jeremy Rock's lab)

Amino Acid Sequence

VSWNHQSVEIAVRRTTVPSPNLPPGFDFTDPAIYAERLPVAEFAELRSAAPIWWNGQDPGKGGGFHDGGFWAITKLNDVKEISRHSDVFSSYENGVIPRF
KNDIAREDIEVQRFVMLNMDAPHHTRLRKIISRGFTPRAVGRLHDELQERAQKIAAEAAAAGSGDFVEQVSCELPLQAIAGLLGVPQEDRGKLFHWSNEM
TGNEDPEYAHIDPKASSAELIGYAMKMAEEKAKNPADDIVTQLIQADIDGEKLSDDEFGFFVVMLAVAGNETTRNSITQGMMAFAEHPDQWELYKKVRPE
TAADEIVRWATPVTAFQRTALRDYELSGVQIKKGQRVVMFYRSANFDEEVFQDPFTFNILRNPNPHVGFGGTGAHYCIGANLARMTINLIFNAVADHMPD
LKPISAPERLRSGWLNGIKHWQVDYTGRCPVAH

(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
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 24 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 24 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 24 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 25 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 7 non-insertions in a row out of 25 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: 0.52
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:
- Rv0081 (-) (Direct binding)
- Rv0324 (-) (Direct binding)
- Rv0681 (-) (Direct binding)
- Rv3133c (devR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv2887 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv3574	priyadarshinipriyanka2001	IEP		Co-expression (Functional linkage) SL. Kendall,P. Burgess,R. Balhana,M. Withers,A. Ten Bokum,JS. Lott,C. Gao,I. Uhia Castro,NG. Stoker Cholesterol utilisation in mycobacteria is controlled by two TetR-type transcriptional regulators; kstR and kstR2. Microbiology (Reading, England) 2010
Interaction	Regulatory Rv3574	priyadarshinipriyanka2001	IEP		Co-expression (Functional linkage) SL. Kendall, M. Withers et al. A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis. Mol. Microbiol. 2007
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 Rv2034	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 Rv2017	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 Rv1956	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 Rv3574	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Citation	Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. JK. Capyk, R. Kalscheuer et al. J. Biol. Chem. 2009	nsampson		19846551	Assay of protein purified to homogeneity from a heterlogous host
Term	EC:1.2.1.- Oxidoreductases. Acting on the aldehyde or oxo group of donors. With NAD(+) or NADP(+) as acceptor. - NR	nsampson	NR		Assay of protein purified to homogeneity from a heterlogous host JK. Capyk, R. Kalscheuer et al. Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. J. Biol. Chem. 2009
Term	EC:1.1.1.- Oxidoreductases. Acting on the CH-OH group of donors. With NAD(+) or NADP(+) as acceptor. - NR	nsampson	NR		Assay of protein purified to homogeneity from a heterlogous host JK. Capyk, R. Kalscheuer et al. Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. J. Biol. Chem. 2009
Term	EC:1.14.13.- Oxidoreductases. Acting on paired donors, with incorporation or reduction of With NADH or NADPH as one donor, and incorporation of one atom - NR	nsampson	NR		Assay of protein purified to homogeneity from a heterlogous host JK. Capyk, R. Kalscheuer et al. Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids. J. Biol. Chem. 2009

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