TB Genome Annotation Portal

Rv0101 (nrp)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: amino acid adenylation domain-containing protein
  • REFSEQ: peptide synthetase
  • PATRIC: Long-chain-fatty-acid--CoA ligase (EC 6.2.1.3)
  • TUBERCULIST: Probable peptide synthetase Nrp (peptide synthase)
  • NCBI: Probable peptide synthetase Nrp (peptide synthase)
  • updated information (H37Rv4):
    • gene name: nrp
    • function: " $ biosynthesis of chalkophores (isonitrile lipopeptides, at least in M. marinum), which mediate NO resistance and can bind Cu $ $ expression regulated by sigC $ $ Harris NC, Sato M, Herman NA, Twigg F, Cai W, Liu J, Zhu X, Downey J, $ Khalaf R, Martin J, Koshino H, Zhang W. Biosynthesis of isonitrile $ lipopeptides by conserved nonribosomal peptide synthetase gene $ clusters in Actinobacteria. Proc Natl Acad Sci U S A. 2017 Jul $ 3;114(27):7025-7030. doi: 10.1073/pnas.1705016114. Epub 2017 Jun $ 20. PMID: 28634299; PMCID: PMC5502637. $ $ Grosse-Siestrup BT, Gupta T, Helms S, Tucker SL, Voskuil MI, Quinn FD, $ Karls RK. A Role for Mycobacterium tuberculosis Sigma Factor C in $ Copper Nutritional Immunity. Int J Mol Sci. 2021 Feb $ 20;22(4):2118. doi: 10.3390/ijms22042118. PMID: 33672733; PMCID: $ PMC7924339. $ "
    • reference:
• Type: Not Target
• Start: 110001
• End: 117539
• Operon:


• Trans-membrane region:
  
• Role: I.I - Polyketide and non-ribosomal peptide synthesis
• GO terms:
  • GO:0031177 - phosphopantetheine binding (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0003824 - catalytic activity (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: 4dqv
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  4U5Q	97%	Mycobacterium tuberculosis	High resolution crystal structure of reductase (R) domain of nonribosomal peptide synthetase from Mycobacterium tuberculosis
  4DQV	97%	Mycobacterium tuberculosis	Crystal structure of reductase (R) domain of non-ribosomal peptide synthetase from Mycobacterium tuberculosis
  6EBY	63%	Thermobifida fusca (strain YX)	Crystal structure of the MbtH-like protein FscK bound to the interface forming region of FscH adenylation domain from Thermobifida fusca
  6EA3	43%	Thermobifida fusca (strain YX)	Thermobifida fusca FscH adenylation domain complexed with MbtH-like protein FscK and Ser-AMP
  5MSU	43%	Mycobacterium marinum M	Structure of the R domain of carboxylic acid reductase (CAR) from Mycobacterium marinum in complex with NADP, P21 form
  5MSO	43%	Mycobacterium marinum M	Structure of the R domain of carboxylic acid reductase (CAR) from Mycobacterium marinum in complex with NADP
  5ISX	41%	Brevibacillus brevis	Structure of the holo PCP-E didomain of the gramicidin S synthetase A
  5ISW	41%	Brevibacillus brevis	Structure of the apo PCP-E didomain of the gramicidin S synthetase A
  2MR8	41%	Actinoplanes teichomyceticus	holo structure of the Peptidyl Carrier Protein Domain 7 of the teicoplanin producing Non-ribosomal peptide synthetase
  2MR7	41%	Actinoplanes teichomyceticus	apo structure of the Peptidyl Carrier Protein Domain 7 of the teicoplanin producing Non-ribosomal peptide synthetase

• Links to additional information on nrp:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.628 (from Jeremy Rock's lab)
  • BioCyc
  • Systems Biology

Amino Acid Sequence

VHRVRLSRSQRNLYNGVRQDNNPALYLIGKSYRFRRLELARFLAALHATVLDNPVQLCVLENSGADYPDLVPRLRFGDIVRVGSADEHLQSTWCSGILGK
PLVRHTVHTDPNGYVTGLDVHTHHILLDGGATGTIEADLARYLTTDPAGETPSVGAGLAKLREAHRRETAKVEESRGRLSAVVQRELADEAYHGGHGHSV
SDAPGTAAKGVLHESATICGNAFDAILTLSEAQRVPLNVLVAAAAVAVDASLRQNTETLLVHTVDNRFGDSDLNVATCLVNSVAQTVRFPPFASVSDVVR
TLDRGYVKAVRRRWLREEHYRRMYLAINRTSHVEALTLNFIREPCAPGLRPFLSEVPIATDIGPVEGMTVASVLDEEQRTLNLAIWNRADLPACKTHPKV
AERIAAALESMAAMWDRPIAMIVNDWFGIGPDGTRCQGDWPARQPSTPAWFLDSARGVHQFLGRRRFVYPWVAWLVQRGAAPGDVLVFTDDDTDKTIDLL
IACHLAGCGYSVCDTADEISVRTNAITEHGDGILVTVVDVAATQLAVVGHDELRKVVDERVTQVTHDALLATKTAYIMPTSGTTGQPKLVRISHGSLAVF
CDAISRAYGWGAHDTVLQCAPLTSDISVEEIFGGAACGARLVRSAAMKTGDLAALVDDLVARETTIVDLPTAVWQLLCADGDAIDAIGRSRLRQIVIGGE
AIRCSAVDKWLESAASQGISLLSSYGPTEATVVATFLPIVCDQTTMDGALLRLGRPILPNTVFLAFGEVVIVGDLVADGYLGIDGDGFGTVTAADGSRRR
AFATGDRVTVDAEGFPVFSGRKDAVVKISGKRVDIAEVTRRIAEDPAVSDVAVELHSGSLGVWFKSQRTREGEQDAAAATRIRLVLVSLGVSSFFVVGVP
NIPRKPNGKIDSDNLPRLPQWSAAGLNTAETGQRAAGLSQIWSRQLGRAIGPDSSLLGEGIGSLDLIRILPETRRYLGWRLSLLDLIGADTAANLADYAP
TPDAPTGEDRFRPLVAAQRPAAIPLSFAQRRLWFLDQLQRPAPVYNMAVALRLRGYLDTEALGAAVADVVGRHESLRTVFPAVDGVPRQLVIEARRADLG
CDIVDATAWPADRLQRAIEEAARHSFDLATEIPLRTWLFRIADDEHVLVAVAHHIAADGWSVAPLTADLSAAYASRCAGRAPDWAPLPVQYVDYTLWQRE
ILGDLDDSDSPIAAQLAYWENALAGMPERLRLPTARPYPPVADQRGASLVVDWPASVQQQVRRIARQHNATSFMVVAAGLAVLLSKLSGSPDVAVGFPIA
GRSDPALDNLVGFFVNTLVLRVNLAGDPSFAELLGQVRARSLAAYENQDVPFEVLVDRLKPTRALTHHPLIQVMLAWQDNPVGQLNLGDLQATPMPIDTR
TARMDLVFSLAERFSEGSEPAGIGGAVEYRTDVFEAQAIDVLIERLRKVLVAVAAAPERTVSSIDALDGTERARLDEWGNRAVLTAPAPTPVSIPQMLAA
QVARIPEAEAVCCGDASMTYRELDEASNRLAHRLAGCGAGPGECVALLFERCAPAVVAMVAVLKTGAAYLPIDPANPPPRVAFMLGDAVPVAAVTTAGLR
SRLAGHDLPIIDVVDALAAYPGTPPPMPAAVNLAYILYTSGTTGEPKGVGITHRNVTRLFASLPARLSAAQVWSQCHSYGFDASAWEIWGALLGGGRLVI
VPESVAASPNDFHGLLVAEHVSVLTQTPAAVAMLPTQGLESVALVVAGEACPAALVDRWAPGRVMLNAYGPTETTICAAISAPLRPGSGMPPIGVPVSGA
ALFVLDSWLRPVPAGVAGELYIAGAGVGVGYWRRAGLTASRFVACPFGGSGARMYRTGDLVCWRADGQLEFLGRTDDQVKIRGYRIELGEVATALAELAG
VGQAVVIAREDRPGDKRLVGYATEIAPGAVDPAGLRAQLAQRLPGYLVPAAVVVIDALPLTVNGKLDHRALPAPEYGDTNGYRAPAGPVEKTVAGIFARV
LGLERVGVDDSFFELGGDSLAAMRVIAAINTTLNADLPVRALLHASSTRGLSQLLGRDARPTSDPRLVSVHGDNPTEVHASDLTLDRFIDADTLATAVNL
PGPSPELRTVLLTGATGFLGRYLVLELLRRLDVDGRLICLVRAESDEDARRRLEKTFDSGDPELLRHFKELAADRLEVVAGDKSEPDLGLDQPMWRRLAE
TVDLIVDSAAMVNAFPYHELFGPNVAGTAELIRIALTTKLKPFTYVSTADVGAAIEPSAFTEDADIRVISPTRTVDGGWAGGYGTSKWAGEVLLREANDL
CALPVAVFRCGMILADTSYAGQLNMSDWVTRMVLSLMATGIAPRSFYEPDSEGNRQRAHFDGLPVTFVAEAIAVLGARVAGSSLAGFATYHVMNPHDDGI
GLDEYVDWLIEAGYPIRRIDDFAEWLQRFEASLGALPDRQRRHSVLPMLLASNSQRLQPLKPTRGCSAPTDRFRAAVRAAKVGSDKDNPDIPHVSAPTII
NYVTNLQLLGLL

Additional Information

biosynthesis of chalkophores (isonitrile lipopeptides, at least in M. marinum), which mediate NO resistance and can bind Cu

expression regulated by sigC

Harris NC, Sato M, Herman NA, Twigg F, Cai W, Liu J, Zhu X, Downey J,
Khalaf R, Martin J, Koshino H, Zhang W. Biosynthesis of isonitrile
lipopeptides by conserved nonribosomal peptide synthetase gene
clusters in Actinobacteria. Proc Natl Acad Sci U S A. 2017 Jul
3;114(27):7025-7030. doi: 10.1073/pnas.1705016114. Epub 2017 Jun
20. PMID: 28634299; PMCID: PMC5502637.

Grosse-Siestrup BT, Gupta T, Helms S, Tucker SL, Voskuil MI, Quinn FD,
Karls RK. A Role for Mycobacterium tuberculosis Sigma Factor C in
Copper Nutritional Immunity. Int J Mol Sci. 2021 Feb
20;22(4):2118. doi: 10.3390/ijms22042118. PMID: 33672733; PMCID:
PMC7924339.

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)	1.82 (0.45)	1.72 (0.75)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link