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2.A.6.5.6
MmpL3 (Rv0206; 944 aas) May function with MmpL11 (TC# 2.A.6.5.5) (Tullius et al., 2011). MmpL3 exports trehalose monomycolate, involved in mycolic acid donation to the cell wall core (Tahlan et al., 2012). SQ109, a 1,2,-diamine related to ethambutol  is an inhibitor of MmpL3 (Tahlan et al., 2012).  May also transport heme.  Inhibitors have been identified (Rayasam 2013; Li et al. 2014).  MmpL3 has been shown to be a homotrimer of three 12 TMS subunits, confirming its RND-type structure (Belardinelli et al. 2016).  MmpL3 is a flipppase for mycolic acids, transporting them from the cytoplasmic side of the inner membrane to the external side. A 1.5-diarylpyrrole compound, BM212, is a potent inibitor (Xu et al. 2017). Inactivation of the mmpL3 gene in M. neoaurum increased the permeability of the outer membrae and allowed increased uptake of sterols for coversion to other sterols for industrial purposes. One such product is 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), used for the synthesis of various steroids in the industry (Xiong et al. 2017). Sincer iron deprivation decreases expression of the mmpL3 gene, a metal chelation strategy could boost the effectiveness of current anti-TB drug regimes to combat drug resistance TB (Pal et al. 2018). Crystal structures are available for MmpL3 alone and in complex with four TB drug candidates. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear facilitate proton-translocation. SQ109, AU1235, ICA38, and rimonabant bind inside the transmembrane region and disrupt these Asp-Tyr pairs (Zhang et al. 2019). MmpL3 can be directed inhibited by several antitubercular compounds (Li et al. 2019).

Accession Number:O53657
Protein Name:Putative membrane protein mmpL3
Length:944
Molecular Weight:100904.00
Species:Mycobacterium tuberculosis [1773]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate mycolic acids, trehalose monomycolate

Cross database links:

HEGENOM: HBG728607 HBG728607
Entrez Gene ID: 886752    923110   
Pfam: PF03176   
KEGG: mtc:MT0216    mtu:Rv0206c    mtc:MT0216    mtu:Rv0206c   

Gene Ontology

GO:0005618 C:cell wall
GO:0005576 C:extracellular region
GO:0005887 C:integral to plasma membrane

References (4)

[1] “Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.”  Cole S.T.et.al.   9634230
[2] “Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.”  Fleischmann R.D.et.al.   12218036
[3] “Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.”  Cole S.T.et.al.   9634230
[4] “Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.”  Fleischmann R.D.et.al.   12218036

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MFAWWGRTVY RYRFIVIGVM VALCLGGGVF GLSLGKHVTQ SGFYDDGSQS VQASVLGDQV 
61:	YGRDRSGHIV AIFQAPAGKT VDDPAWSKKV VDELNRFQQD HPDQVLGWAG YLRASQATGM 
121:	ATADKKYTFV SIPLKGDDDD TILNNYKAIA PDLQRLDGGT VKLAGLQPVA EALTGTIATD 
181:	QRRMEVLALP LVAVVLFFVF GGVIAAGLPV MVGGLCIAGA LGIMRFLAIF GPVHYFAQPV 
241:	VSLIGLGIAI DYGLFIVSRF REEIAEGYDT ETAVRRTVIT AGRTVTFSAV LIVASAIGLL 
301:	LFPQGFLKSL TYATIASVML SAILSITVLP ACLGILGKHV DALGVRTLFR VPFLANWKIS 
361:	AAYLNWLADR LQRTKTREEV EAGFWGKLVN RVMKRPVLFA APIVIIMILL IIPVGKLSLG 
421:	GISEKYLPPT NSVRQAQEEF DKLFPGYRTN PLTLVIQTSN HQPVTDAQIA DIRSKAMAIG 
481:	GFIEPDNDPA NMWQERAYAV GASKDPSVRV LQNGLINPAD ASKKLTELRA ITPPKGITVL 
541:	VGGTPALELD SIHGLFAKMP LMVVILLTTT IVLMFLAFGS VVLPIKATLM SALTLGSTMG 
601:	ILTWIFVDGH FSKWLNFTPT PLTAPVIGLI IALVFGLSTD YEVFLVSRMV EARERGMSTQ 
661:	EAIRIGTAAT GRIITAAALI VAVVAGAFVF SDLVMMKYLA FGLMAALLLD ATVVRMFLVP 
721:	SVMKLLGDDC WWAPRWARRL QTRIGLGEIH LPDERKRPVS NGRPARPPVT AGLVAARAAG 
781:	DPRPPHDPTH PLAESPRPAR SSPASSPELT PALEATAAPA APSGASTTRM QIGSSTEPPT 
841:	TRLAAAGRSV QSPASTPPPT PTPPSAPSAG QTRAMPLAAN RSTDAAGDPA EPTAALPIIR 
901:	SDGDDSEAAT EQLNARGTSD KTRQRRRGGG ALSAQDLLRR EGRL