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3.A.1.21.2
The Fe3+-mycobactin/carboxymycobactin transporter, IrtAB (Rodriguez and Smith, 2006). IrtA contains an FAD-binding domain (Ryndak et al., 2010). M. tuberculosis produces two classes of siderophore, lipid-bound mycobactin and water-soluble carboxymycobactin. Iron-loaded carboxymycobactin is imported into the cytoplasm by IrtAB which has an additional cytoplasmic siderophore interaction domain that may serve as a periplasmic receptor. Membrane-reconstituted IrtAB is sufficient for the import of mycobactins, which are then reduced by the siderophore interaction domain to facilitate iron release (Arnold et al. 2020). Structure determination by X-ray crystallography and cryo-EM not only confirmed that IrtAB has an ABC exporter fold (as indicated by TC-BLAST searches), but also revealed structural peculiarities at the transmembrane region of IrtAB that result in a partially collapsed inward-facing substrate-binding cavity. The siderophore interaction domain is positioned in close proximity to the inner membrane leaflet, enabling the reduction of membrane-inserted mycobactin. Enzymatic ATPase activity and in vivo growth assays revealed that IrtAB has a preference for mycobactin over carboxymycobactin as its substrate (Arnold et al. 2020). The large transporter (Rv1348-1349) of 859 aas seems to have three domains, an extracytoplasmic receptor domain (IrtA), a central membrane domain of 6 TMSs (IrtB) and a C-terminal ATPase (IrtC). If so, there may be two potential receptors (see Mandal et al. 2021 for a review).

Accession Number:P63391
Protein Name:IrtA
Length:859
Molecular Weight:92966.00
Species:Mycobacterium tuberculosis [1773]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Fe3+-carboxymycobactin

Cross database links:

RefSeq: NP_215864.1    NP_335840.1   
Entrez Gene ID: 886853    924630   
Pfam: PF00664    PF00005    PF08021    PF04954   
KEGG: mtc:MT1390    mtu:Rv1348   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0016491 F:oxidoreductase activity
GO:0055114 P:oxidation reduction
GO:0055085 P:transmembrane transport

References (2)

[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

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MARGLQGVML RSFGARDHTA TVIETISIAP HFVRVRMVSP TLFQDAEAEP AAWLRFWFPD 
61:	PNGSNTEFQR AYTISEADPA AGRFAVDVVL HDPAGPASSW ARTVKPGATI AVMSLMGSSR 
121:	FDVPEEQPAG YLLIGDSASI PGMNGIIETV PNDVPIEMYL EQHDDNDTLI PLAKHPRLRV 
181:	RWVMRRDEKS LAEAIENRDW SDWYAWATPE AAALKCVRVR LRDEFGFPKS EIHAQAYWNA 
241:	GRAMGTHRAT EPAATEPEVG AAPQPESAVP APARGSWRAQ AASRLLAPLK LPLVLSGVLA 
301:	ALVTLAQLAP FVLLVELSRL LVSGAGAHRL FTVGFAAVGL LGTGALLAAA LTLWLHVIDA 
361:	RFARALRLRL LSKLSRLPLG WFTSRGSGSI KKLVTDDTLA LHYLVTHAVP DAVAAVVAPV 
421:	GVLVYLFVVD WRVALVLFGP VLVYLTITSS LTIQSGPRIV QAQRWAEKMN GEAGSYLEGQ 
481:	PVIRVFGAAS SSFRRRLDEY IGFLVAWQRP LAGKKTLMDL ATRPATFLWL IAATGTLLVA 
541:	THRMDPVNLL PFMFLGTTFG ARLLGIAYGL GGLRTGLLAA RHLQVTLDET ELAVREHPRE 
601:	PLDGEAPATV VFDHVTFGYR PGVPVIQDVS LTLRPGTVTA LVGPSGSGKS TLATLLARFH 
661:	DVERGAIRVG GQDIRSLAAD ELYTRVGFVL QEAQLVHGTA AENIALAVPD APAEQVQVAA 
721:	REAQIHDRVL RLPDGYDTVL GANSGLSGGE RQRLTIARAI LGDTPVLILD EATAFADPES 
781:	EYLVQQALNR LTRDRTVLVI AHRLHTITRA DQIVVLDHGR IVERGTHEEL LAAGGRYCRL 
841:	WDTGQGSRVA VAAAQDGTR