IRTA_MYCTU
ID IRTA_MYCTU Reviewed; 859 AA.
AC P9WQJ9; L0T6D6; P63391; Q11018;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Mycobactin import ATP-binding/permease protein IrtA {ECO:0000305};
DE EC=7.2.2.-;
DE AltName: Full=Iron-regulated transporter A;
GN Name=irtA; OrderedLocusNames=Rv1348; ORFNames=MTCY02B10.12;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12065475; DOI=10.1128/iai.70.7.3371-3381.2002;
RA Rodriguez G.M., Voskuil M.I., Gold B., Schoolnik G.K., Smith I.;
RT "IdeR, an essential gene in Mycobacterium tuberculosis: role of IdeR in
RT iron-dependent gene expression, iron metabolism, and oxidative stress
RT response.";
RL Infect. Immun. 70:3371-3381(2002).
RN [3]
RP FUNCTION, SUBUNIT, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16385031; DOI=10.1128/jb.188.2.424-430.2006;
RA Rodriguez G.M., Smith I.;
RT "Identification of an ABC transporter required for iron acquisition and
RT virulence in Mycobacterium tuberculosis.";
RL J. Bacteriol. 188:424-430(2006).
RN [4]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18461140; DOI=10.1371/journal.pone.0002087;
RA Farhana A., Kumar S., Rathore S.S., Ghosh P.C., Ehtesham N.Z., Tyagi A.K.,
RA Hasnain S.E.;
RT "Mechanistic insights into a novel exporter-importer system of
RT Mycobacterium tuberculosis unravel its role in trafficking of iron.";
RL PLoS ONE 3:E2087-E2087(2008).
RN [5]
RP FUNCTION, COFACTOR, SUBUNIT, DOMAIN, TOPOLOGY, AND MUTAGENESIS OF ARG-70;
RP TYR-72 AND THR-73.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19948799; DOI=10.1128/jb.00223-09;
RA Ryndak M.B., Wang S., Smith I., Rodriguez G.M.;
RT "The Mycobacterium tuberculosis high-affinity iron importer, IrtA, contains
RT an FAD-binding domain.";
RL J. Bacteriol. 192:861-869(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Part of the ABC transporter complex IrtAB involved in the
CC import of iron-bound mycobactin (Fe-MBT) and carboxymycobactin (Fe-
CC cMBT) (PubMed:16385031, PubMed:19948799) (By similarity). Mycobactins
CC are then reduced by the siderophore interaction domain to facilitate
CC iron release in the bacterial cell (By similarity). Transmembrane
CC domains (TMD) form a pore in the membrane and the ATP-binding domain
CC (NBD) is responsible for energy generation (By similarity). Required
CC for replication in human macrophages and in mouse lungs
CC (PubMed:16385031). {ECO:0000250|UniProtKB:G7CBF5,
CC ECO:0000269|PubMed:16385031, ECO:0000269|PubMed:19948799}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:19948799};
CC -!- SUBUNIT: Forms a heterodimer with IrtB. {ECO:0000305|PubMed:16385031,
CC ECO:0000305|PubMed:19948799}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:18461140}; Multi-pass membrane protein
CC {ECO:0000255|PROSITE-ProRule:PRU00441, ECO:0000269|PubMed:18461140}.
CC -!- INDUCTION: Repressed by iron and IdeR. {ECO:0000269|PubMed:12065475,
CC ECO:0000269|PubMed:18461140}.
CC -!- DOMAIN: In IrtA the ATP-binding domain (NBD) and the transmembrane
CC domain (TMD) are fused (PubMed:16385031). In addition, IrtA contains an
CC N-terminal siderophore interaction domain (SID) that binds FAD
CC (PubMed:19948799). {ECO:0000269|PubMed:16385031,
CC ECO:0000269|PubMed:19948799}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. Siderophore-
CC Fe(3+) uptake transporter (SIUT) (TC 3.A.1.21) family. {ECO:0000305}.
CC -!- CAUTION: PubMed:18461140 reports that IrtA is a siderophore exporter,
CC however this activity could be due to functional differences of IrtA in
CC the molecular context of M.smegmatis and M.tuberculosis. {ECO:0000305}.
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DR EMBL; AL123456; CCP44106.1; -; Genomic_DNA.
DR PIR; C70740; C70740.
DR RefSeq; NP_215864.1; NC_000962.3.
DR RefSeq; WP_003406958.1; NZ_NVQJ01000031.1.
DR AlphaFoldDB; P9WQJ9; -.
DR SMR; P9WQJ9; -.
DR STRING; 83332.Rv1348; -.
DR PaxDb; P9WQJ9; -.
DR GeneID; 886853; -.
DR KEGG; mtu:Rv1348; -.
DR TubercuList; Rv1348; -.
DR eggNOG; COG1132; Bacteria.
DR eggNOG; COG2375; Bacteria.
DR OMA; GAYLEGQ; -.
DR PhylomeDB; P9WQJ9; -.
DR Reactome; R-HSA-1222449; Mtb iron assimilation by chelation.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IDA:MTBBASE.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0015343; F:siderophore transmembrane transporter activity; IDA:MTBBASE.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:MTBBASE.
DR GO; GO:0044847; P:iron acquisition from host; IMP:MTBBASE.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:MTBBASE.
DR GO; GO:0075139; P:response to host iron concentration; IMP:MTBBASE.
DR GO; GO:0033214; P:siderophore-dependent iron import into cell; IDA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR013113; FAD-bd_9_SIP.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR InterPro; IPR007037; SIP_C.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR Pfam; PF08021; FAD_binding_9; 1.
DR Pfam; PF04954; SIP; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell inner membrane; Cell membrane; FAD; Flavoprotein;
KW Membrane; Nucleotide-binding; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..859
FT /note="Mycobactin import ATP-binding/permease protein IrtA"
FT /id="PRO_0000093255"
FT TOPO_DOM 1..292
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 314..334
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 335..355
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 356..408
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 430..432
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 433..453
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 454..519
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 520..540
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 541..548
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT TRANSMEM 549..569
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 570..859
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19948799"
FT DOMAIN 15..122
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT DOMAIN 293..575
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 610..843
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 247..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 70..73
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G7CBF5"
FT BINDING 87..91
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G7CBF5"
FT BINDING 97..98
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G7CBF5"
FT BINDING 643..650
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MUTAGEN 70
FT /note="R->A: No change in FAD-binding and in activity."
FT /evidence="ECO:0000269|PubMed:19948799"
FT MUTAGEN 72
FT /note="Y->A: Decrease in FAD-binding and loss of activity."
FT /evidence="ECO:0000269|PubMed:19948799"
FT MUTAGEN 73
FT /note="T->A: Decrease in FAD-binding and loss of activity."
FT /evidence="ECO:0000269|PubMed:19948799"
SQ SEQUENCE 859 AA; 92966 MW; 37D756CCB349C9BD CRC64;
MARGLQGVML RSFGARDHTA TVIETISIAP HFVRVRMVSP TLFQDAEAEP AAWLRFWFPD
PNGSNTEFQR AYTISEADPA AGRFAVDVVL HDPAGPASSW ARTVKPGATI AVMSLMGSSR
FDVPEEQPAG YLLIGDSASI PGMNGIIETV PNDVPIEMYL EQHDDNDTLI PLAKHPRLRV
RWVMRRDEKS LAEAIENRDW SDWYAWATPE AAALKCVRVR LRDEFGFPKS EIHAQAYWNA
GRAMGTHRAT EPAATEPEVG AAPQPESAVP APARGSWRAQ AASRLLAPLK LPLVLSGVLA
ALVTLAQLAP FVLLVELSRL LVSGAGAHRL FTVGFAAVGL LGTGALLAAA LTLWLHVIDA
RFARALRLRL LSKLSRLPLG WFTSRGSGSI KKLVTDDTLA LHYLVTHAVP DAVAAVVAPV
GVLVYLFVVD WRVALVLFGP VLVYLTITSS LTIQSGPRIV QAQRWAEKMN GEAGSYLEGQ
PVIRVFGAAS SSFRRRLDEY IGFLVAWQRP LAGKKTLMDL ATRPATFLWL IAATGTLLVA
THRMDPVNLL PFMFLGTTFG ARLLGIAYGL GGLRTGLLAA RHLQVTLDET ELAVREHPRE
PLDGEAPATV VFDHVTFGYR PGVPVIQDVS LTLRPGTVTA LVGPSGSGKS TLATLLARFH
DVERGAIRVG GQDIRSLAAD ELYTRVGFVL QEAQLVHGTA AENIALAVPD APAEQVQVAA
REAQIHDRVL RLPDGYDTVL GANSGLSGGE RQRLTIARAI LGDTPVLILD EATAFADPES
EYLVQQALNR LTRDRTVLVI AHRLHTITRA DQIVVLDHGR IVERGTHEEL LAAGGRYCRL
WDTGQGSRVA VAAAQDGTR
