CTPC_MYCTU
ID CTPC_MYCTU Reviewed; 718 AA.
AC P9WPT5; L0TF47; O66027; P0A502; P96875;
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=Manganese-exporting P-type ATPase {ECO:0000305};
DE EC=7.2.2.- {ECO:0000269|PubMed:23482562};
DE AltName: Full=Cation-transporting P-type ATPase CtpC {ECO:0000305};
DE AltName: Full=Metal-transporting ATPase Mta72 {ECO:0000305|PubMed:9514635};
GN Name=ctpC {ECO:0000303|PubMed:21925112};
GN Synonyms=mtaA {ECO:0000303|PubMed:9514635}; OrderedLocusNames=Rv3270;
GN ORFNames=MTCY71.10;
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 [GENOMIC DNA], AND INDUCTION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=9514635; DOI=10.1006/mpat.1997.9999;
RA Calder K.M., Horwitz M.A.;
RT "Identification of iron-regulated proteins of Mycobacterium tuberculosis
RT and cloning of tandem genes encoding a low iron-induced protein and a metal
RT transporting ATPase with similarities to two-component metal transport
RT systems.";
RL Microb. Pathog. 24:133-143(1998).
RN [2]
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 [3]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21925112; DOI=10.1016/j.chom.2011.08.006;
RA Botella H., Peyron P., Levillain F., Poincloux R., Poquet Y., Brandli I.,
RA Wang C., Tailleux L., Tilleul S., Charriere G.M., Waddell S.J., Foti M.,
RA Lugo-Villarino G., Gao Q., Maridonneau-Parini I., Butcher P.D.,
RA Castagnoli P.R., Gicquel B., de Chastellier C., Neyrolles O.;
RT "Mycobacterial P1-type ATPases mediate resistance to zinc poisoning in
RT human macrophages.";
RL Cell Host Microbe 10:248-259(2011).
RN [4]
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).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, INDUCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-697 AND
RP 700-SER-SER-701.
RC STRAIN=H37Rv;
RX PubMed=23482562; DOI=10.1074/jbc.m112.448175;
RA Padilla-Benavides T., Long J.E., Raimunda D., Sassetti C.M., Arguello J.M.;
RT "A novel P1B-type Mn2+ transporting ATPase is required for secreted protein
RT metallation in Mycobacteria.";
RL J. Biol. Chem. 288:11334-11347(2013).
CC -!- FUNCTION: High affinity, slow turnover Mn(2+) transporting ATPase,
CC which is required for virulence. Controls the Mn(2+) cytoplasmic quota
CC and is involved in the uploading of Mn(2+) into secreted
CC metalloproteins (PubMed:23482562). Required for tolerance to Zn(2+) and
CC oxidative stress (PubMed:23482562). Plays a crucial role in the ability
CC to resist zinc poisoning in human macrophages (PubMed:21925112). Shows
CC a preference for Mn(2+), but Zn(2+), Co(2+) and Cu(2+) can act as
CC alternative substrates although at slower turnover rates
CC (PubMed:23482562). {ECO:0000269|PubMed:21925112,
CC ECO:0000269|PubMed:23482562}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + Mn(2+)(in) = ADP + H(+) + Mn(2+)(out) + phosphate;
CC Xref=Rhea:RHEA:66820, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29035, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:23482562};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=1.1 umol/h/mg enzyme with Mn(2+) as substrate
CC {ECO:0000269|PubMed:23482562};
CC Vmax=0.30 umol/h/mg enzyme with Zn(2+) as substrate
CC {ECO:0000269|PubMed:23482562};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23482562};
CC Multi-pass membrane protein {ECO:0000305|PubMed:23482562}.
CC -!- INDUCTION: Induced by zinc and during infection of human macrophages
CC (PubMed:21925112, PubMed:23482562). Transcriptionally regulated by iron
CC (PubMed:9514635). {ECO:0000269|PubMed:21925112,
CC ECO:0000269|PubMed:23482562, ECO:0000269|PubMed:9514635}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene leads to cytoplasmic Mn(2+)
CC accumulation and a decrease in secreted Mn(2+)-bound proteins
CC (PubMed:23482562). Mutant is hypersensitive to zinc and oxidative
CC stress (PubMed:21925112, PubMed:23482562). It exhibits an impaired
CC growth in human macrophages (PubMed:21925112).
CC {ECO:0000269|PubMed:21925112, ECO:0000269|PubMed:23482562}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IB subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC15948.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U82820; AAC15948.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AL123456; CCP46089.1; -; Genomic_DNA.
DR PIR; G70978; G70978.
DR RefSeq; NP_217787.1; NC_000962.3.
DR RefSeq; WP_003899995.1; NZ_NVQJ01000003.1.
DR AlphaFoldDB; P9WPT5; -.
DR SMR; P9WPT5; -.
DR STRING; 83332.Rv3270; -.
DR PaxDb; P9WPT5; -.
DR DNASU; 888705; -.
DR GeneID; 888705; -.
DR KEGG; mtu:Rv3270; -.
DR TubercuList; Rv3270; -.
DR eggNOG; COG2217; Bacteria.
DR OMA; IVTWLFM; -.
DR PhylomeDB; P9WPT5; -.
DR BRENDA; 7.2.2.22; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; IBA:GO_Central.
DR GO; GO:0043682; F:P-type divalent copper transporter activity; IBA:GO_Central.
DR GO; GO:0140613; F:P-type manganese transporter activity; IEA:RHEA.
DR GO; GO:0055070; P:copper ion homeostasis; IBA:GO_Central.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR027256; P-typ_ATPase_IB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01525; ATPase-IB_hvy; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS50846; HMA_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Virulence.
FT CHAIN 1..718
FT /note="Manganese-exporting P-type ATPase"
FT /id="PRO_0000046337"
FT TRANSMEM 87..105
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 128..146
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 154..168
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 177..191
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 327..351
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 357..375
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 661..680
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT TRANSMEM 690..709
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23482562"
FT DOMAIN 11..78
FT /note="HMA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT ACT_SITE 408
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 408
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 410
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 610
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT MUTAGEN 697
FT /note="H->A: Loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:23482562"
FT MUTAGEN 700..701
FT /note="SS->AA: Loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:23482562"
SQ SEQUENCE 718 AA; 76495 MW; 85D6C93AFE636315 CRC64;
MTLEVVSDAA GRMRVKVDWV RCDSRRAVAV EEAVAKQNGV RVVHAYPRTG SVVVWYSPRR
ADRAAVLAAI KGAAHVAAEL IPARAPHSAE IRNTDVLRMV IGGVALALLG VRRYVFARPP
LLGTTGRTVA TGVTIFTGYP FLRGALRSLR SGKAGTDALV SAATVASLIL RENVVALTVL
WLLNIGEYLQ DLTLRRTRRA ISELLRGNQD TAWVRLTDPS AGSDAATEIQ VPIDTVQIGD
EVVVHEHVAI PVDGEVVDGE AIVNQSAITG ENLPVSVVVG TRVHAGSVVV RGRVVVRAHA
VGNQTTIGRI ISRVEEAQLD RAPIQTVGEN FSRRFVPTSF IVSAIALLIT GDVRRAMTML
LIACPCAVGL STPTAISAAI GNGARRGILI KGGSHLEQAG RVDAIVFDKT GTLTVGRPVV
TNIVAMHKDW EPEQVLAYAA SSEIHSRHPL AEAVIRSTEE RRISIPPHEE CEVLVGLGMR
TWADGRTLLL GSPSLLRAEK VRVSKKASEW VDKLRRQAET PLLLAVDGTL VGLISLRDEV
RPEAAQVLTK LRANGIRRIV MLTGDHPEIA QVVADELGID EWRAEVMPED KLAAVRELQD
DGYVVGMVGD GINDAPALAA ADIGIAMGLA GTDVAVETAD VALANDDLHR LLDVGDLGER
AVDVIRQNYG MSIAVNAAGL LIGAGGALSP VLAAILHNAS SVAVVANSSR LIRYRLDR
