CAIT_PROMH
ID CAIT_PROMH Reviewed; 514 AA.
AC B4EY22;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 25-MAY-2022, entry version 97.
DE RecName: Full=L-carnitine/gamma-butyrobetaine antiporter {ECO:0000255|HAMAP-Rule:MF_01049};
GN Name=caiT {ECO:0000255|HAMAP-Rule:MF_01049, ECO:0000303|PubMed:20829798};
GN OrderedLocusNames=PMI2654 {ECO:0000312|EMBL:CAR45230.1};
OS Proteus mirabilis (strain HI4320).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Morganellaceae; Proteus.
OX NCBI_TaxID=529507;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HI4320;
RX PubMed=18375554; DOI=10.1128/jb.01981-07;
RA Pearson M.M., Sebaihia M., Churcher C., Quail M.A., Seshasayee A.S.,
RA Luscombe N.M., Abdellah Z., Arrosmith C., Atkin B., Chillingworth T.,
RA Hauser H., Jagels K., Moule S., Mungall K., Norbertczak H.,
RA Rabbinowitsch E., Walker D., Whithead S., Thomson N.R., Rather P.N.,
RA Parkhill J., Mobley H.L.T.;
RT "Complete genome sequence of uropathogenic Proteus mirabilis, a master of
RT both adherence and motility.";
RL J. Bacteriol. 190:4027-4037(2008).
RN [2] {ECO:0007744|PDB:2WSW}
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 3-504, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION,
RP TOPOLOGY, AND MUTAGENESIS OF GLU-111; TRP-316 AND MET-331.
RX PubMed=20829798; DOI=10.1038/nature09310;
RA Schulze S., Koster S., Geldmacher U., Terwisscha van Scheltinga A.C.,
RA Kuhlbrandt W.;
RT "Structural basis of Na(+)-independent and cooperative substrate/product
RT antiport in CaiT.";
RL Nature 467:233-236(2010).
RN [3] {ECO:0007744|PDB:4M8J}
RP X-RAY CRYSTALLOGRAPHY (3.29 ANGSTROMS) OF 1-504 OF MUTANT GLU-262,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF ARG-262.
RX PubMed=24101465; DOI=10.1073/pnas.1309071110;
RA Kalayil S., Schulze S., Kuhlbrandt W.;
RT "Arginine oscillation explains Na+ independence in the substrate/product
RT antiporter CaiT.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17296-17301(2013).
CC -!- FUNCTION: Catalyzes the exchange of L-carnitine for gamma-
CC butyrobetaine. {ECO:0000255|HAMAP-Rule:MF_01049,
CC ECO:0000269|PubMed:20829798, ECO:0000269|PubMed:24101465}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-carnitine(out) + 4-(trimethylamino)butanoate(in) = (R)-
CC carnitine(in) + 4-(trimethylamino)butanoate(out);
CC Xref=Rhea:RHEA:29427, ChEBI:CHEBI:16244, ChEBI:CHEBI:16347;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01049,
CC ECO:0000269|PubMed:20829798, ECO:0000269|PubMed:24101465};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=46 uM for L-carnitine {ECO:0000269|PubMed:20829798};
CC KM=8.5 uM for L-carnitine {ECO:0000269|PubMed:24101465};
CC Vmax=4672 nmol/min/mg enzyme {ECO:0000269|PubMed:20829798};
CC Vmax=5172 nmol/min/mg enzyme {ECO:0000269|PubMed:24101465};
CC Note=kcat is 263 min(-1) with L-carnitine as substrate
CC (PubMed:20829798). kcat is 4.9 sec(-1) with L-carnitine as substrate
CC (PubMed:24101465). {ECO:0000269|PubMed:20829798,
CC ECO:0000269|PubMed:24101465};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:24101465};
CC -!- PATHWAY: Amine and polyamine metabolism; carnitine metabolism.
CC {ECO:0000255|HAMAP-Rule:MF_01049}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000255|HAMAP-Rule:MF_01049,
CC ECO:0000269|PubMed:20829798, ECO:0000269|PubMed:24101465}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_01049, ECO:0000269|PubMed:20829798,
CC ECO:0000269|PubMed:24101465}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_01049, ECO:0000269|PubMed:20829798,
CC ECO:0000269|PubMed:24101465}.
CC -!- SIMILARITY: Belongs to the BCCT transporter (TC 2.A.15) family. CaiT
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01049}.
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DR EMBL; AM942759; CAR45230.1; -; Genomic_DNA.
DR RefSeq; WP_012368453.1; NC_010554.1.
DR PDB; 2WSW; X-ray; 2.29 A; A=3-504.
DR PDB; 4M8J; X-ray; 3.29 A; A=1-504.
DR PDBsum; 2WSW; -.
DR PDBsum; 4M8J; -.
DR SMR; B4EY22; -.
DR STRING; 529507.PMI2654; -.
DR TCDB; 2.A.15.2.2; the betaine/carnitine/choline transporter (bcct) family.
DR EnsemblBacteria; CAR45230; CAR45230; PMI2654.
DR GeneID; 6803117; -.
DR KEGG; pmr:PMI2654; -.
DR PATRIC; fig|529507.6.peg.2582; -.
DR eggNOG; COG1292; Bacteria.
DR HOGENOM; CLU_010118_6_0_6; -.
DR OMA; AWAPFTG; -.
DR UniPathway; UPA00117; -.
DR EvolutionaryTrace; B4EY22; -.
DR Proteomes; UP000008319; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044667; F:(R)-carnitine:4-(trimethylammonio)butanoate antiporter activity; IEA:InterPro.
DR GO; GO:1900751; P:4-(trimethylammonio)butanoate transport; IEA:InterPro.
DR GO; GO:0009437; P:carnitine metabolic process; IEA:UniProtKB-UniPathway.
DR HAMAP; MF_01049; CaiT; 1.
DR InterPro; IPR018093; BCCT_CS.
DR InterPro; IPR000060; BCCT_transptr.
DR InterPro; IPR023449; BCCT_transptr_CaiT.
DR PANTHER; PTHR30047; PTHR30047; 1.
DR Pfam; PF02028; BCCT; 1.
DR TIGRFAMs; TIGR00842; bcct; 1.
DR PROSITE; PS01303; BCCT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiport; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..514
FT /note="L-carnitine/gamma-butyrobetaine antiporter"
FT /id="PRO_0000455644"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 12..30
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 31..42
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 43..68
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 69..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 92..112
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 113..131
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 132..154
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 155..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 186..216
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 217..230
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 231..249
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 250..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 252..277
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 278..311
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 312..335
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 336..347
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 348..369
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 370..404
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 405..434
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 435..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 446..464
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 465..468
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TRANSMEM 469..492
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT TOPO_DOM 493..514
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:20829798,
FT ECO:0007744|PDB:2WSW"
FT SITE 262
FT /note="Important for substrate binding and transport
FT mechanism"
FT /evidence="ECO:0000305|PubMed:24101465"
FT MUTAGEN 111
FT /note="E->A: Abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:20829798"
FT MUTAGEN 262
FT /note="R->A,E: Strong decrease in L-carnitine transport.
FT Mutant is Na(+)-dependent for substrate binding and
FT transport."
FT /evidence="ECO:0000269|PubMed:24101465"
FT MUTAGEN 316
FT /note="W->A: 2.5-fold decrease in Vmax."
FT /evidence="ECO:0000269|PubMed:20829798"
FT MUTAGEN 331
FT /note="M->V: 10-fold decrease in Vmax."
FT /evidence="ECO:0000269|PubMed:20829798"
SQ SEQUENCE 514 AA; 57471 MW; 5D2C3237CD751CC7 CRC64;
MSKDNKKAGI EPKVFFPPLI IVGILCWLTV RDLDASNEVI NAVFSYVTNV WGWAFEWYMV
IMFGGWFWLV FGRYAKKRLG DEKPEFSTAS WIFMMFASCT SAAVLFWGSI EIYYYISSPP
FGMEGYSAPA KEIGLAYSLF HWGPLPWATY SFLSVAFAYF FFVRKMEVIR PSSTLTPLVG
EKHVNGLFGT VVDNFYLVAL ILAMGTSLGL ATPLVTECIQ YLFGIPHTLQ LDAIIISCWI
LLNAICVAFG LQKGVKIASD VRTYLSFLML GWVFIVGGAS FIVNYFTDSV GTLLMYMPRM
LFYTDPIGKG GFPQAWTVFY WAWWVIYAIQ MSIFLARISK GRTVRELCLG MVSGLTAGTW
LIWTILGGNT LQLIDQNILN IPQLIDQYGV PRAIIETWAA LPLSTATMWG FFILCFIATV
TLINACSYTL AMSTCRSMKE GAEPPLLVRI GWSVLVGIIG IILLALGGLK PIQTAIIAGG
CPLFFVNIMV TLSFIKDAKV HWKDCSPYTQ KMTH
