ADIC_ECO57
ID ADIC_ECO57 Reviewed; 445 AA.
AC P60063; P39268; P39269;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2003, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Arginine/agmatine antiporter;
GN Name=adiC; OrderedLocusNames=Z5717, ECs5097;
OS Escherichia coli O157:H7.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83334;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX PubMed=11206551; DOI=10.1038/35054089;
RA Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J.,
RA Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G.,
RA Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J.,
RA Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J.,
RA Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A.,
RA Blattner F.R.;
RT "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7.";
RL Nature 409:529-533(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX PubMed=11258796; DOI=10.1093/dnares/8.1.11;
RA Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K.,
RA Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T.,
RA Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S.,
RA Shiba T., Hattori M., Shinagawa H.;
RT "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and
RT genomic comparison with a laboratory strain K-12.";
RL DNA Res. 8:11-22(2001).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-74 AND PHE-337.
RC STRAIN=O157:H7 / EHEC;
RX PubMed=25136114; DOI=10.1073/pnas.1414093111;
RA Wang S., Yan R., Zhang X., Chu Q., Shi Y.;
RT "Molecular mechanism of pH-dependent substrate transport by an arginine-
RT agmatine antiporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12734-12739(2014).
RN [4] {ECO:0007744|PDB:3LRB, ECO:0007744|PDB:3LRC}
RP X-RAY CRYSTALLOGRAPHY (3.61 ANGSTROMS) IN OUTWARD-OPEN CONFORMATION,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, SUBSTRATE-BINDING SITES, DOMAIN,
RP AND MUTAGENESIS OF ASN-22; SER-26; TYR-87; TYR-93; GLU-208 AND TYR-365.
RC STRAIN=O157:H7 / EHEC;
RX PubMed=19478139; DOI=10.1126/science.1173654;
RA Gao X., Lu F., Zhou L., Dang S., Sun L., Li X., Wang J., Shi Y.;
RT "Structure and mechanism of an amino acid antiporter.";
RL Science 324:1565-1568(2009).
RN [5] {ECO:0007744|PDB:3L1L}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN OUTWARD-FACING OCCLUDED
RP CONFORMATION IN COMPLEX WITH SUBSTRATE (ARG), SUBUNIT, DOMAIN, AND
RP MUTAGENESIS OF ASN-22.
RC STRAIN=O157:H7 / EHEC;
RX PubMed=20090677; DOI=10.1038/nature08741;
RA Gao X., Zhou L., Jiao X., Lu F., Yan C., Zeng X., Wang J., Shi Y.;
RT "Mechanism of substrate recognition and transport by an amino acid
RT antiporter.";
RL Nature 463:828-832(2010).
CC -!- FUNCTION: Major component of the acid-resistance (AR) system allowing
CC enteric pathogens to survive the acidic environment in the stomach
CC (Probable). Exchanges extracellular arginine for its intracellular
CC decarboxylation product agmatine (Agm) thereby expelling intracellular
CC protons (PubMed:19478139, PubMed:25136114). Probably undergoes several
CC conformational states in order to translocate the substrate across the
CC membrane; keeps the substrate accessible to only 1 side of the membrane
CC at a time by opening and closing 3 membrane-internal gates (Probable).
CC {ECO:0000269|PubMed:19478139, ECO:0000269|PubMed:25136114,
CC ECO:0000305|PubMed:19478139, ECO:0000305|PubMed:20090677}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=agmatine(in) + L-arginine(out) = agmatine(out) + L-
CC arginine(in); Xref=Rhea:RHEA:29651, ChEBI:CHEBI:32682,
CC ChEBI:CHEBI:58145; Evidence={ECO:0000269|PubMed:19478139,
CC ECO:0000269|PubMed:25136114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29652;
CC Evidence={ECO:0000269|PubMed:25136114};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=1340 nmol/min/mg enzyme for Arg exchange at pH 6.0
CC {ECO:0000269|PubMed:25136114};
CC Vmax=51 nmol/min/mg enzyme for Arg exchange at pH 7.5
CC {ECO:0000269|PubMed:25136114};
CC pH dependence:
CC Optimum pH is 5.5 or less for Arg-Agm exchange, which slows
CC dramatically as pH rises and is almost undetectable at pH 7.0 and
CC higher. {ECO:0000269|PubMed:25136114};
CC -!- SUBUNIT: Homodimer;each subunit has its own individual transport
CC capacity. {ECO:0000269|PubMed:19478139, ECO:0000269|PubMed:20090677}.
CC -!- INTERACTION:
CC P60063; P60063: adiC; NbExp=3; IntAct=EBI-15829035, EBI-15829035;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:19478139}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19478139, ECO:0000269|PubMed:20090677}.
CC -!- DOMAIN: Each subunit has 12 transmembrane (TM) domains, arranged with
CC an internal layer (TM1, TM3, TM6, TM8 and TM10) surrounded by the outer
CC layer (TM2, TM4, TM5, TM7, TM9, TM11 and TM12). TM1 and TM6 are
CC interrupted by short, non-helical, Gly-containing loops in the middle
CC of their transmembrane spans. Homodimerization is mediated by TM3,
CC TM10, TM11 and TM12. Each subunit has a central cavity which binds
CC substrates (PubMed:19478139). Upon Arg-binding the N-terminus of TM6
CC and Trp-202 move to prevent Arg from return to the periplasm
CC (PubMed:20090677). {ECO:0000269|PubMed:19478139,
CC ECO:0000269|PubMed:20090677}.
CC -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC)
CC superfamily. Basic amino acid/polyamine antiporter (APA) (TC 2.A.3.2)
CC family. {ECO:0000305}.
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DR EMBL; AE005174; AAG59314.1; -; Genomic_DNA.
DR EMBL; BA000007; BAB38520.1; -; Genomic_DNA.
DR PIR; A91266; A91266.
DR PIR; F86106; F86106.
DR RefSeq; NP_313124.1; NC_002695.1.
DR RefSeq; WP_000093154.1; NZ_SWKA01000005.1.
DR PDB; 3L1L; X-ray; 3.00 A; A=1-445.
DR PDB; 3LRB; X-ray; 3.61 A; A/B=1-445.
DR PDB; 3LRC; X-ray; 4.00 A; A/B/C/D=1-445.
DR PDBsum; 3L1L; -.
DR PDBsum; 3LRB; -.
DR PDBsum; 3LRC; -.
DR AlphaFoldDB; P60063; -.
DR SMR; P60063; -.
DR DIP; DIP-48684N; -.
DR STRING; 155864.EDL933_5460; -.
DR DrugBank; DB02451; B-nonylglucoside.
DR EnsemblBacteria; AAG59314; AAG59314; Z5717.
DR EnsemblBacteria; BAB38520; BAB38520; ECs_5097.
DR GeneID; 66671974; -.
DR GeneID; 914204; -.
DR KEGG; ece:Z5717; -.
DR KEGG; ecs:ECs_5097; -.
DR PATRIC; fig|386585.9.peg.5327; -.
DR eggNOG; COG0531; Bacteria.
DR HOGENOM; CLU_007946_1_0_6; -.
DR OMA; YDGWILI; -.
DR EvolutionaryTrace; P60063; -.
DR Proteomes; UP000000558; Chromosome.
DR Proteomes; UP000002519; 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:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006865; P:amino acid transport; IEA:UniProtKB-KW.
DR InterPro; IPR002293; AA/rel_permease1.
DR Pfam; PF13520; AA_permease_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid transport; Antiport; Cell inner membrane;
KW Cell membrane; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..445
FT /note="Arginine/agmatine antiporter"
FT /id="PRO_0000054232"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..24
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 25..42
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..61
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 62..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..112
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 113..124
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..142
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..171
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 172..194
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..207
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 208..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 248..277
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..301
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 302..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..340
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 341..352
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..370
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 371..388
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..404
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 405..407
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..426
FT /note="Helical"
FT /evidence="ECO:0007744|PDB:3L1L"
FT TOPO_DOM 427..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 25..27
FT /note="Helix-breaking GSG motif TM1"
FT /evidence="ECO:0000269|PubMed:19478139,
FT ECO:0000269|PubMed:20090677"
FT MOTIF 206..210
FT /note="Helix-breaking GVESA motif TM6"
FT /evidence="ECO:0000269|PubMed:19478139,
FT ECO:0000269|PubMed:20090677"
FT BINDING 23
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 26
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 27
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 96
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 97
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 101
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677"
FT BINDING 202
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 205
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677"
FT BINDING 293
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677,
FT ECO:0007744|PDB:3L1L"
FT BINDING 357
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:20090677"
FT SITE 93
FT /note="Cytoplasmic (distal) gate"
FT /evidence="ECO:0000305|PubMed:20090677"
FT SITE 202
FT /note="Periplasmic (proximal) gate"
FT /evidence="ECO:0000269|PubMed:20090677"
FT SITE 208
FT /note="Cytoplasmic (distal) gate"
FT /evidence="ECO:0000305|PubMed:20090677"
FT SITE 293
FT /note="Middle gate"
FT /evidence="ECO:0000305|PubMed:20090677"
FT SITE 365
FT /note="Cytoplasmic (distal) gate"
FT /evidence="ECO:0000305|PubMed:20090677"
FT MUTAGEN 22
FT /note="N->A: No change in antiport activity, 6-fold higher
FT affinity for Arg."
FT /evidence="ECO:0000269|PubMed:19478139,
FT ECO:0000269|PubMed:20090677"
FT MUTAGEN 26
FT /note="S->K: 5% Agm antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT MUTAGEN 74
FT /note="Y->A: 50% antiport activity at pH 6.0, 10-fold
FT higher than wild-type antiport activity at pH 7.5, i.e.
FT loss of pH-dependence of substrate transport. No change in
FT binding of Arg or Agm."
FT /evidence="ECO:0000269|PubMed:25136114"
FT MUTAGEN 74
FT /note="Y->C,H,L,M,Q,S: Loss of pH-dependence of substrate
FT transport."
FT /evidence="ECO:0000269|PubMed:25136114"
FT MUTAGEN 74
FT /note="Y->F: Approximately wild-type antiport."
FT /evidence="ECO:0000269|PubMed:25136114"
FT MUTAGEN 87
FT /note="Y->A: Markedly reduced binding affinity for Agm but
FT not for Arg. 50% Agm antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT MUTAGEN 93
FT /note="Y->A: Reduced binding affinity for Arg, no binding
FT to Agm. 25% Agm antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT MUTAGEN 93
FT /note="Y->K: Almost no binding to both Arg and Agm. 5% Agm
FT antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT MUTAGEN 208
FT /note="E->A,D: 5-10% Agm antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT MUTAGEN 337
FT /note="F->A: Severely decreased antiport."
FT /evidence="ECO:0000269|PubMed:25136114"
FT MUTAGEN 365
FT /note="Y->A: Markedly weakened binding to Arg but not to
FT Agm. 5% Agm antiport."
FT /evidence="ECO:0000269|PubMed:19478139"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 27..38
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 41..66
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 83..111
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 122..142
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 144..167
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 193..202
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 203..208
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:3L1L"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 220..249
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 262..270
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 274..286
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 290..306
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 324..339
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 351..376
FT /evidence="ECO:0007829|PDB:3L1L"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:3L1L"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 388..404
FT /evidence="ECO:0007829|PDB:3L1L"
FT HELIX 407..428
FT /evidence="ECO:0007829|PDB:3L1L"
SQ SEQUENCE 445 AA; 46843 MW; 359F70C489A20663 CRC64;
MSSDADAHKV GLIPVTLMVS GNIMGSGVFL LPANLASTGG IAIYGWLVTI IGALGLSMVY
AKMSFLDPSP GGSYAYARRC FGPFLGYQTN VLYWLACWIG NIAMVVIGVG YLSYFFPILK
DPLVLTITCV VVLWIFVLLN IVGPKMITRV QAVATVLALI PIVGIAVFGW FWFRGETYMA
AWNVSGLGTF GAIQSTLNVT LWSFIGVESA SVAAGVVKNP KRNVPIATIG GVLIAAVCYV
LSTTAIMGMI PNAALRVSAS PFGDAARMAL GDTAGAIVSF CAAAGCLGSL GGWTLLAGQT
AKAAADDGLF PPIFARVNKA GTPVAGLIIV GILMTIFQLS SISPNATKEF GLVSSVSVIF
TLVPYLYTCA ALLLLGHGHF GKARPAYLAV TTIAFLYCIW AVVGSGAKEV MWSFVTLMVI
TAMYALNYNR LHKNPYPLDA PISKD
