AGCS_METMP
ID AGCS_METMP Reviewed; 453 AA.
AC Q6LX42;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Sodium/alanine symporter AgcS {ECO:0000303|PubMed:15659675, ECO:0000303|PubMed:30659158};
DE AltName: Full=Alanine permease {ECO:0000303|PubMed:15659675};
DE AltName: Full=Alanine/glycine:cation symporter {ECO:0000303|PubMed:30659158};
GN Name=agcS {ECO:0000303|PubMed:15659675}; OrderedLocusNames=MMP1511;
OS Methanococcus maripaludis (strain S2 / LL).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanococcaceae; Methanococcus.
OX NCBI_TaxID=267377;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=S2 / LL;
RX PubMed=15466049; DOI=10.1128/jb.186.20.6956-6969.2004;
RA Hendrickson E.L., Kaul R., Zhou Y., Bovee D., Chapman P., Chung J.,
RA Conway de Macario E., Dodsworth J.A., Gillett W., Graham D.E., Hackett M.,
RA Haydock A.K., Kang A., Land M.L., Levy R., Lie T.J., Major T.A.,
RA Moore B.C., Porat I., Palmeiri A., Rouse G., Saenphimmachak C., Soell D.,
RA Van Dien S., Wang T., Whitman W.B., Xia Q., Zhang Y., Larimer F.W.,
RA Olson M.V., Leigh J.A.;
RT "Complete genome sequence of the genetically tractable hydrogenotrophic
RT methanogen Methanococcus maripaludis.";
RL J. Bacteriol. 186:6956-6969(2004).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=S2 / LL;
RX PubMed=15659675; DOI=10.1128/jb.187.3.972-979.2005;
RA Moore B.C., Leigh J.A.;
RT "Markerless mutagenesis in Methanococcus maripaludis demonstrates roles for
RT alanine dehydrogenase, alanine racemase, and alanine permease.";
RL J. Bacteriol. 187:972-979(2005).
RN [3] {ECO:0007744|PDB:6CSE, ECO:0007744|PDB:6CSF}
RP X-RAY CRYSTALLOGRAPHY (3.24 ANGSTROMS) IN COMPLEXES WITH L-ALANINE AND
RP D-ALANINE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY,
RP DOMAIN, AND MUTAGENESIS OF ASN-80; ILE-165; PHE-273; SER-274; ASP-308 AND
RP TRP-370.
RX PubMed=30659158; DOI=10.1073/pnas.1806206116;
RA Ma J., Lei H.T., Reyes F.E., Sanchez-Martinez S., Sarhan M.F., Hattne J.,
RA Gonen T.;
RT "Structural basis for substrate binding and specificity of a sodium-alanine
RT symporter AgcS.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:2086-2090(2019).
CC -!- FUNCTION: Catalyzes the sodium-dependent uptake of extracellular D-
CC alanine and L-alanine (PubMed:15659675, PubMed:30659158). Can also
CC transport glycine (PubMed:30659158). Binds glycine and both enantiomers
CC of alanine, while strictly excluding other amino acids
CC (PubMed:30659158). {ECO:0000269|PubMed:15659675,
CC ECO:0000269|PubMed:30659158}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-alanine(in) + Na(+)(in) = D-alanine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:71447, ChEBI:CHEBI:29101, ChEBI:CHEBI:57416;
CC Evidence={ECO:0000269|PubMed:30659158, ECO:0000305|PubMed:15659675};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71449;
CC Evidence={ECO:0000305|PubMed:15659675, ECO:0000305|PubMed:30659158};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972;
CC Evidence={ECO:0000269|PubMed:30659158, ECO:0000305|PubMed:15659675};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29285;
CC Evidence={ECO:0000305|PubMed:15659675, ECO:0000305|PubMed:30659158};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68228, ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000269|PubMed:30659158};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68230;
CC Evidence={ECO:0000305|PubMed:30659158};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30659158};
CC Multi-pass membrane protein {ECO:0000269|PubMed:30659158}.
CC -!- DOMAIN: Maintains pseudo twofold symmetry even though it contains an
CC uneven number of transmembrane domains. {ECO:0000269|PubMed:30659158}.
CC -!- DISRUPTION PHENOTYPE: No growth on L- or D-alanine.
CC {ECO:0000269|PubMed:15659675}.
CC -!- SIMILARITY: Belongs to the alanine or glycine:cation symporter (AGCS)
CC (TC 2.A.25) family. {ECO:0000305}.
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DR EMBL; BX950229; CAF31067.1; -; Genomic_DNA.
DR RefSeq; WP_011171455.1; NC_005791.1.
DR PDB; 6CSE; X-ray; 3.24 A; C/M=1-453.
DR PDB; 6CSF; X-ray; 3.30 A; C/M=1-453.
DR PDBsum; 6CSE; -.
DR PDBsum; 6CSF; -.
DR AlphaFoldDB; Q6LX42; -.
DR SMR; Q6LX42; -.
DR STRING; 267377.MMP1511; -.
DR TCDB; 2.A.25.1.3; the alanine or glycine:cation symporter (agcs) family.
DR ABCD; Q6LX42; 1 sequenced antibody.
DR EnsemblBacteria; CAF31067; CAF31067; MMP1511.
DR GeneID; 2761075; -.
DR KEGG; mmp:MMP1511; -.
DR PATRIC; fig|267377.15.peg.1548; -.
DR eggNOG; arCOG05006; Archaea.
DR HOGENOM; CLU_024867_1_2_2; -.
DR OMA; PMMALFY; -.
DR OrthoDB; 29565at2157; -.
DR BioCyc; MMAR267377:MMP_RS07765-MON; -.
DR Proteomes; UP000000590; 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:0015655; F:alanine:sodium symporter activity; IEA:InterPro.
DR InterPro; IPR001463; Na/Ala_symport.
DR PANTHER; PTHR30330; PTHR30330; 1.
DR Pfam; PF01235; Na_Ala_symp; 1.
DR PRINTS; PR00175; NAALASMPORT.
DR TIGRFAMs; TIGR00835; agcS; 1.
DR PROSITE; PS00873; NA_ALANINE_SYMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid transport; Cell membrane; Ion transport; Membrane;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..453
FT /note="Sodium/alanine symporter AgcS"
FT /id="PRO_0000415441"
FT TOPO_DOM 1..17
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 18..32
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 33..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 68..89
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 90..92
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 93..111
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 112..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 149..179
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 180..186
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 187..202
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 203..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 207..233
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 234..258
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 259..274
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 275..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 301..322
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 323..350
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 351..378
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 379..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 387..403
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 404..408
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TRANSMEM 409..430
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT TOPO_DOM 431..453
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT BINDING 75
FT /ligand="D-alanine"
FT /ligand_id="ChEBI:CHEBI:57416"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSF"
FT BINDING 75
FT /ligand="L-alanine"
FT /ligand_id="ChEBI:CHEBI:57972"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT BINDING 79
FT /ligand="L-alanine"
FT /ligand_id="ChEBI:CHEBI:57972"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT BINDING 80
FT /ligand="D-alanine"
FT /ligand_id="ChEBI:CHEBI:57416"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSF"
FT BINDING 170
FT /ligand="D-alanine"
FT /ligand_id="ChEBI:CHEBI:57416"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSF"
FT BINDING 170
FT /ligand="L-alanine"
FT /ligand_id="ChEBI:CHEBI:57972"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT BINDING 273..276
FT /ligand="L-alanine"
FT /ligand_id="ChEBI:CHEBI:57972"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSE"
FT BINDING 273..274
FT /ligand="D-alanine"
FT /ligand_id="ChEBI:CHEBI:57416"
FT /evidence="ECO:0000269|PubMed:30659158,
FT ECO:0007744|PDB:6CSF"
FT MUTAGEN 80
FT /note="N->A: Markedly reduces L-alanine uptake; when
FT associated with A-274 and A-308."
FT /evidence="ECO:0000269|PubMed:30659158"
FT MUTAGEN 165
FT /note="I->A: Shows poor substrate selectivity, allowing
FT additional amino acids such as L-valine and L-leucine to be
FT efficiently transported. Decreases L-alanine uptake."
FT /evidence="ECO:0000269|PubMed:30659158"
FT MUTAGEN 273
FT /note="F->A: Shows poor substrate selectivity, allowing
FT additional amino acids such as L-valine and L-leucine to be
FT efficiently transported. Decreases L-alanine uptake."
FT /evidence="ECO:0000269|PubMed:30659158"
FT MUTAGEN 274
FT /note="S->A: Markedly reduces L-alanine uptake; when
FT associated with A-80 and A-308."
FT /evidence="ECO:0000269|PubMed:30659158"
FT MUTAGEN 308
FT /note="D->A: Markedly reduces L-alanine uptake; when
FT associated with A-80 and A-274."
FT /evidence="ECO:0000269|PubMed:30659158"
FT MUTAGEN 370
FT /note="W->Q: Does not change uptake of L-alanine, but
FT reduces the ability to transport D-alanine."
FT /evidence="ECO:0000269|PubMed:30659158"
FT HELIX 18..33
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 37..49
FT /evidence="ECO:0007829|PDB:6CSE"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 95..116
FT /evidence="ECO:0007829|PDB:6CSE"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 147..166
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 168..181
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 186..202
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 205..233
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:6CSE"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:6CSF"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 259..275
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 283..287
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 294..301
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 303..308
FT /evidence="ECO:0007829|PDB:6CSE"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 312..326
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:6CSF"
FT HELIX 337..347
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 351..382
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 387..403
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 409..430
FT /evidence="ECO:0007829|PDB:6CSE"
FT HELIX 432..445
FT /evidence="ECO:0007829|PDB:6CSE"
FT TURN 446..449
FT /evidence="ECO:0007829|PDB:6CSE"
SQ SEQUENCE 453 AA; 47526 MW; C2158611918A076D CRC64;
MDFVSLVNTV NSFVWGPYML VLLLGTGIFL TLRLGFMQIH TLPYALKLAF SKHQDETSEG
DISHFQALMT ALAATIGTGN IAGVATAYVL GGPGAIFWMW VTAFFGMATK YAEAVLAIKY
RTVDDNGEMA GGPMYFLEKG LPDHGLGKIL GVAFAFFGAF AAFGIGNMVQ TNSVADAVAS
NFGVDPLITG FVLAIFTAAV ILGGIKSIGK ATGIIVPFMA VFYILAGLVI LAMNIGYIIP
AFGTIFSSAF NFSAGFGALI GTAIMWGVKR GVFSNEAGLG SAPIAAAAAK TDHPGRQALV
SMTGTFLDTI VVCTITGLVL TIAGLKAFPG LTDLTGASLT AASFDALMPM GGLIVTIGLV
FFAYSTVLGW SYYGEKCFEY LIGTKGIRLY RIAFVLVAFW GATASLPLVW NIADTLNGAM
AIPNLIGLLL LSGVVVSETK AFNEIRKNEA KNA
