HPPA_THEMA
ID HPPA_THEMA Reviewed; 726 AA.
AC Q9S5X0; O51935;
DT 25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=K(+)-stimulated pyrophosphate-energized sodium pump;
DE EC=7.2.3.- {ECO:0000255|HAMAP-Rule:MF_01129, ECO:0000269|PubMed:15697234, ECO:0000269|PubMed:17605473};
DE AltName: Full=Membrane-bound sodium-translocating pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_01129};
DE AltName: Full=Pyrophosphate-energized inorganic pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_01129};
DE Short=Na(+)-PPase {ECO:0000255|HAMAP-Rule:MF_01129};
DE AltName: Full=Tm-PPase;
GN Name=hppA {ECO:0000255|HAMAP-Rule:MF_01129}; OrderedLocusNames=TM_0174;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-276.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=9440516; DOI=10.1128/jb.180.2.274-281.1998;
RA Bouthier de la Tour C., Portemer C., Kaltoum H., Duguet M.;
RT "Reverse gyrase from the hyperthermophilic bacterium Thermotoga maritima:
RT properties and gene structure.";
RL J. Bacteriol. 180:274-281(1998).
RN [3]
RP CHARACTERIZATION, FUNCTION, COFACTOR, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=11343697; DOI=10.1016/s0014-5793(01)02390-0;
RA Perez-Castineira J.R., Lopez-Marques R.L., Losada M., Serrano A.;
RT "A thermostable K(+)-stimulated vacuolar-type pyrophosphatase from the
RT hyperthermophilic bacterium Thermotoga maritima.";
RL FEBS Lett. 496:6-11(2001).
RN [4]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-190 AND
RP ASP-703.
RX PubMed=15697234; DOI=10.1021/bi048429g;
RA Belogurov G.A., Malinen A.M., Turkina M.V., Jalonen U., Rytkonen K.,
RA Baykov A.A., Lahti R.;
RT "Membrane-bound pyrophosphatase of Thermotoga maritima requires sodium for
RT activity.";
RL Biochemistry 44:2088-2096(2005).
RN [5]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=16182234; DOI=10.1016/j.bbamem.2005.08.004;
RA Lopez-Marques R.L., Perez-Castineira J.R., Buch-Pedersen M.J., Marco S.,
RA Rigaud J.L., Palmgren M.G., Serrano A.;
RT "Large-scale purification of the proton pumping pyrophosphatase from
RT Thermotoga maritima: a 'Hot-Solve' method for isolation of recombinant
RT thermophilic membrane proteins.";
RL Biochim. Biophys. Acta 1716:69-76(2005).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17605473; DOI=10.1021/bi700564b;
RA Malinen A.M., Belogurov G.A., Baykov A.A., Lahti R.;
RT "Na+-pyrophosphatase: a novel primary sodium pump.";
RL Biochemistry 46:8872-8878(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH CALCIUM AND
RP MAGNESIUM, TOPOLOGY, FUNCTION, SUBUNIT, METAL-BINDING SITES, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22837527; DOI=10.1126/science.1222505;
RA Kellosalo J., Kajander T., Kogan K., Pokharel K., Goldman A.;
RT "The structure and catalytic cycle of a sodium-pumping pyrophosphatase.";
RL Science 337:473-476(2012).
CC -!- FUNCTION: Sodium pump that utilizes the energy of pyrophosphate
CC hydrolysis as the driving force for Na(+) movement across the membrane.
CC {ECO:0000255|HAMAP-Rule:MF_01129, ECO:0000269|PubMed:11343697,
CC ECO:0000269|PubMed:17605473, ECO:0000269|PubMed:22837527}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + H2O + Na(+)(in) = H(+) + Na(+)(out) + 2
CC phosphate; Xref=Rhea:RHEA:57884, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000255|HAMAP-Rule:MF_01129,
CC ECO:0000269|PubMed:15697234, ECO:0000269|PubMed:17605473};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01129,
CC ECO:0000269|PubMed:11343697};
CC -!- ACTIVITY REGULATION: Inhibited by GdCl3. Requires K(+) for maximal
CC activity. K(+) greatly stimulates Na(+) binding. Thermostability
CC depends on the binding of Mg(2+). {ECO:0000269|PubMed:11343697,
CC ECO:0000269|PubMed:15697234, ECO:0000269|PubMed:22837527}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Optimum temperature is 70 degrees Celsius.
CC {ECO:0000269|PubMed:11343697, ECO:0000269|PubMed:22837527};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01129,
CC ECO:0000269|PubMed:16182234, ECO:0000269|PubMed:22837527}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_01129, ECO:0000305|PubMed:16182234}; Multi-pass membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_01129, ECO:0000269|PubMed:16182234}.
CC -!- DOMAIN: Has 16 transmembrane helices and a cytoplasmic domain that
CC contains the active site. Pyrophosphate binding is thought to trigger a
CC conformation change that allows Na(+) release. Has at least two binding
CC sites for Na(+) (PubMed:22837527). {ECO:0000269|PubMed:22837527}.
CC -!- SIMILARITY: Belongs to the H(+)-translocating pyrophosphatase (TC
CC 3.A.10) family. K(+)-stimulated subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_01129}.
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DR EMBL; AE000512; AAD35267.1; -; Genomic_DNA.
DR EMBL; AF013268; AAC01564.2; -; Genomic_DNA.
DR PIR; D72409; D72409.
DR RefSeq; NP_227989.1; NC_000853.1.
DR RefSeq; WP_004082809.1; NZ_CP011107.1.
DR PDB; 4AV3; X-ray; 2.60 A; A/B=2-726.
DR PDB; 4AV6; X-ray; 4.00 A; A/B=2-726.
DR PDB; 5LZQ; X-ray; 3.50 A; A/B=2-726.
DR PDB; 5LZR; X-ray; 4.00 A; A/B=2-726.
DR PDB; 6QXA; X-ray; 3.41 A; A/B/C/D=2-726.
DR PDBsum; 4AV3; -.
DR PDBsum; 4AV6; -.
DR PDBsum; 5LZQ; -.
DR PDBsum; 5LZR; -.
DR PDBsum; 6QXA; -.
DR AlphaFoldDB; Q9S5X0; -.
DR SMR; Q9S5X0; -.
DR DIP; DIP-61897N; -.
DR STRING; 243274.THEMA_03930; -.
DR TCDB; 3.A.10.1.4; the h(+), na(+)-translocating pyrophosphatase (m(+)-ppase) family.
DR EnsemblBacteria; AAD35267; AAD35267; TM_0174.
DR KEGG; tma:TM0174; -.
DR eggNOG; COG3808; Bacteria.
DR InParanoid; Q9S5X0; -.
DR OMA; GWKGILF; -.
DR OrthoDB; 98036at2; -.
DR BRENDA; 3.6.1.1; 6331.
DR BRENDA; 7.1.3.1; 6331.
DR BRENDA; 7.1.3.2; 6331.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004427; F:inorganic diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030955; F:potassium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0009678; F:pyrophosphate hydrolysis-driven proton transmembrane transporter activity; IEA:UniProtKB-UniRule.
DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR HAMAP; MF_01129; PPase_energized_pump; 1.
DR InterPro; IPR004131; PPase-energised_H-pump.
DR PANTHER; PTHR31998; PTHR31998; 1.
DR Pfam; PF03030; H_PPase; 1.
DR PIRSF; PIRSF001265; H+-PPase; 1.
DR TIGRFAMs; TIGR01104; V_PPase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell inner membrane; Cell membrane; Ion transport;
KW Magnesium; Membrane; Metal-binding; Potassium; Reference proteome; Sodium;
KW Sodium transport; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..726
FT /note="K(+)-stimulated pyrophosphate-energized sodium pump"
FT /id="PRO_0000217005"
FT TOPO_DOM 1
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 2..22
FT /note="Helical"
FT TOPO_DOM 23..46
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 47..71
FT /note="Helical"
FT TOPO_DOM 72..73
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 74..97
FT /note="Helical"
FT TOPO_DOM 98..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 123..153
FT /note="Helical"
FT TOPO_DOM 154..168
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 169..197
FT /note="Helical"
FT TOPO_DOM 198..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 236..261
FT /note="Helical"
FT TOPO_DOM 262..284
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 285..309
FT /note="Helical"
FT TOPO_DOM 310..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 321..343
FT /note="Helical"
FT TOPO_DOM 344..358
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 359..379
FT /note="Helical"
FT TOPO_DOM 380..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 406..430
FT /note="Helical"
FT TOPO_DOM 431..436
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 437..463
FT /note="Helical"
FT TOPO_DOM 464..492
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 493..520
FT /note="Helical"
FT TOPO_DOM 521..541
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 542..571
FT /note="Helical"
FT TOPO_DOM 572..601
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 602..629
FT /note="Helical"
FT TOPO_DOM 630
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 631..658
FT /note="Helical"
FT TOPO_DOM 659..697
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT TRANSMEM 698..722
FT /note="Helical"
FT TOPO_DOM 723..726
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:22837527"
FT BINDING 199
FT /ligand="substrate"
FT BINDING 202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22837527"
FT BINDING 232
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22837527"
FT BINDING 465
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:22837527"
FT BINDING 660
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:22837527,
FT ECO:0007744|PDB:4AV3"
FT BINDING 688
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:22837527,
FT ECO:0007744|PDB:4AV3"
FT BINDING 692
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:22837527,
FT ECO:0007744|PDB:4AV3"
FT BINDING 695
FT /ligand="substrate"
FT SITE 191
FT /note="Important for ion transport"
FT /evidence="ECO:0000250"
FT SITE 236
FT /note="Important for ion transport"
FT /evidence="ECO:0000250"
FT SITE 243
FT /note="Important for ion transport"
FT /evidence="ECO:0000250"
FT SITE 495
FT /note="Determinant of potassium dependence"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01129, ECO:0000305"
FT SITE 696
FT /note="Important for ion transport"
FT /evidence="ECO:0000250"
FT SITE 707
FT /note="Important for ion transport"
FT /evidence="ECO:0000250"
FT MUTAGEN 190
FT /note="D->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:15697234"
FT MUTAGEN 703
FT /note="D->N: Silences the K(+)-independent activating
FT Na(+)-binding site."
FT /evidence="ECO:0000269|PubMed:15697234"
FT HELIX 3..8
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 10..26
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 33..71
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 74..108
FT /evidence="ECO:0007829|PDB:4AV3"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 116..147
FT /evidence="ECO:0007829|PDB:4AV3"
FT TURN 148..152
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:5LZQ"
FT HELIX 171..192
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 194..205
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 226..236
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 238..265
FT /evidence="ECO:0007829|PDB:4AV3"
FT STRAND 267..270
FT /evidence="ECO:0007829|PDB:4AV3"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 280..310
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 317..344
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 361..384
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 389..397
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 402..416
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 418..447
FT /evidence="ECO:0007829|PDB:4AV3"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 451..474
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 479..519
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:4AV3"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 542..574
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 577..583
FT /evidence="ECO:0007829|PDB:4AV3"
FT TURN 584..587
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 597..609
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 612..629
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 631..667
FT /evidence="ECO:0007829|PDB:4AV3"
FT STRAND 671..673
FT /evidence="ECO:0007829|PDB:4AV3"
FT STRAND 676..678
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 679..696
FT /evidence="ECO:0007829|PDB:4AV3"
FT HELIX 698..723
FT /evidence="ECO:0007829|PDB:4AV3"
SQ SEQUENCE 726 AA; 77046 MW; 492243F8C320BF93 CRC64;
MYVAALFFLI PLVALGFAAA NFAAVVRKPE GTERMKEISS YIRSGADSFL AHETKAIFKV
AIVIAILLMI FTTWQTGVAF LLGAVMSASA GIVGMKMATR ANVRVAEAAR TTKKIGPALK
VAYQGGSVMG LSVGGFALLG LVLVYLIFGK WMGQVDNLNI YTNWLGINFV PFAMTVSGYA
LGCSIIAMFD RVGGGVYTKA ADMAADLVGK TELNLPEDDP RNPATIADNV GDNVGDVAGL
GADLLESFVG AIVSSIILAS YMFPIYVQKI GENLVHQVPK ETIQALISYP IFFALVGLGC
SMLGILYVIV KKPSDNPQRE LNISLWTSAL LTVVLTAFLT YFYLKDLQGL DVVGFRFGAI
SPWFSAIIGI FSGILIGFWA EYYTSYRYKP TQFLSKSSIE GTGMVISNGL SLGMKSVFPP
TLTLVLGILF ADYFAGLYGV AIAALGMLSF VATSVSVDSY GPIADNAGGI SEMCELDPEV
RKITDHLDAV GNTTAAIGKG FAIGSAIFAA LSLFASYMFS QISPSDIGKP PSLVLLLNML
DARVIAGALL GAAITYYFSG YLISAVTKAA MKMVDEIRRQ AREIPGLLEG KAKPDYNRCI
EITSDNALKQ MGYPAFIAIL TPLVTGFLLG AEFVGGVLIG TVLSGAMLAI LTANSGGAWD
NAKKYLEAGN LEGYGKGSEP HKALVIGDTV GDPLKDTVGP SLDILIKIMS VVSVIAVSIF
KHVHLF
