ATIF1_BOVIN
ID ATIF1_BOVIN Reviewed; 109 AA.
AC P01096; Q2M2T4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=ATPase inhibitor, mitochondrial {ECO:0000305};
DE AltName: Full=ATP synthase F1 subunit epsilon {ECO:0000250|UniProtKB:Q9UII2};
DE AltName: Full=Inhibitor of F(1)F(o)-ATPase;
DE Short=IF(1);
DE Short=IF1;
DE Flags: Precursor;
GN Name=ATP5IF1 {ECO:0000250|UniProtKB:Q9UII2}; Synonyms=ATPI, ATPIF1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2894843; DOI=10.1021/bi00400a018;
RA Walker J.E., Gay N.J., Powell S.J., Kostina M., Dyer M.R.;
RT "ATP synthase from bovine mitochondria: sequences of imported precursors of
RT oligomycin sensitivity conferral protein, factor 6, and
RT adenosinetriphosphatase inhibitor protein.";
RL Biochemistry 26:8613-8619(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 26-109.
RX PubMed=6461003; DOI=10.1073/pnas.78.12.7403;
RA Frangione B., Rosenwasser E., Penefsky H.S., Pullman M.E.;
RT "Amino acid sequence of the protein inhibitor of mitochondrial adenosine
RT triphosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:7403-7407(1981).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=7397110; DOI=10.1021/bi00554a016;
RA Klein G., Satre M., Dianoux A.C., Vignais P.V.;
RT "Radiolabeling of natural adenosine triphosphatase inhibitor with phenyl
RT (14C)isothiocyanate and study of its interaction with mitochondrial
RT adenosine triphosphatase. Localization of inhibitor binding sites and
RT stoichiometry of binding.";
RL Biochemistry 19:2919-2925(1980).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10831597; DOI=10.1074/jbc.m003859200;
RA Cabezon E., Butler P.J., Runswick M.J., Walker J.E.;
RT "Modulation of the oligomerization state of the bovine F1-ATPase inhibitor
RT protein, IF1, by pH.";
RL J. Biol. Chem. 275:25460-25464(2000).
RN [6]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-51 AND HIS-74.
RX PubMed=18687699; DOI=10.1093/jb/mvn100;
RA Ando C., Ichikawa N.;
RT "Glutamic acid in the inhibitory site of mitochondrial ATPase inhibitor,
RT IF(1), participates in pH sensing in both mammals and yeast.";
RL J. Biochem. 144:547-553(2008).
RN [7]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF ALA-46; PHE-47; LYS-49; ARG-50;
RP GLU-51; GLN-52; ALA-53; GLU-54; GLU-55; GLU-56; ARG-57; TYR-58; PHE-59;
RP ARG-60; ARG-62; LYS-64; GLU-65; GLN-66; LEU-67; ALA-68; ALA-69 AND LEU-70.
RX PubMed=21192948; DOI=10.1016/j.jmb.2010.12.025;
RA Bason J.V., Runswick M.J., Fearnley I.M., Walker J.E.;
RT "Binding of the inhibitor protein IF(1) to bovine F(1)-ATPase.";
RL J. Mol. Biol. 406:443-453(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 26-109, AND SUBUNIT.
RX PubMed=11742976; DOI=10.1093/emboj/20.24.6990;
RA Cabezon E., Runswick M.J., Leslie A.G., Walker J.E.;
RT "The structure of bovine IF(1), the regulatory subunit of mitochondrial F-
RT ATPase.";
RL EMBO J. 20:6990-6996(2001).
RN [9]
RP STRUCTURE BY NMR OF 69-109.
RX PubMed=11327770; DOI=10.1006/jmbi.2001.4570;
RA Gordon-Smith D.J., Carbajo R.J., Yang J.C., Videler H., Runswick M.J.,
RA Walker J.E., Neuhaus D.;
RT "Solution structure of a C-terminal coiled-coil domain from bovine IF(1):
RT the inhibitor protein of F(1) ATPase.";
RL J. Mol. Biol. 308:325-339(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-109 IN COMPLEX WITH ATP5F1A;
RP ATP5F1B AND ATP5F1C, SUBUNIT, AND FUNCTION.
RX PubMed=12923572; DOI=10.1038/nsb966;
RA Cabezon E., Montgomery M.G., Leslie A.G., Walker J.E.;
RT "The structure of bovine F1-ATPase in complex with its regulatory protein
RT IF1.";
RL Nat. Struct. Biol. 10:744-750(2003).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 26-85 IN COMPLEX WITH ATP5F1A;
RP ATP5F1B; ATP5F1C; ATP5F1D AND ATP5F1E, SUBUNIT, AND FUNCTION.
RX PubMed=17895376; DOI=10.1073/pnas.0707326104;
RA Gledhill J.R., Montgomery M.G., Leslie A.G., Walker J.E.;
RT "How the regulatory protein, IF(1), inhibits F(1)-ATPase from bovine
RT mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:15671-15676(2007).
CC -!- FUNCTION: Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion
CC when the mitochondrial membrane potential falls below a threshold and
CC the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of
CC the mitochondrial matrix. Required to avoid the consumption of cellular
CC ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase
CC (PubMed:10831597, PubMed:12923572, PubMed:17895376, PubMed:18687699,
CC PubMed:21192948, PubMed:7397110). Indirectly acts as a regulator of
CC heme synthesis in erythroid tissues: regulates heme synthesis by
CC modulating the mitochondrial pH and redox potential, allowing FECH to
CC efficiently catalyze the incorporation of iron into protoporphyrin IX
CC to produce heme (By similarity). {ECO:0000250|UniProtKB:Q9UII2,
CC ECO:0000269|PubMed:10831597, ECO:0000269|PubMed:12923572,
CC ECO:0000269|PubMed:17895376, ECO:0000269|PubMed:18687699,
CC ECO:0000269|PubMed:21192948, ECO:0000269|PubMed:7397110}.
CC -!- SUBUNIT: Homodimer; represents the active form and is present at a pH
CC value below 6.5. Homotetramer; represents the inactive form and is
CC present at a pH value above 7.0. {ECO:0000269|PubMed:10831597,
CC ECO:0000269|PubMed:11742976, ECO:0000269|PubMed:12923572,
CC ECO:0000269|PubMed:17895376, ECO:0000269|PubMed:18687699,
CC ECO:0000269|PubMed:21192948}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:7397110}.
CC -!- DOMAIN: Forms an alpha-helical dimer with monomers associated via an
CC antiparallel alpha-helical coiled coil composed of residues 74-106,
CC leaving each N-terminal inhibitory region (residues 26-62) accessible
CC for interaction with an F1 catalytic domain. The inhibitory N-terminal
CC region (residues 26-62) binds the alpha(ADP-bound)-beta(ADP-bound)
CC (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central
CC gamma subunit (ATP5F1C). This dimeric state is favored by pH values
CC below 7.0, and at higher values the dimers associate to form inactive
CC homotetramer, where the inhibitory region is occluded, masking its
CC inhibitory activity (PubMed:11742976, PubMed:12923572 and
CC PubMed:17895376).
CC -!- SIMILARITY: Belongs to the ATPase inhibitor family. {ECO:0000305}.
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DR EMBL; M22559; AAA30396.1; -; mRNA.
DR EMBL; BC111645; AAI11646.1; -; mRNA.
DR PIR; C27382; IWBO.
DR RefSeq; NP_787010.1; NM_175816.3.
DR PDB; 1GMJ; X-ray; 2.20 A; A/B/C/D=26-109.
DR PDB; 1HF9; NMR; -; A/B=69-109.
DR PDB; 1OHH; X-ray; 2.80 A; H=26-109.
DR PDB; 2V7Q; X-ray; 2.10 A; J=26-85.
DR PDB; 4TSF; X-ray; 3.20 A; H/I=26-85.
DR PDB; 4TT3; X-ray; 3.21 A; H/I/J=26-85.
DR PDB; 4Z1M; X-ray; 3.30 A; H/I/J=26-85.
DR PDB; 5LQX; EM; 7.90 A; J=26-85.
DR PDB; 5LQY; EM; 7.80 A; J=26-85.
DR PDB; 5LQZ; EM; 7.00 A; J=26-85.
DR PDB; 6YY0; EM; 3.23 A; J=26-85.
DR PDB; 6Z1R; EM; 3.29 A; J=26-85.
DR PDB; 6Z1U; EM; 3.47 A; J=26-85.
DR PDB; 6ZPO; EM; 4.00 A; J=26-85.
DR PDB; 6ZQM; EM; 3.29 A; J=26-85.
DR PDB; 6ZQN; EM; 4.00 A; J=26-85.
DR PDB; 7AJB; EM; 9.20 A; AJ/J=26-85.
DR PDB; 7AJC; EM; 11.90 A; AJ/J=26-85.
DR PDB; 7AJD; EM; 9.00 A; AJ/J=26-85.
DR PDB; 7AJE; EM; 9.40 A; AJ/J=26-85.
DR PDB; 7AJF; EM; 8.45 A; AJ/J=26-109.
DR PDB; 7AJG; EM; 10.70 A; AJ/J=26-85.
DR PDB; 7AJH; EM; 9.70 A; AJ/J=26-85.
DR PDB; 7AJI; EM; 11.40 A; AJ/J=26-85.
DR PDB; 7AJJ; EM; 13.10 A; AJ/J=26-85.
DR PDBsum; 1GMJ; -.
DR PDBsum; 1HF9; -.
DR PDBsum; 1OHH; -.
DR PDBsum; 2V7Q; -.
DR PDBsum; 4TSF; -.
DR PDBsum; 4TT3; -.
DR PDBsum; 4Z1M; -.
DR PDBsum; 5LQX; -.
DR PDBsum; 5LQY; -.
DR PDBsum; 5LQZ; -.
DR PDBsum; 6YY0; -.
DR PDBsum; 6Z1R; -.
DR PDBsum; 6Z1U; -.
DR PDBsum; 6ZPO; -.
DR PDBsum; 6ZQM; -.
DR PDBsum; 6ZQN; -.
DR PDBsum; 7AJB; -.
DR PDBsum; 7AJC; -.
DR PDBsum; 7AJD; -.
DR PDBsum; 7AJE; -.
DR PDBsum; 7AJF; -.
DR PDBsum; 7AJG; -.
DR PDBsum; 7AJH; -.
DR PDBsum; 7AJI; -.
DR PDBsum; 7AJJ; -.
DR AlphaFoldDB; P01096; -.
DR BMRB; P01096; -.
DR SMR; P01096; -.
DR CORUM; P01096; -.
DR DIP; DIP-46311N; -.
DR IntAct; P01096; 5.
DR STRING; 9913.ENSBTAP00000008319; -.
DR PaxDb; P01096; -.
DR PRIDE; P01096; -.
DR Ensembl; ENSBTAT00000008319; ENSBTAP00000008319; ENSBTAG00000006342.
DR GeneID; 327699; -.
DR KEGG; bta:327699; -.
DR CTD; 93974; -.
DR VEuPathDB; HostDB:ENSBTAG00000006342; -.
DR VGNC; VGNC:103019; ATP5IF1.
DR eggNOG; ENOG502S4JP; Eukaryota.
DR GeneTree; ENSGT00390000006264; -.
DR HOGENOM; CLU_147479_0_0_1; -.
DR InParanoid; P01096; -.
DR OMA; QEVDHHK; -.
DR OrthoDB; 1566610at2759; -.
DR TreeFam; TF320659; -.
DR EvolutionaryTrace; P01096; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000006342; Expressed in tongue muscle and 104 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005753; C:mitochondrial proton-transporting ATP synthase complex; IDA:CAFA.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0043532; F:angiostatin binding; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IDA:UniProtKB.
DR GO; GO:0042030; F:ATPase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IBA:GO_Central.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR DisProt; DP00844; -.
DR InterPro; IPR007648; ATPase_inhibitor_mt.
DR Pfam; PF04568; IATP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Direct protein sequencing; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:6461003"
FT CHAIN 26..109
FT /note="ATPase inhibitor, mitochondrial"
FT /id="PRO_0000002546"
FT REGION 26..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..52
FT /note="N-terminal inhibitory region"
FT REGION 74..106
FT /note="Antiparallel alpha-helical coiled coil region"
FT COILED 69..109
FT SITE 51
FT /note="Participates in pH sensing"
FT SITE 74
FT /note="Participates in pH sensing"
FT MOD_RES 103
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35143"
FT MUTAGEN 46
FT /note="A->V: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 47
FT /note="F->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 49
FT /note="K->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 50
FT /note="R->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 51
FT /note="E->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:18687699,
FT ECO:0000269|PubMed:21192948"
FT MUTAGEN 51
FT /note="E->A: Retains its inhibitory activity at pH 8.2
FT although it still form a homotetramer at high pH."
FT /evidence="ECO:0000269|PubMed:18687699,
FT ECO:0000269|PubMed:21192948"
FT MUTAGEN 52
FT /note="Q->A: Impairs F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 53
FT /note="A->V: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 54
FT /note="E->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 55
FT /note="E->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 56
FT /note="E->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 57
FT /note="R->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 58
FT /note="Y->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 59
FT /note="F->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 60
FT /note="R->A: No effect on F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 62
FT /note="R->A: Impairs F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 64
FT /note="K->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 65
FT /note="E->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 66
FT /note="Q->A: Impairs F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 67
FT /note="L->A: Impairs F(1)F(o)-ATP synthase-binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 68
FT /note="A->V: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 69
FT /note="A->V: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 70
FT /note="L->A: Strongly impairs F(1)F(o)-ATP synthase-
FT binding."
FT /evidence="ECO:0000269|PubMed:21192948"
FT MUTAGEN 74
FT /note="H->K: Retains its inhibitory activity at pH 8.2 and
FT does not form a homotetramer at high pH."
FT /evidence="ECO:0000269|PubMed:18687699"
FT CONFLICT 55
FT /note="E -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:6YY0"
FT HELIX 45..107
FT /evidence="ECO:0007829|PDB:1GMJ"
SQ SEQUENCE 109 AA; 12301 MW; 0F8816DECCAABA7E CRC64;
MAATALAART RQAVWSVWAM QGRGFGSESG DNVRSSAGAV RDAGGAFGKR EQAEEERYFR
ARAKEQLAAL KKHHENEISH HAKEIERLQK EIERHKQSIK KLKQSEDDD
