ID   ATIF_YEAST              Reviewed;          85 AA.
AC   P01097; D6VRH1;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 2.
DT   04-NOV-2026, entry version 197.
DE   RecName: Full=F(1)-ATPase inhibitor IF(1), mitochondrial {ECO:0000305};
DE   AltName: Full=ATPase inhibitory factor 1;
DE            Short=IF(1);
DE            Short=IF1;
DE   Flags: Precursor;
GN   Name=INH1; OrderedLocusNames=YDL181W; ORFNames=D1305;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2138617; DOI=10.1016/s0021-9258(19)39321-4;
RA   Ichikawa N., Yoshida Y., Hashimoto T., Ogasawara N., Yoshikawa H.,
RA   Imamoto F., Tagawa K.;
RT   "Activation of ATP hydrolysis by an uncoupler in mutant mitochondria
RT   lacking an intrinsic ATPase inhibitor in yeast.";
RL   J. Biol. Chem. 265:6274-6278(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=8533471; DOI=10.1002/yea.320111007;
RA   Verhasselt P., Voet M., Volckaert G.;
RT   "New open reading frames, one of which is similar to the nifV gene of
RT   Azotobacter vinelandii, found on a 12.5 kbp fragment of chromosome IV of
RT   Saccharomyces cerevisiae.";
RL   Yeast 11:961-966(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169867; DOI=10.1038/387s075;
RA   Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA   Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA   Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA   Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA   Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA   Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA   Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA   Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA   Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA   Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA   Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA   Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA   Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA   Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA   Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA   Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA   Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA   Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA   Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA   Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA   Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA   Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA   Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA   Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA   Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA   Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA   Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA   Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA   Mewes H.-W., Zollner A., Zaccaria P.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL   Nature 387:75-78(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [6]
RP   PROTEIN SEQUENCE OF 23-85.
RX   PubMed=6458601; DOI=10.1093/oxfordjournals.jbchem.a133568;
RA   Matsubara H., Hase T., Hashimoto T., Tagawa K.;
RT   "Amino acid sequence of an intrinsic inhibitor of mitochondrial ATPase from
RT   yeast.";
RL   J. Biochem. 90:1159-1165(1981).
RN   [7]
RP   PROTEIN SEQUENCE OF 1-28.
RX   PubMed=6619114; DOI=10.1093/oxfordjournals.jbchem.a134342;
RA   Yoshida Y., Hashimoto T., Hase T., Matsubara H., Tagawa K.;
RT   "Partial amino terminal sequence of the precursor of mitochondrial ATPase
RT   inhibitor protein synthesized with mRNA partially purified by gel
RT   permeation chromatography.";
RL   J. Biochem. 94:291-297(1983).
RN   [8]
RP   MUTAGENESIS OF LYS-41.
RX   PubMed=10705452; DOI=10.1271/bbb.64.89;
RA   Ichikawa N., Fujisaka R., Kuribayashi R.;
RT   "Requirement for lysine-19 of the yeast mitochondrial ATPase inhibitor for
RT   the stability of the inactivated inhibitor-F1Fo complex at higher pH.";
RL   Biosci. Biotechnol. Biochem. 64:89-95(2000).
RN   [9]
RP   FUNCTION.
RX   PubMed=12167646; DOI=10.1074/jbc.m205720200;
RA   Dienhart M., Pfeiffer K., Schagger H., Stuart R.A.;
RT   "Formation of the yeast F1F0-ATP synthase dimeric complex does not require
RT   the ATPase inhibitor protein, Inh1.";
RL   J. Biol. Chem. 277:39289-39295(2002).
RN   [10]
RP   SUBUNIT.
RX   PubMed=12186878; DOI=10.1074/jbc.m207169200;
RA   Cabezon E., Butler P.J., Runswick M.J., Carbajo R.J., Walker J.E.;
RT   "Homologous and heterologous inhibitory effects of ATPase inhibitor
RT   proteins on F-ATPases.";
RL   J. Biol. Chem. 277:41334-41341(2002).
RN   [11]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=12809520; DOI=10.1021/bi034394t;
RA   Venard R., Brethes D., Giraud M.F., Vaillier J., Velours J., Haraux F.;
RT   "Investigation of the role and mechanism of IF1 and STF1 proteins, twin
RT   inhibitory peptides which interact with the yeast mitochondrial ATP
RT   synthase.";
RL   Biochemistry 42:7626-7636(2003).
RN   [12]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [13]
RP   FUNCTION.
RX   PubMed=26420258; DOI=10.1007/s10863-015-9627-7;
RA   Sun L., Nakamae N., Ichikawa N.;
RT   "The region from phenylalanine-28 to lysine-50 of a yeast mitochondrial
RT   ATPase inhibitor (IF1) forms an alpha-helix in solution.";
RL   J. Bioenerg. Biomembr. 47:457-465(2015).
RN   [14] {ECO:0007744|PDB:3ZIA}
RP   X-RAY CRYSTALLOGRAPHY.
RX   PubMed=23407639; DOI=10.1098/rsob.120164;
RA   Robinson G.C., Bason J.V., Montgomery M.G., Fearnley I.M., Mueller D.M.,
RA   Leslie A.G., Walker J.E.;
RT   "The structure of F(1)-ATPase from Saccharomyces cerevisiae inhibited by
RT   its regulatory protein IF(1).";
RL   Open Biol. 3:120164-120164(2013).
CC   -!- FUNCTION: Endogenous ATPase inhibitor, which inhibits specifically the
CC       reverse ATPase reaction of mitochondrial F(1)F(0)-type ATP synthase. It
CC       limits ATP depletion when the mitochondrial membrane potential falls
CC       below a threshold and the F(1)F(0)-ATP synthase starts hydrolyzing ATP
CC       to pump protons out of the mitochondrial matrix. Required to avoid the
CC       consumption of cellular ATP when the F(1)F(0)-ATP synthase enzyme acts
CC       as an ATP hydrolase (PubMed:12167646, PubMed:12809520,
CC       PubMed:26420258). Functions through inserting its N-terminal part into
CC       the catalytically active F1-ATPase, thereby blocking its rotational
CC       movement and subsequently the ATP hydrolase activity (PubMed:23407639).
CC       {ECO:0000269|PubMed:12167646, ECO:0000269|PubMed:12809520,
CC       ECO:0000269|PubMed:23407639, ECO:0000269|PubMed:26420258}.
CC   -!- SUBUNIT: Monomer and homodimer. The protein aggregates less strongly
CC       with increasing pH. {ECO:0000269|PubMed:12186878}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12809520}.
CC   -!- DOMAIN: The inhibitory N-terminal region (residues 23-59) is entrapped
CC       between the C-terminal domains of the alpha(ADP-bound)-beta(ADP-bound)
CC       (ATP1-ATP2) subunits in one of the 3 catalytic interfaces of F(1)F(0)-
CC       ATPase. {ECO:0000269|PubMed:23407639}.
CC   -!- MISCELLANEOUS: Present with 981 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the ATPase inhibitor family. {ECO:0000305}.
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DR   EMBL; D00443; BAA00344.1; -; Genomic_DNA.
DR   EMBL; X83276; CAA58265.1; -; Genomic_DNA.
DR   EMBL; Z74229; CAA98755.1; -; Genomic_DNA.
DR   EMBL; AY558374; AAS56700.1; -; Genomic_DNA.
DR   EMBL; BK006938; DAA11681.1; -; Genomic_DNA.
DR   PIR; A35231; IWBY.
DR   RefSeq; NP_010100.1; NM_001180241.1.
DR   PDB; 3ZIA; X-ray; 2.50 A; J/T=23-85.
DR   AlphaFoldDB; P01097; -.
DR   SMR; P01097; -.
DR   BioGRID; 31863; 175.
DR   DIP; DIP-2985N; -.
DR   FunCoup; P01097; 117.
DR   IntAct; P01097; 20.
DR   STRING; 4932.YDL181W; -.
DR   iPTMnet; P01097; -.
DR   PaxDb; 4932-YDL181W; -.
DR   PeptideAtlas; P01097; -.
DR   EnsemblFungi; YDL181W_mRNA; YDL181W; YDL181W.
DR   GeneID; 851347; -.
DR   KEGG; sce:YDL181W; -.
DR   AGR; SGD:S000002340; -.
DR   SGD; S000002340; INH1.
DR   VEuPathDB; FungiDB:YDL181W; -.
DR   eggNOG; ENOG502SCJG; Eukaryota.
DR   HOGENOM; CLU_145563_4_0_1; -.
DR   InParanoid; P01097; -.
DR   OMA; AAQESMY; -.
DR   OrthoDB; 5532350at2759; -.
DR   BioCyc; YEAST:G3O-29568-MONOMER; -.
DR   BioGRID-ORCS; 851347; 2 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P01097; -.
DR   PRO; PR:P01097; -.
DR   Proteomes; UP000002311; Chromosome IV.
DR   RNAct; P01097; protein.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0042030; F:ATPase inhibitor activity; IDA:SGD.
DR   GO; GO:0004857; F:enzyme inhibitor activity; IDA:SGD.
DR   GO; GO:0140678; F:molecular function inhibitor activity; EXP:DisProt.
DR   GO; GO:0032780; P:negative regulation of ATP-dependent activity; IDA:SGD.
DR   DisProt; DP00995; -.
DR   FunFam; 1.20.5.500:FF:000006; ATPase inhibitor, mitochondrial; 1.
DR   Gene3D; 1.20.5.500; Single helix bin; 1.
DR   InterPro; IPR007648; ATPase_inhibitor_mt.
DR   PANTHER; PTHR48417; ATP SYNTHASE F1 SUBUNIT EPSILON; 1.
DR   PANTHER; PTHR48417:SF1; ATP SYNTHASE F1 SUBUNIT EPSILON; 1.
DR   Pfam; PF04568; IATP; 1.
DR   SUPFAM; SSF64602; F1 ATPase inhibitor, IF1, C-terminal domain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Coiled coil; Direct protein sequencing; Mitochondrion;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..22
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:2138617,
FT                   ECO:0000269|PubMed:6458601"
FT   CHAIN           23..85
FT                   /note="F(1)-ATPase inhibitor IF(1), mitochondrial"
FT                   /id="PRO_0000002554"
FT   COILED          41..84
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         41
FT                   /note="K->Q,E: No loss of inhibitory activity."
FT                   /evidence="ECO:0000269|PubMed:10705452"
FT   TURN            24..28
FT                   /evidence="ECO:0007829|PDB:3ZIA"
FT   HELIX           38..57
FT                   /evidence="ECO:0007829|PDB:3ZIA"
SQ   SEQUENCE   85 AA;  9870 MW;  E1AF73A47F63CE58 CRC64;
     MLPRSALARS LQLQRGVAAR FYSEGSTGTP RGSGSEDSFV KRERATEDFF VRQREKEQLR
     HLKEQLEKQR KKIDSLENKI DSMTK
//