ID   ATF1A_DANRE             Reviewed;         105 AA.
AC   A3KNL5;
DT   06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 1.
DT   27-MAR-2024, entry version 99.
DE   RecName: Full=ATPase inhibitor A, mitochondrial {ECO:0000305};
DE   AltName: Full=ATP synthase F1 subunit epsilon A {ECO:0000250|UniProtKB:Q9UII2};
DE   AltName: Full=Inhibitor of F(1)F(o)-ATPase A;
DE            Short=IF(1) A;
DE            Short=IF1 A;
DE   AltName: Full=Protein pinotage;
DE   Flags: Precursor;
GN   Name=atp5if1a {ECO:0000250|UniProtKB:Q9UII2};
GN   Synonyms=atpia, atpif1, pnt; ORFNames=Zgc:162207;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=23135403; DOI=10.1038/nature11536;
RA   Shah D.I., Takahashi-Makise N., Cooney J.D., Li L., Schultz I.J.,
RA   Pierce E.L., Narla A., Seguin A., Hattangadi S.M., Medlock A.E.,
RA   Langer N.B., Dailey T.A., Hurst S.N., Faccenda D., Wiwczar J.M.,
RA   Heggers S.K., Vogin G., Chen W., Chen C., Campagna D.R., Brugnara C.,
RA   Zhou Y., Ebert B.L., Danial N.N., Fleming M.D., Ward D.M., Campanella M.,
RA   Dailey H.A., Kaplan J., Paw B.H.;
RT   "Mitochondrial Atpif1 regulates haem synthesis in developing
RT   erythroblasts.";
RL   Nature 491:608-612(2012).
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 (By
CC       similarity). Indirectly acts as a regulator of heme synthesis in
CC       erythroid tissues: regulates heme synthesis by modulating the
CC       mitochondrial pH and redox potential, allowing fech to efficiently
CC       catalyze the incorporation of iron into protoporphyrin IX to produce
CC       heme (PubMed:23135403). {ECO:0000250|UniProtKB:P01096,
CC       ECO:0000269|PubMed:23135403}.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC   -!- DOMAIN: Forms an alpha-helical dimer with monomers associated via an
CC       antiparallel alpha-helical coiled coil composed of residues 73-105,
CC       leaving each N-terminal inhibitory region (residues 22-51) accessible
CC       for interaction with an F1 catalytic domain. The inhibitory N-terminal
CC       region (residues 22-51) 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 (By similarity). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Defects in circulating erythroid cells. Embryos
CC       are anemic despite normal expression of the erythroid cell markers. The
CC       erythrocytes from embryos that survive to adult stage exhibit
CC       hypochromic, microcytic anemia. Histological analysis of adult
CC       haematopoietic tissues does not show morphological defects. Defects are
CC       due to changes in the mitochondrial pH-and consequently the redox
CC       potential-to change to a level that reduces [2Fe-2S] cluster-containing
CC       fech activity, thereby reducing heme synthesis, resulting in
CC       hypochromic anemia. {ECO:0000269|PubMed:23135403}.
CC   -!- SIMILARITY: Belongs to the ATPase inhibitor family. {ECO:0000305}.
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DR   EMBL; CU633999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CU634003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC133905; AAI33906.1; -; mRNA.
DR   RefSeq; NP_001082990.1; NM_001089521.1.
DR   AlphaFoldDB; A3KNL5; -.
DR   SMR; A3KNL5; -.
DR   STRING; 7955.ENSDARP00000081676; -.
DR   PaxDb; 7955-ENSDARP00000081676; -.
DR   PeptideAtlas; A3KNL5; -.
DR   GeneID; 100037369; -.
DR   KEGG; dre:100037369; -.
DR   AGR; ZFIN:ZDB-GENE-070410-36; -.
DR   CTD; 100037369; -.
DR   ZFIN; ZDB-GENE-070410-36; atp5if1a.
DR   eggNOG; ENOG502S4JP; Eukaryota.
DR   HOGENOM; CLU_147479_1_2_1; -.
DR   InParanoid; A3KNL5; -.
DR   OMA; YFRRQQK; -.
DR   PhylomeDB; A3KNL5; -.
DR   TreeFam; TF320659; -.
DR   PRO; PR:A3KNL5; -.
DR   Proteomes; UP000000437; Chromosome 19.
DR   Bgee; ENSDARG00000067975; Expressed in early embryo and 28 other cell types or tissues.
DR   ExpressionAtlas; A3KNL5; baseline and differential.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0051117; F:ATPase binding; ISS:UniProtKB.
DR   GO; GO:0042030; F:ATPase inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0006783; P:heme biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0051346; P:negative regulation of hydrolase activity; ISS:UniProtKB.
DR   GO; GO:0007634; P:optokinetic behavior; IMP:ZFIN.
DR   GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR   GO; GO:0150077; P:regulation of neuroinflammatory response; IMP:ZFIN.
DR   GO; GO:0007601; P:visual perception; IMP:ZFIN.
DR   Gene3D; 1.20.5.500; Single helix bin; 2.
DR   InterPro; IPR007648; ATPase_inhibitor_mt.
DR   PANTHER; PTHR48329; FI01416P; 1.
DR   PANTHER; PTHR48329:SF1; FI01416P; 1.
DR   Pfam; PF04568; IATP; 1.
DR   SUPFAM; SSF64602; F1 ATPase inhibitor, IF1, C-terminal domain; 1.
PE   3: Inferred from homology;
KW   Coiled coil; Mitochondrion; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..105
FT                   /note="ATPase inhibitor A, mitochondrial"
FT                   /id="PRO_0000421768"
FT   REGION          17..52
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          22..51
FT                   /note="N-terminal inhibitory region"
FT                   /evidence="ECO:0000250"
FT   REGION          73..105
FT                   /note="Antiparallel alpha-helical coiled coil region"
FT                   /evidence="ECO:0000250"
FT   COILED          58..105
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   105 AA;  11944 MW;  851D1A097A16239E CRC64;
     MARLLLRRGF FSSHIRMSSD QLGELGTGAG KGGGGGGSVR AAGGSFGRRE AAEEERYFRQ
     KEREQLAALK NHHEEEIDHH KKEIERLQRE IDRHKGKIRK LKHDD
//