ATF1A_DANRE
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 03-AUG-2022, entry version 92.
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}; Synonyms=atpia, atpif1, pnt;
GN 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; A3KNL5; -.
DR PeptideAtlas; A3KNL5; -.
DR Ensembl; ENSDART00000087242; ENSDARP00000081676; ENSDARG00000067975.
DR GeneID; 100037369; -.
DR KEGG; dre:100037369; -.
DR CTD; 100037369; -.
DR ZFIN; ZDB-GENE-070410-36; atp5if1a.
DR eggNOG; ENOG502S4JP; Eukaryota.
DR GeneTree; ENSGT00940000165091; -.
DR HOGENOM; CLU_147479_1_2_1; -.
DR InParanoid; A3KNL5; -.
DR OMA; YFRARNK; -.
DR PhylomeDB; A3KNL5; -.
DR TreeFam; TF320659; -.
DR PRO; PR:A3KNL5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000067975; Expressed in early embryo and 28 other tissues.
DR ExpressionAtlas; A3KNL5; baseline.
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:0032780; P:negative regulation of ATP-dependent activity; IBA:GO_Central.
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 InterPro; IPR007648; ATPase_inhibitor_mt.
DR Pfam; PF04568; IATP; 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
