ADT3_BOVIN
ID ADT3_BOVIN Reviewed; 298 AA.
AC P32007; A1L5C3; A6QQX7;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=ADP/ATP translocase 3 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 3 {ECO:0000250|UniProtKB:P12236};
DE AltName: Full=ADP,ATP carrier protein, isoform T2 {ECO:0000303|PubMed:2540808};
DE Short=ANT 2 {ECO:0000303|PubMed:2540808};
DE AltName: Full=Adenine nucleotide translocator 3 {ECO:0000303|PubMed:11809823};
DE Short=ANT 3 {ECO:0000303|PubMed:11809823};
DE AltName: Full=Solute carrier family 25 member 6 {ECO:0000305};
DE Contains:
DE RecName: Full=ADP/ATP translocase 3, N-terminally processed;
GN Name=SLC25A6 {ECO:0000250|UniProtKB:P12236};
GN Synonyms=AAC3 {ECO:0000250|UniProtKB:P12236},
GN ANT3 {ECO:0000303|PubMed:11809823};
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=2540808; DOI=10.1021/bi00428a069;
RA Powell S.J., Medd S.M., Runswick M.J., Walker J.E.;
RT "Two bovine genes for mitochondrial ADP/ATP translocase expressed
RT differences in various tissues.";
RL Biochemistry 28:866-873(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ovary;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 3-9; 35-43; 65-80 AND 274-280, IDENTIFICATION IN A
RP COMPLEX WITH ARL2 AND ARL2BP, AND TISSUE SPECIFICITY.
RX PubMed=11809823; DOI=10.1091/mbc.01-05-0245;
RA Sharer J.D., Shern J.F., Van Valkenburgh H., Wallace D.C., Kahn R.A.;
RT "ARL2 and BART enter mitochondria and bind the adenine nucleotide
RT transporter.";
RL Mol. Biol. Cell 13:71-83(2002).
CC -!- FUNCTION: ADP:ATP antiporter that mediates import of ADP into the
CC mitochondrial matrix for ATP synthesis, and export of ATP out to fuel
CC the cell (By similarity). Cycles between the cytoplasmic-open state (c-
CC state) and the matrix-open state (m-state): operates by the alternating
CC access mechanism with a single substrate-binding site intermittently
CC exposed to either the cytosolic (c-state) or matrix (m-state) side of
CC the inner mitochondrial membrane (By similarity). In addition to its
CC ADP:ATP antiporter activity, also involved in mitochondrial uncoupling
CC and mitochondrial permeability transition pore (mPTP) activity (By
CC similarity). Plays a role in mitochondrial uncoupling by acting as a
CC proton transporter: proton transport uncouples the proton flows via the
CC electron transport chain and ATP synthase to reduce the efficiency of
CC ATP production and cause mitochondrial thermogenesis. Proton
CC transporter activity is inhibited by ADP:ATP antiporter activity,
CC suggesting that SLC25A6/ANT3 acts as a master regulator of
CC mitochondrial energy output by maintaining a delicate balance between
CC ATP production (ADP:ATP antiporter activity) and thermogenesis (proton
CC transporter activity). Proton transporter activity requires free fatty
CC acids as cofactor, but does not transport it (By similarity). Also
CC plays a key role in mPTP opening, a non-specific pore that enables free
CC passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and
CC which contributes to cell death (By similarity). It is however unclear
CC if SLC25A6/ANT3 constitutes a pore-forming component of mPTP or
CC regulates it (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P12236, ECO:0000250|UniProtKB:P48962}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P48962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:P48962};
CC -!- ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by
CC the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open
CC state (c-state) is inhibited by the membrane-impermeable toxic
CC inhibitor carboxyatractyloside (CATR) (By similarity). Proton
CC transporter activity is inhibited by ADP:ATP antiporter activity (By
CC similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P48962}.
CC -!- SUBUNIT: Monomer (By similarity). Found in a complex with ARL2, ARL2BP
CC and SLC25A6/ANT3 (PubMed:11809823). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P02722, ECO:0000269|PubMed:11809823}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P02722}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:P12236}; Multi-pass
CC membrane protein {ECO:0000255}. Note=The complex formed with ARL2BP,
CC ARL2 and SLC25A6/ANT3 is expressed in mitochondria (By similarity). May
CC localize to non-mitochondrial membranes (By similarity).
CC {ECO:0000250|UniProtKB:P12235}.
CC -!- DOMAIN: The transmembrane helices are not perpendicular to the plane of
CC the membrane, but cross the membrane at an angle. Odd-numbered
CC transmembrane helices exhibit a sharp kink, due to the presence of a
CC conserved proline residue. {ECO:0000250|UniProtKB:P02722}.
CC -!- PTM: Trimethylated by ANTKMT at Lys-52. {ECO:0000250|UniProtKB:P12236}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
CC -!- CAUTION: Was reported as a homodimer (PubMed:11809823). However, 3D
CC structure data show that it forms a monomer (By similarity).
CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P02722,
CC ECO:0000269|PubMed:11809823}.
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DR EMBL; M24103; AAA30769.1; -; mRNA.
DR EMBL; BT029910; ABM06156.1; -; mRNA.
DR EMBL; BC150034; AAI50035.1; -; mRNA.
DR PIR; B43646; B43646.
DR RefSeq; NP_777085.1; NM_174660.2.
DR AlphaFoldDB; P32007; -.
DR SMR; P32007; -.
DR BioGRID; 159733; 1.
DR STRING; 9913.ENSBTAP00000055370; -.
DR PaxDb; P32007; -.
DR PeptideAtlas; P32007; -.
DR PRIDE; P32007; -.
DR Ensembl; ENSBTAT00000063682; ENSBTAP00000055370; ENSBTAG00000047418.
DR GeneID; 282480; -.
DR KEGG; bta:282480; -.
DR CTD; 293; -.
DR VEuPathDB; HostDB:ENSBTAG00000047418; -.
DR VGNC; VGNC:49967; SLC25A6.
DR eggNOG; KOG0749; Eukaryota.
DR GeneTree; ENSGT00940000154400; -.
DR HOGENOM; CLU_015166_12_0_1; -.
DR InParanoid; P32007; -.
DR OMA; FSGVCAY; -.
DR OrthoDB; 870903at2759; -.
DR TreeFam; TF300743; -.
DR Reactome; R-BTA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR Proteomes; UP000009136; Chromosome 26.
DR Bgee; ENSBTAG00000047418; Expressed in digestive system secreted substance and 103 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005471; F:ATP:ADP antiporter activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; IEA:InterPro.
DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; IBA:GO_Central.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IBA:GO_Central.
DR Gene3D; 1.50.40.10; -; 1.
DR InterPro; IPR002113; ADT_euk_type.
DR InterPro; IPR002067; Mit_carrier.
DR InterPro; IPR018108; Mitochondrial_sb/sol_carrier.
DR InterPro; IPR023395; Mt_carrier_dom_sf.
DR PANTHER; PTHR45635; PTHR45635; 1.
DR Pfam; PF00153; Mito_carr; 3.
DR PRINTS; PR00927; ADPTRNSLCASE.
DR PRINTS; PR00926; MITOCARRIER.
DR SUPFAM; SSF103506; SSF103506; 1.
DR PROSITE; PS50920; SOLCAR; 3.
PE 1: Evidence at protein level;
KW Acetylation; Antiport; Apoptosis; Direct protein sequencing; Membrane;
KW Methylation; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..298
FT /note="ADP/ATP translocase 3"
FT /id="PRO_0000425780"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P12236"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 3, N-terminally processed"
FT /id="PRO_0000090583"
FT TOPO_DOM 1..7
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 8..37
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 38..74
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 75..99
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 100..109
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 110..130
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 131..178
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 179..199
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 200..210
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 211..231
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 232..273
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 274..291
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT TOPO_DOM 292..298
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT REPEAT 6..98
FT /note="Solcar 1"
FT REPEAT 111..201
FT /note="Solcar 2"
FT REPEAT 212..297
FT /note="Solcar 3"
FT REGION 235..240
FT /note="Important for transport activity"
FT /evidence="ECO:0000250|UniProtKB:P12235"
FT MOTIF 235..240
FT /note="Nucleotide carrier signature motif"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 80
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 92
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT BINDING 235
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P02722"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P12236"
FT MOD_RES 2
FT /note="N-acetylthreonine; in ADP/ATP translocase 3, N-
FT terminally processed"
FT /evidence="ECO:0000250|UniProtKB:P12236"
FT MOD_RES 52
FT /note="N6,N6,N6-trimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12236"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12236"
FT MOD_RES 268
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12236"
SQ SEQUENCE 298 AA; 32877 MW; 1C34E7DF6EDE4061 CRC64;
MTEQAISFAK DFLAGGIAAA ISKTAVAPIE RVKLLLQVQH ASKQIAADKQ YKGIVDCIVR
IPKEQGVLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDKRTQFW RYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKSGS EREFRGLGDC LVKITKSDGI RGLYQGFNVS
VQGIIIYRAA YFGIYDTAKG MLPDPKNTHI VVSWMIAQTV TAVAGVVSYP FDTVRRRMMM
QSGRKGADIM YKGTVDCWRK ILKDEGGKAF FKGAWSNVLR GMGGAFVLVL YDELKKVI
