ADT2_TACAC
ID ADT2_TACAC Reviewed; 298 AA.
AC Q000K2;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=ADP/ATP translocase 2 {ECO:0000305};
DE AltName: Full=ADP,ATP carrier protein 2 {ECO:0000250|UniProtKB:P05141};
DE AltName: Full=Adenine nucleotide translocator 2 {ECO:0000250|UniProtKB:P05141};
DE Short=ANT 2 {ECO:0000303|Ref.1};
DE AltName: Full=Solute carrier family 25 member 5 {ECO:0000305};
DE Contains:
DE RecName: Full=ADP/ATP translocase 2, N-terminally processed;
GN Name=SLC25A5 {ECO:0000250|UniProtKB:P05141};
OS Tachyglossus aculeatus aculeatus (Southeast Australian short-beaked
OS echidna).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Monotremata; Tachyglossidae; Tachyglossus.
OX NCBI_TaxID=49271;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wistow G.;
RT "Echidna ANT2.";
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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. Plays a
CC role in mitochondrial uncoupling by acting as a proton transporter:
CC proton transport uncouples the proton flows via the electron transport
CC chain and ATP synthase to reduce the efficiency of ATP production and
CC cause mitochondrial thermogenesis. Proton transporter activity is
CC inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2
CC acts as a master regulator of mitochondrial energy output by
CC maintaining a delicate balance between ATP production (ADP:ATP
CC antiporter activity) and thermogenesis (proton transporter activity).
CC Proton transporter activity requires free fatty acids as cofactor, but
CC does not transport it. Probably mediates mitochondrial uncoupling in
CC tissues that do not express UCP1. Also plays a key role in mPTP
CC opening, a non-specific pore that enables free passage of the
CC mitochondrial membranes to solutes of up to 1.5 kDa, and which
CC contributes to cell death. It is however unclear if SLC25A5/ANT2
CC constitutes a pore-forming component of mPTP or regulates it (By
CC similarity). Acts as a regulator of mitophagy independently of ADP:ATP
CC antiporter activity: promotes mitophagy via interaction with TIMM44,
CC leading to inhibit the presequence translocase TIMM23, thereby
CC promoting stabilization of PINK1 (By similarity). As part of the
CC mitotic spindle-associated MMXD complex it may play a role in
CC chromosome segregation (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P05141, ECO:0000250|UniProtKB:P51881}.
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:P51881};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:P51881};
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:P51881}.
CC -!- SUBUNIT: Monomer (By similarity). Component of the MMXD complex, which
CC includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2. Interacts with
CC AK4 (By similarity). Interacts with TIMM44; leading to inhibit the
CC presequence translocase TIMM23, thereby promoting stabilization of
CC PINK1 (By similarity). {ECO:0000250|UniProtKB:G2QNH0,
CC ECO:0000250|UniProtKB:P02722, ECO:0000250|UniProtKB:P05141,
CC ECO:0000250|UniProtKB:P51881}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P02722}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane {ECO:0000250|UniProtKB:P05141}; Multi-pass
CC membrane protein {ECO:0000255}. Note=May localize to non-mitochondrial
CC membranes. {ECO:0000250|UniProtKB:P05141}.
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:P05141}.
CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.
CC {ECO:0000305}.
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DR EMBL; DQ987710; ABJ90459.1; -; mRNA.
DR AlphaFoldDB; Q000K2; -.
DR SMR; Q000K2; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0071817; C:MMXD complex; ISS:UniProtKB.
DR GO; GO:0005471; F:ATP:ADP antiporter activity; ISS:UniProtKB.
DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; ISS:UniProtKB.
DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; ISS:UniProtKB.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Antiport; Chromosome partition; Membrane; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..298
FT /note="ADP/ATP translocase 2"
FT /id="PRO_0000423224"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT CHAIN 2..298
FT /note="ADP/ATP translocase 2, N-terminally processed"
FT /id="PRO_0000289602"
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:P05141"
FT MOD_RES 2
FT /note="N-acetylthreonine; in ADP/ATP translocase 2, N-
FT terminally processed"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q09073"
FT MOD_RES 23
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000250"
FT MOD_RES 43
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 52
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 52
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 52
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 92
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000250"
FT MOD_RES 96
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000250"
FT MOD_RES 105
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 105
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 147
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 147
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 147
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 147
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 155
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 155
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 163
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P05141"
FT MOD_RES 166
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 268
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
FT MOD_RES 268
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51881"
SQ SEQUENCE 298 AA; 32859 MW; 79B7785202284A0B CRC64;
MTDAAVSFAK DFLAGGVAAA ISKTAVAPIE RVKLLLQVQH ASKQITADKQ YKGIMDCVVR
IPKEQGVLSF WRGNLANVIR YFPTQALNFA FKDKYKQIFL GGVDKRTQFW RYFAGNLASG
GAAGATSLCF VYPLDFARTR LAADVGKAGD AREFKGLGDC LVKITKSDGI RGLYQGFNVS
VQGIIIYRAA YFGIYDTAKG MLPDPKNTHI FISWMIAQSV TAVAGLTSYP FDTVRRRMMM
QSGRKGSDIM YTGTIDCWKK IARDEGSKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYT
