IDHP_PIG
ID IDHP_PIG Reviewed; 421 AA.
AC P33198;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Isocitrate dehydrogenase [NADP], mitochondrial;
DE Short=IDH;
DE EC=1.1.1.42 {ECO:0000269|PubMed:14512428};
DE AltName: Full=ICD-M;
DE AltName: Full=IDP;
DE AltName: Full=NADP(+)-specific ICDH;
DE AltName: Full=Oxalosuccinate decarboxylase;
DE Flags: Precursor; Fragment;
GN Name=IDH2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1627563; DOI=10.1021/bi00142a007;
RA Haselbeck R.J., Colman R.F., McAlister-Henn L.;
RT "Isolation and sequence of a cDNA encoding porcine mitochondrial NADP-
RT specific isocitrate dehydrogenase.";
RL Biochemistry 31:6219-6223(1992).
RN [2]
RP PROTEIN SEQUENCE OF 82-91; 59-64; 201-211; 269-278 AND 369-392, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Heart;
RX PubMed=1869531; DOI=10.1016/s0021-9258(18)98565-0;
RA Smyth G.E., Colman R.F.;
RT "Cysteinyl peptides of pig heart NADP-dependent isocitrate dehydrogenase
RT that are modified upon inactivation by N-ethylmaleimide.";
RL J. Biol. Chem. 266:14918-14925(1991).
RN [3]
RP PROTEIN SEQUENCE OF 383-395.
RX PubMed=3624273; DOI=10.1016/s0021-9258(18)45250-7;
RA Ehrlich R.S., Colman R.F.;
RT "Characterization of an active site peptide modified by the substrate
RT analogue 3-bromo-2-ketoglutarate on a single chain of dimeric NADP+-
RT dependent isocitrate dehydrogenase.";
RL J. Biol. Chem. 262:12614-12619(1987).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-148 AND LYS-220.
RX PubMed=14512428; DOI=10.1074/jbc.m303781200;
RA Kim T.K., Lee P., Colman R.F.;
RT "Critical role of Lys212 and Tyr140 in porcine NADP-dependent isocitrate
RT dehydrogenase.";
RL J. Biol. Chem. 278:49323-49331(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 9-421 IN COMPLEX WITH MANGANESE
RP AND ISOCITRATE, COFACTOR, AND SUBUNIT.
RX PubMed=12207025; DOI=10.1074/jbc.m207306200;
RA Ceccarelli C., Grodsky N.B., Ariyaratne N., Colman R.F., Bahnson B.J.;
RT "Crystal structure of porcine mitochondrial NADP+-dependent isocitrate
RT dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme
RT mechanism.";
RL J. Biol. Chem. 277:43454-43462(2002).
CC -!- FUNCTION: Plays a role in intermediary metabolism and energy production
CC (PubMed:14512428). It may tightly associate or interact with the
CC pyruvate dehydrogenase complex (PubMed:14512428).
CC {ECO:0000269|PubMed:14512428}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC Evidence={ECO:0000269|PubMed:14512428};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12207025};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:12207025};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000269|PubMed:12207025};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.47 uM for isocitrate {ECO:0000269|PubMed:14512428};
CC KM=9.85 uM for NADP {ECO:0000269|PubMed:14512428};
CC KM=0.11 uM for manganese {ECO:0000269|PubMed:14512428};
CC Vmax=39.6 umol/min/mg enzyme with isocitrate as substrate
CC {ECO:0000269|PubMed:14512428};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12207025}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305|PubMed:1869531}.
CC -!- PTM: Acetylation at Lys-382 dramatically reduces catalytic activity.
CC Deacetylated by SIRT3 (By similarity). {ECO:0000250|UniProtKB:P48735}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases 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; M86719; AAA31089.1; -; mRNA.
DR PIR; A43294; A43294.
DR PDB; 1LWD; X-ray; 1.85 A; A/B=9-421.
DR PDBsum; 1LWD; -.
DR AlphaFoldDB; P33198; -.
DR SMR; P33198; -.
DR STRING; 9823.ENSSSCP00000002026; -.
DR PaxDb; P33198; -.
DR PeptideAtlas; P33198; -.
DR PRIDE; P33198; -.
DR eggNOG; KOG1526; Eukaryota.
DR HOGENOM; CLU_023296_1_1_1; -.
DR InParanoid; P33198; -.
DR BRENDA; 1.1.1.42; 6170.
DR SABIO-RK; P33198; -.
DR EvolutionaryTrace; P33198; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Genevisible; P33198; SS.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004790; Isocitrate_DH_NADP.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR PANTHER; PTHR11822; PTHR11822; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR PIRSF; PIRSF000108; IDH_NADP; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00127; nadp_idh_euk; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Glyoxylate bypass;
KW Magnesium; Manganese; Metal-binding; Mitochondrion; NADP; Oxidoreductase;
KW Reference proteome; Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT <1..8
FT /note="Mitochondrion"
FT CHAIN 9..421
FT /note="Isocitrate dehydrogenase [NADP], mitochondrial"
FT /id="PRO_0000014422"
FT BINDING 84..86
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 86
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 91
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 103..109
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 118
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 141
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 260
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 268
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 283
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:12207025,
FT ECO:0007744|PDB:1LWD"
FT BINDING 318..323
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 336
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT SITE 148
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:14512428"
FT SITE 220
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:14512428"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 17
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 36
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 38
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 49
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 49
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 75
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 75
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 135
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 135
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 149
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 149
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 162
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 162
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 168
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 225
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 225
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 244
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 249
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 251
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 251
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 353
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 353
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 369
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54071"
FT MOD_RES 382
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MOD_RES 411
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P48735"
FT MUTAGEN 148
FT /note="Y->F: Large decrease in Vmax and insignificant
FT change in KM for isocitrate and NADP."
FT /evidence="ECO:0000269|PubMed:14512428"
FT MUTAGEN 220
FT /note="K->Q,Y: Large decrease in Vmax and insignificant
FT change in KM for isocitrate and NADP."
FT /evidence="ECO:0000269|PubMed:14512428"
FT NON_TER 1
FT STRAND 19..23
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 26..38
FT /evidence="ECO:0007829|PDB:1LWD"
FT TURN 39..43
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:1LWD"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 104..112
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 157..167
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 174..183
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 185..193
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 194..211
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:1LWD"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 227..242
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 244..249
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 259..268
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 279..293
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 298..304
FT /evidence="ECO:0007829|PDB:1LWD"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 321..328
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 338..355
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 358..376
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 382..389
FT /evidence="ECO:0007829|PDB:1LWD"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:1LWD"
FT HELIX 403..419
FT /evidence="ECO:0007829|PDB:1LWD"
SQ SEQUENCE 421 AA; 47526 MW; 14862D47C00A053F CRC64;
ARAAARHYAD QRIKVAKPVV EMDGDEMTRI IWQFIKEKLI LPHVDVQLKY FDLGLPNRDQ
TNDQVTIDSA LATQKYSVAV KCATITPDEA RVEEFKLKKM WKSPNGTIRN ILGGTVFREP
IICKNIPRLV PGWTKPITIG RHAHGDQYKA TDFVVDRAGT FKIVFTPKDG SSAKQWEVYN
FPAGGVGMGM YNTDESISGF AHSCFQYAIQ KKWPLYMSTK NTILKAYDGR FKDIFQEIFE
KHYKTDFDKY KIWYEHRLID DMVAQVLKSS GGFVWACKNY DGDVQSDILA QGFGSLGLMT
SVLVCPDGKT IEAEAAHGTV TRHYREHQKG RPTSTNPIAS IFAWTRGLEH RGKLDGNQDL
IRFAQTLEKV CVETVESGAM TKDLAGCIHG LSNVKLNEHF LNTSDFLDTI KSNLDRALGR
Q
