ODO2_HUMAN
ID ODO2_HUMAN Reviewed; 453 AA.
AC P36957; B7Z5W8; E7ESY5; Q7LDY7; Q9BQ32;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial;
DE EC=2.3.1.61 {ECO:0000269|PubMed:30929736};
DE AltName: Full=2-oxoglutarate dehydrogenase complex component E2;
DE Short=OGDC-E2;
DE AltName: Full=Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex;
DE AltName: Full=E2K;
DE Flags: Precursor;
GN Name=DLST; Synonyms=DLTS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-213.
RX PubMed=8268217; DOI=10.1016/0167-4781(93)90002-u;
RA Nakano K., Matsuda S., Sakamoto T., Takase C., Nakagawa S., Ohta S.,
RA Ariyama T., Inazawa J., Abe T., Miyata T.;
RT "Human dihydrolipoamide succinyltransferase: cDNA cloning and localization
RT on chromosome 14q24.2-q24.3.";
RL Biochim. Biophys. Acta 1216:360-368(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-213.
RC TISSUE=Peripheral blood;
RX PubMed=8076640; DOI=10.1111/j.1432-1033.1994.tb20010.x;
RA Nakano K., Takase C., Sakamoto T., Nakagawa S., Inazawa J., Ohta S.,
RA Matuda S.;
RT "Isolation, characterization and structural organization of the gene and
RT pseudogene for the dihydrolipoamide succinyltransferase component of the
RT human 2-oxoglutarate dehydrogenase complex.";
RL Eur. J. Biochem. 224:179-189(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RA Keryanov S., Liang Y., Rogaev E.I., Sherrington R., Tsuda T., Rogaeva E.,
RA Chi H., Crapper-Mclachlan D., Chumakov Y., Rommens J.M.,
RA St George-Hyslop P.H.;
RT "Physical mapping and nucleotide sequence analysis of the human
RT dihydrolipoamide succinyltransferase gene.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 68-89.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF
RP 224-ARG--LYS-226.
RX PubMed=29211711; DOI=10.1038/nature25003;
RA Wang Y., Guo Y.R., Liu K., Yin Z., Liu R., Xia Y., Tan L., Yang P.,
RA Lee J.H., Li X.J., Hawke D., Zheng Y., Qian X., Lyu J., He J., Xing D.,
RA Tao Y.J., Lu Z.;
RT "KAT2A coupled with the alpha-KGDH complex acts as a histone H3
RT succinyltransferase.";
RL Nature 552:273-277(2017).
RN [13]
RP INVOLVEMENT IN PGL7, VARIANTS PGL7 GLN-231; GLU-374 AND CYS-422, VARIANT
RP ASN-304, CHARACTERIZATION OF VARIANTS PGL7 GLN-231; GLU-374 AND CYS-422,
RP CHARACTERIZATION OF VARIANT ASN-304, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP MUTAGENESIS OF HIS-424, AND ACTIVE SITE.
RX PubMed=30929736; DOI=10.1016/j.ajhg.2019.02.017;
RA Remacha L., Pirman D., Mahoney C.E., Coloma J., Calsina B.,
RA Curras-Freixes M., Leton R., Torres-Perez R., Richter S., Pita G.,
RA Herraez B., Cianchetta G., Honrado E., Maestre L., Urioste M., Aller J.,
RA Garcia-Uriarte O., Galvez M.A., Luque R.M., Lahera M., Moreno-Rengel C.,
RA Eisenhofer G., Montero-Conde C., Rodriguez-Antona C., Llorca O.,
RA Smolen G.A., Robledo M., Cascon A.;
RT "Recurrent germline DLST mutations in individuals with multiple
RT pheochromocytomas and paragangliomas.";
RL Am. J. Hum. Genet. 104:651-664(2019).
CC -!- FUNCTION: Dihydrolipoamide succinyltransferase (E2) component of the 2-
CC oxoglutarate dehydrogenase complex. The 2-oxoglutarate dehydrogenase
CC complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-
CC CoA and CO(2). The 2-oxoglutarate dehydrogenase complex is mainly
CC active in the mitochondrion (PubMed:29211711, PubMed:30929736). A
CC fraction of the 2-oxoglutarate dehydrogenase complex also localizes in
CC the nucleus and is required for lysine succinylation of histones:
CC associates with KAT2A on chromatin and provides succinyl-CoA to histone
CC succinyltransferase KAT2A (PubMed:29211711).
CC {ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:30929736}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[2-oxoglutarate dehydrogenase
CC complex component E2] + succinyl-CoA = (R)-N(6)-(S(8)-
CC succinyldihydrolipoyl)-L-lysyl-[2-oxoglutarate dehydrogenase complex
CC component E2] + CoA; Xref=Rhea:RHEA:15213, Rhea:RHEA-COMP:10581,
CC Rhea:RHEA-COMP:10582, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:83100, ChEBI:CHEBI:83120; EC=2.3.1.61;
CC Evidence={ECO:0000269|PubMed:30929736};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15215;
CC Evidence={ECO:0000305|PubMed:30929736};
CC -!- COFACTOR:
CC Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC Evidence={ECO:0000250|UniProtKB:P11179};
CC Note=Binds 1 lipoyl cofactor covalently.
CC {ECO:0000250|UniProtKB:P11179};
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine
CC pathway; glutaryl-CoA from L-lysine: step 6/6.
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle.
CC {ECO:0000269|PubMed:30929736}.
CC -!- SUBUNIT: The 2-oxoglutarate dehydrogenase complex is composed of OGDH
CC (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide
CC succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3).
CC It contains multiple copies of the three enzymatic components (E1, E2
CC and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex
CC associates with KAT2A (PubMed:29211711). {ECO:0000269|PubMed:29211711}.
CC -!- INTERACTION:
CC P36957; Q8N1W1-4: ARHGEF28; NbExp=3; IntAct=EBI-351007, EBI-13062134;
CC P36957; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-351007, EBI-747505;
CC P36957; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-351007, EBI-10176008;
CC P36957; P06493: CDK1; NbExp=3; IntAct=EBI-351007, EBI-444308;
CC P36957; O75175: CNOT3; NbExp=3; IntAct=EBI-351007, EBI-743073;
CC P36957; Q6UXH1-2: CRELD2; NbExp=3; IntAct=EBI-351007, EBI-21670927;
CC P36957; P49184: DNASE1L1; NbExp=3; IntAct=EBI-351007, EBI-20894690;
CC P36957; Q8IY82: DRC7; NbExp=3; IntAct=EBI-351007, EBI-10262896;
CC P36957; Q99944: EGFL8; NbExp=3; IntAct=EBI-351007, EBI-3924130;
CC P36957; P16422: EPCAM; NbExp=3; IntAct=EBI-351007, EBI-1171184;
CC P36957; Q9NVM1: EVA1B; NbExp=3; IntAct=EBI-351007, EBI-10314666;
CC P36957; Q96GK7: FAHD2A; NbExp=3; IntAct=EBI-351007, EBI-21647872;
CC P36957; Q10981: FUT2; NbExp=3; IntAct=EBI-351007, EBI-9090702;
CC P36957; P36382: GJA5; NbExp=3; IntAct=EBI-351007, EBI-750433;
CC P36957; P09471: GNAO1; NbExp=3; IntAct=EBI-351007, EBI-715087;
CC P36957; P79483: HLA-DRB3; NbExp=3; IntAct=EBI-351007, EBI-3910269;
CC P36957; P14060: HSD3B1; NbExp=3; IntAct=EBI-351007, EBI-17426018;
CC P36957; P42858: HTT; NbExp=3; IntAct=EBI-351007, EBI-466029;
CC P36957; Q7Z6Z7-2: HUWE1; NbExp=3; IntAct=EBI-351007, EBI-10975491;
CC P36957; O75874: IDH1; NbExp=3; IntAct=EBI-351007, EBI-715695;
CC P36957; Q9ULR0: ISY1; NbExp=3; IntAct=EBI-351007, EBI-2557660;
CC P36957; A0JP07: KIAA1683; NbExp=3; IntAct=EBI-351007, EBI-10171456;
CC P36957; P26715: KLRC1; NbExp=3; IntAct=EBI-351007, EBI-9018187;
CC P36957; Q6P5S2: LEG1; NbExp=3; IntAct=EBI-351007, EBI-11750531;
CC P36957; P09382: LGALS1; NbExp=3; IntAct=EBI-351007, EBI-1048875;
CC P36957; O00214-2: LGALS8; NbExp=3; IntAct=EBI-351007, EBI-12069522;
CC P36957; P43356: MAGEA2B; NbExp=3; IntAct=EBI-351007, EBI-5650739;
CC P36957; Q7Z434: MAVS; NbExp=3; IntAct=EBI-351007, EBI-995373;
CC P36957; Q8NCR3: MFI; NbExp=3; IntAct=EBI-351007, EBI-744790;
CC P36957; Q8TB02: MGC39372; NbExp=3; IntAct=EBI-351007, EBI-25834188;
CC P36957; Q96EY8: MMAB; NbExp=3; IntAct=EBI-351007, EBI-7825413;
CC P36957; A2RUH7: MYBPHL; NbExp=3; IntAct=EBI-351007, EBI-9088235;
CC P36957; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-351007, EBI-3446748;
CC P36957; P55209: NAP1L1; NbExp=3; IntAct=EBI-351007, EBI-356392;
CC P36957; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-351007, EBI-11750983;
CC P36957; Q8NCF5-2: NFATC2IP; NbExp=3; IntAct=EBI-351007, EBI-12305293;
CC P36957; Q96P20: NLRP3; NbExp=3; IntAct=EBI-351007, EBI-6253230;
CC P36957; Q8N323: NXPE1; NbExp=3; IntAct=EBI-351007, EBI-25834085;
CC P36957; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-351007, EBI-9091052;
CC P36957; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-351007, EBI-473160;
CC P36957; Q8NBT0: POC1A; NbExp=3; IntAct=EBI-351007, EBI-2557132;
CC P36957; O14829: PPEF1; NbExp=3; IntAct=EBI-351007, EBI-2931238;
CC P36957; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-351007, EBI-2860740;
CC P36957; Q9Y617: PSAT1; NbExp=3; IntAct=EBI-351007, EBI-709652;
CC P36957; P43686: PSMC4; NbExp=5; IntAct=EBI-351007, EBI-743997;
CC P36957; Q13200: PSMD2; NbExp=3; IntAct=EBI-351007, EBI-357648;
CC P36957; Q9Y3Y4: PYGO1; NbExp=3; IntAct=EBI-351007, EBI-3397474;
CC P36957; Q13636: RAB31; NbExp=3; IntAct=EBI-351007, EBI-725987;
CC P36957; Q96E17: RAB3C; NbExp=3; IntAct=EBI-351007, EBI-4287022;
CC P36957; P61224: RAP1B; NbExp=3; IntAct=EBI-351007, EBI-358143;
CC P36957; P50749: RASSF2; NbExp=3; IntAct=EBI-351007, EBI-960081;
CC P36957; Q96I25: RBM17; NbExp=3; IntAct=EBI-351007, EBI-740272;
CC P36957; P52756: RBM5; NbExp=3; IntAct=EBI-351007, EBI-714003;
CC P36957; Q02978: SLC25A11; NbExp=3; IntAct=EBI-351007, EBI-359174;
CC P36957; Q3SY56: SP6; NbExp=3; IntAct=EBI-351007, EBI-11175533;
CC P36957; Q96L03: SPATA17; NbExp=3; IntAct=EBI-351007, EBI-13322423;
CC P36957; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-351007, EBI-7082156;
CC P36957; F6Y2X3: TAZ; NbExp=3; IntAct=EBI-351007, EBI-25833693;
CC P36957; P48775: TDO2; NbExp=3; IntAct=EBI-351007, EBI-743494;
CC P36957; Q9BQ29: THAP4; NbExp=3; IntAct=EBI-351007, EBI-22013570;
CC P36957; Q9BT49: THAP7; NbExp=3; IntAct=EBI-351007, EBI-741350;
CC P36957; P49746: THBS3; NbExp=3; IntAct=EBI-351007, EBI-2530931;
CC P36957; Q96JJ7-2: TMX3; NbExp=3; IntAct=EBI-351007, EBI-25833898;
CC P36957; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-351007, EBI-12003398;
CC P36957; Q68CL5-3: TPGS2; NbExp=3; IntAct=EBI-351007, EBI-9091010;
CC P36957; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-351007, EBI-1037322;
CC P36957; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-351007, EBI-12581310;
CC P36957; P07437: TUBB; NbExp=3; IntAct=EBI-351007, EBI-350864;
CC P36957; Q7Z780: U2AF1; NbExp=3; IntAct=EBI-351007, EBI-25833730;
CC P36957; O75317: USP12; NbExp=3; IntAct=EBI-351007, EBI-2511507;
CC P36957; P62258: YWHAE; NbExp=4; IntAct=EBI-351007, EBI-356498;
CC P36957; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-351007, EBI-25830993;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:29211711}. Nucleus {ECO:0000269|PubMed:29211711}.
CC Note=Mainly localizes in the mitochondrion. A small fraction localizes
CC to the nucleus, where the 2-oxoglutarate dehydrogenase complex is
CC required for histone succinylation. {ECO:0000269|PubMed:29211711}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P36957-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36957-2; Sequence=VSP_056439, VSP_056440;
CC -!- DISEASE: Paragangliomas 7 (PGL7) [MIM:618475]: An autosomal dominant
CC tumor predisposition syndrome characterized by adult-onset development
CC of paragangliomas, neural crest tumors usually derived from the
CC chromoreceptor tissue of a paraganglion. PGL7 tumors are generally
CC benign, tend to be abdominal, and often secrete normetanephrine.
CC {ECO:0000269|PubMed:30929736}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; D16373; BAA03871.1; -; mRNA.
DR EMBL; D26535; BAA05536.1; -; Genomic_DNA.
DR EMBL; L37418; AAB59629.1; -; mRNA.
DR EMBL; AK289414; BAF82103.1; -; mRNA.
DR EMBL; AK299505; BAH13054.1; -; mRNA.
DR EMBL; AC006530; AAD30181.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81199.1; -; Genomic_DNA.
DR EMBL; BC000302; AAH00302.1; -; mRNA.
DR EMBL; BC001922; AAH01922.1; -; mRNA.
DR CCDS; CCDS9833.1; -. [P36957-1]
DR PIR; S39786; PN0673.
DR RefSeq; NP_001924.2; NM_001933.4. [P36957-1]
DR PDB; 6H05; EM; 2.90 A; A=68-453.
DR PDBsum; 6H05; -.
DR AlphaFoldDB; P36957; -.
DR SMR; P36957; -.
DR BioGRID; 108087; 412.
DR CORUM; P36957; -.
DR IntAct; P36957; 361.
DR MINT; P36957; -.
DR STRING; 9606.ENSP00000335304; -.
DR iPTMnet; P36957; -.
DR MetOSite; P36957; -.
DR PhosphoSitePlus; P36957; -.
DR SwissPalm; P36957; -.
DR BioMuta; DLST; -.
DR DMDM; 317373578; -.
DR OGP; P36957; -.
DR UCD-2DPAGE; P36957; -.
DR EPD; P36957; -.
DR jPOST; P36957; -.
DR MassIVE; P36957; -.
DR MaxQB; P36957; -.
DR PaxDb; P36957; -.
DR PeptideAtlas; P36957; -.
DR PRIDE; P36957; -.
DR ProteomicsDB; 55248; -. [P36957-1]
DR ProteomicsDB; 6726; -.
DR TopDownProteomics; P36957-1; -. [P36957-1]
DR ABCD; P36957; 1 sequenced antibody.
DR Antibodypedia; 45; 208 antibodies from 29 providers.
DR DNASU; 1743; -.
DR Ensembl; ENST00000334220.9; ENSP00000335304.4; ENSG00000119689.15. [P36957-1]
DR GeneID; 1743; -.
DR KEGG; hsa:1743; -.
DR MANE-Select; ENST00000334220.9; ENSP00000335304.4; NM_001933.5; NP_001924.2.
DR UCSC; uc001xqv.3; human. [P36957-1]
DR CTD; 1743; -.
DR DisGeNET; 1743; -.
DR GeneCards; DLST; -.
DR HGNC; HGNC:2911; DLST.
DR HPA; ENSG00000119689; Low tissue specificity.
DR MalaCards; DLST; -.
DR MIM; 126063; gene.
DR MIM; 618475; phenotype.
DR neXtProt; NX_P36957; -.
DR OpenTargets; ENSG00000119689; -.
DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma.
DR PharmGKB; PA27367; -.
DR VEuPathDB; HostDB:ENSG00000119689; -.
DR eggNOG; KOG0559; Eukaryota.
DR GeneTree; ENSGT00930000151014; -.
DR HOGENOM; CLU_016733_0_0_1; -.
DR InParanoid; P36957; -.
DR OMA; MKVPSPG; -.
DR PhylomeDB; P36957; -.
DR TreeFam; TF314164; -.
DR BioCyc; MetaCyc:HS04324-MON; -.
DR BRENDA; 1.2.1.105; 2681.
DR PathwayCommons; P36957; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-71064; Lysine catabolism.
DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; P36957; -.
DR SignaLink; P36957; -.
DR SIGNOR; P36957; -.
DR UniPathway; UPA00223; -.
DR UniPathway; UPA00868; UER00840.
DR BioGRID-ORCS; 1743; 212 hits in 1083 CRISPR screens.
DR ChiTaRS; DLST; human.
DR GeneWiki; DLST; -.
DR GenomeRNAi; 1743; -.
DR Pharos; P36957; Tbio.
DR PRO; PR:P36957; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P36957; protein.
DR Bgee; ENSG00000119689; Expressed in apex of heart and 200 other tissues.
DR ExpressionAtlas; P36957; baseline and differential.
DR Genevisible; P36957; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; IDA:UniProtKB.
DR GO; GO:0016746; F:acyltransferase activity; IMP:UniProtKB.
DR GO; GO:0004149; F:dihydrolipoyllysine-residue succinyltransferase activity; IMP:UniProtKB.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0106077; P:histone succinylation; IDA:UniProtKB.
DR GO; GO:0033512; P:L-lysine catabolic process to acetyl-CoA via saccharopine; IEA:UniProtKB-UniPathway.
DR GO; GO:0006104; P:succinyl-CoA metabolic process; ISS:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IMP:UniProtKB.
DR Gene3D; 3.30.559.10; -; 1.
DR InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR011053; Single_hybrid_motif.
DR InterPro; IPR006255; SucB.
DR Pfam; PF00198; 2-oxoacid_dh; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR TIGRFAMs; TIGR01347; sucB; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS00189; LIPOYL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW Direct protein sequencing; Disease variant; Lipoyl; Mitochondrion; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..67
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:19892738"
FT CHAIN 68..453
FT /note="Dihydrolipoyllysine-residue succinyltransferase
FT component of 2-oxoglutarate dehydrogenase complex,
FT mitochondrial"
FT /id="PRO_0000020472"
FT DOMAIN 70..144
FT /note="Lipoyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT REGION 152..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..197
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 424
FT /evidence="ECO:0000269|PubMed:30929736"
FT ACT_SITE 428
FT /evidence="ECO:0000250|UniProtKB:Q9N0F1"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 110
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT MOD_RES 154
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 273
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 277
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT MOD_RES 307
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D2G2"
FT VAR_SEQ 1..23
FT /note="MLSRSRCVSRAFSRSLSAFQKGN -> MTWLQSKPQRLQNLSQREMSGGR
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056439"
FT VAR_SEQ 24..109
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056440"
FT VARIANT 213
FT /note="P -> A"
FT /evidence="ECO:0000269|PubMed:8076640,
FT ECO:0000269|PubMed:8268217"
FT /id="VAR_004976"
FT VARIANT 231
FT /note="R -> Q (in PGL7; unknown pathological significance;
FT not changed dihydrolipoyllysine-residue succinyltransferase
FT activity; dbSNP:rs771616810)"
FT /evidence="ECO:0000269|PubMed:30929736"
FT /id="VAR_083034"
FT VARIANT 304
FT /note="D -> N (not changed dihydrolipoyllysine-residue
FT succinyltransferase activity; dbSNP:rs373295097)"
FT /evidence="ECO:0000269|PubMed:30929736"
FT /id="VAR_083035"
FT VARIANT 374
FT /note="G -> E (in PGL7; decreased dihydrolipoyllysine-
FT residue succinyltransferase activity; dbSNP:rs1270341616)"
FT /evidence="ECO:0000269|PubMed:30929736"
FT /id="VAR_083036"
FT VARIANT 384
FT /note="P -> T"
FT /id="VAR_004977"
FT VARIANT 422
FT /note="Y -> C (in PGL7; unknown pathological significance;
FT not changed dihydrolipoyllysine-residue succinyltransferase
FT activity; dbSNP:rs778239022)"
FT /evidence="ECO:0000269|PubMed:30929736"
FT /id="VAR_083037"
FT MUTAGEN 224..226
FT /note="REK->AEA: Reduced nuclear localization of the 2-
FT oxoglutarate dehydrogenase complex. Reduced histone
FT succinylation."
FT /evidence="ECO:0000269|PubMed:29211711"
FT MUTAGEN 424
FT /note="H->A: Loss of dihydrolipoyllysine-residue
FT succinyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30929736"
FT CONFLICT 14..15
FT /note="RS -> AP (in Ref. 1; BAA03871, 2; BAA05536 and 3;
FT AAB59629)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="G -> T (in Ref. 1; BAA03871)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="E -> D (in Ref. 1; BAA03871 and 2; BAA05536)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="R -> T (in Ref. 2; BAA05536)"
FT /evidence="ECO:0000305"
FT HELIX 229..238
FT /evidence="ECO:0007829|PDB:6H05"
FT TURN 239..244
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 267..274
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 282..294
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 296..299
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:6H05"
FT TURN 304..307
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 342..355
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 361..364
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 370..373
FT /evidence="ECO:0007829|PDB:6H05"
FT TURN 375..378
FT /evidence="ECO:0007829|PDB:6H05"
FT STRAND 391..423
FT /evidence="ECO:0007829|PDB:6H05"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 430..444
FT /evidence="ECO:0007829|PDB:6H05"
FT HELIX 448..451
FT /evidence="ECO:0007829|PDB:6H05"
SQ SEQUENCE 453 AA; 48755 MW; A30E8CC959106B8F CRC64;
MLSRSRCVSR AFSRSLSAFQ KGNCPLGRRS LPGVSLCQGP GYPNSRKVVI NNSVFSVRFF
RTTAVCKDDL VTVKTPAFAE SVTEGDVRWE KAVGDTVAED EVVCEIETDK TSVQVPSPAN
GVIEALLVPD GGKVEGGTPL FTLRKTGAAP AKAKPAEAPA AAAPKAEPTA AAVPPPAAPI
PTQMPPVPSP SQPPSGKPVS AVKPTVAPPL AEPGAGKGLR SEHREKMNRM RQRIAQRLKE
AQNTCAMLTT FNEIDMSNIQ EMRARHKEAF LKKHNLKLGF MSAFVKASAF ALQEQPVVNA
VIDDTTKEVV YRDYIDISVA VATPRGLVVP VIRNVEAMNF ADIERTITEL GEKARKNELA
IEDMDGGTFT ISNGGVFGSL FGTPIINPPQ SAILGMHGIF DRPVAIGGKV EVRPMMYVAL
TYDHRLIDGR EAVTFLRKIK AAVEDPRVLL LDL
