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 27-MAR-2024, entry version 234. DE RecName: Full=Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial {ECO:0000305}; 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 {ECO:0000312|HGNC:HGNC:2911}; 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 INTERACTION WITH ABHD11. RX PubMed=32792488; DOI=10.1038/s41467-020-17862-6; RA Bailey P.S.J., Ortmann B.M., Martinelli A.W., Houghton J.W., Costa A.S.H., RA Burr S.P., Antrobus R., Frezza C., Nathan J.A.; RT "ABHD11 maintains 2-oxoglutarate metabolism by preserving functional RT lipoylation of the 2-oxoglutarate dehydrogenase complex."; RL Nat. Commun. 11:4046-4046(2020). RN [14] RP INVOLVEMENT IN PPGL7, VARIANTS PPGL7 GLN-231; GLU-374 AND CYS-422, VARIANT RP ASN-304, CHARACTERIZATION OF VARIANTS PPGL7 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=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[2-oxoglutarate dehydrogenase CC complex component E2] + succinyl-CoA = CoA + N(6)-[(R)-S(8)- CC succinyldihydrolipoyl]-L-lysyl-[2-oxoglutarate dehydrogenase complex CC component E2]; Xref=Rhea:RHEA:15213, Rhea:RHEA-COMP:10581, Rhea:RHEA- CC COMP:10582, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:83100, CC 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), DLD (dihydrolipoamide dehydrogenase; E3) and CC the assembly factor KGD4 (By similarity). It contains multiple copies CC of the three enzymatic components (E1, E2 and E3). In the nucleus, the CC 2-oxoglutarate dehydrogenase complex associates with KAT2A CC (PubMed:29211711). Interacts with ABHD11; this interaction maintains CC the functional lipoylation of the 2-oxoglutarate dehydrogenase complex CC (PubMed:32792488). {ECO:0000250|UniProtKB:Q9D2G2, CC ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:32792488}. 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: TAFAZZIN; NbExp=3; IntAct=EBI-351007, EBI-25833693; CC P36957; P48775: TDO2; NbExp=3; IntAct=EBI-351007, EBI-743494; 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 P36957; Q9BQ29; NbExp=3; IntAct=EBI-351007, EBI-22013570; 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: Pheochromocytoma/paraganglioma syndrome 7 (PPGL7) CC [MIM:618475]: A form of pheochromocytoma/paraganglioma syndrome, a CC tumor predisposition syndrome characterized by the development of CC neuroendocrine tumors, usually in adulthood. Pheochromocytomas are CC catecholamine-producing tumors that arise from chromaffin cells in the CC adrenal medulla. Paragangliomas develop from sympathetic paraganglia in CC the thorax, abdomen, and pelvis, as well as from parasympathetic CC paraganglia in the head and neck. PPGL7 tumors are generally benign, CC tend to be abdominal, and often secrete normetanephrine. PPGL7 CC inheritance is autosomal dominant. {ECO:0000269|PubMed:30929736}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family. CC {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; 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 EMDB; EMD-0108; -. DR EMDB; EMD-10556; -. DR EMDB; EMD-11014; -. DR SMR; P36957; -. DR BioGRID; 108087; 465. DR CORUM; P36957; -. DR IntAct; P36957; 375. DR MINT; P36957; -. DR STRING; 9606.ENSP00000335304; -. DR GlyGen; P36957; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P36957; -. DR MetOSite; P36957; -. DR PhosphoSitePlus; P36957; -. DR SwissPalm; P36957; -. DR BioMuta; DLST; -. DR DMDM; 317373578; -. DR OGP; P36957; -. DR CPTAC; CPTAC-2756; -. DR EPD; P36957; -. DR jPOST; P36957; -. DR MassIVE; P36957; -. DR MaxQB; P36957; -. DR PaxDb; 9606-ENSP00000335304; -. DR PeptideAtlas; P36957; -. DR ProteomicsDB; 55248; -. [P36957-1] DR ProteomicsDB; 6726; -. DR Pumba; P36957; -. DR TopDownProteomics; P36957-1; -. [P36957-1] DR ABCD; P36957; 1 sequenced antibody. DR Antibodypedia; 45; 224 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 AGR; HGNC:2911; -. 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 OrthoDB; 672at2759; -. DR PhylomeDB; P36957; -. DR TreeFam; TF314164; -. DR BioCyc; MetaCyc:HS04324-MONOMER; -. 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; 242 hits in 1166 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 202 other cell types or tissues. DR ExpressionAtlas; P36957; baseline and differential. 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:HPA. 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 CDD; cd06849; lipoyl_domain; 1. DR Gene3D; 2.40.50.100; -; 1. DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 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 NCBIfam; TIGR01347; sucB; 1. DR PANTHER; PTHR43416:SF18; DIHYDROLIPOYLLYSINE-RESIDUE SUCCINYLTRANSFERASE COMPONENT OF 2-OXOGLUTARATE DEHYDROGENASE COMPLEX, MITOCHONDRIAL; 1. DR PANTHER; PTHR43416; DIHYDROLIPOYLLYSINE-RESIDUE SUCCINYLTRANSFERASE COMPONENT OF 2-OXOGLUTARATE DEHYDROGENASE COMPLEX, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF00198; 2-oxoacid_dh; 1. DR Pfam; PF00364; Biotin_lipoyl; 1. DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 1. DR SUPFAM; SSF51230; Single hybrid motif; 1. DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1. DR PROSITE; PS00189; LIPOYL; 1. DR UCD-2DPAGE; P36957; -. DR Genevisible; P36957; HS. 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 PPGL7; uncertain significance; not FT 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 PPGL7; decreased FT dihydrolipoyllysine-residue succinyltransferase activity; FT 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 PPGL7; uncertain significance; not FT 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 FT 2-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 //