ID ODPB_HUMAN Reviewed; 359 AA. AC P11177; B2R7L0; Q6FH45; Q9BQ27; Q9UFK3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-2007, sequence version 3. DT 11-JAN-2011, entry version 136. DE RecName: Full=Pyruvate dehydrogenase E1 component subunit beta, mitochondrial; DE Short=PDHE1-B; DE EC=1.2.4.1; DE Flags: Precursor; GN Name=PDHB; Synonyms=PHE1B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=90215313; PubMed=2323578; DOI=10.1016/0378-1119(90)90294-2; RA Ho L., Patel M.S.; RT "Cloning and cDNA sequence of the beta-subunit component of human RT pyruvate dehydrogenase complex."; RL Gene 86:297-302(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=91099335; PubMed=1702713; RX DOI=10.1111/j.1432-1033.1990.tb15656.x; RA Chun K., MacKay N., Willard H.F., Robinson B.H.; RT "Isolation, characterization and chromosomal localization of cDNA RT clones for the E1 beta subunit of the pyruvate dehydrogenase RT complex."; RL Eur. J. Biochem. 194:587-592(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-31. RX MEDLINE=90330681; PubMed=2376596; RA Huh T.L., Casazza J.P., Huh J.W., Chi Y.T., Song B.J.; RT "Characterization of two cDNA clones for pyruvate dehydrogenase E1 RT beta subunit and its regulation in tricarboxylic acid cycle-deficient RT fibroblast."; RL J. Biol. Chem. 265:13320-13326(1990). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX MEDLINE=90332628; PubMed=2377599; DOI=10.1073/pnas.87.15.5594; RA Koike K., Urata Y., Koike M.; RT "Molecular cloning and characterization of human pyruvate RT dehydrogenase beta subunit gene."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5594-5597(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-31. RX MEDLINE=88124815; PubMed=3422424; DOI=10.1073/pnas.85.1.41; RA Koike K., Ohta S., Urata Y., Kagawa Y., Koike M.; RT "Cloning and sequencing of cDNAs encoding alpha and beta subunits of RT human pyruvate dehydrogenase."; RL Proc. Natl. Acad. Sci. U.S.A. 85:41-45(1988). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX MEDLINE=21154917; PubMed=11230166; DOI=10.1101/gr.GR1547R; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain cortex; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 23-69. RX MEDLINE=88134251; PubMed=2829898; DOI=10.1016/0006-291X(88)90714-0; RA Ho L., Javed A.A., Pepin R.A., Thekkumkara T.J., Raefsky C., RA Mole J.E., Caliendo A.M., Kwon M.S., Kerr D.S., Patel M.S.; RT "Identification of a cDNA clone for the beta-subunit of the pyruvate RT dehydrogenase component of human pyruvate dehydrogenase complex."; RL Biochem. Biophys. Res. Commun. 150:904-908(1988). RN [12] RP PROTEIN SEQUENCE OF 31-43. RC TISSUE=Heart; RX MEDLINE=95203287; PubMed=7895732; DOI=10.1002/elps.11501501209; RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.; RT "The human myocardial two-dimensional gel protein database: update RT 1994."; RL Electrophoresis 15:1459-1465(1994). RN [13] RP PROTEIN SEQUENCE OF 31-55. RX MEDLINE=90109038; PubMed=2295468; DOI=10.1002/hep.1840110105; RA Muno D., Kominami E., Ishii H., Usui K., Saifuku K., Sakakibara Y., RA Namihisa T.; RT "Isolation of tryptic fragment of antigen from mitochondrial inner RT membrane proteins reacting with antimitochondrial antibody in sera of RT patients with primary biliary cirrhosis."; RL Hepatology 11:16-23(1990). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [15] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 32-359 IN COMPLEX WITH RP THIAMINE PYROPHOSPHATE. RX MEDLINE=22662261; PubMed=12651851; DOI=10.1074/jbc.M300339200; RA Ciszak E.M., Korotchkina L.G., Dominiak P.M., Sidhu S., Patel M.S.; RT "Structural basis for flip-flop action of thiamin pyrophosphate- RT dependent enzymes revealed by human pyruvate dehydrogenase."; RL J. Biol. Chem. 278:21240-21246(2003). RN [16] RP VARIANTS PDHE1 DEFICIENCY CYS-132 AND SER-344. RX PubMed=15138885; DOI=10.1007/s00439-004-1124-8; RA Brown R.M., Head R.A., Boubriak I.I., Leonard J.V., Thomas N.H., RA Brown G.K.; RT "Mutations in the gene for the E1beta subunit: a novel cause of RT pyruvate dehydrogenase deficiency."; RL Hum. Genet. 115:123-127(2004). CC -!- FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall CC conversion of pyruvate to acetyl-CoA and CO(2). It contains CC multiple copies of three enzymatic components: pyruvate CC dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and CC lipoamide dehydrogenase (E3). CC -!- CATALYTIC ACTIVITY: Pyruvate + [dihydrolipoyllysine-residue CC acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue CC acetyltransferase] S-acetyldihydrolipoyllysine + CO(2). CC -!- COFACTOR: Thiamine pyrophosphate. CC -!- SUBUNIT: Tetramer of 2 alpha and 2 beta subunits. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11177-1; Sequence=Displayed; CC Name=2; CC IsoId=P11177-2; Sequence=VSP_012675; CC Note=No experimental confirmation available; CC -!- DISEASE: Defects in PDHB are a cause of pyruvate dehydrogenase E1 CC component deficiency (PDHE1 deficiency) [MIM:312170]. PDHE1 CC deficiency is the most common enzyme defect in patients with CC primary lactic acidosis. It is associated with variable clinical CC phenotypes ranging from neonatal death to prolonged survival CC complicated by developmental delay, seizures, ataxia, apnea, and CC in some cases to an X-linked form of Leigh syndrome (LS) (Leigh CC encephalomyelopathy). 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; M34479; AAA36428.1; -; mRNA. DR EMBL; M19123; AAA60052.1; ALT_SEQ; mRNA. DR EMBL; M54788; AAA60053.1; -; mRNA. DR EMBL; M34055; AAA60233.1; -; mRNA. DR EMBL; M34056; AAA60054.1; -; mRNA. DR EMBL; D90086; BAA14123.1; -; Genomic_DNA. DR EMBL; J03576; AAA88097.1; -; mRNA. DR EMBL; AL117618; CAB56017.1; -; mRNA. DR EMBL; CR541911; CAG46709.1; -; mRNA. DR EMBL; AK313022; BAG35857.1; -; mRNA. DR EMBL; CH471055; EAW65371.1; -; Genomic_DNA. DR EMBL; BC000439; AAH00439.1; -; mRNA. DR EMBL; BC001924; AAH01924.1; -; mRNA. DR EMBL; X57778; CAA40924.1; -; mRNA. DR IPI; IPI00003925; -. DR IPI; IPI00549885; -. DR PIR; JU0145; DEHUPB. DR RefSeq; NP_000916.2; NM_000925.3. DR UniGene; Hs.161357; -. DR PDB; 1NI4; X-ray; 1.95 A; B/D=31-359. DR PDB; 2OZL; X-ray; 1.90 A; B/D=32-359. DR PDB; 3EXE; X-ray; 1.98 A; B/D/F/H=31-359. DR PDB; 3EXF; X-ray; 3.00 A; B/D/F/H=31-359. DR PDB; 3EXG; X-ray; 3.01 A; 2/4/6/B/D/F/H/J/L/N/P/R/T/V/X/Z=31-359. DR PDB; 3EXH; X-ray; 2.44 A; B/D/F/H=31-359. DR PDB; 3EXI; X-ray; 2.20 A; B=31-359. DR PDBsum; 1NI4; -. DR PDBsum; 2OZL; -. DR PDBsum; 3EXE; -. DR PDBsum; 3EXF; -. DR PDBsum; 3EXG; -. DR PDBsum; 3EXH; -. DR PDBsum; 3EXI; -. DR ProteinModelPortal; P11177; -. DR SMR; P11177; 30-359. DR DIP; DIP-37651N; -. DR IntAct; P11177; 8. DR MINT; MINT-3007546; -. DR STRING; P11177; -. DR PhosphoSite; P11177; -. DR SWISS-2DPAGE; P11177; -. DR REPRODUCTION-2DPAGE; IPI00549885; -. DR UCD-2DPAGE; P11177; -. DR PRIDE; P11177; -. DR Ensembl; ENST00000302746; ENSP00000307241; ENSG00000168291. DR GeneID; 5162; -. DR KEGG; hsa:5162; -. DR UCSC; uc003dkf.2; human. DR UCSC; uc003dkg.2; human. DR CTD; 5162; -. DR GeneCards; GC03M058388; -. DR H-InvDB; HIX0003404; -. DR HGNC; HGNC:8808; PDHB. DR MIM; 179060; gene+phenotype. DR MIM; 312170; phenotype. DR Orphanet; 765; Pyruvate dehydrogenase deficiency. DR eggNOG; prNOG06752; -. DR HOGENOM; HBG753264; -. DR HOVERGEN; HBG000917; -. DR InParanoid; P11177; -. DR OMA; QIPGLKV; -. DR OrthoDB; EOG99GP20; -. DR PhylomeDB; P11177; -. DR BRENDA; 1.2.4.1; 247. DR Reactome; REACT_1046; Pyruvate metabolism and Citric Acid (TCA) cycle. DR DrugBank; DB00157; NADH. DR DrugBank; DB00119; Pyruvic acid. DR NextBio; 19970; -. DR ArrayExpress; P11177; -. DR Bgee; P11177; -. DR CleanEx; HS_PDHB; -. DR Genevestigator; P11177; -. DR GermOnline; ENSG00000168291; Homo sapiens. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0004739; F:pyruvate dehydrogenase (acetyl-transferring) activity; TAS:ProtInc. DR GO; GO:0006096; P:glycolysis; IEA:UniProtKB-KW. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR GO; GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; EXP:Reactome. DR GO; GO:0006099; P:tricarboxylic acid cycle; TAS:ProtInc. DR InterPro; IPR009014; Transketo_C/Pyr-ferredox_oxred. DR InterPro; IPR015941; Transketolase-like_C. DR InterPro; IPR005475; Transketolase-like_Pyr-bd. DR InterPro; IPR005476; Transketolase_C. DR Gene3D; G3DSA:3.40.50.920; Transketo_C_like; 1. DR Pfam; PF02779; Transket_pyr; 1. DR Pfam; PF02780; Transketolase_C; 1. DR SMART; SM00861; Transket_pyr; 1. DR SUPFAM; SSF52922; Transketo_C_like; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disease mutation; Glycolysis; KW Mitochondrion; Oxidoreductase; Phosphoprotein; Polymorphism; Pyruvate; KW Thiamine pyrophosphate; Transit peptide. FT TRANSIT 1 30 Mitochondrion. FT CHAIN 31 359 Pyruvate dehydrogenase E1 component FT subunit beta, mitochondrial. FT /FTId=PRO_0000020457. FT BINDING 89 89 Thiamine pyrophosphate. FT MOD_RES 67 67 Phosphotyrosine (By similarity). FT VAR_SEQ 16 33 Missing (in isoform 2). FT /FTId=VSP_012675. FT VARIANT 31 31 L -> V. FT /FTId=VAR_004967. FT VARIANT 132 132 Y -> C (in PDHE1 deficiency; FT dbSNP:rs28935769). FT /FTId=VAR_030954. FT VARIANT 344 344 P -> S (in PDHE1 deficiency; FT dbSNP:rs28933391). FT /FTId=VAR_021058. FT CONFLICT 9 13 RRPLR -> AETPS (in Ref. 5). FT CONFLICT 43 43 M -> G (in Ref. 12; AA sequence). FT CONFLICT 160 160 Q -> G (in Ref. 5). FT CONFLICT 213 221 PPEAQSKDF -> LRKLSQKIL (in Ref. 5). FT CONFLICT 213 213 P -> L (in Ref. 4; AAA88097/BAA14123). FT CONFLICT 310 312 MEG -> NGS (in Ref. 5). FT STRAND 32 34 FT HELIX 35 49 FT STRAND 53 57 FT TURN 69 72 FT HELIX 73 77 FT TURN 79 81 FT STRAND 82 84 FT HELIX 89 101 FT STRAND 105 109 FT HELIX 113 119 FT HELIX 120 125 FT TURN 126 128 FT HELIX 130 133 FT STRAND 143 147 FT HELIX 156 158 FT HELIX 163 167 FT STRAND 173 175 FT HELIX 180 192 FT STRAND 193 195 FT STRAND 197 201 FT HELIX 203 205 FT STRAND 209 211 FT HELIX 214 217 FT STRAND 229 232 FT STRAND 235 241 FT HELIX 245 257 FT TURN 258 260 FT STRAND 263 267 FT STRAND 270 272 FT HELIX 276 286 FT STRAND 289 292 FT HELIX 301 311 FT HELIX 313 317 FT STRAND 323 325 FT HELIX 336 340 FT HELIX 346 356 SQ SEQUENCE 359 AA; 39233 MW; AB459B1259FBDBD3 CRC64; MAAVSGLVRR PLREVSGLLK RRFHWTAPAA LQVTVRDAIN QGMDEELERD EKVFLLGEEV AQYDGAYKVS RGLWKKYGDK RIIDTPISEM GFAGIAVGAA MAGLRPICEF MTFNFSMQAI DQVINSAAKT YYMSGGLQPV PIVFRGPNGA SAGVAAQHSQ CFAAWYGHCP GLKVVSPWNS EDAKGLIKSA IRDNNPVVVL ENELMYGVPF EFPPEAQSKD FLIPIGKAKI ERQGTHITVV SHSRPVGHCL EAAAVLSKEG VECEVINMRT IRPMDMETIE ASVMKTNHLV TVEGGWPQFG VGAEICARIM EGPAFNFLDA PAVRVTGADV PMPYAKILED NSIPQVKDII FAIKKTLNI //