ID LDHB_HUMAN Reviewed; 334 AA. AC P07195; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 29-APR-2008, entry version 105. DE L-lactate dehydrogenase B chain (EC 1.1.1.27) (LDH-B) (LDH heart DE subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46). GN Name=LDHB; 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 [GENOMIC DNA]. RX MEDLINE=89193506; PubMed=2930497; RA Takeno T., Li S.S.-L.; RT "Structure of the human lactate dehydrogenase B gene."; RL Biochem. J. 257:921-924(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=T-cell; RX MEDLINE=88133965; PubMed=3435492; RA Sakai I., Sharief F.S., Pan Y.-C.E., Li S.S.-L.; RT "The cDNA and protein sequences of human lactate dehydrogenase B."; RL Biochem. J. 248:933-936(1987). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle, and Urinary bladder; 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 [4] RP PROTEIN SEQUENCE OF 2-23; 44-58; 78-100; 108-113; 120-127; 159-170; RP 234-244; 271-279 AND 300-329, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (MAY-2005) to UniProtKB. RN [5] RP PROTEIN SEQUENCE OF 44-58; 120-127 AND 280-299, AND MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [6] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX MEDLINE=99438124; PubMed=10508479; RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal- RT cell carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, AND MASS RP SPECTROMETRY. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NADH AND RP SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION. RX PubMed=11276087; RX DOI=10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#; RA Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L.; RT "Structural basis for altered activity of M- and H-isozyme forms of RT human lactate dehydrogenase."; RL Proteins 43:175-185(2001). RN [9] RP VARIANT GLU-7. RX MEDLINE=93300477; PubMed=8314553; DOI=10.1007/BF00217765; RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.; RT "Analysis of a genetic mutation in an electrophoretic variant of the RT human lactate dehydrogenase-B(H) subunit."; RL Hum. Genet. 91:423-426(1993). RN [10] RP VARIANTS GLU-35; VAL-171 AND LEU-175. RX MEDLINE=93216283; PubMed=8462975; DOI=10.1007/BF00222718; RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.; RT "Detection and characterization of new genetic mutations in RT individuals heterozygous for lactate dehydrogenase-B(H) deficiency RT using DNA conformation polymorphism analysis and silver staining."; RL Hum. Genet. 91:163-168(1993). RN [11] RP VARIANTS ARG-129 AND HIS-172. RX MEDLINE=92267519; PubMed=1587525; DOI=10.1007/BF00217116; RA Sudo K., Maekawa M., Tomonaga A., Tsukada T., Nakayama T., RA Kitamura M., Li S.S.-L., Kanno T., Toriumi J.; RT "Molecular characterization of genetic mutations in human lactate RT dehydrogenase (LDH) B (H) variant."; RL Hum. Genet. 89:158-162(1992). RN [12] RP VARIANT HIS-172. RX MEDLINE=90241237; PubMed=2334429; DOI=10.1016/0006-291X(90)92373-8; RA Sudo K., Maekawa M., Ikawa S., Machida K., Kitamura M., Li S.S.-L.; RT "A missense mutation found in human lactate dehydrogenase-B (H) RT variant gene."; RL Biochem. Biophys. Res. Commun. 168:672-676(1990). RN [13] RP VARIANT VAL-322. RA Maekawa M., Sudo K., Fujita K., Yoshioka N., Sakurabayashi I., RA Li S.S.-L., Kanno T.; RT "DNA analysis of slow type of electrophoretic lactate dehydrogenase RT B(H) variant."; RL Seibutsu Butsuri Kagaku 38:25-29(1994). RN [14] RP VARIANT GUA1 TRP-107. RX MEDLINE=96190774; PubMed=8611651; DOI=10.1016/0925-4439(95)00089-5; RA Shonnard G.C., Hud N.V., Mohrenweiser H.W.; RT "Arginine to tryptophan substitution in the active site of a human RT lactate dehydrogenase variant -- LDHB GUA1: postulated effects on RT subunit structure and catalysis."; RL Biochim. Biophys. Acta 1315:9-14(1996). RN [15] RP VARIANT ASN-223 DEL. RX MEDLINE=99226613; PubMed=10211631; DOI=10.1016/S0009-9120(98)00097-6; RA Sudo K., Maekawa M., Houki N., Okuda T., Akizuki S., Magara T., RA Kawano K.; RT "A novel in-frame deletion mutation in a case of lactate dehydrogenase RT (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in RT serum and erythrocytes."; RL Clin. Biochem. 32:137-141(1999). RN [16] RP VARIANT PRO-172. RX MEDLINE=99128844; PubMed=9929983; DOI=10.1007/s100380050111; RA Hidaka K., Ueda N., Hirata I., Watanabe Y., Minatogawa Y., Iuchi I.; RT "First case of missense mutation (LDH-H:R171P) in exon 4 of the RT lactate dehydrogenase gene detected in a Japanese patient."; RL J. Hum. Genet. 44:69-72(1999). RN [17] RP VARIANT GLU-69. RX MEDLINE=21400984; PubMed=11509017; DOI=10.1006/mgme.2001.3203; RA Takatani T., Takaoka N., Tatsumi M., Kawamoto H., Okuno Y., Morita K., RA Masutani T., Murakawa K., Okamoto Y.; RT "A novel missense mutation in human lactate dehydrogenase b-subunit RT gene."; RL Mol. Genet. Metab. 73:344-348(2001). CC -!- CATALYTIC ACTIVITY: (S)-lactate + NAD(+) = pyruvate + NADH. CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)- CC lactate from pyruvate: step 1/1. CC -!- SUBUNIT: Homotetramer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- DISEASE: Defects in LDHB are a cause of hereditary LDHB deficiency CC [MIM:150100]. LDHB deficiency is usually asymptomatic. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=LDHB"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactate dehydrogenase entry; CC URL="http://en.wikipedia.org/wiki/Lactate_dehydrogenase"; 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; X13794; CAA32033.1; -; Genomic_DNA. DR EMBL; X13795; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; X13796; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; X13797; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; X13798; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; X13799; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; X13800; CAA32033.1; JOINED; Genomic_DNA. DR EMBL; Y00711; CAA68701.1; -; mRNA. DR EMBL; BC002362; AAH02362.1; -; mRNA. DR EMBL; BC015122; AAH15122.1; -; mRNA. DR EMBL; BC071860; AAH71860.1; -; mRNA. DR PIR; S02795; DEHULH. DR RefSeq; NP_002291.1; -. DR UniGene; Hs.446149; -. DR PDB; 1I0Z; X-ray; 2.10 A; A/B=1-334. DR PDB; 1T2F; X-ray; 3.00 A; A/B/C/D=1-334. DR PDBsum; 1I0Z; -. DR PDBsum; 1T2F; -. DR PhosphoSite; P07195; -. DR SWISS-2DPAGE; P07195; -. DR Cornea-2DPAGE; P07195; -. DR DOSAC-COBS-2DPAGE; P07195; -. DR HSC-2DPAGE; P07195; -. DR OGP; P07195; -. DR REPRODUCTION-2DPAGE; IPI00219217; -. DR Ensembl; ENSG00000111716; Homo sapiens. DR GeneID; 3945; -. DR KEGG; hsa:3945; -. DR H-InvDB; HIX0010481; -. DR HGNC; HGNC:6541; LDHB. DR HPA; CAB004641; -. DR MIM; 150100; gene+phenotype. DR Orphanet; 2364; Lactate dehydrogenase deficiency. DR PharmGKB; PA30325; -. DR DrugBank; DB00157; NADH. DR LinkHub; P07195; -. DR ArrayExpress; P07195; -. DR CleanEx; HS_LDHB; -. DR GermOnline; ENSG00000111716; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0004459; F:L-lactate dehydrogenase activity; TAS:ProtInc. DR InterPro; IPR001557; L-lactate/malate_DHase. DR InterPro; IPR011304; L-lactate_DHase. DR InterPro; IPR001236; Lactate/malate_DHase. DR InterPro; IPR015955; Lactate_DHase/Glyco_Ohase_4_C. DR Gene3D; G3DSA:3.90.110.10; lact_mal_DH; 1. DR Pfam; PF02866; Ldh_1_C; 1. DR Pfam; PF00056; Ldh_1_N; 1. DR PIRSF; PIRSF000102; Lac_mal_DH; 1. DR PRINTS; PR00086; LLDHDRGNASE. DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1. DR PROSITE; PS00064; L_LDH; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Disease mutation; Glycolysis; NAD; Oxidoreductase; Phosphoprotein. FT INIT_MET 1 1 Removed. FT CHAIN 2 334 L-lactate dehydrogenase B chain. FT /FTId=PRO_0000168459. FT NP_BIND 31 53 NAD (By similarity). FT ACT_SITE 194 194 Proton acceptor. FT BINDING 100 100 NAD. FT BINDING 107 107 Substrate. FT BINDING 139 139 NAD or substrate. FT BINDING 170 170 Substrate. FT BINDING 249 249 Substrate. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 240 240 Phosphotyrosine. FT VARIANT 7 7 K -> E (in LDHB deficiency; slightly FT decreased activity). FT /FTId=VAR_004173. FT VARIANT 35 35 A -> E (in LDHB deficiency). FT /FTId=VAR_004174. FT VARIANT 69 69 G -> E (in LDHB deficiency). FT /FTId=VAR_011634. FT VARIANT 107 107 R -> W (in GUA1; LDHB deficiency; FT inactive). FT /FTId=VAR_011635. FT VARIANT 129 129 S -> R (in LDHB deficiency). FT /FTId=VAR_004175. FT VARIANT 171 171 F -> V (in LDHB deficiency). FT /FTId=VAR_004176. FT VARIANT 172 172 R -> H (in LDHB deficiency; unstable). FT /FTId=VAR_004177. FT VARIANT 172 172 R -> P (in LDHB deficiency). FT /FTId=VAR_011636. FT VARIANT 175 175 M -> L (in LDHB deficiency). FT /FTId=VAR_004178. FT VARIANT 223 223 Missing (in LDHB deficiency). FT /FTId=VAR_011637. FT VARIANT 322 322 D -> V (in LDHB deficiency). FT /FTId=VAR_004179. FT VARIANT 325 325 W -> R (in LDHB deficiency). FT /FTId=VAR_011638. FT HELIX 4 8 FT STRAND 9 13 FT STRAND 21 27 FT HELIX 31 42 FT STRAND 47 52 FT HELIX 56 68 FT HELIX 69 72 FT STRAND 76 80 FT HELIX 84 87 FT STRAND 91 95 FT HELIX 107 110 FT HELIX 111 128 FT STRAND 133 136 FT STRAND 138 140 FT HELIX 141 152 FT HELIX 156 158 FT STRAND 159 161 FT HELIX 165 179 FT HELIX 183 185 FT STRAND 190 192 FT HELIX 202 204 FT HELIX 212 215 FT TURN 217 220 FT STRAND 221 223 FT HELIX 229 246 FT HELIX 251 265 FT STRAND 270 277 FT STRAND 289 297 FT STRAND 300 305 FT HELIX 311 328 SQ SEQUENCE 334 AA; 36638 MW; 3AD605DEED0D54A2 CRC64; MATLKEKLIA PVAEEEATVP NNKITVVGVG QVGMACAISI LGKSLADELA LVDVLEDKLK GEMMDLQHGS LFLQTPKIVA DKDYSVTANS KIVVVTAGVR QQEGESRLNL VQRNVNVFKF IIPQIVKYSP DCIIIVVSNP VDILTYVTWK LSGLPKHRVI GSGCNLDSAR FRYLMAEKLG IHPSSCHGWI LGEHGDSSVA VWSGVNVAGV SLQELNPEMG TDNDSENWKE VHKMVVESAY EVIKLKGYTN WAIGLSVADL IESMLKNLSR IHPVSTMVKG MYGIENEVFL SLPCILNARG LTSVINQKLK DDEVAQLKKS ADTLWDIQKD LKDL //