Reviewed, UniProtKB/Swiss-Prot P07195 (LDHB_HUMAN)

Names and origin

Protein names

Recommended name:
    L-lactate dehydrogenase B chain
      Short name=LDH-B
    EC=1.1.1.27
Alternative name(s):
    LDH heart subunit
      Short name=LDH-H
    Renal carcinoma antigen NY-REN-46

Gene names

Name:

LDHB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	334 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	(S)-lactate + NAD+ = pyruvate + NADH.
Pathway	Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1.
Subunit structure	Homotetramer. Ref.10
Subcellular location	Cytoplasm.
Involvement in disease	Defects in LDHB are a cause of hereditary LDHB deficiency [MIM:150100]. LDHB deficiency is usually asymptomatic.
Sequence similarities	Belongs to the LDH/MDH superfamily. LDH family.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anaerobic glycolysis Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB
Molecular function	L-lactate dehydrogenase activity Ref.11 Traceable author statement. Source: ProtInc binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 334

333

L-lactate dehydrogenase B chain

PRO_0000168459

Regions

Nucleotide binding

31 – 53

23

NAD By similarity

Sites

Active site

194

1

Proton acceptor

Binding site

100

1

NAD

Binding site

107

1

Substrate

Binding site

139

1

NAD or substrate

Binding site

170

1

Substrate

Binding site

249

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.4

Modified residue

240

1

Phosphotyrosine Ref.7 Ref.8

Natural variations

Natural variant

7

1

K → E in LDHB deficiency; slightly decreased activity.

VAR_004173

Natural variant

35

1

A → E in LDHB deficiency.

VAR_004174

Natural variant

69

1

G → E in LDHB deficiency.

VAR_011634

Natural variant

107

1

R → W in GUA1; LDHB deficiency; inactive. Ref.16

VAR_011635

Natural variant

129

1

S → R in LDHB deficiency.

VAR_004175

Natural variant

171

1

F → V in LDHB deficiency.

VAR_004176

Natural variant

172

1

R → H in LDHB deficiency; unstable.

VAR_004177

Natural variant

172

1

R → P in LDHB deficiency.

VAR_011636

Natural variant

175

1

M → L in LDHB deficiency.

VAR_004178

Natural variant

175

1

M → V: dbSNP rs7966339. Ref.12

VAR_049758

Natural variant

223

1

Missing in LDHB deficiency.

VAR_011637

Natural variant

322

1

D → V in LDHB deficiency.

VAR_004179

Natural variant

325

1

W → R in LDHB deficiency.

VAR_011638

Secondary structure

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334

Helix Strand Turn

Details...

Helix

4 – 8

5

Beta strand

9 – 13

5

Beta strand

21 – 27

7

Helix

31 – 42

12

Beta strand

47 – 52

6

Helix

56 – 68

13

Helix

69 – 72

4

Beta strand

76 – 80

5

Helix

84 – 87

4

Beta strand

91 – 95

5

Helix

107 – 110

4

Helix

111 – 128

18

Beta strand

133 – 136

4

Beta strand

138 – 140

3

Helix

141 – 152

12

Helix

156 – 158

3

Beta strand

159 – 161

3

Helix

165 – 179

15

Helix

183 – 185

3

Beta strand

190 – 192

3

Helix

202 – 204

3

Helix

212 – 215

4

Turn

217 – 220

4

Beta strand

221 – 223

3

Helix

229 – 246

18

Helix

251 – 265

15

Beta strand

270 – 277

8

Beta strand

289 – 297

9

Beta strand

300 – 305

6

Helix

311 – 328

18

Sequences

	Sequence		Length	Mass (Da)
	P07195-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 3AD605DEED0D54A2	FASTA	334	36,638
	10 20 30 40 50 60 MATLKEKLIA PVAEEEATVP NNKITVVGVG QVGMACAISI LGKSLADELA LVDVLEDKLK 70 80 90 100 110 120 GEMMDLQHGS LFLQTPKIVA DKDYSVTANS KIVVVTAGVR QQEGESRLNL VQRNVNVFKF 130 140 150 160 170 180 IIPQIVKYSP DCIIIVVSNP VDILTYVTWK LSGLPKHRVI GSGCNLDSAR FRYLMAEKLG 190 200 210 220 230 240 IHPSSCHGWI LGEHGDSSVA VWSGVNVAGV SLQELNPEMG TDNDSENWKE VHKMVVESAY 250 260 270 280 290 300 EVIKLKGYTN WAIGLSVADL IESMLKNLSR IHPVSTMVKG MYGIENEVFL SLPCILNARG 310 320 330 LTSVINQKLK DDEVAQLKKS ADTLWDIQKD LKDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the human lactate dehydrogenase B gene." Takeno T., Li S.S.-L. Biochem. J. 257:921-924(1989) [PubMed: 2930497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The cDNA and protein sequences of human lactate dehydrogenase B." Sakai I., Sharief F.S., Pan Y.-C.E., Li S.S.-L. Biochem. J. 248:933-936(1987) [PubMed: 3435492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle and Urinary bladder.
[4]	Bienvenut W.V. Submitted (MAY-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-23; 44-58; 78-100; 108-113; 120-127; 159-170; 234-244; 271-279 AND 300-329, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[5]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 8-23; 44-58; 78-91; 108-113; 120-127; 159-170; 234-244; 280-299 AND 300-318, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[6]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, MASS SPECTROMETRY.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase." Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L. Proteins 43:175-185(2001) [PubMed: 11276087] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NADH AND SUBSTRATE ANALOG, HOMOTETRAMERIZATION.
[11]	"Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit." Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T. Hum. Genet. 91:423-426(1993) [PubMed: 8314553] [Abstract] Cited for: VARIANT GLU-7.
[12]	"Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining." Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T. Hum. Genet. 91:163-168(1993) [PubMed: 8462975] [Abstract] Cited for: VARIANTS GLU-35; VAL-171 AND LEU-175.
[13]	"Molecular characterization of genetic mutations in human lactate dehydrogenase (LDH) B (H) variant." Sudo K., Maekawa M., Tomonaga A., Tsukada T., Nakayama T., Kitamura M., Li S.S.-L., Kanno T., Toriumi J. Hum. Genet. 89:158-162(1992) [PubMed: 1587525] [Abstract] Cited for: VARIANTS ARG-129 AND HIS-172.
[14]	"A missense mutation found in human lactate dehydrogenase-B (H) variant gene." Sudo K., Maekawa M., Ikawa S., Machida K., Kitamura M., Li S.S.-L. Biochem. Biophys. Res. Commun. 168:672-676(1990) [PubMed: 2334429] [Abstract] Cited for: VARIANT HIS-172.
[15]	"DNA analysis of slow type of electrophoretic lactate dehydrogenase B(H) variant." Maekawa M., Sudo K., Fujita K., Yoshioka N., Sakurabayashi I., Li S.S.-L., Kanno T. Seibutsu Butsuri Kagaku 38:25-29(1994) Cited for: VARIANT VAL-322.
[16]	"Arginine to tryptophan substitution in the active site of a human lactate dehydrogenase variant -- LDHB GUA1: postulated effects on subunit structure and catalysis." Shonnard G.C., Hud N.V., Mohrenweiser H.W. Biochim. Biophys. Acta 1315:9-14(1996) [PubMed: 8611651] [Abstract] Cited for: VARIANT GUA1 TRP-107.
[17]	"A novel in-frame deletion mutation in a case of lactate dehydrogenase (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in serum and erythrocytes." Sudo K., Maekawa M., Houki N., Okuda T., Akizuki S., Magara T., Kawano K. Clin. Biochem. 32:137-141(1999) [PubMed: 10211631] [Abstract] Cited for: VARIANT ASN-223 DEL.
[18]	"First case of missense mutation (LDH-H:R171P) in exon 4 of the lactate dehydrogenase gene detected in a Japanese patient." Hidaka K., Ueda N., Hirata I., Watanabe Y., Minatogawa Y., Iuchi I. J. Hum. Genet. 44:69-72(1999) [PubMed: 9929983] [Abstract] Cited for: VARIANT PRO-172.
[19]	"A novel missense mutation in human lactate dehydrogenase b-subunit gene." Takatani T., Takaoka N., Tatsumi M., Kawamoto H., Okuno Y., Morita K., Masutani T., Murakawa K., Okamoto Y. Mol. Genet. Metab. 73:344-348(2001) [PubMed: 11509017] [Abstract] Cited for: VARIANT GLU-69.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Lactate dehydrogenase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X13794 , X13795, X13796, X13797, X13798, X13799, X13800 Genomic DNA. Translation: CAA32033.1.
Y00711 mRNA. Translation: CAA68701.1.
BC002362 mRNA. Translation: AAH02362.1.
BC015122 mRNA. Translation: AAH15122.1.
BC071860 mRNA. Translation: AAH71860.1.

IPI

IPI00219217.

PIR

DEHULH. S02795.

RefSeq

NP_002291.1.

UniGene

Hs.446149

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I0Z	X-ray	2.10	A/B	2-334	[»]
1T2F	X-ray	3.00	A/B/C/D	2-332	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P07195. 2 interactions.

PTM databases

PhosphoSite

P07195.

2-D gel databases

SWISS-2DPAGE

P07195.

Cornea-2DPAGE

P07195.

DOSAC-COBS-2DPAGE

P07195.

HSC-2DPAGE

P07195.

OGP

P07195.

REPRODUCTION-2DPAGE

IPI00219217.

Proteomic databases

PRIDE

P07195.

Genome annotation databases

Ensembl

ENSG00000111716. Homo sapiens. [Contig view]

GeneID

3945.

KEGG

hsa:3945.

Organism-specific databases

GeneCards

GC12M021679.

H-InvDB

HIX0010481.

HGNC

HGNC:6541. LDHB.

HPA

CAB004641.

MIM

150100. gene+phenotype.

Orphanet

2364. Lactate dehydrogenase deficiency.
79338. Lactate dehydrogenase deficiency type B.

PharmGKB

PA30325.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07195.

HOVERGEN

P07195.

OMA

P07195. YSPDCTI.

Enzyme and pathway databases

BRENDA

1.1.1.27. 247.

Reactome

REACT_1046. Pyruvate metabolism and TCA cycle.
REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P07195.

Bgee

P07195.

CleanEx

HS_LDHB.

GermOnline

ENSG00000111716. Homo sapiens.

Family and domain databases

InterPro

IPR001557. L-lactate/malate_DH.
IPR011304. L-lactate_DH.
IPR018177. L-lactate_DH_AS.
IPR001236. Lactate/malate_DH.
IPR015955. Lactate_DH/Glyco_Ohase_4_C.
[Graphical view]

Gene3D

G3DSA:3.90.110.10. lact_mal_DH. 1 hit.

Pfam

PF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000102. Lac_mal_DH. 1 hit.

PRINTS

PR00086. LLDHDRGNASE.

TIGRFAMs

TIGR01771. L-LDH-NAD. 1 hit.

PROSITE

PS00064. L_LDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P07195.

DrugBank

DB00157. NADH.

NextBio

15479.

SOURCE

Search...

Entry information

Entry name

LDHB_HUMAN

Accession

Primary (citable) accession number: P07195

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)