P07195 (LDHB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.12
Subcellular location	Cytoplasm.
Polymorphism	Rare LDHB variants result in deficiency of lactate dehydrogenase, a condition with no deleterious effects on health. LDHB deficiency is of interest to laboratory medicine mainly because it can cause misdiagnosis in those disorders in which elevation of serum LDH is expected. Lactate dehydrogenase deficiency can probably be considered a non-disease [MIM:614128].
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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	NAD metabolic process Inferred from electronic annotation. Source: Compara cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro glycolysis Inferred from electronic annotation. Source: UniProtKB-KW lactate metabolic process Inferred from electronic annotation. Source: Compara pyruvate metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	L-lactate dehydrogenase activity Traceable author statement Ref.13. Source: ProtInc NAD binding Inferred from electronic annotation. Source: Compara
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

7

1

N6-acetyllysine Ref.9

Modified residue

44

1

Phosphoserine Ref.8

Modified residue

58

1

N6-acetyllysine Ref.9

Modified residue

119

1

N6-acetyllysine Ref.9

Modified residue

240

1

Phosphotyrosine Ref.8 Ref.10

Modified residue

329

1

N6-acetyllysine Ref.9

Natural variations

Natural variant

7

1

K → E in LDHB deficiency; slightly decreased activity. Ref.13

VAR_004173

Natural variant

35

1

A → E in LDHB deficiency. Ref.14

VAR_004174

Natural variant

69

1

G → E in LDHB deficiency. Ref.21

VAR_011634

Natural variant

107

1

R → W in LDHB deficiency; inactive. Ref.18

VAR_011635

Natural variant

129

1

S → R in LDHB deficiency. Ref.15

VAR_004175

Natural variant

171

1

F → V in LDHB deficiency. Ref.14

VAR_004176

Natural variant

172

1

R → H in LDHB deficiency; unstable. Ref.15 Ref.16

VAR_004177

Natural variant

172

1

R → P in LDHB deficiency. Ref.20

VAR_011636

Natural variant

175

1

M → L in LDHB deficiency. Ref.14

VAR_004178

Natural variant

175

1

M → V.
Corresponds to variant rs7966339 [ dbSNP | Ensembl ].

VAR_049758

Natural variant

223

1

Missing in LDHB deficiency. Ref.19

VAR_011637

Natural variant

322

1

D → V in LDHB deficiency. Ref.17

VAR_004179

Natural variant

325

1

W → R in LDHB deficiency.

VAR_011638

Secondary structure

1

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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

Beta strand

225 – 227

3

Helix

229 – 246

18

Helix

251 – 265

15

Beta strand

270 – 277

8

Turn

279 – 282

4

Beta strand

289 – 297

9

Beta strand

300 – 304

5

Helix

311 – 328

18

Sequences

	Sequence		Length	Mass (Da)
	P07195 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND TYR-240, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-7; LYS-58; LYS-119 AND LYS-329, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NADH AND SUBSTRATE ANALOG, HOMOTETRAMERIZATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY GLU-7.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS LDHB DEFICIENCY GLU-35; VAL-171 AND LEU-175.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS LDHB DEFICIENCY ARG-129 AND HIS-172.
[16]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY HIS-172.
[17]	"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 LDHB DEFICIENCY VAL-322.
[18]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY TRP-107.
[19]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY ASN-223 DEL.
[20]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY PRO-172.
[21]	"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] [Europe PMC] [Abstract] Cited for: VARIANT LDHB DEFICIENCY GLU-69.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Lactate dehydrogenase entry

Protein Spotlight

Another dark horse - Issue 109 of September 2009

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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_001167568.1. NM_001174097.1.
NP_002291.1. NM_002300.6.

UniGene

Hs.446149.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P07195.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07195. 12 interactions.

MINT

MINT-1144561.

STRING

9606.ENSP00000229319.

PTM databases

PhosphoSite

P07195.

Polymorphism databases

DMDM

126041.

2D gel databases

DOSAC-COBS-2DPAGE

P07195.

OGP

P07195.

REPRODUCTION-2DPAGE

IPI00219217.

SWISS-2DPAGE

P07195.

UCD-2DPAGE

P07195.

Proteomic databases

PaxDb

P07195.

PRIDE

P07195.

Protocols and materials databases

DNASU

3945.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000350669; ENSP00000229319; ENSG00000111716.
ENST00000396076; ENSP00000379386; ENSG00000111716.

GeneID

3945.

KEGG

hsa:3945.

UCSC

uc001rfd.3. human.

Organism-specific databases

CTD

3945.

GeneCards

GC12M021788.

HGNC

HGNC:6541. LDHB.

HPA

CAB004641.

MIM

150100. gene.
614128. phenotype.

neXtProt

NX_P07195.

Orphanet

284435. Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency.

PharmGKB

PA30325.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0039.

HOGENOM

HOG000213793.

HOVERGEN

HBG000462.

InParanoid

P07195.

KO

K00016.

OMA

CLIDVCA.

OrthoDB

EOG4RR6HR.

PhylomeDB

P07195.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.

SABIO-RK

P07195.

UniPathway

UPA00554; UER00611.

Gene expression databases

ArrayExpress

P07195.

Bgee

P07195.

CleanEx

HS_LDHB.

Genevestigator

P07195.

GermOnline

ENSG00000111716. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.
3.90.110.10. 1 hit.

InterPro

IPR001557. L-lactate/malate_DH.
IPR011304. L-lactate_DH.
IPR018177. L-lactate_DH_AS.
IPR022383. Lactate/malate_DH_C.
IPR001236. Lactate/malate_DH_N.
IPR015955. Lactate_DH/Glyco_Ohase_4_C.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11540. PTHR11540. 1 hit.
PTHR11540:SF3. PTHR11540:SF3. 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.

SUPFAM

SSF56327. Lactate_DH/Glyco_hydro_4_C. 1 hit.

TIGRFAMs

TIGR01771. L-LDH-NAD. 1 hit.

PROSITE

PS00064. L_LDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07195.

ChEMBL

CHEMBL4940.

ChiTaRS

LDHB. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P07195.

GenomeRNAi

3945.

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:	May 29, 2013
This is version 163 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.