Dihydrolipoyl dehydrogenase, mitochondrial

Details

Name

Dihydrolipoyl dehydrogenase, mitochondrial

Synonyms

• 1.8.1.4
• Dihydrolipoamide dehydrogenase
• GCSL
• Glycine cleavage system L protein
• LAD
• PHE3

Gene Name

DLD

Organism

Humans

Amino acid sequence

>lcl|BSEQ0037066|Dihydrolipoyl dehydrogenase, mitochondrial
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA
AQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNL
DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL
IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVT
AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK
AEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGP
MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK
FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI
ARVCHAHPTLSEAFREANLAASFGKSINF

Number of residues

509

Molecular Weight

54176.91

Theoretical pI

7.76

GO Classification

Functions

dihydrolipoyl dehydrogenase activity / flavin adenine dinucleotide binding / lipoamide binding / NAD binding

Processes

2-oxoglutarate metabolic process / aging / branched-chain amino acid catabolic process / cell redox homeostasis / cellular metabolic process / cellular nitrogen compound metabolic process / dihydrolipoamide metabolic process / gastrulation / glyoxylate metabolic process / lipoate metabolic process / lysine catabolic process / mitochondrial acetyl-CoA biosynthetic process from pyruvate / mitochondrial electron transport, NADH to ubiquinone / proteolysis / pyruvate metabolic process / regulation of acetyl-CoA biosynthetic process from pyruvate / regulation of membrane potential / small molecule metabolic process / sperm capacitation / tricarboxylic acid cycle

Components

acrosomal matrix / cilium / mitochondrial matrix / mitochondrion / myelin sheath / nucleoplasm / oxoglutarate dehydrogenase complex / pyruvate dehydrogenase complex

General Function

Nad binding

Specific Function

Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.

Pfam Domain Function

• Pyr_redox_2 (PF07992)
• Pyr_redox_dim (PF02852)

Transmembrane Regions

Not Available

Cellular Location

Mitochondrion matrix

Gene sequence

>lcl|BSEQ0010519|Dihydrolipoyl dehydrogenase, mitochondrial (DLD)
ATGCAGAGCTGGAGTCGTGTGTACTGCTCCTTGGCCAAGAGAGGCCATTTCAATCGAATA
TCTCATGGCCTACAGGGACTTTCTGCAGTGCCTCTGAGAACTTACGCAGATCAGCCGATT
GATGCTGATGTAACAGTTATAGGTTCTGGTCCTGGAGGATATGTTGCTGCTATTAAAGCT
GCCCAGTTAGGCTTCAAGACAGTCTGCATTGAGAAAAATGAAACACTTGGTGGAACATGC
TTGAATGTTGGTTGTATTCCTTCTAAGGCTTTATTGAACAACTCTCATTATTACCATATG
GCCCATGGAAAAGATTTTGCATCTAGAGGAATTGAAATGTCCGAAGTTCGCTTGAATTTA
GACAAGATGATGGAGCAGAAGAGTACTGCAGTAAAAGCTTTAACAGGTGGAATTGCCCAC
TTATTCAAACAGAATAAGGTTGTTCATGTCAATGGATATGGAAAGATAACTGGCAAAAAT
CAAGTCACTGCTACGAAAGCTGATGGCGGCACTCAGGTTATTGATACAAAGAACATTCTT
ATAGCCACGGGTTCAGAAGTTACTCCTTTTCCTGGAATCACGATAGATGAAGATACAATA
GTGTCATCTACAGGTGCTTTATCTTTAAAAAAAGTTCCAGAAAAGATGGTTGTTATTGGT
GCAGGAGTAATAGGTGTAGAATTGGGTTCAGTTTGGCAAAGACTTGGTGCAGATGTGACA
GCAGTTGAATTTTTAGGTCATGTAGGTGGAGTTGGAATTGATATGGAGATATCTAAAAAC
TTTCAACGCATCCTTCAAAAACAGGGGTTTAAATTTAAATTGAATACAAAGGTTACTGGT
GCTACCAAGAAGTCAGATGGAAAAATTGATGTTTCTATTGAAGCTGCTTCTGGTGGTAAA
GCTGAAGTTATCACTTGTGATGTACTCTTGGTTTGCATTGGCCGACGACCCTTTACTAAG
AATTTGGGACTAGAAGAGCTGGGAATTGAACTAGATCCCAGAGGTAGAATTCCAGTCAAT
ACCAGATTTCAAACTAAAATTCCAAATATCTATGCCATTGGTGATGTAGTTGCTGGTCCA
ATGCTGGCTCACAAAGCAGAGGATGAAGGCATTATCTGTGTTGAAGGAATGGCTGGTGGT
GCTGTGCACATTGACTACAATTGTGTGCCATCAGTGATTTACACACACCCTGAAGTTGCT
TGGGTTGGCAAATCAGAAGAGCAGTTGAAAGAAGAGGGTATTGAGTACAAAGTTGGGAAA
TTCCCATTTGCTGCTAACAGCAGAGCTAAGACAAATGCTGACACAGATGGCATGGTGAAG
ATCCTTGGGCAGAAATCGACAGACAGAGTACTGGGAGCACATATTCTTGGACCAGGTGCT
GGAGAAATGGTAAATGAAGCTGCTCTTGCTTTGGAATATGGAGCATCCTGTGAAGATATA
GCTAGAGTCTGTCATGCACATCCGACCTTATCAGAAGCTTTTAGAGAAGCAAATCTTGCT
GCGTCATTTGGCAAATCAATCAACTTTTGA

Chromosome Location

7

Locus

7q31-q32

External Identifiers

Resource	Link
UniProtKB ID	P09622
UniProtKB Entry Name	DLDH_HUMAN
GenBank Protein ID	307137
GenBank Gene ID	J03490
GenAtlas ID	DLD
HGNC ID	HGNC:2898

General References

1. Otulakowski G, Robinson BH: Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases. J Biol Chem. 1987 Dec 25;262(36):17313-8. [Article]
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8. Johanning GL, Morris JI, Madhusudhan KT, Samols D, Patel MS: Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10964-8. [Article]
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14. Brautigam CA, Chuang JL, Tomchick DR, Machius M, Chuang DT: Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. J Mol Biol. 2005 Jul 15;350(3):543-52. [Article]
15. Ciszak EM, Makal A, Hong YS, Vettaikkorumakankauv AK, Korotchkina LG, Patel MS: How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex. J Biol Chem. 2006 Jan 6;281(1):648-55. Epub 2005 Nov 1. [Article]
16. Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT: Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. [Article]
17. Liu TC, Kim H, Arizmendi C, Kitano A, Patel MS: Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5186-90. [Article]
18. Hong YS, Kerr DS, Craigen WJ, Tan J, Pan Y, Lusk M, Patel MS: Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. Hum Mol Genet. 1996 Dec;5(12):1925-30. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB00157	NADH	approved, nutraceutical	unknown		Details
DB03147	Flavin adenine dinucleotide	approved	unknown		Details
DB00145	Glycine	approved, nutraceutical, vet_approved	unknown	substrate	Details