Gene/Proteome Database (LMPD)

LMPD ID
LMP001594
Gene ID
1738
Species
Homo sapiens (Human)
Gene Name
dihydrolipoamide dehydrogenase
Gene Symbol
DLD
Synonyms
DLDD; DLDH; E3; GCSL; LAD; PHE3
Alternate Names
dihydrolipoyl dehydrogenase, mitochondrial; diaphorase; lipoamide reductase; lipoyl dehydrogenase; lipoamide dehydrogenase; glycine cleavage system L protein; glycine cleavage system protein L; E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex
Chromosome
7
Map Location
7q31-q32
EC Number
1.8.1.4
Summary
This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Orthologs
View orthologs and multiple alignments for DLD

Proteins

dihydrolipoyl dehydrogenase, mitochondrial isoform 1 precursor
Refseq ID NP_000099
Protein GI 91199540
UniProt ID P09622
mRNA ID NM_000108
Length 509
RefSeq Status REVIEWED
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF
dihydrolipoyl dehydrogenase, mitochondrial isoform 2
Refseq ID NP_001276679
Protein GI 576583534
UniProt ID P09622
mRNA ID NM_001289750
Length 410
RefSeq Status REVIEWED
MAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF
dihydrolipoyl dehydrogenase, mitochondrial isoform 3
Refseq ID NP_001276680
Protein GI 576583534
UniProt ID P09622
mRNA ID NM_001289751
Length 410
RefSeq Status REVIEWED
MAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF
dihydrolipoyl dehydrogenase, mitochondrial isoform 4
Refseq ID NP_001276681
Protein GI 576583544
UniProt ID P09622
mRNA ID NM_001289752
Length 461
RefSeq Status REVIEWED
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF
transit_peptide: 1..35 experiment: experimental evidence, no additional details recorded note: Mitochondrion; propagated from UniProtKB/Swiss-Prot (P09622.2) calculated_mol_wt: 4021 peptide sequence: MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTY mat_peptide: 36..509 product: Dihydrolipoyl dehydrogenase, mitochondrial experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P09622.2) calculated_mol_wt: 50175 peptide sequence: ADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF

Gene Information

Entrez Gene ID
1738
Gene Name
dihydrolipoamide dehydrogenase
Gene Symbol
DLD
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0043159 IEA:Ensembl C acrosomal matrix
GO:0005929 IEA:Ensembl C cilium
GO:0005759 TAS:Reactome C mitochondrial matrix
GO:0005739 IDA:UniProt C mitochondrion
GO:0005634 IDA:HPA C nucleus
GO:0004148 TAS:ProtInc F dihydrolipoyl dehydrogenase activity
GO:0050660 IEA:InterPro F flavin adenine dinucleotide binding
GO:0009083 TAS:Reactome P branched-chain amino acid catabolic process
GO:0045454 IEA:InterPro P cell redox homeostasis
GO:0044237 TAS:Reactome P cellular metabolic process
GO:0034641 TAS:Reactome P cellular nitrogen compound metabolic process
GO:0007369 IEA:Ensembl P gastrulation
GO:0006554 TAS:Reactome P lysine catabolic process
GO:0006120 IEA:Ensembl P mitochondrial electron transport, NADH to ubiquinone
GO:0006508 IEA:Ensembl P proteolysis
GO:0006090 TAS:Reactome P pyruvate metabolic process
GO:0010510 TAS:Reactome P regulation of acetyl-CoA biosynthetic process from pyruvate
GO:0042391 IEA:Ensembl P regulation of membrane potential
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0048240 IEA:Ensembl P sperm capacitation
GO:0006099 TAS:Reactome P tricarboxylic acid cycle

KEGG Pathway Links

KEGG Pathway ID Description
hsa00020 Citrate cycle (TCA cycle)
hsa00260 Glycine, serine and threonine metabolism
hsa00010 Glycolysis / Gluconeogenesis

Domain Information

InterPro Annotations

Accession Description
IPR006258 Dihydrolipoamide dehydrogenase
IPR013027 FAD-dependent pyridine nucleotide-disulphide oxidoreductase
IPR016156 FAD/NAD-linked reductase, dimerisation domain
IPR023753 Pyridine nucleotide-disulphide oxidoreductase, FAD/NAD(P)-binding domain
IPR001327 Pyridine nucleotide-disulphide oxidoreductase, NAD-binding domain
IPR012999 Pyridine nucleotide-disulphide oxidoreductase, class I, active site
IPR004099 Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

UniProt Annotations

Entry Information

Gene Name
dihydrolipoamide dehydrogenase
Protein Entry
DLDH_HUMAN
UniProt ID
P09622
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P09622-1; Sequence=Displayed; Name=2; IsoId=P09622-2; Sequence=VSP_055855; Note=No experimental confirmation available.; Name=3; IsoId=P09622-3; Sequence=VSP_055856; Note=No experimental confirmation available.;
Catalytic Activity Protein N(6)-(dihydrolipoyl)lysine + NAD(+) = protein N(6)-(lipoyl)lysine + NADH.
Cofactor Name=FAD; Xref=ChEBI
Disease Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM
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.
Miscellaneous The active site is a redox-active disulfide bond.
Ptm Tyrosine phosphorylated.
Sequence Caution Sequence=BAD92940.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
Similarity Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Subcellular Location Mitochondrion matrix.
Subunit Homodimer. Eukaryotic pyruvate dehydrogenase complexes are organized about a core consisting of the oligomeric dihydrolipoamide acetyl-transferase, around which are arranged multiple copies of pyruvate dehydrogenase, dihydrolipoamide dehydrogenase and protein X bound by non-covalent bonds.

Identical and Related Proteins

Unique RefSeq proteins for LMP001594 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
91199540 RefSeq NP_000099 509 dihydrolipoyl dehydrogenase, mitochondrial isoform 1 precursor
576583534 RefSeq NP_001276679 410 dihydrolipoyl dehydrogenase, mitochondrial isoform 2
576583534 RefSeq NP_001276680 410 dihydrolipoyl dehydrogenase, mitochondrial isoform 3
576583544 RefSeq NP_001276681 461 dihydrolipoyl dehydrogenase, mitochondrial isoform 4

Identical Sequences to LMP001594 proteins

Reference Database Accession Length Protein Name
GI:576583534 DBBJ BAG58122.1 410 unnamed protein product [Homo sapiens]
GI:576583534 DBBJ BAG58122.1 410 unnamed protein product [Homo sapiens]
GI:576583544 DBBJ BAG61881.1 461 unnamed protein product [Homo sapiens]
GI:91199540 GenBank ADA19620.1 509 Sequence 1444 from patent US 7608413
GI:91199540 GenBank ADQ32070.1 509 dihydrolipoamide dehydrogenase, partial [synthetic construct]
GI:91199540 GenBank AEF74610.1 509 Sequence 144 from patent US 7939271
GI:91199540 GenBank AEN35515.1 509 Sequence 1443 from patent US 7998689
GI:91199540 GenBank AEN35516.1 509 Sequence 1444 from patent US 7998689
GI:91199540 GenBank AIC48643.1 509 DLD, partial [synthetic construct]

Related Sequences to LMP001594 proteins

Reference Database Accession Length Protein Name
GI:576583534 DBBJ BAG35267.1 509 unnamed protein product [Homo sapiens]
GI:576583534 DBBJ BAG35267.1 509 unnamed protein product [Homo sapiens]
GI:576583544 EMBL CAI29613.1 461 hypothetical protein [Pongo abelii]
GI:576583534 GenBank EAW83421.1 509 dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex), isoform CRA_a [Homo sapiens]
GI:576583534 GenBank EAW83421.1 509 dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex), isoform CRA_a [Homo sapiens]
GI:576583534 GenBank EAW83422.1 509 dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex), isoform CRA_a [Homo sapiens]
GI:576583534 GenBank EAW83422.1 509 dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex), isoform CRA_a [Homo sapiens]
GI:91199540 GenBank ACM85997.1 520 Sequence 11495 from patent US 6812339
GI:576583534 GenBank AEF74610.1 509 Sequence 144 from patent US 7939271
GI:576583534 GenBank AEF74610.1 509 Sequence 144 from patent US 7939271
GI:576583534 GenBank AEN35515.1 509 Sequence 1443 from patent US 7998689
GI:576583534 GenBank AEN35515.1 509 Sequence 1443 from patent US 7998689
GI:576583534 GenBank AEN35516.1 509 Sequence 1444 from patent US 7998689
GI:576583534 GenBank AEN35516.1 509 Sequence 1444 from patent US 7998689
GI:91199540 GenBank JAA16055.1 509 dihydrolipoamide dehydrogenase [Pan troglodytes]
GI:91199540 GenBank JAA31142.1 538 dihydrolipoamide dehydrogenase [Pan troglodytes]
GI:91199540 GenBank JAA37434.1 509 dihydrolipoamide dehydrogenase [Pan troglodytes]
GI:91199540 GenBank JAA37435.1 509 dihydrolipoamide dehydrogenase [Pan troglodytes]
GI:576583544 RefSeq NP_001128915.1 461 dihydrolipoyl dehydrogenase, mitochondrial [Pongo abelii]
GI:576583544 RefSeq XP_002803472.1 461 PREDICTED: dihydrolipoyl dehydrogenase, mitochondrial [Macaca mulatta]
GI:576583544 RefSeq XP_004702646.1 461 PREDICTED: dihydrolipoyl dehydrogenase, mitochondrial isoform X3 [Echinops telfairi]
GI:576583544 RefSeq XP_006745892.1 461 PREDICTED: dihydrolipoyl dehydrogenase, mitochondrial isoform X3 [Leptonychotes weddellii]
GI:576583544 RefSeq XP_007455412.1 461 PREDICTED: dihydrolipoyl dehydrogenase, mitochondrial isoform X3 [Lipotes vexillifer]
GI:91199540 RefSeq XP_009452252.1 538 PREDICTED: dihydrolipoyl dehydrogenase, mitochondrial [Pan troglodytes]