DLD

Protein identityUniProt · HPA

UniProt accession

P09622

Gene

DLD

Ensembl

ENSG00000091140

Chromosome

7

Canonical length

509 aa

Protein class

Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Mitochondria,Principal piece

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

509 residues, UniProt reviewed canonical sequence.

>P09622|DLD
     1  MQSWSRVYCS LAKRGHFNRI SHGLQGLSAV PLRTYADQPI DADVTVIGSG PGGYVAAIKA
    61  AQLGFKTVCI EKNETLGGTC LNVGCIPSKA LLNNSHYYHM AHGKDFASRG IEMSEVRLNL
   121  DKMMEQKSTA VKALTGGIAH LFKQNKVVHV NGYGKITGKN QVTATKADGG TQVIDTKNIL
   181  IATGSEVTPF PGITIDEDTI VSSTGALSLK KVPEKMVVIG AGVIGVELGS VWQRLGADVT
   241  AVEFLGHVGG VGIDMEISKN FQRILQKQGF KFKLNTKVTG ATKKSDGKID VSIEAASGGK
   301  AEVITCDVLL VCIGRRPFTK NLGLEELGIE LDPRGRIPVN TRFQTKIPNI YAIGDVVAGP
   361  MLAHKAEDEG IICVEGMAGG AVHIDYNCVP SVIYTHPEVA WVGKSEEQLK EEGIEYKVGK
   421  FPFAANSRAK TNADTDGMVK ILGQKSTDRV LGAHILGPGA GEMVNEAALA LEYGASCEDI
   481  ARVCHAHPTL SEAFREANLA ASFGKSINF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DLD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

229 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DLD.

Disease | AllUniProt

Conditions DLD is implicated in, by any mechanism.

• Dihydrolipoamide dehydrogenase deficiency (DLDD) MIM:246900

Disease | GeneticClinVar

139 pathogenic / likely-pathogenic of 742 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate dehydrogenase E3 deficiency
• Inborn genetic diseases
• DLD-related disorder
• Thyroid cancer, nonmedullary, 1
• See cases

ReferencesPubMed · IEDB

Publications for DLD from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.55

gnomAD pLI

0.01

gnomAD missense Z

1.1

DepMap mean gene effect

-0.24

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2-oxoglutarate decarboxylation to succinyl-CoA
• 2-oxoglutarate metabolic process
• branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA
• branched-chain amino acid catabolic process
• gastrulation
• mitochondrial electron transport, NADH to ubiquinone
• proteolysis
• pyruvate decarboxylation to acetyl-CoA
• regulation of membrane potential
• sperm capacitation
• L-lysine catabolic process to acetyl-CoA

Molecular functions

• flavin adenine dinucleotide binding
• dihydrolipoyl dehydrogenase (NADH) activity

Cellular components

• acrosomal matrix
• branched-chain alpha-ketoacid dehydrogenase complex
• mitochondrial matrix
• mitochondrion
• motile cilium
• nucleus
• oxoadipate dehydrogenase complex
• oxoglutarate dehydrogenase complex
• pyruvate dehydrogenase complex

Protein domainsUniProt · Pfam · InterPro

• Pyridine nucleotide-disulphide oxidoreductase, class I
• Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
• Pyridine nucleotide-disulphide oxidoreductase, class I, active site
• FAD/NAD-linked reductase, dimerisation domain superfamily
• FAD/NAD(P)-binding domain
• FAD/NAD(P)-binding domain superfamily
• Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
• Pyridine nucleotide-disulphide oxidoreductase
• Dihydrolipoamide dehydrogenase
• Class-I pyridine nucleotide-disulfide oxidoreductase

KeywordsUniProt

• Acetylation
• Cell projection
• Cilium
• Cytoplasmic vesicle
• Disulfide bond
• FAD
• Flagellum
• Flavoprotein
• Mitochondrion
• NAD
• Nucleus
• Oxidoreductase
• Phosphoprotein
• Redox-active center
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of DLD in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PDHX
• KGD4