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Protein

Lipoyl synthase, mitochondrial

Gene

LIAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives.UniRule annotation

Catalytic activityi

Protein N6-(octanoyl)lysine + an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster + 2 S-adenosyl-L-methionine + 2 oxidized [2Fe-2S] ferredoxin + 6 H+ = protein N6-(dihydrolipoyl)lysine + an [Fe-S] cluster scaffold protein + 2 sulfide + 4 Fe3+ + 2 L-methionine + 2 5'-deoxyadenosine + 2 reduced [2Fe-2S] ferredoxin.UniRule annotation

Cofactori

[4Fe-4S] clusterUniRule annotationNote: Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.UniRule annotation

Pathwayi: protein lipoylation via endogenous pathway

This protein is involved in step 2 of the subpathway that synthesizes protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein].UniRule annotation
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Putative lipoyltransferase 2, mitochondrial (LIPT2), Putative lipoyltransferase 2, mitochondrial (lipB)
  2. Lipoyl synthase, mitochondrial (LIAS), Lipoyl synthase, mitochondrial (LIAS), Lipoyl synthase, mitochondrial (LIAS), Lipoyl synthase, mitochondrial (lipA)
This subpathway is part of the pathway protein lipoylation via endogenous pathway, which is itself part of Protein modification.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein], the pathway protein lipoylation via endogenous pathway and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi106Iron-sulfur 1 (4Fe-4S)UniRule annotation1
Metal bindingi111Iron-sulfur 1 (4Fe-4S)UniRule annotation1
Metal bindingi117Iron-sulfur 1 (4Fe-4S)UniRule annotation1
Metal bindingi137Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation1
Metal bindingi141Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation1
Metal bindingi144Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-HSA-389661 Glyoxylate metabolism and glycine degradation
UniPathwayi
UPA00538;UER00593

Names & Taxonomyi

Protein namesi
Recommended name:
Lipoyl synthase, mitochondrialUniRule annotation (EC:2.8.1.8UniRule annotation)
Alternative name(s):
Lipoate synthaseUniRule annotation
Short name:
LSUniRule annotation
Short name:
Lip-synUniRule annotation
Lipoic acid synthaseUniRule annotation
Gene namesi
Name:LIASUniRule annotation
Synonyms:LAS
ORF Names:HUSSY-01
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000121897.13
HGNCiHGNC:16429 LIAS
MIMi607031 gene
neXtProtiNX_O43766

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Hyperglycinemia, lactic acidosis, and seizures (HGCLAS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn enzymatic defect resulting in an autosomal recessive disorder of mitochondrial metabolism. It is characterized by early-onset lactic acidosis, severe encephalomyopathy, and a pyruvate oxidation defect. Affected individuals have neonatal-onset epilepsy, poor growth, psychomotor retardation, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine.
See also OMIM:614462
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067839249R → H in HGCLAS. 1 PublicationCorresponds to variant dbSNP:rs144133667EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi11019
MalaCardsiLIAS
MIMi614462 phenotype
OpenTargetsiENSG00000121897
Orphaneti401859 Lipoic acid synthetase deficiency
PharmGKBiPA30369

Chemistry databases

DrugBankiDB00166 Lipoic Acid

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 27MitochondrionUniRule annotationAdd BLAST27
ChainiPRO_000001772328 – 372Lipoyl synthase, mitochondrialAdd BLAST345

Proteomic databases

EPDiO43766
MaxQBiO43766
PaxDbiO43766
PeptideAtlasiO43766
PRIDEiO43766
ProteomicsDBi49157
TopDownProteomicsiO43766-2 [O43766-2]

PTM databases

iPTMnetiO43766
PhosphoSitePlusiO43766

Expressioni

Gene expression databases

BgeeiENSG00000121897 Expressed in 196 organ(s), highest expression level in muscle of leg
CleanExiHS_LIAS
ExpressionAtlasiO43766 baseline and differential
GenevisibleiO43766 HS

Organism-specific databases

HPAiHPA018842
HPA019076

Interactioni

Protein-protein interaction databases

BioGridi116209, 1 interactor
STRINGi9606.ENSP00000261434

Structurei

3D structure databases

ProteinModelPortaliO43766
SMRiO43766
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the radical SAM superfamily. Lipoyl synthase family.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2672 Eukaryota
COG0320 LUCA
GeneTreeiENSGT00390000006234
HOGENOMiHOG000235998
HOVERGENiHBG023328
InParanoidiO43766
KOiK03644
OMAiPYCDIDF
OrthoDBiEOG091G0AXJ
PhylomeDBiO43766
TreeFamiTF300817

Family and domain databases

Gene3Di3.20.20.70, 1 hit
HAMAPiMF_00206 Lipoyl_synth, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR006638 Elp3/MiaB/NifB
IPR031691 LIAS_N
IPR003698 Lipoyl_synth
IPR007197 rSAM
PANTHERiPTHR10949 PTHR10949, 1 hit
PfamiView protein in Pfam
PF16881 LIAS_N, 1 hit
PF04055 Radical_SAM, 1 hit
PIRSFiPIRSF005963 Lipoyl_synth, 1 hit
SFLDiSFLDF00271 lipoyl_synthase, 1 hit
SFLDS00029 Radical_SAM, 1 hit
SMARTiView protein in SMART
SM00729 Elp3, 1 hit
TIGRFAMsiTIGR00510 lipA, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 14 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O43766-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSLRCGDAAR TLGPRVFGRY FCSPVRPLSS LPDKKKELLQ NGPDLQDFVS
60 70 80 90 100
GDLADRSTWD EYKGNLKRQK GERLRLPPWL KTEIPMGKNY NKLKNTLRNL
110 120 130 140 150
NLHTVCEEAR CPNIGECWGG GEYATATATI MLMGDTCTRG CRFCSVKTAR
160 170 180 190 200
NPPPLDASEP YNTAKAIAEW GLDYVVLTSV DRDDMPDGGA EHIAKTVSYL
210 220 230 240 250
KERNPKILVE CLTPDFRGDL KAIEKVALSG LDVYAHNVET VPELQSKVRD
260 270 280 290 300
PRANFDQSLR VLKHAKKVQP DVISKTSIML GLGENDEQVY ATMKALREAD
310 320 330 340 350
VDCLTLGQYM QPTRRHLKVE EYITPEKFKY WEKVGNELGF HYTASGPLVR
360 370
SSYKAGEFFL KNLVAKRKTK DL
Length:372
Mass (Da):41,911
Last modified:September 23, 2008 - v3
Checksum:iA5BEACA1F36CEB74
GO
Isoform 2 (identifier: O43766-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     320-322: EEY → NFS
     323-372: Missing.

Note: Gene prediction based on EST data.
Show »
Length:322
Mass (Da):36,062
Checksum:iFBD44E3F52882DEF
GO
Isoform 3 (identifier: O43766-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     203-245: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:329
Mass (Da):37,137
Checksum:i8752725F433F3A95
GO

Computationally mapped potential isoform sequencesi

There are 14 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2PNQ5A0A1W2PNQ5_HUMAN
Lipoyl synthase, mitochondrial
LIAS
261Annotation score:
D6RCP8D6RCP8_HUMAN
Lipoyl synthase, mitochondrial
LIAS
242Annotation score:
A0A1X7SBR7A0A1X7SBR7_HUMAN
Lipoyl synthase, mitochondrial
LIAS
269Annotation score:
A0A1W2PRE7A0A1W2PRE7_HUMAN
Lipoyl synthase, mitochondrial
LIAS
265Annotation score:
A0A1W2PPM2A0A1W2PPM2_HUMAN
Lipoyl synthase, mitochondrial
LIAS
321Annotation score:
A0A1W2PQE9A0A1W2PQE9_HUMAN
Lipoyl synthase, mitochondrial
LIAS
226Annotation score:
Q6P5Q6Q6P5Q6_HUMAN
LIAS protein
LIAS
142Annotation score:
B4E0L7B4E0L7_HUMAN
Lipoyl synthase, mitochondrial
LIAS
100Annotation score:
A0A1W2PR81A0A1W2PR81_HUMAN
Lipoyl synthase, mitochondrial
LIAS
104Annotation score:
A0A1W2PQS9A0A1W2PQS9_HUMAN
Lipoyl synthase, mitochondrial
LIAS
142Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti253A → V in AAH23635 (PubMed:15489334).Curated1
Sequence conflicti260R → G in CAA11859 (PubMed:11124703).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067839249R → H in HGCLAS. 1 PublicationCorresponds to variant dbSNP:rs144133667EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054764203 – 245Missing in isoform 3. CuratedAdd BLAST43
Alternative sequenceiVSP_047380320 – 322EEY → NFS in isoform 2. Curated3
Alternative sequenceiVSP_047381323 – 372Missing in isoform 2. CuratedAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK292238 mRNA Translation: BAF84927.1
AC021148 Genomic DNA No translation available.
CH471069 Genomic DNA Translation: EAW92932.1
BC023635 mRNA Translation: AAH23635.1
AJ224162 mRNA Translation: CAA11859.1
CCDSiCCDS3453.1 [O43766-1]
CCDS3454.1 [O43766-2]
CCDS63950.1 [O43766-3]
RefSeqiNP_001265519.1, NM_001278590.1 [O43766-3]
NP_001265520.1, NM_001278591.1
NP_001265521.1, NM_001278592.1
NP_006850.2, NM_006859.3 [O43766-1]
NP_919433.1, NM_194451.2 [O43766-2]
UniGeneiHs.550502

Genome annotation databases

EnsembliENST00000340169; ENSP00000340676; ENSG00000121897 [O43766-2]
ENST00000381846; ENSP00000371270; ENSG00000121897 [O43766-3]
ENST00000640888; ENSP00000492260; ENSG00000121897 [O43766-1]
GeneIDi11019
KEGGihsa:11019
UCSCiuc003guf.5 human [O43766-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK292238 mRNA Translation: BAF84927.1
AC021148 Genomic DNA No translation available.
CH471069 Genomic DNA Translation: EAW92932.1
BC023635 mRNA Translation: AAH23635.1
AJ224162 mRNA Translation: CAA11859.1
CCDSiCCDS3453.1 [O43766-1]
CCDS3454.1 [O43766-2]
CCDS63950.1 [O43766-3]
RefSeqiNP_001265519.1, NM_001278590.1 [O43766-3]
NP_001265520.1, NM_001278591.1
NP_001265521.1, NM_001278592.1
NP_006850.2, NM_006859.3 [O43766-1]
NP_919433.1, NM_194451.2 [O43766-2]
UniGeneiHs.550502

3D structure databases

ProteinModelPortaliO43766
SMRiO43766
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116209, 1 interactor
STRINGi9606.ENSP00000261434

Chemistry databases

DrugBankiDB00166 Lipoic Acid

PTM databases

iPTMnetiO43766
PhosphoSitePlusiO43766

Proteomic databases

EPDiO43766
MaxQBiO43766
PaxDbiO43766
PeptideAtlasiO43766
PRIDEiO43766
ProteomicsDBi49157
TopDownProteomicsiO43766-2 [O43766-2]

Protocols and materials databases

DNASUi11019
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340169; ENSP00000340676; ENSG00000121897 [O43766-2]
ENST00000381846; ENSP00000371270; ENSG00000121897 [O43766-3]
ENST00000640888; ENSP00000492260; ENSG00000121897 [O43766-1]
GeneIDi11019
KEGGihsa:11019
UCSCiuc003guf.5 human [O43766-1]

Organism-specific databases

CTDi11019
DisGeNETi11019
EuPathDBiHostDB:ENSG00000121897.13
GeneCardsiLIAS
HGNCiHGNC:16429 LIAS
HPAiHPA018842
HPA019076
MalaCardsiLIAS
MIMi607031 gene
614462 phenotype
neXtProtiNX_O43766
OpenTargetsiENSG00000121897
Orphaneti401859 Lipoic acid synthetase deficiency
PharmGKBiPA30369
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2672 Eukaryota
COG0320 LUCA
GeneTreeiENSGT00390000006234
HOGENOMiHOG000235998
HOVERGENiHBG023328
InParanoidiO43766
KOiK03644
OMAiPYCDIDF
OrthoDBiEOG091G0AXJ
PhylomeDBiO43766
TreeFamiTF300817

Enzyme and pathway databases

UniPathwayi
UPA00538;UER00593

ReactomeiR-HSA-389661 Glyoxylate metabolism and glycine degradation

Miscellaneous databases

GenomeRNAii11019
PROiPR:O43766
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121897 Expressed in 196 organ(s), highest expression level in muscle of leg
CleanExiHS_LIAS
ExpressionAtlasiO43766 baseline and differential
GenevisibleiO43766 HS

Family and domain databases

Gene3Di3.20.20.70, 1 hit
HAMAPiMF_00206 Lipoyl_synth, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR006638 Elp3/MiaB/NifB
IPR031691 LIAS_N
IPR003698 Lipoyl_synth
IPR007197 rSAM
PANTHERiPTHR10949 PTHR10949, 1 hit
PfamiView protein in Pfam
PF16881 LIAS_N, 1 hit
PF04055 Radical_SAM, 1 hit
PIRSFiPIRSF005963 Lipoyl_synth, 1 hit
SFLDiSFLDF00271 lipoyl_synthase, 1 hit
SFLDS00029 Radical_SAM, 1 hit
SMARTiView protein in SMART
SM00729 Elp3, 1 hit
TIGRFAMsiTIGR00510 lipA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLIAS_HUMAN
AccessioniPrimary (citable) accession number: O43766
Secondary accession number(s): A8K873, C9JCF6, Q8IV62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: September 23, 2008
Last modified: October 10, 2018
This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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