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O43766 (LIAS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lipoyl synthase, mitochondrial

EC=2.8.1.8
Alternative name(s):
Lipoate synthase
Short name=LS
Short name=Lip-syn
Lipoic acid synthase
Gene names
Name:LIAS
Synonyms:LAS
ORF Names:HUSSY-01
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length372 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. HAMAP-Rule MF_03123

Catalytic activity

Protein N(6)-(octanoyl)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine = protein N(6)-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine. HAMAP-Rule MF_03123

Cofactor

Binds 2 4Fe-4S clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine By similarity.

Pathway

Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 2/2. HAMAP-Rule MF_03123

Subcellular location

Mitochondrion By similarity HAMAP-Rule MF_03123.

Involvement in disease

Pyruvate dehydrogenase lipoic acid synthetase deficiency (PDHLD) [MIM:614462]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the radical SAM superfamily. Lipoyl synthase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43766-1)

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.
Isoform 2 (identifier: O43766-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2727Mitochondrion Potential
Chain28 – 372345Lipoyl synthase, mitochondrial HAMAP-Rule MF_03123
PRO_0000017723

Sites

Metal binding1061Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1111Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1171Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1371Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity
Metal binding1411Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity
Metal binding1441Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity

Natural variations

Alternative sequence320 – 3223EEY → NFS in isoform 2.
VSP_047380
Alternative sequence323 – 37250Missing in isoform 2.
VSP_047381
Natural variant2491R → H in PDHLD. Ref.6
Corresponds to variant rs144133667 [ dbSNP | Ensembl ].
VAR_067839

Experimental info

Sequence conflict2531A → V in AAH23635. Ref.4
Sequence conflict2601R → G in CAA11859. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 23, 2008. Version 3.
Checksum: A5BEACA1F36CEB74

FASTA37241,911
        10         20         30         40         50         60 
MSLRCGDAAR TLGPRVFGRY FCSPVRPLSS LPDKKKELLQ NGPDLQDFVS GDLADRSTWD 

        70         80         90        100        110        120 
EYKGNLKRQK GERLRLPPWL KTEIPMGKNY NKLKNTLRNL NLHTVCEEAR CPNIGECWGG 

       130        140        150        160        170        180 
GEYATATATI MLMGDTCTRG CRFCSVKTAR NPPPLDASEP YNTAKAIAEW GLDYVVLTSV 

       190        200        210        220        230        240 
DRDDMPDGGA EHIAKTVSYL KERNPKILVE CLTPDFRGDL KAIEKVALSG LDVYAHNVET 

       250        260        270        280        290        300 
VPELQSKVRD PRANFDQSLR VLKHAKKVQP DVISKTSIML GLGENDEQVY ATMKALREAD 

       310        320        330        340        350        360 
VDCLTLGQYM QPTRRHLKVE EYITPEKFKY WEKVGNELGF HYTASGPLVR SSYKAGEFFL 

       370 
KNLVAKRKTK DL 

« Hide

Isoform 2 [UniParc].

Checksum: FBD44E3F52882DEF
Show »

FASTA32236,062

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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: Skin.
[5]"Characterization of 16 novel human genes showing high similarity to yeast sequences."
Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G.
Yeast 18:69-80(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 260-372.
[6]"Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation."
Mayr J.A., Zimmermann F.A., Fauth C., Bergheim C., Meierhofer D., Radmayr D., Zschocke J., Koch J., Sperl W.
Am. J. Hum. Genet. 89:792-797(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PDHLD HIS-249.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001265519.1. NM_001278590.1.
NP_001265520.1. NM_001278591.1.
NP_001265521.1. NM_001278592.1.
NP_006850.2. NM_006859.3.
NP_919433.1. NM_194451.2.
UniGeneHs.550502.

3D structure databases

ProteinModelPortalO43766.
SMRO43766. Positions 129-310.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000261434.

Chemistry

DrugBankDB00166. Lipoic Acid.

Proteomic databases

PaxDbO43766.
PRIDEO43766.

Protocols and materials databases

DNASU11019.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261434; ENSP00000261434; ENSG00000121897. [O43766-1]
ENST00000340169; ENSP00000340676; ENSG00000121897. [O43766-2]
GeneID11019.
KEGGhsa:11019.
UCSCuc003guf.3. human. [O43766-1]

Organism-specific databases

CTD11019.
GeneCardsGC04P039463.
HGNCHGNC:16429. LIAS.
HPAHPA018842.
HPA019076.
MIM607031. gene.
614462. phenotype.
neXtProtNX_O43766.
PharmGKBPA30369.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0320.
HOGENOMHOG000235998.
HOVERGENHBG023328.
InParanoidO43766.
KOK03644.
OMAEEYVTPE.
OrthoDBEOG7P2XS7.
PhylomeDBO43766.
TreeFamTF300817.

Enzyme and pathway databases

UniPathwayUPA00538; UER00593.

Gene expression databases

ArrayExpressO43766.
BgeeO43766.
CleanExHS_LIAS.
GenevestigatorO43766.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
HAMAPMF_00206. Lipoyl_synth.
InterProIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view]
PANTHERPTHR10949. PTHR10949. 1 hit.
PfamPF04055. Radical_SAM. 1 hit.
[Graphical view]
PIRSFPIRSF005963. Lipoyl_synth. 1 hit.
SMARTSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsTIGR00510. lipA. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi11019.
NextBio41864.
PROO43766.
SOURCESearch...

Entry information

Entry nameLIAS_HUMAN
AccessionPrimary (citable) accession number: O43766
Secondary accession number(s): A8K873, Q8IV62
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: September 23, 2008
Last modified: March 19, 2014
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM