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O43766

- LIAS_HUMAN

UniProt

O43766 - LIAS_HUMAN

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Protein

Lipoyl synthase, mitochondrial

Gene

LIAS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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 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.

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi106 – 1061Iron-sulfur 1 (4Fe-4S)UniRule annotation
Metal bindingi111 – 1111Iron-sulfur 1 (4Fe-4S)UniRule annotation
Metal bindingi117 – 1171Iron-sulfur 1 (4Fe-4S)UniRule annotation
Metal bindingi137 – 1371Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation
Metal bindingi141 – 1411Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation
Metal bindingi144 – 1441Iron-sulfur 2 (4Fe-4S-S-AdoMet)UniRule annotation

GO - Molecular functioni

  1. 4 iron, 4 sulfur cluster binding Source: UniProtKB-HAMAP
  2. lipoate synthase activity Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. inflammatory response Source: UniProtKB
  2. lipoate biosynthetic process Source: UniProtKB
  3. neural tube closure Source: Ensembl
  4. protein lipoylation Source: UniProtKB-HAMAP
  5. response to lipopolysaccharide Source: UniProtKB
  6. response to oxidative stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Ligandi

4Fe-4S, Iron, Iron-sulfur, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

UniPathwayiUPA00538; 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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:16429. LIAS.

Subcellular locationi

Mitochondrion UniRule annotation

GO - Cellular componenti

  1. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti249 – 2491R → H in PDHLD. 1 Publication
Corresponds to variant rs144133667 [ dbSNP | Ensembl ].
VAR_067839

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614462. phenotype.
Orphaneti401859. Lipoic acid synthetase deficiency.
PharmGKBiPA30369.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2727MitochondrionUniRule annotationAdd
BLAST
Chaini28 – 372345Lipoyl synthase, mitochondrialPRO_0000017723Add
BLAST

Proteomic databases

MaxQBiO43766.
PaxDbiO43766.
PRIDEiO43766.

Expressioni

Gene expression databases

BgeeiO43766.
CleanExiHS_LIAS.
ExpressionAtlasiO43766. baseline and differential.
GenevestigatoriO43766.

Organism-specific databases

HPAiHPA018842.
HPA019076.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000261434.

Structurei

3D structure databases

ProteinModelPortaliO43766.
SMRiO43766. Positions 77-357.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0320.
GeneTreeiENSGT00390000006234.
HOGENOMiHOG000235998.
HOVERGENiHBG023328.
InParanoidiO43766.
KOiK03644.
OMAiTIRAVRH.
OrthoDBiEOG7P2XS7.
PhylomeDBiO43766.
TreeFamiTF300817.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00206. Lipoyl_synth.
InterProiIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view]
PANTHERiPTHR10949. PTHR10949. 1 hit.
PfamiPF04055. Radical_SAM. 1 hit.
[Graphical view]
PIRSFiPIRSF005963. Lipoyl_synth. 1 hit.
SMARTiSM00729. Elp3. 1 hit.
[Graphical view]
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. Align

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti253 – 2531A → V in AAH23635. (PubMed:15489334)Curated
Sequence conflicti260 – 2601R → G in CAA11859. (PubMed:11124703)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti249 – 2491R → H in PDHLD. 1 Publication
Corresponds to variant rs144133667 [ dbSNP | Ensembl ].
VAR_067839

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei203 – 24543Missing in isoform 3. CuratedVSP_054764Add
BLAST
Alternative sequencei320 – 3223EEY → NFS in isoform 2. CuratedVSP_047380
Alternative sequencei323 – 37250Missing in isoform 2. CuratedVSP_047381Add
BLAST

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

EnsembliENST00000261434; ENSP00000261434; ENSG00000121897. [O43766-1]
ENST00000340169; ENSP00000340676; ENSG00000121897. [O43766-2]
ENST00000381846; ENSP00000371270; ENSG00000121897. [O43766-3]
GeneIDi11019.
KEGGihsa:11019.
UCSCiuc003guf.3. human. [O43766-1]

Keywords - Coding sequence diversityi

Alternative splicing

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 .
CCDSi CCDS3453.1. [O43766-1 ]
CCDS3454.1. [O43766-2 ]
CCDS63950.1. [O43766-3 ]
RefSeqi NP_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 ]
UniGenei Hs.550502.

3D structure databases

ProteinModelPortali O43766.
SMRi O43766. Positions 77-357.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000261434.

Chemistry

DrugBanki DB00166. Lipoic Acid.

Proteomic databases

MaxQBi O43766.
PaxDbi O43766.
PRIDEi O43766.

Protocols and materials databases

DNASUi 11019.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261434 ; ENSP00000261434 ; ENSG00000121897 . [O43766-1 ]
ENST00000340169 ; ENSP00000340676 ; ENSG00000121897 . [O43766-2 ]
ENST00000381846 ; ENSP00000371270 ; ENSG00000121897 . [O43766-3 ]
GeneIDi 11019.
KEGGi hsa:11019.
UCSCi uc003guf.3. human. [O43766-1 ]

Organism-specific databases

CTDi 11019.
GeneCardsi GC04P039463.
HGNCi HGNC:16429. LIAS.
HPAi HPA018842.
HPA019076.
MIMi 607031. gene.
614462. phenotype.
neXtProti NX_O43766.
Orphaneti 401859. Lipoic acid synthetase deficiency.
PharmGKBi PA30369.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0320.
GeneTreei ENSGT00390000006234.
HOGENOMi HOG000235998.
HOVERGENi HBG023328.
InParanoidi O43766.
KOi K03644.
OMAi TIRAVRH.
OrthoDBi EOG7P2XS7.
PhylomeDBi O43766.
TreeFami TF300817.

Enzyme and pathway databases

UniPathwayi UPA00538 ; UER00593 .

Miscellaneous databases

GenomeRNAii 11019.
NextBioi 35485958.
PROi O43766.
SOURCEi Search...

Gene expression databases

Bgeei O43766.
CleanExi HS_LIAS.
ExpressionAtlasi O43766. baseline and differential.
Genevestigatori O43766.

Family and domain databases

Gene3Di 3.20.20.70. 1 hit.
HAMAPi MF_00206. Lipoyl_synth.
InterProi IPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view ]
PANTHERi PTHR10949. PTHR10949. 1 hit.
Pfami PF04055. Radical_SAM. 1 hit.
[Graphical view ]
PIRSFi PIRSF005963. Lipoyl_synth. 1 hit.
SMARTi SM00729. Elp3. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00510. lipA. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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] (ISOFORM 1).
    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.
    , 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. 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] (ISOFORM 1).
    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 (ISOFORM 1).
  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.

Entry informationi

Entry nameiLIAS_HUMAN
AccessioniPrimary (citable) accession number: O43766
Secondary accession number(s): A8K873, C9JCF6, Q8IV62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: September 23, 2008
Last modified: November 26, 2014
This is version 126 of the entry and version 3 of the sequence. [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. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3