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O43766

- LIAS_HUMAN

UniProt

O43766 - LIAS_HUMAN

Protein

Lipoyl synthase, mitochondrial

Gene

LIAS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 3 (23 Sep 2008)
      Previous versions | rss
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    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

    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

    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

    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.
    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

    ArrayExpressiO43766.
    BgeeiO43766.
    CleanExiHS_LIAS.
    GenevestigatoriO43766.

    Organism-specific databases

    HPAiHPA018842.
    HPA019076.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000261434.

    Structurei

    3D structure databases

    ProteinModelPortaliO43766.
    SMRiO43766. Positions 129-310.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

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

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0320.
    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

    MSLRCGDAAR TLGPRVFGRY FCSPVRPLSS LPDKKKELLQ NGPDLQDFVS    50
    GDLADRSTWD EYKGNLKRQK GERLRLPPWL KTEIPMGKNY NKLKNTLRNL 100
    NLHTVCEEAR CPNIGECWGG GEYATATATI MLMGDTCTRG CRFCSVKTAR 150
    NPPPLDASEP YNTAKAIAEW GLDYVVLTSV DRDDMPDGGA EHIAKTVSYL 200
    KERNPKILVE CLTPDFRGDL KAIEKVALSG LDVYAHNVET VPELQSKVRD 250
    PRANFDQSLR VLKHAKKVQP DVISKTSIML GLGENDEQVY ATMKALREAD 300
    VDCLTLGQYM QPTRRHLKVE EYITPEKFKY WEKVGNELGF HYTASGPLVR 350
    SSYKAGEFFL KNLVAKRKTK DL 372
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 129-310.
    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.
    PharmGKBi PA30369.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0320.
    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

    ArrayExpressi O43766.
    Bgeei O43766.
    CleanExi HS_LIAS.
    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

    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: October 1, 2014
    This is version 124 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