O43766 (LIAS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	372 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 + 2 S-adenosyl-L-methionine = protein N(6)-(lipoyl)lysine + 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.
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.5
Sequence similarities	Belongs to the radical SAM superfamily. Lipoyl synthase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	4Fe-4S Iron Iron-sulfur Metal-binding S-adenosyl-L-methionine
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB neural tube closure Inferred from electronic annotation. Source: Compara protein lipoylation Inferred from electronic annotation. Source: HAMAP response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: HAMAP lipoate synthase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 27	27	Mitochondrion Potential
	Chain	28 – 372	345	Lipoyl synthase, mitochondrial HAMAP-Rule MF_03123		PRO_0000017723
Sites
	Metal binding	106	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	111	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	117	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	137	1	Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity
	Metal binding	141	1	Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity
	Metal binding	144	1	Iron-sulfur 2 (4Fe-4S-S-AdoMet) By similarity
Natural variations
	Natural variant	249	1	R → H in PDHLD. Ref.5 Corresponds to variant rs144133667 [ dbSNP | Ensembl ].		VAR_067839
Experimental info
	Sequence conflict	253	1	A → V in AAH23635. Ref.3
	Sequence conflict	260	1	R → G in CAA11859. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	O43766 [UniParc]. Last modified September 23, 2008. Version 3. Checksum: A5BEACA1F36CEB74	FASTA	372	41,911
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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].
[3]	"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.
[4]	"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.
[5]	"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. CH471069 Genomic DNA. Translation: EAW92932.1. BC023635 mRNA. Translation: AAH23635.1. AJ224162 mRNA. Translation: CAA11859.1.
IPI	IPI00216886.
RefSeq	NP_006850.2. NM_006859.2. NP_919433.1. NM_194451.1.
UniGene	Hs.550502.
3D structure databases
ProteinModelPortal	O43766.
SMR	O43766. Positions 129-310.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000261434.
Proteomic databases
PaxDb	O43766.
PRIDE	O43766.
Protocols and materials databases
DNASU	11019.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261434; ENSP00000261434; ENSG00000121897.
GeneID	11019.
KEGG	hsa:11019.
UCSC	uc003guf.3. human.
Organism-specific databases
CTD	11019.
GeneCards	GC04P039463.
HGNC	HGNC:16429. LIAS.
HPA	HPA018842. HPA019076.
MIM	607031. gene. 614462. phenotype.
neXtProt	NX_O43766.
PharmGKB	PA30369.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0320.
HOGENOM	HOG000235998.
HOVERGEN	HBG023328.
InParanoid	O43766.
KO	K03644.
OMA	EEYVTPE.
OrthoDB	EOG4T1HMX.
PhylomeDB	O43766.
Enzyme and pathway databases
UniPathway	UPA00538; UER00593.
Gene expression databases
ArrayExpress	O43766.
Bgee	O43766.
CleanEx	HS_LIAS.
Genevestigator	O43766.
GermOnline	ENSG00000121897. Homo sapiens.
Family and domain databases
Gene3D	3.20.20.70. 1 hit.
HAMAP	MF_00206. Lipoyl_synth.
InterPro	IPR013785. Aldolase_TIM. IPR006638. Elp3/MiaB/NifB. IPR003698. Lipoyl_synth. IPR007197. rSAM. [Graphical view]
PANTHER	PTHR10949. PTHR10949. 1 hit.
Pfam	PF04055. Radical_SAM. 1 hit. [Graphical view]
PIRSF	PIRSF005963. Lipoyl_synth. 1 hit.
SMART	SM00729. Elp3. 1 hit. [Graphical view]
TIGRFAMs	TIGR00510. lipA. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00166. Lipoic Acid.
GenomeRNAi	11019.
NextBio	41864.
SOURCE	Search...

Entry information

Entry name

LIAS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.