LIPT_HUMAN
ID LIPT_HUMAN Reviewed; 373 AA.
AC Q9Y234; Q4ZFZ1;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Lipoyltransferase 1, mitochondrial;
DE EC=2.3.1.-;
DE AltName: Full=Lipoate biosynthesis protein;
DE AltName: Full=Lipoate-protein ligase;
DE AltName: Full=Lipoyl ligase;
DE Flags: Precursor;
GN Name=LIPT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10103005; DOI=10.1046/j.1432-1327.1999.00204.x;
RA Fujiwara K., Suzuki M., Okumachi Y., Okamura-Ikeda K., Fujiwara T.,
RA Takahashi E., Motokawa Y.;
RT "Molecular cloning, structural characterization and chromosomal
RT localization of human lipoyltransferase gene.";
RL Eur. J. Biochem. 260:761-767(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Lung, and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INVOLVEMENT IN LIPT1D, AND VARIANT LIPT1D ALA-179.
RX PubMed=24341803; DOI=10.1186/1750-1172-8-192;
RA Soreze Y., Boutron A., Habarou F., Barnerias C., Nonnenmacher L.,
RA Delpech H., Mamoune A., Chretien D., Hubert L., Bole-Feysot C.,
RA Nitschke P., Correia I., Sardet C., Boddaert N., Hamel Y., Delahodde A.,
RA Ottolenghi C., de Lonlay P.;
RT "Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with
RT secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase.";
RL Orphanet J. Rare Dis. 8:192-192(2013).
RN [6]
RP VARIANTS LIPT1D PHE-71 AND GLY-98.
RX PubMed=24256811; DOI=10.1093/hmg/ddt585;
RA Tort F., Ferrer-Cortes X., Thio M., Navarro-Sastre A., Matalonga L.,
RA Quintana E., Bujan N., Arias A., Garcia-Villoria J., Acquaviva C.,
RA Vianey-Saban C., Artuch R., Garcia-Cazorla A., Briones P., Ribes A.;
RT "Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease
RT associated with a specific lipoylation defect of the 2-ketoacid
RT dehydrogenase complexes.";
RL Hum. Mol. Genet. 23:1907-1915(2014).
CC -!- FUNCTION: Catalyzes the transfer of the lipoyl group from lipoyl-AMP to
CC the specific lysine residue of lipoyl domains of lipoate-dependent
CC enzymes. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-lipoyl-5'-AMP + L-lysyl-[lipoyl-carrier protein] = (R)-
CC N(6)-lipoyl-L-lysyl-[lipoyl-carrier protein] + AMP + 2 H(+);
CC Xref=Rhea:RHEA:20473, Rhea:RHEA-COMP:10500, Rhea:RHEA-COMP:10502,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:83091,
CC ChEBI:CHEBI:83099, ChEBI:CHEBI:456215;
CC -!- PATHWAY: Protein modification; protein lipoylation via exogenous
CC pathway; protein N(6)-(lipoyl)lysine from lipoate: step 2/2.
CC -!- INTERACTION:
CC Q9Y234; P55212: CASP6; NbExp=3; IntAct=EBI-727376, EBI-718729;
CC Q9Y234; Q92993: KAT5; NbExp=3; IntAct=EBI-727376, EBI-399080;
CC Q9Y234; P13473-2: LAMP2; NbExp=3; IntAct=EBI-727376, EBI-21591415;
CC Q9Y234; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-727376, EBI-11742507;
CC Q9Y234; P17252: PRKCA; NbExp=3; IntAct=EBI-727376, EBI-1383528;
CC Q9Y234; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-727376, EBI-9090795;
CC Q9Y234; P61981: YWHAG; NbExp=3; IntAct=EBI-727376, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle and heart,
CC moderately in kidney and pancreas, and detected at lower levels in
CC liver, brain, placenta and lung. {ECO:0000269|PubMed:10103005}.
CC -!- DISEASE: Lipoyltransferase 1 deficiency (LIPT1D) [MIM:616299]: A
CC disorder due to a defect in lipoic acid metabolism, resulting in severe
CC lactic acidosis and metabolic decompensation. Variable clinical
CC manifestations include delayed psychomotor development, severe
CC hypotonia, dystonia, loss of head control, coma, bradycardia, and
CC pulmonary hypertension. {ECO:0000269|PubMed:24256811,
CC ECO:0000269|PubMed:24341803}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LplA family. {ECO:0000305}.
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DR EMBL; AB017566; BAA76367.1; -; mRNA.
DR EMBL; AB017567; BAA76368.1; -; Genomic_DNA.
DR EMBL; AC092587; AAX88927.1; -; Genomic_DNA.
DR EMBL; CH471127; EAX01877.1; -; Genomic_DNA.
DR EMBL; BC007001; AAH07001.1; -; mRNA.
DR EMBL; BC009772; AAH09772.1; -; mRNA.
DR EMBL; BC070145; AAH70145.1; -; mRNA.
DR CCDS; CCDS2039.1; -.
DR RefSeq; NP_001191759.1; NM_001204830.1.
DR RefSeq; NP_057013.1; NM_015929.3.
DR RefSeq; NP_660198.1; NM_145197.2.
DR RefSeq; NP_660199.1; NM_145198.2.
DR RefSeq; NP_660200.1; NM_145199.2.
DR AlphaFoldDB; Q9Y234; -.
DR SMR; Q9Y234; -.
DR BioGRID; 119630; 13.
DR IntAct; Q9Y234; 16.
DR STRING; 9606.ENSP00000377115; -.
DR DrugBank; DB00166; Lipoic acid.
DR iPTMnet; Q9Y234; -.
DR PhosphoSitePlus; Q9Y234; -.
DR BioMuta; LIPT1; -.
DR DMDM; 25167326; -.
DR EPD; Q9Y234; -.
DR jPOST; Q9Y234; -.
DR MassIVE; Q9Y234; -.
DR MaxQB; Q9Y234; -.
DR PaxDb; Q9Y234; -.
DR PeptideAtlas; Q9Y234; -.
DR PRIDE; Q9Y234; -.
DR ProteomicsDB; 85627; -.
DR Antibodypedia; 32790; 46 antibodies from 18 providers.
DR DNASU; 51601; -.
DR Ensembl; ENST00000393471.2; ENSP00000377114.2; ENSG00000144182.17.
DR Ensembl; ENST00000393473.6; ENSP00000377115.2; ENSG00000144182.17.
DR Ensembl; ENST00000651691.1; ENSP00000498546.1; ENSG00000144182.17.
DR GeneID; 51601; -.
DR KEGG; hsa:51601; -.
DR MANE-Select; ENST00000651691.1; ENSP00000498546.1; NM_145199.3; NP_660200.1.
DR UCSC; uc002szo.5; human.
DR CTD; 51601; -.
DR DisGeNET; 51601; -.
DR GeneCards; LIPT1; -.
DR HGNC; HGNC:29569; LIPT1.
DR HPA; ENSG00000144182; Low tissue specificity.
DR MalaCards; LIPT1; -.
DR MIM; 610284; gene.
DR MIM; 616299; phenotype.
DR neXtProt; NX_Q9Y234; -.
DR OpenTargets; ENSG00000144182; -.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR Orphanet; 401862; Lipoyl transferase 1 deficiency.
DR PharmGKB; PA134940073; -.
DR VEuPathDB; HostDB:ENSG00000144182; -.
DR eggNOG; KOG3159; Eukaryota.
DR GeneTree; ENSGT00390000008846; -.
DR HOGENOM; CLU_022986_4_1_1; -.
DR InParanoid; Q9Y234; -.
DR OMA; RTCPEDD; -.
DR OrthoDB; 1090038at2759; -.
DR PhylomeDB; Q9Y234; -.
DR TreeFam; TF314085; -.
DR PathwayCommons; Q9Y234; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR SignaLink; Q9Y234; -.
DR UniPathway; UPA00537; UER00595.
DR BioGRID-ORCS; 51601; 151 hits in 1082 CRISPR screens.
DR GenomeRNAi; 51601; -.
DR Pharos; Q9Y234; Tdark.
DR PRO; PR:Q9Y234; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y234; protein.
DR Bgee; ENSG00000144182; Expressed in calcaneal tendon and 202 other tissues.
DR ExpressionAtlas; Q9Y234; baseline and differential.
DR Genevisible; Q9Y234; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0016746; F:acyltransferase activity; TAS:Reactome.
DR GO; GO:0017118; F:lipoyltransferase activity; IBA:GO_Central.
DR GO; GO:0019752; P:carboxylic acid metabolic process; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0009249; P:protein lipoylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004143; BPL_LPL_catalytic.
DR InterPro; IPR004562; LipoylTrfase_LipoateP_Ligase.
DR PANTHER; PTHR12561; PTHR12561; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00545; lipoyltrans; 1.
DR PROSITE; PS51733; BPL_LPL_CATALYTIC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Disease variant; Mitochondrion; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..25
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 26..373
FT /note="Lipoyltransferase 1, mitochondrial"
FT /id="PRO_0000017856"
FT DOMAIN 57..243
FT /note="BPL/LPL catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01067"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 161
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 71
FT /note="S -> F (in LIPT1D; dbSNP:rs767568897)"
FT /evidence="ECO:0000269|PubMed:24256811"
FT /id="VAR_073669"
FT VARIANT 98
FT /note="R -> G (in LIPT1D; dbSNP:rs137973334)"
FT /evidence="ECO:0000269|PubMed:24256811"
FT /id="VAR_073670"
FT VARIANT 179
FT /note="T -> A (in LIPT1D; dbSNP:rs786205156)"
FT /evidence="ECO:0000269|PubMed:24341803"
FT /id="VAR_073671"
SQ SEQUENCE 373 AA; 42479 MW; 51E72E1E4F943C96 CRC64;
MLIPFSMKNC FQLLCNCQVP AAGFKKTVKN GLILQSISND VYQNLAVEDW IHDHMNLEGK
PILFFWQNSP SVVIGRHQNP WQECNLNLMR EEGIKLARRR SGGGTVYHDM GNINLTFFTT
KKKYDRMENL KLIVRALNAV QPQLDVQATK RFDLLLDGQF KISGTASKIG RTTAYHHCTL
LCSTDGTFLS SLLKSPYQGI RSNATASIPS LVKNLLEKDP TLTCEVLMNA VATEYAAYHQ
IDNHIHLINP TDETLFPGIN SKAKELQTWE WIYGKTPKFS INTSFHVLYE QSHLEIKVFI
DIKNGRIEIC NIEAPDHWLP LEIRDKLNSS LIGSKFCPTE TTMLTNILLR TCPQDHKLNS
KWNILCEKIK GIM
