LIPT2_HUMAN
ID LIPT2_HUMAN Reviewed; 231 AA.
AC A6NK58;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Putative lipoyltransferase 2, mitochondrial;
DE EC=2.3.1.181;
DE AltName: Full=Lipoate-protein ligase B;
DE AltName: Full=Lipoyl/octanoyl transferase;
DE AltName: Full=Octanoyl-[acyl-carrier-protein]-protein N-octanoyltransferase;
DE Flags: Precursor;
GN Name=LIPT2;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP INVOLVEMENT IN NELABA, VARIANTS NELABA PRO-30; ARG-105 AND ARG-126,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28757203; DOI=10.1016/j.ajhg.2017.07.001;
RA Habarou F., Hamel Y., Haack T.B., Feichtinger R.G., Lebigot E.,
RA Marquardt I., Busiah K., Laroche C., Madrange M., Grisel C., Pontoizeau C.,
RA Eisermann M., Boutron A., Chretien D., Chadefaux-Vekemans B., Barouki R.,
RA Bole-Feysot C., Nitschke P., Goudin N., Boddaert N., Nemazanyy I.,
RA Delahodde A., Koelker S., Rodenburg R.J., Korenke G.C., Meitinger T.,
RA Strom T.M., Prokisch H., Rotig A., Ottolenghi C., Mayr J.A., de Lonlay P.;
RT "Biallelic mutations in LIPT2 cause a mitochondrial lipoylation defect
RT associated with severe neonatal encephalopathy.";
RL Am. J. Hum. Genet. 101:283-290(2017).
RN [3]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 1-MET--GLN-31.
RX PubMed=28628643; DOI=10.1371/journal.pone.0179591;
RA Bernardinelli E., Costa R., Scantamburlo G., To J., Morabito R.,
RA Nofziger C., Doerrier C., Krumschnabel G., Paulmichl M., Dossena S.;
RT "Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell
RT death.";
RL PLoS ONE 12:E0179591-E0179591(2017).
CC -!- FUNCTION: Catalyzes the transfer of endogenously produced octanoic acid
CC from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-
CC dependent enzymes, which catalyze essential redox reactions
CC (PubMed:28757203). Lipoyl-ACP can also act as a substrate although
CC octanoyl-ACP is likely to be the physiological substrate (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:28757203}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + octanoyl-[ACP] = H(+) + holo-[ACP] + N(6)-
CC octanoyl-L-lysyl-[protein]; Xref=Rhea:RHEA:17665, Rhea:RHEA-
CC COMP:9636, Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:9928, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78463, ChEBI:CHEBI:78809; EC=2.3.1.181;
CC -!- PATHWAY: Protein modification; protein lipoylation via endogenous
CC pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-
CC protein]: step 1/2.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:28628643,
CC ECO:0000269|PubMed:28757203}.
CC -!- DISEASE: Encephalopathy, neonatal severe, with lactic acidosis and
CC brain abnormalities (NELABA) [MIM:617668]: An autosomal recessive
CC disorder characterized by severe encephalopathy with neonatal onset,
CC metabolic features including lactic acidosis, little or no psychomotor
CC development, and brain abnormalities including cerebral atrophy, cysts,
CC and white matter abnormalities. {ECO:0000269|PubMed:28757203}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: In the reaction, the free carboxyl group of octanoic
CC acid is attached via an amide linkage to the epsilon-amino group of a
CC specific lysine residue of lipoyl domains of lipoate-dependent enzymes.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LipB family. {ECO:0000305}.
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DR EMBL; AP001372; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44679.1; -.
DR RefSeq; NP_001138341.1; NM_001144869.2.
DR AlphaFoldDB; A6NK58; -.
DR SMR; A6NK58; -.
DR BioGRID; 132443; 2.
DR STRING; 9606.ENSP00000309463; -.
DR PhosphoSitePlus; A6NK58; -.
DR BioMuta; LIPT2; -.
DR EPD; A6NK58; -.
DR jPOST; A6NK58; -.
DR MassIVE; A6NK58; -.
DR MaxQB; A6NK58; -.
DR PaxDb; A6NK58; -.
DR PeptideAtlas; A6NK58; -.
DR PRIDE; A6NK58; -.
DR ProteomicsDB; 1379; -.
DR Antibodypedia; 48064; 86 antibodies from 16 providers.
DR DNASU; 387787; -.
DR Ensembl; ENST00000310109.5; ENSP00000309463.4; ENSG00000175536.7.
DR GeneID; 387787; -.
DR KEGG; hsa:387787; -.
DR MANE-Select; ENST00000310109.5; ENSP00000309463.4; NM_001144869.3; NP_001138341.1.
DR UCSC; uc010rrk.3; human.
DR CTD; 387787; -.
DR DisGeNET; 387787; -.
DR GeneCards; LIPT2; -.
DR HGNC; HGNC:37216; LIPT2.
DR HPA; ENSG00000175536; Tissue enhanced (testis).
DR MalaCards; LIPT2; -.
DR MIM; 617659; gene.
DR MIM; 617668; phenotype.
DR neXtProt; NX_A6NK58; -.
DR OpenTargets; ENSG00000175536; -.
DR Orphanet; 447795; Lipoyl transferase 2 deficiency.
DR PharmGKB; PA165543447; -.
DR VEuPathDB; HostDB:ENSG00000175536; -.
DR eggNOG; KOG0325; Eukaryota.
DR GeneTree; ENSGT00390000006450; -.
DR HOGENOM; CLU_035168_1_2_1; -.
DR InParanoid; A6NK58; -.
DR OMA; GEVTYHC; -.
DR OrthoDB; 1491838at2759; -.
DR PhylomeDB; A6NK58; -.
DR TreeFam; TF314262; -.
DR BRENDA; 2.3.1.181; 2681.
DR PathwayCommons; A6NK58; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR SignaLink; A6NK58; -.
DR UniPathway; UPA00538; UER00592.
DR BioGRID-ORCS; 387787; 70 hits in 1080 CRISPR screens.
DR GenomeRNAi; 387787; -.
DR Pharos; A6NK58; Tbio.
DR PRO; PR:A6NK58; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; A6NK58; protein.
DR Bgee; ENSG00000175536; Expressed in left testis and 101 other tissues.
DR ExpressionAtlas; A6NK58; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0033819; F:lipoyl(octanoyl) transferase activity; TAS:Reactome.
DR GO; GO:0019752; P:carboxylic acid metabolic process; TAS:Reactome.
DR GO; GO:2000376; P:positive regulation of oxygen metabolic process; IMP:UniProtKB.
DR GO; GO:0009249; P:protein lipoylation; IMP:UniProtKB.
DR CDD; cd16444; LipB; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004143; BPL_LPL_catalytic.
DR InterPro; IPR000544; Octanoyltransferase.
DR PIRSF; PIRSF016262; LPLase; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00214; lipB; 1.
DR PROSITE; PS51733; BPL_LPL_CATALYTIC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Disease variant; Ligase; Mitochondrion;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 32..231
FT /note="Putative lipoyltransferase 2, mitochondrial"
FT /id="PRO_0000332305"
FT DOMAIN 41..224
FT /note="BPL/LPL catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01067"
FT ACT_SITE 185
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250"
FT BINDING 85..92
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 154..156
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 167..169
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 151
FT /note="Lowers pKa of active site Cys"
FT /evidence="ECO:0000250"
FT VARIANT 30
FT /note="L -> P (in NELABA; dbSNP:rs539962457)"
FT /evidence="ECO:0000269|PubMed:28757203"
FT /id="VAR_080037"
FT VARIANT 105
FT /note="L -> R (in NELABA; dbSNP:rs1190703859)"
FT /evidence="ECO:0000269|PubMed:28757203"
FT /id="VAR_080038"
FT VARIANT 126
FT /note="L -> R (in NELABA; dbSNP:rs753904927)"
FT /evidence="ECO:0000269|PubMed:28757203"
FT /id="VAR_080039"
FT MUTAGEN 1..31
FT /note="Missing: Mislocalization to the cytosol; induces
FT apoptotic cell death."
FT /evidence="ECO:0000269|PubMed:28628643"
SQ SEQUENCE 231 AA; 25195 MW; D6713EF69C49FF44 CRC64;
MRQPAVRLVR LGRVPYAELL GLQDRWLRRL QAEPGIEAPS GTEAGALLLC EPAGPVYTAG
LRGGLTPEET ARLRALGAEV RVTGRGGLAT FHGPGQLLCH PVLDLRRLGL RLRMHVASLE
ACAVRLCELQ GLQDARARPP PYTGVWLDDR KICAIGVRCG RHITSHGLAL NCSTDLTWFE
HIVPCGLVGT GVTSLSKELQ RHVTVEEVMP PFLVAFKEIY KCTLISEDSP N
