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Protein

Lysocardiolipin acyltransferase 1

Gene

LCLAT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acyl-CoA:lysocardiolipin acyltransferase. Possesses both lysophosphatidylinositol acyltransferase (LPIAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities. Recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors. Acts as a remodeling enzyme for cardiolipin, a major membrane polyglycerophospholipid. Converts lysophosphatidic acid (LPA) into phosphatidic acid (PA) with a relatively low activity. Required for establishment of the hematopoietic and endothelial lineages.2 Publications

Catalytic activityi

Acyl-CoA + 1-acyl-sn-glycerol 3-phosphate = CoA + 1,2-diacyl-sn-glycerol 3-phosphate.

Kineticsi

  1. KM=39 µM for arachidonoyl-CoA (20:4) for LPIAT activity1 Publication
  2. KM=289 µM for oleoyl-CoA (18:1) for LPIAT activity1 Publication
  3. KM=134 µM for linoleoyl-CoA (18:2) for LPIAT activity1 Publication
  4. KM=34 µM for stearoyl-CoA (18:0) for LPIAT activity1 Publication
  5. KM=53 µM for palmitoyl-CoA (16:0) for LPIAT activity1 Publication
  6. KM=54 µM for oleoyl-CoA (18:1) for LPGAT activity1 Publication
  7. KM=36 µM for linoleoyl-CoA (18:2) for LPGAT activity1 Publication
  8. KM=70 µM for stearoyl-CoA (18:0) for LPGAT activity1 Publication
  9. KM=34 µM for palmitoyl-CoA (16:0) for LPGAT activity1 Publication
  1. Vmax=3230 nmol/min/mg enzyme toward arachidonoyl-CoA (20:4) for LPIAT activity1 Publication
  2. Vmax=7489 nmol/min/mg enzyme toward oleoyl-CoA (18:1) for LPIAT activity1 Publication
  3. Vmax=4696 nmol/min/mg enzyme toward linoleoyl-CoA (18:2) for LPIAT activity1 Publication
  4. Vmax=1078 nmol/min/mg enzyme toward stearoyl-CoA (18:0) for LPIAT activity1 Publication
  5. Vmax=11203 nmol/min/mg enzyme toward palmitoyl-CoA (16:0) for LPIAT activity1 Publication
  6. Vmax=5514 nmol/min/mg enzyme toward oleoyl-CoA (18:1) for LPGAT activity1 Publication
  7. Vmax=1358 nmol/min/mg enzyme toward linoleoyl-CoA (18:2) for LPGAT activity1 Publication
  8. Vmax=3530 nmol/min/mg enzyme toward stearoyl-CoA (18:0) for LPGAT activity1 Publication
  9. Vmax=1673 nmol/min/mg enzyme toward palmitoyl-CoA (16:0) for LPGAT activity1 Publication

Pathwayi: CDP-diacylglycerol biosynthesis

This protein is involved in step 2 of the subpathway that synthesizes CDP-diacylglycerol from sn-glycerol 3-phosphate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Glycerol-3-phosphate acyltransferase 2, mitochondrial (GPAT2), Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM), Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM), Glycerol-3-phosphate acyltransferase 4 (GPAT4), Glycerol-3-phosphate acyltransferase 3 (GPAT3), Glycerol-3-phosphate acyltransferase 1, mitochondrial, Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM), Glycerol-3-phosphate acyltransferase 1, mitochondrial (DKFZp451B1115)
  2. 1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2), 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4), 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3), 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon (AGPAT5), 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1), Lysocardiolipin acyltransferase 1 (LCLAT1)
  3. Phosphatidate cytidylyltransferase 1 (CDS1), Phosphatidate cytidylyltransferase 2 (CDS2), Phosphatidate cytidylyltransferase, mitochondrial (TAMM41), Phosphatidate cytidylyltransferase (CDS1), Phosphatidate cytidylyltransferase, Phosphatidate cytidylyltransferase, Phosphatidate cytidylyltransferase, Phosphatidate cytidylyltransferase
This subpathway is part of the pathway CDP-diacylglycerol biosynthesis, which is itself part of Phospholipid metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes CDP-diacylglycerol from sn-glycerol 3-phosphate, the pathway CDP-diacylglycerol biosynthesis and in Phospholipid metabolism.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Developmental protein, Transferase

Keywords - Biological processi

Lipid biosynthesis, Lipid metabolism, Phospholipid biosynthesis, Phospholipid metabolism

Enzyme and pathway databases

BioCyciZFISH:HS10599-MONOMER.
ReactomeiR-HSA-1482798. Acyl chain remodeling of CL.
R-HSA-1483166. Synthesis of PA.
R-HSA-75109. Triglyceride Biosynthesis.
UniPathwayiUPA00557; UER00613.

Chemistry databases

SwissLipidsiSLP:000000126.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysocardiolipin acyltransferase 1 (EC:2.3.1.-, EC:2.3.1.51)
Alternative name(s):
1-acylglycerol-3-phosphate O-acyltransferase 8
Short name:
1-AGP acyltransferase 8
Short name:
1-AGPAT 8
Acyl-CoA:lysocardiolipin acyltransferase 1
Gene namesi
Name:LCLAT1
Synonyms:AGPAT8, ALCAT1, LYCAT
ORF Names:UNQ1849/PRO3579
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:26756. LCLAT1.

Subcellular locationi

  • Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei47 – 67HelicalSequence analysisAdd BLAST21
Transmembranei86 – 106HelicalSequence analysisAdd BLAST21
Transmembranei340 – 360HelicalSequence analysisAdd BLAST21
Transmembranei362 – 382HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi206D → C: Abolishes LPIAT and LPGAT activities. 2 Publications1
Mutagenesisi206D → R: Does not increase enzyme activity. 2 Publications1
Mutagenesisi207L → T: Abolishes LPIAT activity. No effect on LPGAT activity. 1 Publication1

Organism-specific databases

DisGeNETi253558.
OpenTargetsiENSG00000172954.
PharmGKBiPA164722072.

Polymorphism and mutation databases

BioMutaiLCLAT1.
DMDMi74749398.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002915771 – 414Lysocardiolipin acyltransferase 1Add BLAST414

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei221N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ6UWP7.
MaxQBiQ6UWP7.
PaxDbiQ6UWP7.
PeptideAtlasiQ6UWP7.
PRIDEiQ6UWP7.
TopDownProteomicsiQ6UWP7-1. [Q6UWP7-1]

PTM databases

iPTMnetiQ6UWP7.
PhosphoSitePlusiQ6UWP7.

Expressioni

Tissue specificityi

Expressed at higher level in heart, kidney and pancreas than in brain, spleen, liver, lung, small intestine and placenta.2 Publications

Gene expression databases

BgeeiENSG00000172954.
CleanExiHS_LCLAT1.
ExpressionAtlasiQ6UWP7. baseline and differential.
GenevisibleiQ6UWP7. HS.

Organism-specific databases

HPAiHPA031880.
HPA049217.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
GOPCQ9HD263EBI-10254507,EBI-349832
LNX1Q8TBB13EBI-10254507,EBI-739832

Protein-protein interaction databases

BioGridi128972. 27 interactors.
IntActiQ6UWP7. 4 interactors.
STRINGi9606.ENSP00000310551.

Structurei

3D structure databases

ProteinModelPortaliQ6UWP7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi123 – 128HXXXXD motif6

Domaini

The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1505. Eukaryota.
COG0204. LUCA.
GeneTreeiENSGT00530000062943.
HOGENOMiHOG000290725.
HOVERGENiHBG055624.
InParanoidiQ6UWP7.
KOiK13513.
OMAiPQSEKHL.
OrthoDBiEOG091G0C4Z.
PhylomeDBiQ6UWP7.
TreeFamiTF314346.

Family and domain databases

InterProiIPR032098. Acyltransf_C.
IPR002123. Plipid/glycerol_acylTrfase.
[Graphical view]
PfamiPF16076. Acyltransf_C. 1 hit.
PF01553. Acyltransferase. 1 hit.
[Graphical view]
SMARTiSM00563. PlsC. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6UWP7-1) [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
MHSRGREIVV LLNPWSINEA VSSYCTYFIK QDSKSFGIMV SWKGIYFILT
60 70 80 90 100
LFWGSFFGSI FMLSPFLPLM FVNPSWYRWI NNRLVATWLT LPVALLETMF
110 120 130 140 150
GVKVIITGDA FVPGERSVII MNHRTRMDWM FLWNCLMRYS YLRLEKICLK
160 170 180 190 200
ASLKGVPGFG WAMQAAAYIF IHRKWKDDKS HFEDMIDYFC DIHEPLQLLI
210 220 230 240 250
FPEGTDLTEN SKSRSNAFAE KNGLQKYEYV LHPRTTGFTF VVDRLREGKN
260 270 280 290 300
LDAVHDITVA YPHNIPQSEK HLLQGDFPRE IHFHVHRYPI DTLPTSKEDL
310 320 330 340 350
QLWCHKRWEE KEERLRSFYQ GEKNFYFTGQ SVIPPCKSEL RVLVVKLLSI
360 370 380 390 400
LYWTLFSPAM CLLIYLYSLV KWYFIITIVI FVLQERIFGG LEIIELACYR
410
LLHKQPHLNS KKNE
Length:414
Mass (Da):48,920
Last modified:July 5, 2004 - v1
Checksum:iF83A1911CC19F959
GO
Isoform 2 (identifier: Q6UWP7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     249-308: KNLDAVHDIT...DLQLWCHKRW → RRQSEGSKGP...SNLQIQCYSH
     309-414: Missing.

Note: No experimental confirmation available.
Show »
Length:308
Mass (Da):36,045
Checksum:i6325F89469A35016
GO
Isoform 3 (identifier: Q6UWP7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.

Show »
Length:376
Mass (Da):44,561
Checksum:iFB658F500239F789
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032830290I → V.Corresponds to variant rs12471868dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443071 – 38Missing in isoform 3. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_026181249 – 308KNLDA…CHKRW → RRQSEGSKGPLQGELQITAQ GNQRGHKQMEKHSMLMDWKN QYREIGHTAQSNLQIQCYSH in isoform 2. 1 PublicationAdd BLAST60
Alternative sequenceiVSP_026182309 – 414Missing in isoform 2. 1 PublicationAdd BLAST106

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358702 mRNA. Translation: AAQ89065.1.
AK095284 mRNA. Translation: BAC04522.1.
AC073255 Genomic DNA. No translation available.
AC132154 Genomic DNA. No translation available.
BC146817 mRNA. Translation: AAI46818.1.
CCDSiCCDS1772.1. [Q6UWP7-1]
CCDS42670.1. [Q6UWP7-3]
RefSeqiNP_001002257.1. NM_001002257.2. [Q6UWP7-3]
NP_001291374.1. NM_001304445.1. [Q6UWP7-3]
NP_872357.2. NM_182551.4. [Q6UWP7-1]
XP_005264301.1. XM_005264244.1. [Q6UWP7-1]
XP_005264302.1. XM_005264245.3. [Q6UWP7-3]
XP_011531043.1. XM_011532741.2. [Q6UWP7-1]
XP_011531044.1. XM_011532742.2. [Q6UWP7-3]
XP_011531045.1. XM_011532743.2. [Q6UWP7-3]
XP_016859235.1. XM_017003746.1. [Q6UWP7-3]
UniGeneiHs.468048.
Hs.662770.

Genome annotation databases

EnsembliENST00000309052; ENSP00000310551; ENSG00000172954. [Q6UWP7-1]
ENST00000319406; ENSP00000368826; ENSG00000172954. [Q6UWP7-2]
ENST00000379509; ENSP00000368823; ENSG00000172954. [Q6UWP7-3]
GeneIDi253558.
KEGGihsa:253558.
UCSCiuc002rnj.3. human. [Q6UWP7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358702 mRNA. Translation: AAQ89065.1.
AK095284 mRNA. Translation: BAC04522.1.
AC073255 Genomic DNA. No translation available.
AC132154 Genomic DNA. No translation available.
BC146817 mRNA. Translation: AAI46818.1.
CCDSiCCDS1772.1. [Q6UWP7-1]
CCDS42670.1. [Q6UWP7-3]
RefSeqiNP_001002257.1. NM_001002257.2. [Q6UWP7-3]
NP_001291374.1. NM_001304445.1. [Q6UWP7-3]
NP_872357.2. NM_182551.4. [Q6UWP7-1]
XP_005264301.1. XM_005264244.1. [Q6UWP7-1]
XP_005264302.1. XM_005264245.3. [Q6UWP7-3]
XP_011531043.1. XM_011532741.2. [Q6UWP7-1]
XP_011531044.1. XM_011532742.2. [Q6UWP7-3]
XP_011531045.1. XM_011532743.2. [Q6UWP7-3]
XP_016859235.1. XM_017003746.1. [Q6UWP7-3]
UniGeneiHs.468048.
Hs.662770.

3D structure databases

ProteinModelPortaliQ6UWP7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128972. 27 interactors.
IntActiQ6UWP7. 4 interactors.
STRINGi9606.ENSP00000310551.

Chemistry databases

SwissLipidsiSLP:000000126.

PTM databases

iPTMnetiQ6UWP7.
PhosphoSitePlusiQ6UWP7.

Polymorphism and mutation databases

BioMutaiLCLAT1.
DMDMi74749398.

Proteomic databases

EPDiQ6UWP7.
MaxQBiQ6UWP7.
PaxDbiQ6UWP7.
PeptideAtlasiQ6UWP7.
PRIDEiQ6UWP7.
TopDownProteomicsiQ6UWP7-1. [Q6UWP7-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309052; ENSP00000310551; ENSG00000172954. [Q6UWP7-1]
ENST00000319406; ENSP00000368826; ENSG00000172954. [Q6UWP7-2]
ENST00000379509; ENSP00000368823; ENSG00000172954. [Q6UWP7-3]
GeneIDi253558.
KEGGihsa:253558.
UCSCiuc002rnj.3. human. [Q6UWP7-1]

Organism-specific databases

CTDi253558.
DisGeNETi253558.
GeneCardsiLCLAT1.
HGNCiHGNC:26756. LCLAT1.
HPAiHPA031880.
HPA049217.
neXtProtiNX_Q6UWP7.
OpenTargetsiENSG00000172954.
PharmGKBiPA164722072.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1505. Eukaryota.
COG0204. LUCA.
GeneTreeiENSGT00530000062943.
HOGENOMiHOG000290725.
HOVERGENiHBG055624.
InParanoidiQ6UWP7.
KOiK13513.
OMAiPQSEKHL.
OrthoDBiEOG091G0C4Z.
PhylomeDBiQ6UWP7.
TreeFamiTF314346.

Enzyme and pathway databases

UniPathwayiUPA00557; UER00613.
BioCyciZFISH:HS10599-MONOMER.
ReactomeiR-HSA-1482798. Acyl chain remodeling of CL.
R-HSA-1483166. Synthesis of PA.
R-HSA-75109. Triglyceride Biosynthesis.

Miscellaneous databases

ChiTaRSiLCLAT1. human.
GenomeRNAii253558.
PROiQ6UWP7.

Gene expression databases

BgeeiENSG00000172954.
CleanExiHS_LCLAT1.
ExpressionAtlasiQ6UWP7. baseline and differential.
GenevisibleiQ6UWP7. HS.

Family and domain databases

InterProiIPR032098. Acyltransf_C.
IPR002123. Plipid/glycerol_acylTrfase.
[Graphical view]
PfamiPF16076. Acyltransf_C. 1 hit.
PF01553. Acyltransferase. 1 hit.
[Graphical view]
SMARTiSM00563. PlsC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLCLT1_HUMAN
AccessioniPrimary (citable) accession number: Q6UWP7
Secondary accession number(s): A6H8Z7, Q8N1Q7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 112 of the entry and version 1 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

Caution

PubMed:16620771 does not detect acyl-CoA:lysocardiolipin acyltransferase activity.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.