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Q6UWP7 (LCLT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:LCLAT1
Synonyms:AGPAT8, ALCAT1, LYCAT
ORF Names:UNQ1849/PRO3579
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length414 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Catalytic activity

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

Pathway

Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-diacylglycerol from sn-glycerol 3-phosphate: step 2/3.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6.

Tissue specificity

Expressed at higher level in heart, kidney and pancreas than in brain, spleen, liver, lung, small intestine and placenta. Ref.5 Ref.6

Domain

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 similarities

Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.

Caution

Ref.5 does not detect acyl-CoA:lysocardiolipin acyltransferase activity.

Biophysicochemical properties

Kinetic parameters:

KM=39 µM for arachidonoyl-CoA (20:4) for LPIAT activity Ref.6

KM=289 µM for oleoyl-CoA (18:1) for LPIAT activity

KM=134 µM for linoleoyl-CoA (18:2) for LPIAT activity

KM=34 µM for stearoyl-CoA (18:0) for LPIAT activity

KM=53 µM for palmitoyl-CoA (16:0) for LPIAT activity

KM=54 µM for oleoyl-CoA (18:1) for LPGAT activity

KM=36 µM for linoleoyl-CoA (18:2) for LPGAT activity

KM=70 µM for stearoyl-CoA (18:0) for LPGAT activity

KM=34 µM for palmitoyl-CoA (16:0) for LPGAT activity

Vmax=3230 nmol/min/mg enzyme toward arachidonoyl-CoA (20:4) for LPIAT activity

Vmax=7489 nmol/min/mg enzyme toward oleoyl-CoA (18:1) for LPIAT activity

Vmax=4696 nmol/min/mg enzyme toward linoleoyl-CoA (18:2) for LPIAT activity

Vmax=1078 nmol/min/mg enzyme toward stearoyl-CoA (18:0) for LPIAT activity

Vmax=11203 nmol/min/mg enzyme toward palmitoyl-CoA (16:0) for LPIAT activity

Vmax=5514 nmol/min/mg enzyme toward oleoyl-CoA (18:1) for LPGAT activity

Vmax=1358 nmol/min/mg enzyme toward linoleoyl-CoA (18:2) for LPGAT activity

Vmax=3530 nmol/min/mg enzyme toward stearoyl-CoA (18:0) for LPGAT activity

Vmax=1673 nmol/min/mg enzyme toward palmitoyl-CoA (16:0) for LPGAT activity

Ontologies

Keywords
   Biological processLipid biosynthesis
Lipid metabolism
Phospholipid biosynthesis
Phospholipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionAcyltransferase
Developmental protein
Transferase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCDP-diacylglycerol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

cardiolipin acyl-chain remodeling

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

glycerophospholipid biosynthetic process

Traceable author statement. Source: Reactome

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidic acid biosynthetic process

Traceable author statement. Source: Reactome

phospholipid metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_function1-acylglycerol-3-phosphate O-acyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6UWP7-1)

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.
Isoform 2 (identifier: Q6UWP7-2)

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.
Isoform 3 (identifier: Q6UWP7-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 414414Lysocardiolipin acyltransferase 1
PRO_0000291577

Regions

Transmembrane47 – 6721Helical; Potential
Transmembrane86 – 10621Helical; Potential
Transmembrane340 – 36021Helical; Potential
Transmembrane362 – 38221Helical; Potential
Motif123 – 1286HXXXXD motif

Amino acid modifications

Modified residue2211N6-acetyllysine Ref.7

Natural variations

Alternative sequence1 – 3838Missing in isoform 3.
VSP_044307
Alternative sequence249 – 30860KNLDA…CHKRW → RRQSEGSKGPLQGELQITAQ GNQRGHKQMEKHSMLMDWKN QYREIGHTAQSNLQIQCYSH in isoform 2.
VSP_026181
Alternative sequence309 – 414106Missing in isoform 2.
VSP_026182
Natural variant2901I → V.
Corresponds to variant rs12471868 [ dbSNP | Ensembl ].
VAR_032830

Experimental info

Mutagenesis2061D → C: Abolishes LPIAT and LPGAT activities. Ref.5 Ref.6
Mutagenesis2061D → R: Does not increase enzyme activity. Ref.5 Ref.6
Mutagenesis2071L → T: Abolishes LPIAT activity. No effect on LPGAT activity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: F83A1911CC19F959

FASTA41448,920
        10         20         30         40         50         60 
MHSRGREIVV LLNPWSINEA VSSYCTYFIK QDSKSFGIMV SWKGIYFILT LFWGSFFGSI 

        70         80         90        100        110        120 
FMLSPFLPLM FVNPSWYRWI NNRLVATWLT LPVALLETMF GVKVIITGDA FVPGERSVII 

       130        140        150        160        170        180 
MNHRTRMDWM FLWNCLMRYS YLRLEKICLK ASLKGVPGFG WAMQAAAYIF IHRKWKDDKS 

       190        200        210        220        230        240 
HFEDMIDYFC DIHEPLQLLI FPEGTDLTEN SKSRSNAFAE KNGLQKYEYV LHPRTTGFTF 

       250        260        270        280        290        300 
VVDRLREGKN LDAVHDITVA YPHNIPQSEK HLLQGDFPRE IHFHVHRYPI DTLPTSKEDL 

       310        320        330        340        350        360 
QLWCHKRWEE KEERLRSFYQ GEKNFYFTGQ SVIPPCKSEL RVLVVKLLSI LYWTLFSPAM 

       370        380        390        400        410 
CLLIYLYSLV KWYFIITIVI FVLQERIFGG LEIIELACYR LLHKQPHLNS KKNE 

« Hide

Isoform 2 [UniParc].

Checksum: 6325F89469A35016
Show »

FASTA30836,045
Isoform 3 [UniParc].

Checksum: FB658F500239F789
Show »

FASTA37644,561

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]"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. expand/collapse author list , 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 2).
Tissue: Tongue.
[3]"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. expand/collapse author list , 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].
[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 3).
[5]"Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity."
Agarwal A.K., Barnes R.I., Garg A.
Arch. Biochem. Biophys. 449:64-76(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-206.
[6]"The microsomal cardiolipin remodeling enzyme acyl-CoA lysocardiolipin acyltransferase is an acyltransferase of multiple anionic lysophospholipids."
Zhao Y., Chen Y.-Q., Li S., Konrad R.J., Cao G.
J. Lipid Res. 50:945-956(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-206 AND LEU-207.
[7]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-221, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001002257.1. NM_001002257.1.
NP_872357.2. NM_182551.3.
XP_005264301.1. XM_005264244.1.
XP_005264302.1. XM_005264245.1.
UniGeneHs.468048.
Hs.662770.

3D structure databases

ProteinModelPortalQ6UWP7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128972. 2 interactions.
STRING9606.ENSP00000310551.

PTM databases

PhosphoSiteQ6UWP7.

Polymorphism databases

DMDM74749398.

Proteomic databases

PaxDbQ6UWP7.
PRIDEQ6UWP7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309052; ENSP00000310551; ENSG00000172954. [Q6UWP7-1]
ENST00000319406; ENSP00000368826; ENSG00000172954. [Q6UWP7-2]
ENST00000359433; ENSP00000352406; ENSG00000172954. [Q6UWP7-2]
ENST00000379509; ENSP00000368823; ENSG00000172954. [Q6UWP7-3]
ENST00000540623; ENSP00000442857; ENSG00000172954. [Q6UWP7-3]
GeneID253558.
KEGGhsa:253558.
UCSCuc002rnj.3. human. [Q6UWP7-1]
uc002rnk.1. human. [Q6UWP7-2]

Organism-specific databases

CTD253558.
GeneCardsGC02P030670.
HGNCHGNC:26756. LCLAT1.
HPAHPA031880.
HPA049217.
neXtProtNX_Q6UWP7.
PharmGKBPA164722072.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0204.
HOGENOMHOG000290725.
HOVERGENHBG055624.
InParanoidQ6UWP7.
KOK13513.
OMAYFCDIRE.
PhylomeDBQ6UWP7.
TreeFamTF314346.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00557; UER00613.

Gene expression databases

ArrayExpressQ6UWP7.
BgeeQ6UWP7.
CleanExHS_LCLAT1.
GenevestigatorQ6UWP7.

Family and domain databases

InterProIPR002123. Plipid/glycerol_acylTrfase.
[Graphical view]
PfamPF01553. Acyltransferase. 1 hit.
[Graphical view]
SMARTSM00563. PlsC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi253558.
NextBio92116.
PROQ6UWP7.

Entry information

Entry nameLCLT1_HUMAN
AccessionPrimary (citable) accession number: Q6UWP7
Secondary accession number(s): A6H8Z7, Q8N1Q7
Entry history
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM