Q6UWP7 (LCLT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	LCLAT1
Synonyms:	AGPAT8, ALCAT1, LYCAT
ORF Names:	UNQ1849/PRO3579

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	414 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Lipid biosynthesis Lipid metabolism Phospholipid biosynthesis Phospholipid metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Acyltransferase Developmental protein Transferase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CDP-diacylglycerol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway cardiolipin acyl-chain remodeling Traceable author statement. Source: Reactome multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW phosphatidic acid biosynthetic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	1-acylglycerol-3-phosphate O-acyltransferase activity Inferred from electronic annotation. Source: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 414	414	Lysocardiolipin acyltransferase 1		PRO_0000291577
Regions
	Transmembrane	47 – 67	21	Helical; Potential
	Transmembrane	86 – 106	21	Helical; Potential
	Transmembrane	340 – 360	21	Helical; Potential
	Transmembrane	362 – 382	21	Helical; Potential
	Motif	123 – 128	6	HXXXXD motif
Amino acid modifications
	Modified residue	221	1	N6-acetyllysine Ref.7
Natural variations
	Alternative sequence	1 – 38	38	Missing in isoform 3.		VSP_044307
	Alternative sequence	249 – 308	60	KNLDA…CHKRW → RRQSEGSKGPLQGELQITAQ GNQRGHKQMEKHSMLMDWKN QYREIGHTAQSNLQIQCYSH in isoform 2.		VSP_026181
	Alternative sequence	309 – 414	106	Missing in isoform 2.		VSP_026182
	Natural variant	290	1	I → V. Corresponds to variant rs12471868 [ dbSNP | Ensembl ].		VAR_032830
Experimental info
	Mutagenesis	206	1	D → C: Abolishes LPIAT and LPGAT activities. Ref.5 Ref.6
	Mutagenesis	206	1	D → R: Does not increase enzyme activity. Ref.5 Ref.6
	Mutagenesis	207	1	L → T: Abolishes LPIAT activity. No effect on LPGAT activity. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: F83A1911CC19F959	FASTA	414	48,920
	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
	Isoform 2 [UniParc]. Checksum: 6325F89469A35016	FASTA	308	36,045
	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 VVDRLREGRR QSEGSKGPLQ GELQITAQGN QRGHKQMEKH SMLMDWKNQY REIGHTAQSN LQIQCYSH
	Isoform 3 [UniParc]. Checksum: FB658F500239F789	FASTA	376	44,561
	10 20 30 40 50 60 MVSWKGIYFI LTLFWGSFFG SIFMLSPFLP LMFVNPSWYR WINNRLVATW LTLPVALLET 70 80 90 100 110 120 MFGVKVIITG DAFVPGERSV IIMNHRTRMD WMFLWNCLMR YSYLRLEKIC LKASLKGVPG 130 140 150 160 170 180 FGWAMQAAAY IFIHRKWKDD KSHFEDMIDY FCDIHEPLQL LIFPEGTDLT ENSKSRSNAF 190 200 210 220 230 240 AEKNGLQKYE YVLHPRTTGF TFVVDRLREG KNLDAVHDIT VAYPHNIPQS EKHLLQGDFP 250 260 270 280 290 300 REIHFHVHRY PIDTLPTSKE DLQLWCHKRW EEKEERLRSF YQGEKNFYFT GQSVIPPCKS 310 320 330 340 350 360 ELRVLVVKLL SILYWTLFSP AMCLLIYLYS LVKWYFIITI VIFVLQERIF GGLEIIELAC 370 YRLLHKQPHL NSKKNE

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY.
[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.
IPI	IPI00166225. IPI00419643.
RefSeq	NP_001002257.1. NM_001002257.1. NP_872357.2. NM_182551.3.
UniGene	Hs.468048. Hs.662770.
3D structure databases
ProteinModelPortal	Q6UWP7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000310551.
PTM databases
PhosphoSite	Q6UWP7.
Polymorphism databases
DMDM	74749398.
Proteomic databases
PaxDb	Q6UWP7.
PRIDE	Q6UWP7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309052; ENSP00000310551; ENSG00000172954. ENST00000319406; ENSP00000368826; ENSG00000172954. ENST00000359433; ENSP00000352406; ENSG00000172954. ENST00000379509; ENSP00000368823; ENSG00000172954. ENST00000540623; ENSP00000442857; ENSG00000172954.
GeneID	253558.
KEGG	hsa:253558.
UCSC	uc002rnj.3. human. uc002rnk.1. human.
Organism-specific databases
CTD	253558.
GeneCards	GC02P030670.
HGNC	HGNC:26756. LCLAT1.
HPA	HPA031880. HPA049217.
neXtProt	NX_Q6UWP7.
PharmGKB	PA164722072.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0204.
HOGENOM	HOG000290725.
HOVERGEN	HBG055624.
InParanoid	Q6UWP7.
KO	K13513.
OMA	YFCDIRE.
PhylomeDB	Q6UWP7.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00557; UER00613.
Gene expression databases
ArrayExpress	Q6UWP7.
Bgee	Q6UWP7.
CleanEx	HS_LCLAT1.
Genevestigator	Q6UWP7.
Family and domain databases
InterPro	IPR002123. Plipid/glycerol_acylTrfase. [Graphical view]
Pfam	PF01553. Acyltransferase. 1 hit. [Graphical view]
SMART	SM00563. PlsC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	253558.
NextBio	92116.

Entry information

Entry name

LCLT1_HUMAN

Accession

Primary (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 3, 2013
This is version 79 of the entry and version 1 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.