PLCD_MOUSE
ID PLCD_MOUSE Reviewed; 378 AA.
AC Q8K4X7; Q3TKN0; Q9DB84;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=1-acyl-sn-glycerol-3-phosphate acyltransferase delta;
DE EC=2.3.1.51 {ECO:0000269|PubMed:15367102, ECO:0000269|PubMed:24333445};
DE AltName: Full=1-acylglycerol-3-phosphate O-acyltransferase 4;
DE Short=1-AGP acyltransferase 4;
DE Short=1-AGPAT 4;
DE AltName: Full=Lysophosphatidic acid acyltransferase delta;
DE Short=LPAAT-delta;
GN Name=Agpat4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RA Brathwaite M.E., Waeltz P., Qian Y., Dudekula D., Schlessinger D.,
RA Nagaraja R.;
RT "Genomic sequence analysis in the mouse T-complex region.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=15367102; DOI=10.1042/bj20041348;
RA Lu B., Jiang Y.J., Zhou Y., Xu F.Y., Hatch G.M., Choy P.C.;
RT "Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate
RT acyltransferases and their regulation by PPARalpha in murine heart.";
RL Biochem. J. 385:469-477(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24333445; DOI=10.1016/j.bbrc.2013.12.043;
RA Eto M., Shindou H., Shimizu T.;
RT "A novel lysophosphatidic acid acyltransferase enzyme (LPAAT4) with a
RT possible role for incorporating docosahexaenoic acid into brain
RT glycerophospholipids.";
RL Biochem. Biophys. Res. Commun. 443:718-724(2014).
CC -!- FUNCTION: Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic
CC acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid
CC or PA) by incorporating an acyl moiety at the sn-2 position of the
CC glycerol backbone (PubMed:15367102). Exhibits high acyl-CoA specificity
CC for polyunsaturated fatty acyl-CoA, especially docosahexaenoyl-CoA
CC (22:6-CoA, DHA-CoA) (PubMed:24333445). {ECO:0000269|PubMed:15367102,
CC ECO:0000269|PubMed:24333445}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-
CC sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:19709,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57970, ChEBI:CHEBI:58342,
CC ChEBI:CHEBI:58608; EC=2.3.1.51;
CC Evidence={ECO:0000269|PubMed:15367102, ECO:0000269|PubMed:24333445};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19710;
CC Evidence={ECO:0000305|PubMed:15367102, ECO:0000305|PubMed:24333445};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + 1-hexadecanoyl-
CC sn-glycero-3-phosphate = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:55300,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57518, ChEBI:CHEBI:74298,
CC ChEBI:CHEBI:82928; Evidence={ECO:0000269|PubMed:24333445};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55301;
CC Evidence={ECO:0000305|PubMed:24333445};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + 1-octadecanoyl-sn-glycero-3-
CC phosphate = 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + CoA; Xref=Rhea:RHEA:55304, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57383, ChEBI:CHEBI:74565, ChEBI:CHEBI:77098;
CC Evidence={ECO:0000269|PubMed:24333445};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55305;
CC Evidence={ECO:0000305|PubMed:24333445};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + 1-octadecanoyl-
CC sn-glycero-3-phosphate = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:55308,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:74298, ChEBI:CHEBI:74565,
CC ChEBI:CHEBI:77130; Evidence={ECO:0000269|PubMed:24333445};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55309;
CC Evidence={ECO:0000305|PubMed:24333445};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + 1-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z-octadecenoyl)-2-
CC (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphate + CoA;
CC Xref=Rhea:RHEA:55312, ChEBI:CHEBI:57287, ChEBI:CHEBI:74298,
CC ChEBI:CHEBI:74544, ChEBI:CHEBI:138723;
CC Evidence={ECO:0000269|PubMed:24333445};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55313;
CC Evidence={ECO:0000305|PubMed:24333445};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=79.3 uM for LPA C16:0 {ECO:0000269|PubMed:24333445};
CC KM=42.9 uM for LPA C18:0 {ECO:0000269|PubMed:24333445};
CC KM=6.3 uM for docosahexaenoyl-CoA {ECO:0000269|PubMed:24333445};
CC Vmax=276.6 nmol/min/mg enzyme for LPA C16:0
CC {ECO:0000269|PubMed:24333445};
CC Vmax=23.2 nmol/min/mg enzyme for LPA C18:0
CC {ECO:0000269|PubMed:24333445};
CC Vmax=109.3 nmol/min/mg enzyme for docosahexaenoyl-CoA
CC {ECO:0000269|PubMed:24333445};
CC -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-
CC diacylglycerol from sn-glycerol 3-phosphate: step 2/3.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24333445}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed at a high levels in the brain, at
CC intermediate or low levels in skeletal muscles, gut, kidney, spleen and
CC lung (PubMed:15367102, PubMed:24333445). Barely detectable in heart and
CC liver (PubMed:15367102). {ECO:0000269|PubMed:15367102,
CC ECO:0000269|PubMed:24333445}.
CC -!- DOMAIN: The HXXXXD motif is essential for acyltransferase activity and
CC may constitute the binding site for the phosphate moiety of the
CC glycerol-3-phosphate. {ECO:0000250|UniProtKB:Q9D517}.
CC -!- SIMILARITY: Belongs to the 1-acyl-sn-glycerol-3-phosphate
CC acyltransferase family. {ECO:0000305}.
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DR EMBL; AK005139; BAB23837.2; -; mRNA.
DR EMBL; AK166917; BAE39115.1; -; mRNA.
DR EMBL; AF485269; AAM33375.1; -; Genomic_DNA.
DR EMBL; BC047281; AAH47281.1; -; mRNA.
DR CCDS; CCDS28389.1; -.
DR RefSeq; NP_080920.2; NM_026644.2.
DR RefSeq; XP_006523408.2; XM_006523345.2.
DR AlphaFoldDB; Q8K4X7; -.
DR BioGRID; 212767; 1.
DR IntAct; Q8K4X7; 1.
DR STRING; 10090.ENSMUSP00000024594; -.
DR SwissLipids; SLP:000001828; -.
DR iPTMnet; Q8K4X7; -.
DR PhosphoSitePlus; Q8K4X7; -.
DR EPD; Q8K4X7; -.
DR MaxQB; Q8K4X7; -.
DR PaxDb; Q8K4X7; -.
DR PeptideAtlas; Q8K4X7; -.
DR PRIDE; Q8K4X7; -.
DR ProteomicsDB; 289614; -.
DR Antibodypedia; 33497; 209 antibodies from 28 providers.
DR Ensembl; ENSMUST00000024594; ENSMUSP00000024594; ENSMUSG00000023827.
DR GeneID; 68262; -.
DR KEGG; mmu:68262; -.
DR UCSC; uc008akm.1; mouse.
DR CTD; 56895; -.
DR MGI; MGI:1915512; Agpat4.
DR VEuPathDB; HostDB:ENSMUSG00000023827; -.
DR eggNOG; KOG1505; Eukaryota.
DR GeneTree; ENSGT00950000182836; -.
DR HOGENOM; CLU_041844_5_2_1; -.
DR InParanoid; Q8K4X7; -.
DR OMA; KSVNFYW; -.
DR OrthoDB; 959325at2759; -.
DR PhylomeDB; Q8K4X7; -.
DR TreeFam; TF314065; -.
DR BRENDA; 2.3.1.51; 3474.
DR Reactome; R-MMU-1483166; Synthesis of PA.
DR UniPathway; UPA00557; UER00613.
DR BioGRID-ORCS; 68262; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Agpat4; mouse.
DR PRO; PR:Q8K4X7; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8K4X7; protein.
DR Bgee; ENSMUSG00000023827; Expressed in aortic valve and 210 other tissues.
DR ExpressionAtlas; Q8K4X7; baseline and differential.
DR Genevisible; Q8K4X7; MM.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:MGI.
DR GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016746; F:acyltransferase activity; IBA:GO_Central.
DR GO; GO:0042171; F:lysophosphatidic acid acyltransferase activity; IDA:MGI.
DR GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:MGI.
DR InterPro; IPR032098; Acyltransf_C.
DR InterPro; IPR002123; Plipid/glycerol_acylTrfase.
DR Pfam; PF16076; Acyltransf_C; 1.
DR Pfam; PF01553; Acyltransferase; 1.
DR SMART; SM00563; PlsC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..378
FT /note="1-acyl-sn-glycerol-3-phosphate acyltransferase
FT delta"
FT /id="PRO_0000208198"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 96..101
FT /note="HXXXXD motif"
FT /evidence="ECO:0000250|UniProtKB:Q9D517"
SQ SEQUENCE 378 AA; 43810 MW; 3D9EF15B6A5E49BC CRC64;
MDLIGLLKSQ FLCHLVFCYV FIASGLIVNA IQLCTLVIWP INKQLFRKIN ARLCYCVSSQ
LVMLLEWWSG TECTIYTDPK ACPHYGKENA IVVLNHKFEI DFLCGWSLAE RLGILGNSKV
LAKKELAYVP IIGWMWYFVE MIFCTRKWEQ DRQTVAKSLL HLRDYPEKYL FLIHCEGTRF
TEKKHQISMQ VAQAKGLPSL KHHLLPRTKG FAITVKCLRD VVPAVYDCTL NFRNNENPTL
LGVLNGKKYH ADCYVRRIPM EDIPEDEDKC SAWLHKLYQE KDAFQEEYYR TGVFPETPWV
PPRRPWSLVN WLFWASLLLY PFFQFLVSMV SSGSSVTLAS LVLIFCMASM GVRWMIGVTE
IDKGSAYGNI DNKRKQTD
