GPAT4_HUMAN
ID GPAT4_HUMAN Reviewed; 456 AA.
AC Q86UL3; Q2TU73; Q86V89;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Glycerol-3-phosphate acyltransferase 4 {ECO:0000312|HGNC:HGNC:20880};
DE EC=2.3.1.15 {ECO:0000269|PubMed:18238778};
DE AltName: Full=1-acylglycerol-3-phosphate O-acyltransferase 6;
DE Short=1-AGP acyltransferase 6;
DE Short=1-AGPAT 6;
DE AltName: Full=Acyl-CoA:glycerol-3-phosphate acyltransferase 4;
DE AltName: Full=Lysophosphatidic acid acyltransferase zeta;
DE Short=LPAAT-zeta;
DE AltName: Full=Testis spermatogenesis apoptosis-related protein 7 {ECO:0000303|PubMed:16625827};
DE Short=TSARG7 {ECO:0000303|PubMed:16625827};
DE Flags: Precursor;
GN Name=GPAT4 {ECO:0000312|HGNC:HGNC:20880};
GN Synonyms=AGPAT6 {ECO:0000303|PubMed:18238778},
GN TSARG7 {ECO:0000303|PubMed:16625827}; ORFNames=UNQ551/PRO1108;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12938015; DOI=10.1007/s10038-003-0045-z;
RA Li D., Yu L., Wu H., Shan Y., Guo J., Dang Y., Wei Y., Zhao S.;
RT "Cloning and identification of the human LPAAT-zeta gene, a novel member of
RT the lysophosphatidic acid acyltransferase family.";
RL J. Hum. Genet. 48:438-442(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=16625827; DOI=10.1016/s0379-4172(06)60054-1;
RA Tan X.J., Huang Z.P., Li L.Y., Nie D.S., Zhong C.G., Fu J.J., Lu G.X.;
RT "Molecular cloning and preliminary function study of a novel human gene,
RT TSARG7, related to spermatogenesis.";
RL Yi Chuan Xue Bao 33:294-303(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=18238778; DOI=10.1074/jbc.m708151200;
RA Chen Y.Q., Kuo M.-S., Li S., Bui H.H., Peake D.A., Sanders P.E.,
RA Thibodeaux S.J., Chu S., Qian Y.-W., Zhao Y., Bredt D.S., Moller D.E.,
RA Konrad R.J., Beigneux A.P., Young S.G., Cao G.;
RT "AGPAT6 is a novel microsomal glycerol-3-phosphate acyltransferase.";
RL J. Biol. Chem. 283:10048-10057(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 [7]
RP FUNCTION.
RX PubMed=30846318; DOI=10.1016/j.molcel.2019.01.036;
RA Piccolis M., Bond L.M., Kampmann M., Pulimeno P., Chitraju C.,
RA Jayson C.B.K., Vaites L.P., Boland S., Lai Z.W., Gabriel K.R.,
RA Elliott S.D., Paulo J.A., Harper J.W., Weissman J.S., Walther T.C.,
RA Farese R.V. Jr.;
RT "Probing the global cellular responses to lipotoxicity caused by saturated
RT fatty acids.";
RL Mol. Cell 74:32-44(2019).
CC -!- FUNCTION: Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-
CC phosphate (lysophosphatidic acid or LPA) by incorporating an acyl
CC moiety at the sn-1 position of the glycerol backbone (PubMed:18238778).
CC Active against both saturated and unsaturated long-chain fatty acyl-
CC CoAs (PubMed:18238778). Protects cells against lipotoxicity
CC (PubMed:30846318). {ECO:0000269|PubMed:18238778,
CC ECO:0000269|PubMed:30846318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acyl-CoA + sn-glycerol 3-phosphate = a 1-acyl-sn-glycero-3-
CC phosphate + CoA; Xref=Rhea:RHEA:15325, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:57970, ChEBI:CHEBI:58342; EC=2.3.1.15;
CC Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15326;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + sn-glycerol 3-phosphate = 1-dodecanoyl-sn-
CC glycerol 3-phosphate + CoA; Xref=Rhea:RHEA:35727, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:57597, ChEBI:CHEBI:72682;
CC Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35728;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + sn-glycerol 3-phosphate = 1-hexadecanoyl-
CC sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:35723,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57518,
CC ChEBI:CHEBI:57597; Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35724;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-CoA + sn-glycerol 3-phosphate = 1-octadecanoyl-
CC sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37195,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:57597,
CC ChEBI:CHEBI:74565; Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37196;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + sn-glycerol 3-phosphate = 1-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37199,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57387, ChEBI:CHEBI:57597,
CC ChEBI:CHEBI:74544; Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37200;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + sn-glycerol 3-phosphate = 1-
CC (9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA;
CC Xref=Rhea:RHEA:37203, ChEBI:CHEBI:57287, ChEBI:CHEBI:57383,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:74547;
CC Evidence={ECO:0000269|PubMed:18238778};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37204;
CC Evidence={ECO:0000305|PubMed:18238778};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide (NEM).
CC {ECO:0000269|PubMed:18238778}.
CC -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-
CC diacylglycerol from sn-glycerol 3-phosphate: step 1/3.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18238778}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. High levels in testis. Relatively high
CC level of expression in skeletal muscle and heart. Relatively low level
CC of expression in lung. {ECO:0000269|PubMed:12938015,
CC ECO:0000269|PubMed:16625827, ECO:0000269|PubMed:18238778}.
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; AF406612; AAP21893.1; -; mRNA.
DR EMBL; AY513610; AAS82774.1; -; mRNA.
DR EMBL; AY358670; AAQ89033.1; -; mRNA.
DR EMBL; CH471080; EAW63254.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63255.1; -; Genomic_DNA.
DR EMBL; BC051377; AAH51377.2; -; mRNA.
DR EMBL; BC061884; AAH61884.1; -; mRNA.
DR CCDS; CCDS6117.1; -.
DR RefSeq; NP_848934.1; NM_178819.3.
DR RefSeq; XP_011542694.1; XM_011544392.2.
DR RefSeq; XP_011542695.1; XM_011544393.1.
DR RefSeq; XP_011542696.1; XM_011544394.1.
DR RefSeq; XP_016868531.1; XM_017013042.1.
DR AlphaFoldDB; Q86UL3; -.
DR BioGRID; 126493; 156.
DR IntAct; Q86UL3; 19.
DR MINT; Q86UL3; -.
DR STRING; 9606.ENSP00000380184; -.
DR ChEMBL; CHEMBL4523372; -.
DR SwissLipids; SLP:000000280; -.
DR GlyGen; Q86UL3; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q86UL3; -.
DR PhosphoSitePlus; Q86UL3; -.
DR SwissPalm; Q86UL3; -.
DR BioMuta; GPAT4; -.
DR DMDM; 68052729; -.
DR EPD; Q86UL3; -.
DR jPOST; Q86UL3; -.
DR MassIVE; Q86UL3; -.
DR MaxQB; Q86UL3; -.
DR PaxDb; Q86UL3; -.
DR PeptideAtlas; Q86UL3; -.
DR PRIDE; Q86UL3; -.
DR ProteomicsDB; 69830; -.
DR TopDownProteomics; Q86UL3; -.
DR Antibodypedia; 3092; 282 antibodies from 22 providers.
DR DNASU; 137964; -.
DR Ensembl; ENST00000396987.7; ENSP00000380184.3; ENSG00000158669.11.
DR GeneID; 137964; -.
DR KEGG; hsa:137964; -.
DR MANE-Select; ENST00000396987.7; ENSP00000380184.3; NM_178819.4; NP_848934.1.
DR UCSC; uc003xnz.3; human.
DR CTD; 137964; -.
DR DisGeNET; 137964; -.
DR GeneCards; GPAT4; -.
DR HGNC; HGNC:20880; GPAT4.
DR HPA; ENSG00000158669; Low tissue specificity.
DR MIM; 608143; gene.
DR neXtProt; NX_Q86UL3; -.
DR OpenTargets; ENSG00000158669; -.
DR PharmGKB; PA142672637; -.
DR VEuPathDB; HostDB:ENSG00000158669; -.
DR eggNOG; KOG2898; Eukaryota.
DR GeneTree; ENSGT01030000234574; -.
DR HOGENOM; CLU_031080_0_1_1; -.
DR InParanoid; Q86UL3; -.
DR OMA; CVMFKKG; -.
DR OrthoDB; 526132at2759; -.
DR PhylomeDB; Q86UL3; -.
DR TreeFam; TF315039; -.
DR BRENDA; 2.3.1.15; 2681.
DR PathwayCommons; Q86UL3; -.
DR Reactome; R-HSA-1483166; Synthesis of PA.
DR SignaLink; Q86UL3; -.
DR UniPathway; UPA00557; UER00612.
DR BioGRID-ORCS; 137964; 26 hits in 1075 CRISPR screens.
DR ChiTaRS; GPAT4; human.
DR GenomeRNAi; 137964; -.
DR Pharos; Q86UL3; Tbio.
DR PRO; PR:Q86UL3; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q86UL3; protein.
DR Bgee; ENSG00000158669; Expressed in islet of Langerhans and 175 other tissues.
DR ExpressionAtlas; Q86UL3; baseline and differential.
DR Genevisible; Q86UL3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferase activity; TAS:Reactome.
DR GO; GO:0004366; F:glycerol-3-phosphate O-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0102420; F:sn-1-glycerol-3-phosphate C16:0-DCA-CoA acyl transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IDA:UniProtKB.
DR GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0002071; P:glandular epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; ISS:UniProtKB.
DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; TAS:Reactome.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0019432; P:triglyceride biosynthetic process; ISS:UniProtKB.
DR CDD; cd07991; LPLAT_LPCAT1-like; 1.
DR InterPro; IPR045252; LPCAT1-like.
DR InterPro; IPR002123; Plipid/glycerol_acylTrfase.
DR Pfam; PF01553; Acyltransferase; 1.
DR SMART; SM00563; PlsC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Direct protein sequencing; Endoplasmic reticulum;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Phospholipid biosynthesis; Phospholipid metabolism; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..456
FT /note="Glycerol-3-phosphate acyltransferase 4"
FT /id="PRO_0000024703"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 248..253
FT /note="HXXXXD motif"
FT /evidence="ECO:0000250|UniProtKB:Q9D517"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 456 AA; 52071 MW; 5B9DEB2912E989E5 CRC64;
MFLLLPFDSL IVNLLGISLT VLFTLLLVFI IVPAIFGVSF GIRKLYMKSL LKIFAWATLR
MERGAKEKNH QLYKPYTNGI IAKDPTSLEE EIKEIRRSGS SKALDNTPEF ELSDIFYFCR
KGMETIMDDE VTKRFSAEEL ESWNLLSRTN YNFQYISLRL TVLWGLGVLI RYCFLLPLRI
ALAFTGISLL VVGTTVVGYL PNGRFKEFMS KHVHLMCYRI CVRALTAIIT YHDRENRPRN
GGICVANHTS PIDVIILASD GYYAMVGQVH GGLMGVIQRA MVKACPHVWF ERSEVKDRHL
VAKRLTEHVQ DKSKLPILIF PEGTCINNTS VMMFKKGSFE IGATVYPVAI KYDPQFGDAF
WNSSKYGMVT YLLRMMTSWA IVCSVWYLPP MTREADEDAV QFANRVKSAI ARQGGLVDLL
WDGGLKREKV KDTFKEEQQK LYSKMIVGNH KDRSRS
