ID PLCB_HUMAN Reviewed; 278 AA. AC O15120; O00516; O15106; Q5VUD3; Q5VUD4; Q9BSV7; Q9BWR7; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 13-FEB-2019, entry version 173. DE RecName: Full=1-acyl-sn-glycerol-3-phosphate acyltransferase beta; DE EC=2.3.1.51; DE AltName: Full=1-acylglycerol-3-phosphate O-acyltransferase 2; DE Short=1-AGP acyltransferase 2; DE Short=1-AGPAT 2; DE AltName: Full=Lysophosphatidic acid acyltransferase beta; DE Short=LPAAT-beta; DE Flags: Precursor; GN Name=AGPAT2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=9242711; DOI=10.1074/jbc.272.32.20299; RA Eberhardt C., Gray P.W., Tjoelker L.W.; RT "Human lysophosphatidic acid acyltransferase. cDNA cloning, RT expression, and localization to chromosome 9q34.3."; RL J. Biol. Chem. 272:20299-20305(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9291118; DOI=10.1042/bj3260455; RA Stamps A.C., Elmore M.A., Hill M.E., Kelly K., Makda A.A., RA Finnen M.J.; RT "A human cDNA sequence with homology to non-mammalian lysophosphatidic RT acid acyltransferases."; RL Biochem. J. 326:455-461(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9212163; RA West J., Tompkins C.K., Balantac N., Nudelman E., Meengs B., White T., RA Bursten S., Coleman J., Kumar A., Singer J.W., Leung D.W.; RT "Cloning and expression of two human lysophosphatidic acid RT acyltransferase cDNAs that enhance cytokine-induced signaling RT responses in cells."; RL DNA Cell Biol. 16:691-701(1997). RN [4] RP SEQUENCE REVISION TO 51. RA Leung D.W., Tompkin C.K., West J.; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney, and Skin; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP REVIEW. RX PubMed=15028826; DOI=10.1056/NEJMra025261; RA Garg A.; RT "Acquired and inherited lipodystrophies."; RL N. Engl. J. Med. 350:1220-1234(2004). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS CGL1 RP ARG-136; PHE-140 DEL; PRO-228 AND VAL-239. RX PubMed=15629135; DOI=10.1016/j.bbrc.2004.12.024; RA Haque W., Garg A., Agarwal A.K.; RT "Enzymatic activity of naturally occurring 1-acylglycerol-3-phosphate- RT O-acyltransferase 2 mutants associated with congenital generalized RT lipodystrophy."; RL Biochem. Biophys. Res. Commun. 327:446-453(2005). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=21873652; DOI=10.1074/jbc.M111.250449; RA Agarwal A.K., Sukumaran S., Cortes V.A., Tunison K., Mizrachi D., RA Sankella S., Gerard R.D., Horton J.D., Garg A.; RT "Human 1-acylglycerol-3-phosphate O-acyltransferase isoforms 1 and 2: RT biochemical characterization and inability to rescue hepatic steatosis RT in Agpat2(-/-) gene lipodystrophic mice."; RL J. Biol. Chem. 286:37676-37691(2011). RN [12] RP VARIANTS CGL1 ARG-136; PHE-140 DEL; PRO-228 AND VAL-239. RX PubMed=11967537; DOI=10.1038/ng880; RA Agarwal A.K., Arioglu E., de Almeida S., Akkoc N., Taylor S.I., RA Bowcock A.M., Barnes R.I., Garg A.; RT "AGPAT2 is mutated in congenital generalized lipodystrophy linked to RT chromosome 9q34."; RL Nat. Genet. 31:21-23(2002). CC -!- FUNCTION: Converts lysophosphatidic acid (LPA) into phosphatidic CC acid by incorporating an acyl moiety at the sn-2 position of the CC glycerol backbone. {ECO:0000269|PubMed:15629135, CC ECO:0000269|PubMed:21873652, ECO:0000269|PubMed:9242711}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2- CC diacyl-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:15629135, CC ECO:0000269|PubMed:21873652, ECO:0000269|PubMed:9242711}; CC -!- PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CC CDP-diacylglycerol from sn-glycerol 3-phosphate: step 2/3. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:21873652}; Multi-pass membrane protein CC {ECO:0000269|PubMed:21873652}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15120-1; Sequence=Displayed; CC Name=2; CC IsoId=O15120-2; Sequence=VSP_005071; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed predominantly in adipose tissue, CC pancreas and liver. {ECO:0000269|PubMed:21873652}. CC -!- DOMAIN: The HXXXXD motif is essential for acyltransferase activity CC and may constitute the binding site for the phosphate moiety of CC the glycerol-3-phosphate. {ECO:0000250}. CC -!- DISEASE: Congenital generalized lipodystrophy 1 (CGL1) CC [MIM:608594]: An autosomal recessive disorder characterized by a CC near complete absence of adipose tissue, extreme insulin CC resistance, hypertriglyceridemia, hepatic steatosis and early CC onset of diabetes. {ECO:0000269|PubMed:11967537, CC ECO:0000269|PubMed:15629135}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the 1-acyl-sn-glycerol-3-phosphate CC acyltransferase family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF000237; AAC51649.1; -; mRNA. DR EMBL; AF011374; AAB64299.1; -; mRNA. DR EMBL; U56418; AAB58776.2; -; mRNA. DR EMBL; AL590226; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW88249.1; -; Genomic_DNA. DR EMBL; CH471090; EAW88251.1; -; Genomic_DNA. DR EMBL; BC000026; AAH00026.1; -; mRNA. DR EMBL; BC004529; AAH04529.1; -; mRNA. DR CCDS; CCDS35181.1; -. [O15120-2] DR CCDS; CCDS7003.1; -. [O15120-1] DR RefSeq; NP_001012745.1; NM_001012727.1. [O15120-2] DR RefSeq; NP_006403.2; NM_006412.3. [O15120-1] DR UniGene; Hs.320151; -. DR ProteinModelPortal; O15120; -. DR BioGrid; 115806; 13. DR CORUM; O15120; -. DR IntAct; O15120; 7. DR STRING; 9606.ENSP00000360761; -. DR BindingDB; O15120; -. DR ChEMBL; CHEMBL4772; -. DR SwissLipids; SLP:000000096; -. DR iPTMnet; O15120; -. DR PhosphoSitePlus; O15120; -. DR BioMuta; AGPAT2; -. DR EPD; O15120; -. DR jPOST; O15120; -. DR MaxQB; O15120; -. DR PaxDb; O15120; -. DR PeptideAtlas; O15120; -. DR PRIDE; O15120; -. DR ProteomicsDB; 48457; -. DR ProteomicsDB; 48458; -. [O15120-2] DR DNASU; 10555; -. DR Ensembl; ENST00000371694; ENSP00000360759; ENSG00000169692. [O15120-2] DR Ensembl; ENST00000371696; ENSP00000360761; ENSG00000169692. [O15120-1] DR Ensembl; ENST00000538402; ENSP00000438919; ENSG00000169692. [O15120-1] DR GeneID; 10555; -. DR KEGG; hsa:10555; -. DR UCSC; uc004cii.2; human. [O15120-1] DR CTD; 10555; -. DR DisGeNET; 10555; -. DR EuPathDB; HostDB:ENSG00000169692.12; -. DR GeneCards; AGPAT2; -. DR GeneReviews; AGPAT2; -. DR HGNC; HGNC:325; AGPAT2. DR HPA; HPA019544; -. DR MalaCards; AGPAT2; -. DR MIM; 603100; gene. DR MIM; 608594; phenotype. DR neXtProt; NX_O15120; -. DR OpenTargets; ENSG00000169692; -. DR Orphanet; 528; Berardinelli-Seip congenital lipodystrophy. DR PharmGKB; PA24622; -. DR eggNOG; KOG2848; Eukaryota. DR eggNOG; COG0204; LUCA. DR GeneTree; ENSGT00390000008726; -. DR HOVERGEN; HBG000676; -. DR InParanoid; O15120; -. DR KO; K13509; -. DR OMA; FKWVSKA; -. DR OrthoDB; 1623097at2759; -. DR PhylomeDB; O15120; -. DR TreeFam; TF314867; -. DR BioCyc; MetaCyc:HS09990-MONOMER; -. DR BRENDA; 2.3.1.51; 2681. DR Reactome; R-HSA-1483166; Synthesis of PA. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR UniPathway; UPA00557; UER00613. DR GeneWiki; AGPAT2; -. DR GenomeRNAi; 10555; -. DR PRO; PR:O15120; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; ENSG00000169692; Expressed in 196 organ(s), highest expression level in subcutaneous adipose tissue. DR ExpressionAtlas; O15120; baseline and differential. DR Genevisible; O15120; HS. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferase activity; IDA:BHF-UCL. DR GO; GO:0016024; P:CDP-diacylglycerol biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0008544; P:epidermis development; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IGI:BHF-UCL. DR GO; GO:0006644; P:phospholipid metabolic process; NAS:UniProtKB. DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:BHF-UCL. DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IC:BHF-UCL. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR InterPro; IPR004552; AGP_acyltrans. DR InterPro; IPR002123; Plipid/glycerol_acylTrfase. DR Pfam; PF01553; Acyltransferase; 1. DR SMART; SM00563; PlsC; 1. DR TIGRFAMs; TIGR00530; AGP_acyltrn; 1. PE 1: Evidence at protein level; KW Acyltransferase; Alternative splicing; Complete proteome; KW Congenital generalized lipodystrophy; Diabetes mellitus; KW Disease mutation; Endoplasmic reticulum; Lipid biosynthesis; KW Lipid metabolism; Membrane; Phospholipid biosynthesis; KW Phospholipid metabolism; Reference proteome; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 23 {ECO:0000255}. FT CHAIN 24 278 1-acyl-sn-glycerol-3-phosphate FT acyltransferase beta. FT /FTId=PRO_0000208192. FT TRANSMEM 30 50 Helical. {ECO:0000255}. FT TRANSMEM 122 142 Helical. {ECO:0000255}. FT TRANSMEM 187 207 Helical. {ECO:0000255}. FT MOTIF 98 103 HXXXXD motif. FT MOTIF 172 175 EGTR motif. FT VAR_SEQ 165 196 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_005071. FT VARIANT 136 136 G -> R (in CGL1; reduced 1-acyl-sn- FT glycerol-3-phosphate acyltransferase FT activity; dbSNP:rs797045222). FT {ECO:0000269|PubMed:11967537, FT ECO:0000269|PubMed:15629135}. FT /FTId=VAR_017328. FT VARIANT 140 140 Missing (in CGL1; reduced 1-acyl-sn- FT glycerol-3-phosphate acyltransferase FT activity). {ECO:0000269|PubMed:11967537, FT ECO:0000269|PubMed:15629135}. FT /FTId=VAR_017326. FT VARIANT 228 228 L -> P (in CGL1; reduced 1-acyl-sn- FT glycerol-3-phosphate acyltransferase FT activity; dbSNP:rs104894100). FT {ECO:0000269|PubMed:11967537, FT ECO:0000269|PubMed:15629135}. FT /FTId=VAR_017327. FT VARIANT 239 239 A -> V (in CGL1; 90% of wild-type 1-acyl- FT sn-glycerol-3-phosphate acyltransferase FT activity; dbSNP:rs145975461). FT {ECO:0000269|PubMed:11967537, FT ECO:0000269|PubMed:15629135}. FT /FTId=VAR_017325. FT CONFLICT 126 126 L -> V (in Ref. 2; AAB64299). FT {ECO:0000305}. FT CONFLICT 200 200 V -> F (in Ref. 7; AAH00026). FT {ECO:0000305}. SQ SEQUENCE 278 AA; 30914 MW; 1E58F537F703BE9F CRC64; MELWPCLAAA LLLLLLLVQL SRAAEFYAKV ALYCALCFTV SAVASLVCLL RHGGRTVENM SIIGWFVRSF KYFYGLRFEV RDPRRLQEAR PCVIVSNHQS ILDMMGLMEV LPERCVQIAK RELLFLGPVG LIMYLGGVFF INRQRSSTAM TVMADLGERM VRENLKVWIY PEGTRNDNGD LLPFKKGAFY LAVQAQVPIV PVVYSSFSSF YNTKKKFFTS GTVTVQVLEA IPTSGLTAAD VPALVDTCHR AMRTTFLHIS KTPQENGATA GSGVQPAQ //