AGPAT2 1-acylglycerol-3-phosphate O-acyltransferase 2 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: AGPAT2provided by HGNC
Official Full Name: 1-acylglycerol-3-phosphate O-acyltransferase 2provided by HGNC
Primary source: HGNC:325
See related: Ensembl:ENSG00000169692; HPRD:04373; MIM:603100; Vega:OTTHUMG00000020936
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BSCL; BSCL1; LPAAB; 1-AGPAT2; LPAAT-beta
Summary: This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 9q34.3

Sequence :: Chromosome: 9; NC_000009.11 (139567595..139581911, complement)

See AGPAT2 in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

novel nonsense a missense mutations were found in two patients with congenital generalized lipodystrophy type 1.
Title: Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1.
Data suggest that AGPAT2 regulates adipogenesis through modulation of lipid metabolism/signal transduction, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/protooncogene c-Akt and PPARgamma signaling in early stage of adipogenesis.
Title: Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.
the role of AGPAT1 or AGPAT2 in liver lipogenesis is minimal and that accumulation of liver fat is primarily a consequence of insulin resistance
Title: Human 1-acylglycerol-3-phosphate O-acyltransferase isoforms 1 and 2: biochemical characterization and inability to rescue hepatic steatosis in Agpat2(-/-) gene lipodystrophic mice.
lpaat beta gene overexpression exists in both AML and CML patients. lpaat beta produced by AML cells probably plays an important role in abnormal proliferation and drug-resistance of AML cells.
Title: [Lysophosphatidic acid acyltransferase β gene expression in newly diagnosed leukemia patients].
Lysophosphatidic acid acyltransferase beta (LPAATbeta) promotes the tumor growth of human osteosarcoma
Title: Lysophosphatidic acid acyltransferase β (LPAATβ) promotes the tumor growth of human osteosarcoma.
We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).
Title: Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome.
Study showed that the cellular level of lysophosphatidic acid was increased in AGPAT2 deficient cells.
Title: Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy.
A new subtype of congenital generalized lipodystrophy is not associated with the AGPAT2 gene.
Title: Novel subtype of congenital generalized lipodystrophy associated with muscular weakness and cervical spine instability.
Berardinelli-Seip syndrome is a congenital form of generalized lipodystrophy, transmitted as an autosomal recessive trait. It is well documented in medicine and skin. It is a rare disorder caused by mutations of AGPAT2 gene or BSCL2 gene.
Title: Talon cusps, macrodontia, and aberrant tooth morphology in Berardinelli-Seip syndrome.
Congenital lipodystrophy patients with Seipin mutations have a more severe lack of body fat, which affects both metabolically active and mechanical adipose tissue, compared with patients with mutations in the AGPAT2 gene.
Title: Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes.

Submit: New GeneRIF Correction See all (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Congenital generalized lipodystrophy type 1

MIM: 608594

Genetic Testing Registry

Summary from GeneReviews: Berardinelli-Seip Congenital Lipodystrophy

Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.

Diagnosis Testing

The diagnosis of BSCL is established by clinical findings including lipoatrophy affecting the trunk, limbs, and face; acromegaloid features; hepatomegaly; elevated serum concentration of triglycerides; and insulin resistance. AGPAT2 and BSCL2 are the genes in which mutations are known to cause Berardinelli-Seip congenital generalized lipodystrophy type 1 and type 2 respectively. Molecular genetic testing is available on a clinical basis for both genes.

Genetic Counseling

BSCL is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

References

PMID: 20301391

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:115806	BioGRID:122125	ABCG8	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:116847	ANKRD28	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:114360	GMPS	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:119318	PHF11	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:121694	PHRF1	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:115287	SLC23A2	BioGRID	PubMed	Two-hybrid
BioGRID:115806	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Adipogenesis, organism-specific biosystem (from WikiPathways)
Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
CDP-diacylglycerol biosynthesis I, organism-specific biosystem (from BIOCYC)
CDP-diacylglycerol biosynthesis I, organism-specific biosystemGeneral Background Phospholipids are important membrane components. Most of the phospholipids belong to the category of phosphoglycerides. The simplest phosphoglycerides, which are known as phosphat...
CDP-diacylglycerol biosynthesis I, conserved biosystem (from BIOCYC)
CDP-diacylglycerol biosynthesis I, conserved biosystemGeneral Background Phospholipids are important membrane components. Most of the phospholipids belong to the category of phosphoglycerides. The simplest phosphoglycerides, which are known as phosphat...
Fat digestion and absorption, organism-specific biosystem (from KEGG)
Fat digestion and absorption, organism-specific biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
Fat digestion and absorption, conserved biosystem (from KEGG)
Fat digestion and absorption, conserved biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
Glycerolipid metabolism, organism-specific biosystem (from KEGG)
Glycerolipid metabolism, organism-specific biosystem
Glycerolipid metabolism
Glycerolipid metabolism, conserved biosystem (from KEGG)
Glycerolipid metabolism, conserved biosystem
Glycerolipid metabolism
Glycerophospholipid biosynthesis, organism-specific biosystem (from REACTOME)
Glycerophospholipid biosynthesis, organism-specific biosystemGlycerophospholipids are important structural and functional components of biological membranes and constituents of serum lipoproteins and the pulmonary surfactant. In addition, glycerophospholipids...
Glycerophospholipid metabolism, organism-specific biosystem (from KEGG)
Glycerophospholipid metabolism, organism-specific biosystem
Glycerophospholipid metabolism
Glycerophospholipid metabolism, conserved biosystem (from KEGG)
Glycerophospholipid metabolism, conserved biosystem
Glycerophospholipid metabolism
Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Phospholipid metabolism, organism-specific biosystem (from REACTOME)
Phospholipid metabolism, organism-specific biosystemPhospholipids contain a polar head group and two long-chain fatty acyl moieties, one of which is generally unsaturated. The head group is a glycerol or serine phosphate attached to a polar group such...
Synthesis of PA, organism-specific biosystem (from REACTOME)
Synthesis of PA, organism-specific biosystemIn the de novo synthesis of phosphatidic acid (PA), lysophosphatidic acid (LPA) is initially formed by the esterification of sn-1 by glycerol 3-phosphate acyltransferase (GPAT) from glycerol 3-phosph...
Triacylglyceride Synthesis, organism-specific biosystem (from WikiPathways)
Triacylglyceride Synthesis, organism-specific biosystem
Triacylglyceride Synthesis
Triacylglycerol biosynthesis, organism-specific biosystem (from KEGG)
Triacylglycerol biosynthesis, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Triacylglycerol biosynthesis, conserved biosystem (from KEGG)
Triacylglycerol biosynthesis, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Lipid metabolism
Triglyceride Biosynthesis, organism-specific biosystem (from REACTOME)
Triglyceride Biosynthesis, organism-specific biosystemThe overall process of triglyceride (triacylglycerol) biosynthesis consists of four biochemical pathways: fatty acyl-CoA biosynthesis, conversion of fatty acyl-CoA to phosphatidic acid, conversion of...
phosphatidylglycerol biosynthesis II (non-plastidic), organism-specific biosystem (from BIOCYC)
phosphatidylglycerol biosynthesis II (non-plastidic), organism-specific biosystem
phosphatidylglycerol biosynthesis II (non-plastidic)
triacylglycerol biosynthesis, organism-specific biosystem (from BIOCYC)
triacylglycerol biosynthesis, organism-specific biosystem
triacylglycerol biosynthesis

General gene information

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Markers

D9S1818 (e-PCR), detects polymorphism
- UniSTS:52265

AGPAT2_9138 (e-PCR)
- UniSTS:471339

RH41872 (e-PCR)
- UniSTS:86338

D9S1826 (e-PCR), detects polymorphism
- UniSTS:20356

Genotypes

See AGPAT2 SNP Geneview Report
See AGPAT2 SNP Genotype Report
See AGPAT2 SNP Variation Viewer Report

Homology

Homologs of the AGPAT2 gene: The AGPAT2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, and N.crassa.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
1-acylglycerol-3-phosphate O-acyltransferase activity	IGI Inferred from Genetic Interaction more info	PubMed
1-acylglycerol-3-phosphate O-acyltransferase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
CDP-diacylglycerol biosynthetic process	IEA Inferred from Electronic Annotation more info
cellular lipid metabolic process	TAS Traceable Author Statement more info
glycerophospholipid biosynthetic process	TAS Traceable Author Statement more info
phosphatidic acid biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
phosphatidic acid biosynthetic process	TAS Traceable Author Statement more info
phospholipid metabolic process	NAS Non-traceable Author Statement more info	PubMed
phospholipid metabolic process	TAS Traceable Author Statement more info
positive regulation of cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytokine-mediated signaling pathway	IC Inferred by Curator more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
triglyceride biosynthetic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
integral to membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: 1-acyl-sn-glycerol-3-phosphate acyltransferase beta

Names: 1-acyl-sn-glycerol-3-phosphate acyltransferase beta; 1-AGPAT 2; 1-AGP acyltransferase 2; lysophosphatidic acid acyltransferase beta; lysophosphatidic acid acyltransferase-beta; 1-acylglycerol-3-phosphate O-acyltransferase 2 (lysophosphatidic acid acyltransferase, beta)

NP_001012745.1

EC 2.3.1.51

NP_006403.2

EC 2.3.1.51

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008090.1 RefSeqGene

Range

5001..19317

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001012727.1 → NP_001012745.1 1-acyl-sn-glycerol-3-phosphate acyltransferase beta isoform b precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1, resulting in a shorter protein (isoform b).

Source sequence(s)

AL590226, BC000026, BC004529, BF347518, CN407343

Consensus CDS

CCDS35181.1

UniProtKB/Swiss-Prot

O15120

Related

ENSP00000360759, OTTHUMP00000022596, ENST00000371694, OTTHUMT00000055091

Conserved Domains (2) summary

COG0204
Location:26 – 154
Blast Score: 145

PlsC; 1-acyl-sn-glycerol-3-phosphate acyltransferase [Lipid metabolism]

cd07989
Location:67 – 217
Blast Score: 207

LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like
NM_006412.3 → NP_006403.2 1-acyl-sn-glycerol-3-phosphate acyltransferase beta isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AF000237, AL590226, BC000026, BF347518

Consensus CDS

CCDS7003.1

UniProtKB/Swiss-Prot

O15120

Related

ENSP00000360761, OTTHUMP00000022595, ENST00000371696, OTTHUMT00000055090

Conserved Domains (2) summary

cd07989
Location:67 – 249
Blast Score: 351

LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

PRK15018
Location:37 – 270
Blast Score: 199

PRK15018; 1-acyl-sn-glycerol-3-phosphate acyltransferase; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p10 Primary Assembly

Range

139567595..139581911, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

109027535..109041933, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018920.1 Alternate CHM1_1.0

Range

139604647..139618791, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01022716.1 (6827..21225)	None
genomic	AL590226.23 (99194..113510)	None
genomic	AMYH01021869.1 (6947..21091)	None
genomic	CH471090.1	EAW88249.1
		EAW88250.1
		EAW88251.1
		EAW88252.1
mRNA	AF000237.1	AAC51649.1
mRNA	AF011374.1	AAB64299.1
mRNA	BC000026.2	AAH00026.1
mRNA	BC004529.2	AAH04529.1
mRNA	BC007269.1	AAH07269.1
mRNA	BC019292.1	AAH19292.1
mRNA	BF347518.1	None
mRNA	CN407343.1	None
mRNA	U56418.2	AAB58776.2
other-genetic	DQ892146.2	ABM83072.1
other-genetic	DQ895342.2	ABM86268.1