UniProtKB - Q9NST1 (PLPL3_HUMAN)
Protein
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
Gene
PNPLA3
Organism
Homo sapiens (Human)
Status
Functioni
Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (PubMed:15364929, PubMed:20034933, PubMed:22560221).3 Publications
Caution
Variant Met-148 was initially reported to reduce triglyceride hydrolysis activity in vitro (PubMed:20034933). However further in vitro and in vivo data demonstrated that it actually does not affect triglyceride hydrolysis activity, but rather increases 1-acylglycerol-3-phosphate O-acyltransferase activity (PubMed:22560221).2 Publications
Catalytic activityi
- a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA1 PublicationEC:2.3.1.511 Publication
- EC:3.1.1.33 Publications
- (9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoyl-CoA = 1-(9Z)-octadecenoyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (9Z,12Z)-octadecadienoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CoA1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- 1,2-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol1 PublicationThis reaction proceeds in the forward1 Publication direction.
: Phospholipid metabolism Pathwayi
This protein is involved in Phospholipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in Phospholipid metabolism.
Pathwayi: Glycerolipid metabolism
This protein is involved in Glycerolipid metabolism.3 PublicationsView all proteins of this organism that are known to be involved in Glycerolipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 47 | NucleophilePROSITE-ProRule annotation | 1 | |
Active sitei | 166 | Proton acceptorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- 1-acylglycerol-3-phosphate O-acyltransferase activity Source: UniProtKB
- diolein transacylation activity Source: UniProtKB
- long-chain fatty acyl-CoA binding Source: BHF-UCL
- lysophosphatidic acid acyltransferase activity Source: BHF-UCL
- lysophosphatidic acid binding Source: BHF-UCL
- mono-olein transacylation activity Source: UniProtKB
- phospholipase A2 activity Source: UniProtKB
- triglyceride lipase activity Source: UniProtKB
GO - Biological processi
- acylglycerol acyl-chain remodeling Source: Reactome
- cellular response to 3,3',5-triiodo-L-thyronine Source: Ensembl
- cellular response to insulin stimulus Source: Ensembl
- glycerophospholipid metabolic process Source: BHF-UCL
- lipid droplet organization Source: BHF-UCL
- lipid homeostasis Source: GO_Central
- long-chain fatty acid metabolic process Source: BHF-UCL
- phosphatidic acid biosynthetic process Source: BHF-UCL
- response to sucrose Source: Ensembl
- triglyceride acyl-chain remodeling Source: CACAO
- triglyceride biosynthetic process Source: UniProtKB
- triglyceride catabolic process Source: UniProtKB
- white fat cell differentiation Source: Ensembl
Keywordsi
Molecular function | Acyltransferase, Hydrolase, Transferase |
Biological process | Lipid biosynthesis, Lipid metabolism, Phospholipid biosynthesis, Phospholipid metabolism |
Enzyme and pathway databases
PathwayCommonsi | Q9NST1 |
Reactomei | R-HSA-1482883, Acyl chain remodeling of DAG and TAG |
Chemistry databases
SwissLipidsi | SLP:000000282 |
Names & Taxonomyi
Protein namesi | Recommended name: 1-acylglycerol-3-phosphate O-acyltransferase PNPLA31 Publication (EC:2.3.1.511 Publication)Alternative name(s): Acylglycerol transacylase1 Publication Adiponutrin1 Publication Short name: ADPN1 Publication Calcium-independent phospholipase A2-epsilon1 Publication Short name: iPLA2-epsilon1 Publication Lysophosphatidic acid acyltransferase1 Publication Patatin-like phospholipase domain-containing protein 31 Publication (EC:3.1.1.33 Publications) |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100344.10 |
HGNCi | HGNC:18590, PNPLA3 |
MIMi | 609567, gene |
neXtProti | NX_Q9NST1 |
Subcellular locationi
Other locations
- Membrane 2 Publications; Single-pass type II membrane protein 1 Publication
- Lipid droplet 2 Publications
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: Reactome
Other locations
- cytoplasm Source: GO_Central
- integral component of membrane Source: UniProtKB-KW
- lipid droplet Source: UniProtKB
- membrane Source: BHF-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 41 | CytoplasmicSequence analysisAdd BLAST | 41 | |
Transmembranei | 42 – 62 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 63 – 481 | LumenalSequence analysisAdd BLAST | 419 |
Keywords - Cellular componenti
Lipid droplet, MembranePathology & Biotechi
Involvement in diseasei
Non-alcoholic fatty liver disease 1 (NAFLD1)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA condition characterized by accumulation of triglycerides in the liver. It is associated with adverse metabolic consequences, including insulin resistance and dyslipidemia. In a subset of individuals, hepatic steatosis promotes an inflammatory response in the liver, referred to as steatohepatitis, which can progress to cirrhosis and liver cancer. NAFLD is the most common form of liver disease in Western countries.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077543 | 76 | A → T in NAFLD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs746140741Ensembl. | 1 | |
Natural variantiVAR_077544 | 104 | A → V in NAFLD1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077545 | 200 | T → M in NAFLD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs190477302Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 15 | C → S: 65% loss of 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 47 | S → A: No effect on 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 206 | D → A: No effect on 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 311 | P → G: 67% loss of 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, ObesityOrganism-specific databases
DisGeNETi | 80339 |
MIMi | 613282, phenotype |
OpenTargetsi | ENSG00000100344 |
Orphaneti | 33271, NON RARE IN EUROPE: Non-alcoholic fatty liver disease |
PharmGKBi | PA38592 |
Miscellaneous databases
Pharosi | Q9NST1, Tbio |
Polymorphism and mutation databases
BioMutai | PNPLA3 |
DMDMi | 32469599 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000064458 | 1 – 481 | 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3Add BLAST | 481 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 89 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 280 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
MassIVEi | Q9NST1 |
MaxQBi | Q9NST1 |
PaxDbi | Q9NST1 |
PeptideAtlasi | Q9NST1 |
PRIDEi | Q9NST1 |
ProteomicsDBi | 82577 [Q9NST1-1] 82578 [Q9NST1-2] |
PTM databases
GlyGeni | Q9NST1, 2 sites |
iPTMneti | Q9NST1 |
PhosphoSitePlusi | Q9NST1 |
Expressioni
Inductioni
By changes in energy balance: down-regulated following very low-calorie diet, whereas refeeding elevates the mRNA level.1 Publication
Gene expression databases
Bgeei | ENSG00000100344, Expressed in pigmented layer of retina and 159 other tissues |
ExpressionAtlasi | Q9NST1, baseline and differential |
Genevisiblei | Q9NST1, HS |
Organism-specific databases
HPAi | ENSG00000100344, Group enriched (liver, retina) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 123247, 5 interactors |
IntActi | Q9NST1, 5 interactors |
STRINGi | 9606.ENSP00000216180 |
Miscellaneous databases
RNActi | Q9NST1, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 179 | PNPLAPROSITE-ProRule annotationAdd BLAST | 170 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 14 – 19 | GXGXXGPROSITE-ProRule annotation | 6 | |
Motifi | 45 – 49 | GXSXGPROSITE-ProRule annotation | 5 | |
Motifi | 166 – 168 | DGA/GPROSITE-ProRule annotation | 3 |
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3773, Eukaryota |
GeneTreei | ENSGT00940000155662 |
HOGENOMi | CLU_018371_0_1_1 |
InParanoidi | Q9NST1 |
OMAi | WLQWATS |
OrthoDBi | 1204225at2759 |
PhylomeDBi | Q9NST1 |
TreeFami | TF314272 |
Family and domain databases
CDDi | cd07221, Pat_PNPLA3, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR039185, Pat_PNPLA3 IPR033562, PLPL IPR002641, PNPLA_dom |
PANTHERi | PTHR12406, PTHR12406, 1 hit |
Pfami | View protein in Pfam PF01734, Patatin, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS51635, PNPLA, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9NST1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MYDAERGWSL SFAGCGFLGF YHVGATRCLS EHAPHLLRDA RMLFGASAGA
60 70 80 90 100
LHCVGVLSGI PLEQTLQVLS DLVRKARSRN IGIFHPSFNL SKFLRQGLCK
110 120 130 140 150
CLPANVHQLI SGKIGISLTR VSDGENVLVS DFRSKDEVVD ALVCSCFIPF
160 170 180 190 200
YSGLIPPSFR GVRYVDGGVS DNVPFIDAKT TITVSPFYGE YDICPKVKST
210 220 230 240 250
NFLHVDITKL SLRLCTGNLY LLSRAFVPPD LKVLGEICLR GYLDAFRFLE
260 270 280 290 300
EKGICNRPQP GLKSSSEGMD PEVAMPSWAN MSLDSSPESA ALAVRLEGDE
310 320 330 340 350
LLDHLRLSIL PWDESILDTL SPRLATALSE EMKDKGGYMS KICNLLPIRI
360 370 380 390 400
MSYVMLPCTL PVESAIAIVQ RLVTWLPDMP DDVLWLQWVT SQVFTRVLMC
410 420 430 440 450
LLPASRSQMP VSSQQASPCT PEQDWPCWTP CSPKGCPAET KAEATPRSIL
460 470 480
RSSLNFFLGN KVPAGAEGLS TFPSFSLEKS L
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF8W8E5 | F8W8E5_HUMAN | 1-acylglycerol-3-phosphate O-acyltr... | PNPLA3 | 120 | Annotation score: |
Polymorphismi
Polymorphic variation at position 148 influences insulin secretion levels and obesity. In obese subjects the body mass index and waist are higher in carriers of the Ile-148 allele. The Ile-148 carriers also display decreased insulin secretion in response to oral glucose tolerance test. Met-148 allele carriers are seemingly more insulin resistant at a lower body mass index.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077543 | 76 | A → T in NAFLD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs746140741Ensembl. | 1 | |
Natural variantiVAR_015845 | 99 | C → G1 PublicationCorresponds to variant dbSNP:rs2076213EnsemblClinVar. | 1 | |
Natural variantiVAR_077544 | 104 | A → V in NAFLD1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_015846 | 115 | G → C1 PublicationCorresponds to variant dbSNP:rs2076212EnsemblClinVar. | 1 | |
Natural variantiVAR_019961 | 148 | I → M Common polymorphism; associated with increased hepatic fat content and serum aspartate aminotransferase concentrations; increases 1-acylglycerol-3-phosphate O-acyltransferase activity 2-fold. 7 PublicationsCorresponds to variant dbSNP:rs738409EnsemblClinVar. | 1 | |
Natural variantiVAR_077545 | 200 | T → M in NAFLD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs190477302Ensembl. | 1 | |
Natural variantiVAR_053814 | 216 | T → P. Corresponds to variant dbSNP:rs35726887EnsemblClinVar. | 1 | |
Natural variantiVAR_015847 | 434 | K → E4 PublicationsCorresponds to variant dbSNP:rs2294918EnsemblClinVar. | 1 | |
Natural variantiVAR_053815 | 453 | S → I Common polymorphism; associated with lower hepatic fat content in African Americans. 1 PublicationCorresponds to variant dbSNP:rs6006460EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_036222 | 59 – 62 | Missing in isoform 2. 1 Publication | 4 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL138578 mRNA Translation: CAB71238.2 CR456476 mRNA Translation: CAG30362.1 AK123806 mRNA Translation: BAG53962.1 AK315166 mRNA Translation: BAG37610.1 AL023654 Genomic DNA No translation available. AL035398 Genomic DNA No translation available. CH471138 Genomic DNA Translation: EAW73324.1 BC014449 mRNA Translation: AAH14449.2 BC065195 mRNA Translation: AAH65195.1 |
CCDSi | CCDS14054.1 [Q9NST1-1] |
RefSeqi | NP_079501.2, NM_025225.2 [Q9NST1-1] |
Genome annotation databases
Ensembli | ENST00000216180; ENSP00000216180; ENSG00000100344 [Q9NST1-1] ENST00000423180; ENSP00000397987; ENSG00000100344 [Q9NST1-2] |
GeneIDi | 80339 |
KEGGi | hsa:80339 |
UCSCi | uc003bei.1, human [Q9NST1-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL138578 mRNA Translation: CAB71238.2 CR456476 mRNA Translation: CAG30362.1 AK123806 mRNA Translation: BAG53962.1 AK315166 mRNA Translation: BAG37610.1 AL023654 Genomic DNA No translation available. AL035398 Genomic DNA No translation available. CH471138 Genomic DNA Translation: EAW73324.1 BC014449 mRNA Translation: AAH14449.2 BC065195 mRNA Translation: AAH65195.1 |
CCDSi | CCDS14054.1 [Q9NST1-1] |
RefSeqi | NP_079501.2, NM_025225.2 [Q9NST1-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 123247, 5 interactors |
IntActi | Q9NST1, 5 interactors |
STRINGi | 9606.ENSP00000216180 |
Chemistry databases
SwissLipidsi | SLP:000000282 |
PTM databases
GlyGeni | Q9NST1, 2 sites |
iPTMneti | Q9NST1 |
PhosphoSitePlusi | Q9NST1 |
Polymorphism and mutation databases
BioMutai | PNPLA3 |
DMDMi | 32469599 |
Proteomic databases
MassIVEi | Q9NST1 |
MaxQBi | Q9NST1 |
PaxDbi | Q9NST1 |
PeptideAtlasi | Q9NST1 |
PRIDEi | Q9NST1 |
ProteomicsDBi | 82577 [Q9NST1-1] 82578 [Q9NST1-2] |
Protocols and materials databases
Antibodypediai | 27572, 228 antibodies |
DNASUi | 80339 |
Genome annotation databases
Ensembli | ENST00000216180; ENSP00000216180; ENSG00000100344 [Q9NST1-1] ENST00000423180; ENSP00000397987; ENSG00000100344 [Q9NST1-2] |
GeneIDi | 80339 |
KEGGi | hsa:80339 |
UCSCi | uc003bei.1, human [Q9NST1-1] |
Organism-specific databases
CTDi | 80339 |
DisGeNETi | 80339 |
EuPathDBi | HostDB:ENSG00000100344.10 |
GeneCardsi | PNPLA3 |
HGNCi | HGNC:18590, PNPLA3 |
HPAi | ENSG00000100344, Group enriched (liver, retina) |
MIMi | 609567, gene 613282, phenotype |
neXtProti | NX_Q9NST1 |
OpenTargetsi | ENSG00000100344 |
Orphaneti | 33271, NON RARE IN EUROPE: Non-alcoholic fatty liver disease |
PharmGKBi | PA38592 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3773, Eukaryota |
GeneTreei | ENSGT00940000155662 |
HOGENOMi | CLU_018371_0_1_1 |
InParanoidi | Q9NST1 |
OMAi | WLQWATS |
OrthoDBi | 1204225at2759 |
PhylomeDBi | Q9NST1 |
TreeFami | TF314272 |
Enzyme and pathway databases
PathwayCommonsi | Q9NST1 |
Reactomei | R-HSA-1482883, Acyl chain remodeling of DAG and TAG |
Miscellaneous databases
BioGRID-ORCSi | 80339, 2 hits in 840 CRISPR screens |
ChiTaRSi | PNPLA3, human |
GeneWikii | PNPLA3 |
GenomeRNAii | 80339 |
Pharosi | Q9NST1, Tbio |
PROi | PR:Q9NST1 |
RNActi | Q9NST1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100344, Expressed in pigmented layer of retina and 159 other tissues |
ExpressionAtlasi | Q9NST1, baseline and differential |
Genevisiblei | Q9NST1, HS |
Family and domain databases
CDDi | cd07221, Pat_PNPLA3, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR039185, Pat_PNPLA3 IPR033562, PLPL IPR002641, PNPLA_dom |
PANTHERi | PTHR12406, PTHR12406, 1 hit |
Pfami | View protein in Pfam PF01734, Patatin, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS51635, PNPLA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PLPL3_HUMAN | |
Accessioni | Q9NST1Primary (citable) accession number: Q9NST1 Secondary accession number(s): B0QYI0 Q96CB4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 3, 2003 |
Last sequence update: | March 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 160 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations