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Protein

Patatin-like phospholipase domain-containing protein 2

Gene

Pnpla2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15550674). Also has acylglycerol transacylase activity. May act coordinately with LIPE/HLS within the lipolytic cascade. Regulates adiposome size and may be involved in the degradation of adiposomes. May play an important role in energy homeostasis. May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion.6 Publications

Catalytic activityi

Triacylglycerol + H2O = diacylglycerol + a carboxylate.1 Publication

Enzyme regulationi

Stimulated by PKA-dependent PLIN phosphorylation.3 Publications

Pathwayi: triacylglycerol degradation

This protein is involved in the pathway triacylglycerol degradation, which is part of Glycerolipid metabolism.
View all proteins of this organism that are known to be involved in the pathway triacylglycerol degradation and in Glycerolipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei47NucleophilePROSITE-ProRule annotation1
Active sitei166Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • triglyceride lipase activity Source: UniProtKB

GO - Biological processi

  • lipid homeostasis Source: GO_Central
  • lipid particle organization Source: MGI
  • lipid storage Source: UniProtKB
  • negative regulation of sequestering of triglyceride Source: UniProtKB
  • positive regulation of triglyceride catabolic process Source: UniProtKB
  • triglyceride catabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Enzyme and pathway databases

BRENDAi3.1.1.3. 3474.
ReactomeiR-MMU-1482883. Acyl chain remodeling of DAG and TAG.
UniPathwayiUPA00256.

Chemistry databases

SwissLipidsiSLP:000000317.

Names & Taxonomyi

Protein namesi
Recommended name:
Patatin-like phospholipase domain-containing protein 2 (EC:3.1.1.3)
Alternative name(s):
Adipose triglyceride lipase
Desnutrin
Gene namesi
Name:Pnpla2
Synonyms:Atgl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1914103. Pnpla2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8CytoplasmicSequence analysis8
Transmembranei9 – 29Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini30 – 486LumenalSequence analysisAdd BLAST457

GO - Cellular componenti

  • cytosol Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • lipid particle Source: UniProtKB
  • membrane Source: GO_Central
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Lipid droplet, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show increased adipose mass and triacylglycerol deposition in multiple tissues. They accumulate large amounts of lipid in the heart, causing cardiac dysfunction and premature death.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47S → A: Loss of triacylglycerol hydrolysis activity. 1 Publication1
Mutagenesisi396S → A: Slightly reduced TG hydrolase activity. 1 Publication1
Mutagenesisi406S → A: Reduced TG hydrolase activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3425391.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002925281 – 486Patatin-like phospholipase domain-containing protein 2Add BLAST486

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...)Sequence analysis1
Modified residuei374Phosphoserine; in vitro1 Publication1
Modified residuei396Phosphoserine; by PKA1 Publication1
Modified residuei406Phosphoserine; by PKACombined sources1 Publication1
Modified residuei430Phosphoserine; in vitroCombined sources1 Publication1
Modified residuei468Phosphoserine; in vitro1 Publication1

Post-translational modificationi

Phosphorylation at Ser-406 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8BJ56.
PeptideAtlasiQ8BJ56.
PRIDEiQ8BJ56.

PTM databases

iPTMnetiQ8BJ56.
PhosphoSitePlusiQ8BJ56.
SwissPalmiQ8BJ56.

Expressioni

Tissue specificityi

Expressed at high levels in white and brown adipose tissue, and to a lesser degree in testis and cardiac muscle. Barely detected in liver, spleen, thymus, kidney, skeletal muscle, and brain. Among the white adipose depots, gonadal fat showed the highest level of expression compared with inguinal and renal white adipose tissues.4 Publications

Developmental stagei

Increased expression when preadipocytes are induced to differentiate to adipocytes. Not detected in proliferating or confluent preadipocytes.4 Publications

Inductioni

Transiently induced during fasting. cAMP and glucagon may not be involved in the induction during fasting. Induced by dexamethasone. Down-regulated by insulin, isoprotenerol and TNF-alfa. Expression is not affected by glucose and by growth hormone. Expression is reduced in fasted leptin deficient mouse (ob/ob), an obese mouse model. Expression is not affected in fed ob/ob mouse.5 Publications

Gene expression databases

BgeeiENSMUSG00000025509.
CleanExiMM_PNPLA2.
ExpressionAtlasiQ8BJ56. baseline and differential.
GenevisibleiQ8BJ56. MM.

Interactioni

Subunit structurei

Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (PubMed:16679289, PubMed:17189257). Interacts with SERPINF1; interacts at one site of interaction (By similarity). Despite a colocalization in lipid droplets, it probably does not interact with PLIN. Interacts with PLIN5; prevents interaction with ABHD5 (PubMed:21148142, PubMed:21393244). Interacts with FAF2 (By similarity).By similarity4 Publications

Protein-protein interaction databases

BioGridi211763. 4 interactors.
DIPiDIP-61641N.
STRINGi10090.ENSMUSP00000127149.

Chemistry databases

BindingDBiQ8BJ56.

Structurei

3D structure databases

ProteinModelPortaliQ8BJ56.
SMRiQ8BJ56.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 179PNPLAPROSITE-ProRule annotationAdd BLAST170

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi14 – 19GXGXXGPROSITE-ProRule annotation6
Motifi45 – 49GXSXGPROSITE-ProRule annotation5
Motifi166 – 168DGA/GPROSITE-ProRule annotation3

Sequence similaritiesi

Contains 1 PNPLA (patatin-like phospholipase) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3773. Eukaryota.
ENOG410XSQS. LUCA.
GeneTreeiENSGT00390000005295.
HOVERGENiHBG007046.
InParanoidiQ8BJ56.
KOiK16816.
OMAiDSHEHAS.
OrthoDBiEOG091G05MG.
PhylomeDBiQ8BJ56.
TreeFamiTF314272.

Family and domain databases

CDDicd07220. Pat_PNPLA2. 1 hit.
InterProiIPR016035. Acyl_Trfase/lysoPLipase.
IPR002641. Patatin/PLipase_A2-rel.
IPR033562. PLPL.
IPR033903. PNPLA2.
[Graphical view]
PANTHERiPTHR12406. PTHR12406. 1 hit.
PfamiPF01734. Patatin. 1 hit.
[Graphical view]
SUPFAMiSSF52151. SSF52151. 1 hit.
PROSITEiPS51635. PNPLA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BJ56-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MFPRETKWNI SFAGCGFLGV YHIGVASCLR EHAPFLVANA THIYGASAGA
60 70 80 90 100
LTATALVTGA CLGEAGANII EVSKEARKRF LGPLHPSFNL VKTIRGCLLK
110 120 130 140 150
TLPADCHERA NGRLGISLTR VSDGENVIIS HFSSKDELIQ ANVCSTFIPV
160 170 180 190 200
YCGLIPPTLQ GVRYVDGGIS DNLPLYELKN TITVSPFSGE SDICPQDSST
210 220 230 240 250
NIHELRVTNT SIQFNLRNLY RLSKALFPPE PMVLREMCKQ GYRDGLRFLR
260 270 280 290 300
RNGLLNQPNP LLALPPVVPQ EEDAEEAAVV EERAGEEDQL QPYRKDRILE
310 320 330 340 350
HLPARLNEAL LEACVEPKDL MTTLSNMLPV RLATAMMVPY TLPLESAVSF
360 370 380 390 400
TIRLLEWLPD VPEDIRWMKE QTGSICQYLV MRAKRKLGDH LPSRLSEQVE
410 420 430 440 450
LRRAQSLPSV PLSCATYSEA LPNWVRNNLS LGDALAKWEE CQRQLLLGLF
460 470 480
CTNVAFPPDA LRMRAPASPT AADPATPQDP PGLPPC
Length:486
Mass (Da):53,657
Last modified:March 1, 2003 - v1
Checksum:i512FE1931B72FC9C
GO
Isoform 2 (identifier: Q8BJ56-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     253-308: Missing.

Note: No experimental confirmation available.
Show »
Length:430
Mass (Da):47,364
Checksum:i16F03A3A9B559E6A
GO
Isoform 3 (identifier: Q8BJ56-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     57-62: VTGACL → MSHACQ

Note: No experimental confirmation available.
Show »
Length:430
Mass (Da):47,877
Checksum:i1A66AF92E3D62A4F
GO

Sequence cautioni

The sequence BAB22643 differs from that shown. Reason: Frameshift at positions 301, 317 and 460.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3P → T in BAB22387 (PubMed:16141072).Curated1
Sequence conflicti30R → H in AAU33824 (PubMed:15337759).Curated1
Sequence conflicti193I → V in BAE29364 (PubMed:16141072).Curated1
Sequence conflicti319 – 320DL → VG in BAB22643 (PubMed:16141072).Curated2
Sequence conflicti362P → T in BAE29364 (PubMed:16141072).Curated1
Sequence conflicti385R → G in AAC36536 (PubMed:9798653).Curated1
Sequence conflicti389D → G in AAH64747 (PubMed:15489334).Curated1
Sequence conflicti412L → P in AAC36536 (PubMed:9798653).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0264221 – 56Missing in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_02642357 – 62VTGACL → MSHACQ in isoform 3. 1 Publication6
Alternative sequenceiVSP_026424253 – 308Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY731699 mRNA. Translation: AAU33824.1.
AY894805 mRNA. Translation: AAW81963.1.
AY510273 mRNA. Translation: AAS48458.1.
AK002826 mRNA. Translation: BAB22387.1.
AK003207 mRNA. Translation: BAB22643.1. Frameshift.
AK031609 mRNA. Translation: BAC27476.1.
AK150184 mRNA. Translation: BAE29364.1.
BC019188 mRNA. Translation: AAH19188.1.
BC044781 mRNA. Translation: AAH44781.1.
BC064747 mRNA. Translation: AAH64747.1.
U89431 mRNA. Translation: AAC36536.1.
CCDSiCCDS22015.1. [Q8BJ56-2]
CCDS52445.1. [Q8BJ56-1]
RefSeqiNP_001157161.1. NM_001163689.1. [Q8BJ56-1]
NP_080078.2. NM_025802.3. [Q8BJ56-2]
UniGeneiMm.29998.

Genome annotation databases

EnsembliENSMUST00000064151; ENSMUSP00000065116; ENSMUSG00000025509. [Q8BJ56-2]
ENSMUST00000164016; ENSMUSP00000127149; ENSMUSG00000025509. [Q8BJ56-1]
GeneIDi66853.
KEGGimmu:66853.
UCSCiuc009klg.2. mouse. [Q8BJ56-2]
uc009klh.2. mouse. [Q8BJ56-3]
uc009kli.2. mouse. [Q8BJ56-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY731699 mRNA. Translation: AAU33824.1.
AY894805 mRNA. Translation: AAW81963.1.
AY510273 mRNA. Translation: AAS48458.1.
AK002826 mRNA. Translation: BAB22387.1.
AK003207 mRNA. Translation: BAB22643.1. Frameshift.
AK031609 mRNA. Translation: BAC27476.1.
AK150184 mRNA. Translation: BAE29364.1.
BC019188 mRNA. Translation: AAH19188.1.
BC044781 mRNA. Translation: AAH44781.1.
BC064747 mRNA. Translation: AAH64747.1.
U89431 mRNA. Translation: AAC36536.1.
CCDSiCCDS22015.1. [Q8BJ56-2]
CCDS52445.1. [Q8BJ56-1]
RefSeqiNP_001157161.1. NM_001163689.1. [Q8BJ56-1]
NP_080078.2. NM_025802.3. [Q8BJ56-2]
UniGeneiMm.29998.

3D structure databases

ProteinModelPortaliQ8BJ56.
SMRiQ8BJ56.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211763. 4 interactors.
DIPiDIP-61641N.
STRINGi10090.ENSMUSP00000127149.

Chemistry databases

BindingDBiQ8BJ56.
ChEMBLiCHEMBL3425391.
SwissLipidsiSLP:000000317.

PTM databases

iPTMnetiQ8BJ56.
PhosphoSitePlusiQ8BJ56.
SwissPalmiQ8BJ56.

Proteomic databases

PaxDbiQ8BJ56.
PeptideAtlasiQ8BJ56.
PRIDEiQ8BJ56.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000064151; ENSMUSP00000065116; ENSMUSG00000025509. [Q8BJ56-2]
ENSMUST00000164016; ENSMUSP00000127149; ENSMUSG00000025509. [Q8BJ56-1]
GeneIDi66853.
KEGGimmu:66853.
UCSCiuc009klg.2. mouse. [Q8BJ56-2]
uc009klh.2. mouse. [Q8BJ56-3]
uc009kli.2. mouse. [Q8BJ56-1]

Organism-specific databases

CTDi57104.
MGIiMGI:1914103. Pnpla2.

Phylogenomic databases

eggNOGiKOG3773. Eukaryota.
ENOG410XSQS. LUCA.
GeneTreeiENSGT00390000005295.
HOVERGENiHBG007046.
InParanoidiQ8BJ56.
KOiK16816.
OMAiDSHEHAS.
OrthoDBiEOG091G05MG.
PhylomeDBiQ8BJ56.
TreeFamiTF314272.

Enzyme and pathway databases

UniPathwayiUPA00256.
BRENDAi3.1.1.3. 3474.
ReactomeiR-MMU-1482883. Acyl chain remodeling of DAG and TAG.

Miscellaneous databases

ChiTaRSiPnpla2. mouse.
PROiQ8BJ56.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025509.
CleanExiMM_PNPLA2.
ExpressionAtlasiQ8BJ56. baseline and differential.
GenevisibleiQ8BJ56. MM.

Family and domain databases

CDDicd07220. Pat_PNPLA2. 1 hit.
InterProiIPR016035. Acyl_Trfase/lysoPLipase.
IPR002641. Patatin/PLipase_A2-rel.
IPR033562. PLPL.
IPR033903. PNPLA2.
[Graphical view]
PANTHERiPTHR12406. PTHR12406. 1 hit.
PfamiPF01734. Patatin. 1 hit.
[Graphical view]
SUPFAMiSSF52151. SSF52151. 1 hit.
PROSITEiPS51635. PNPLA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPLPL2_MOUSE
AccessioniPrimary (citable) accession number: Q8BJ56
Secondary accession number(s): O89080
, Q05BJ0, Q3UD97, Q643S0, Q6P234, Q9D1Q9, Q9DCF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.