Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8BJ56 (PLPL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Patatin-like phospholipase domain-containing protein 2

EC=3.1.1.3
Alternative name(s):
Adipose triglyceride lipase
Desnutrin
Gene names
Name:Pnpla2
Synonyms:Atgl
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length486 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets. 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. Ref.1 Ref.2 Ref.7 Ref.9 Ref.11 Ref.12

Catalytic activity

Triacylglycerol + H2O = diacylglycerol + a carboxylate. Ref.9

Enzyme regulation

Stimulated by PKA-dependent PLIN phosphorylation. Ref.2 Ref.11 Ref.13

Pathway

Glycerolipid metabolism; triacylglycerol degradation.

Subunit structure

Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity. 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. Ref.9 Ref.14 Ref.15 Ref.16

Subcellular location

Lipid droplet. Cell membrane; Single-pass type II membrane protein Ref.1 Ref.2 Ref.3.

Tissue specificity

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. Ref.1 Ref.2 Ref.3 Ref.7

Developmental stage

Increased expression when preadipocytes are induced to differentiate to adipocytes. Not detected in proliferating or confluent preadipocytes. Ref.1 Ref.2 Ref.3 Ref.7

Induction

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. Ref.1 Ref.2 Ref.3 Ref.7 Ref.8 Ref.10 Ref.11 Ref.13

Post-translational modification

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

Disruption phenotype

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. Ref.12

Sequence similarities

Contains 1 patatin domain.

Sequence caution

The sequence BAB22643.1 differs from that shown. Reason: Frameshift at positions 301, 317 and 460.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8BJ56-1)

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.
Isoform 2 (identifier: Q8BJ56-2)

The sequence of this isoform differs from the canonical sequence as follows:
     253-308: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8BJ56-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     57-62: VTGACL → MSHACQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 486486Patatin-like phospholipase domain-containing protein 2
PRO_0000292528

Regions

Topological domain1 – 88Cytoplasmic Potential
Transmembrane9 – 2921Helical; Signal-anchor for type II membrane protein; Potential
Topological domain30 – 486457Lumenal Potential
Domain10 – 179170Patatin
Motif45 – 495GXSXG

Sites

Active site471

Amino acid modifications

Modified residue3741Phosphoserine; in vitro Ref.17
Modified residue3961Phosphoserine; by PKA Ref.17
Modified residue4061Phosphoserine; by PKA Ref.17
Modified residue4301Phosphoserine; in vitro Ref.17
Modified residue4681Phosphoserine; in vitro Ref.17
Glycosylation391N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 5656Missing in isoform 3.
VSP_026422
Alternative sequence57 – 626VTGACL → MSHACQ in isoform 3.
VSP_026423
Alternative sequence253 – 30856Missing in isoform 2.
VSP_026424

Experimental info

Mutagenesis471S → A: Loss of triacylglycerol hydrolysis activity. Ref.9
Mutagenesis3961S → A: Slightly reduced TG hydrolase activity. Ref.17
Mutagenesis4061S → A: Reduced TG hydrolase activity. Ref.17
Sequence conflict31P → T in BAB22387. Ref.4
Sequence conflict301R → H in AAU33824. Ref.1
Sequence conflict1931I → V in BAE29364. Ref.4
Sequence conflict319 – 3202DL → VG in BAB22643. Ref.4
Sequence conflict3621P → T in BAE29364. Ref.4
Sequence conflict3851R → G in AAC36536. Ref.6
Sequence conflict3891D → G in AAH64747. Ref.5
Sequence conflict4121L → P in AAC36536. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 512FE1931B72FC9C

FASTA48653,657
        10         20         30         40         50         60 
MFPRETKWNI SFAGCGFLGV YHIGVASCLR EHAPFLVANA THIYGASAGA LTATALVTGA 

        70         80         90        100        110        120 
CLGEAGANII EVSKEARKRF LGPLHPSFNL VKTIRGCLLK TLPADCHERA NGRLGISLTR 

       130        140        150        160        170        180 
VSDGENVIIS HFSSKDELIQ ANVCSTFIPV YCGLIPPTLQ GVRYVDGGIS DNLPLYELKN 

       190        200        210        220        230        240 
TITVSPFSGE SDICPQDSST NIHELRVTNT SIQFNLRNLY RLSKALFPPE PMVLREMCKQ 

       250        260        270        280        290        300 
GYRDGLRFLR RNGLLNQPNP LLALPPVVPQ EEDAEEAAVV EERAGEEDQL QPYRKDRILE 

       310        320        330        340        350        360 
HLPARLNEAL LEACVEPKDL MTTLSNMLPV RLATAMMVPY TLPLESAVSF TIRLLEWLPD 

       370        380        390        400        410        420 
VPEDIRWMKE QTGSICQYLV MRAKRKLGDH LPSRLSEQVE LRRAQSLPSV PLSCATYSEA 

       430        440        450        460        470        480 
LPNWVRNNLS LGDALAKWEE CQRQLLLGLF CTNVAFPPDA LRMRAPASPT AADPATPQDP 


PGLPPC 

« Hide

Isoform 2 [UniParc].

Checksum: 16F03A3A9B559E6A
Show »

FASTA43047,364
Isoform 3 [UniParc].

Checksum: 1A66AF92E3D62A4F
Show »

FASTA43047,877

References

« Hide 'large scale' references
[1]"Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis."
Villena J.A., Roy S., Sarkadi-Nagy E., Kim K.-H., Sul H.S.
J. Biol. Chem. 279:47066-47075(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
Strain: C57BL/6.
Tissue: White adipose tissue.
[2]"Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase."
Zimmermann R., Strauss J.G., Haemmerle G., Schoiswohl G., Birner-Gruenberger R., Riederer M., Lass A., Neuberger G., Eisenhaber F., Hermetter A., Zechner R.
Science 306:1383-1386(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
Strain: C57BL/6.
[3]"The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma."
Kim J.Y., Tillison K., Lee J.-H., Rearick D.A., Smas C.M.
Am. J. Physiol. 291:E115-E127(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
Strain: C57BL/6.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
Tissue: Bone marrow, Kidney and Testis.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Strain: FVB/N.
Tissue: Trophoblast stem cell.
[6]"Expressed genes in interleukin-4 treated B cells identified by cDNA representational difference analysis."
Chu C.C., Paul W.E.
Mol. Immunol. 35:487-502(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 296-473.
Strain: BALB/c.
Tissue: Spleen.
[7]"Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members."
Lake A.C., Sun Y., Li J.-L., Kim J.E., Johnson J.W., Li D., Revett T., Shih H.H., Liu W., Paulsen J.E., Gimeno R.E.
J. Lipid Res. 46:2477-2487(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
[8]"Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes."
Kralisch S., Klein J., Lossner U., Bluher M., Paschke R., Stumvoll M., Fasshauer M.
Mol. Cell. Endocrinol. 240:43-49(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome."
Lass A., Zimmermann R., Haemmerle G., Riederer M., Schoiswohl G., Schweiger M., Kienesberger P., Strauss J.G., Gorkiewicz G., Zechner R.
Cell Metab. 3:309-319(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ABHD5, MUTAGENESIS OF SER-47.
[10]"Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin."
Kershaw E.E., Hamm J.K., Verhagen L.A.W., Peroni O., Katic M., Flier J.S.
Diabetes 55:148-157(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism."
Schweiger M., Schreiber R., Haemmerle G., Lass A., Fledelius C., Jacobsen P., Tornqvist H., Zechner R., Zimmermann R.
J. Biol. Chem. 281:40236-40241(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[12]"Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase."
Haemmerle G., Lass A., Zimmermann R., Gorkiewicz G., Meyer C., Rozman J., Heldmaier G., Maier R., Theussl C., Eder S., Kratky D., Wagner E.F., Klingenspor M., Hoefler G., Zechner R.
Science 312:734-737(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[13]"Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes."
Miyoshi H., Perfield J.W. II, Souza S.C., Shen W.-J., Zhang H.-H., Stancheva Z.S., Kraemer F.B., Obin M.S., Greenberg A.S.
J. Biol. Chem. 282:996-1002(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[14]"Analysis of lipolytic protein trafficking and interactions in adipocytes."
Granneman J.G., Moore H.-P.H., Granneman R.L., Greenberg A.S., Obin M.S., Zhu Z.
J. Biol. Chem. 282:5726-5735(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ABHD5, LACK OF INTERACTION WITH PLIN.
[15]"Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase."
Granneman J.G., Moore H.P., Mottillo E.P., Zhu Z., Zhou L.
J. Biol. Chem. 286:5126-5135(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLIN5, EXCLUSION OF INTERACTION WITH ABHD5.
[16]"Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein."
Wang H., Bell M., Sreenivasan U., Sreenevasan U., Hu H., Liu J., Dalen K., Londos C., Yamaguchi T., Rizzo M.A., Coleman R., Gong D., Brasaemle D., Sztalryd C.
J. Biol. Chem. 286:15707-15715(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLIN5.
[17]"Identification and functional characterization of protein kinase A phosphorylation sites in the major lipolytic protein, adipose triglyceride lipase."
Pagnon J., Matzaris M., Stark R., Meex R.C., Macaulay S.L., Brown W., O'Brien P.E., Tiganis T., Watt M.J.
Endocrinology 153:4278-4289(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-374; SER-396; SER-406; SER-430 AND SER-468, MUTAGENESIS OF SER-396 AND SER-406.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS22015.1. [Q8BJ56-2]
CCDS52445.1. [Q8BJ56-1]
RefSeqNP_001157161.1. NM_001163689.1. [Q8BJ56-1]
NP_080078.2. NM_025802.3. [Q8BJ56-2]
UniGeneMm.29998.

3D structure databases

ProteinModelPortalQ8BJ56.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid211763. 4 interactions.

PTM databases

PhosphoSiteQ8BJ56.

Proteomic databases

MaxQBQ8BJ56.
PaxDbQ8BJ56.
PRIDEQ8BJ56.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000064151; ENSMUSP00000065116; ENSMUSG00000025509. [Q8BJ56-2]
ENSMUST00000164016; ENSMUSP00000127149; ENSMUSG00000025509. [Q8BJ56-1]
GeneID66853.
KEGGmmu:66853.
UCSCuc009klg.2. mouse. [Q8BJ56-2]
uc009klh.2. mouse. [Q8BJ56-3]
uc009kli.2. mouse. [Q8BJ56-1]

Organism-specific databases

CTD57104.
MGIMGI:1914103. Pnpla2.

Phylogenomic databases

eggNOGNOG261571.
GeneTreeENSGT00390000005295.
HOVERGENHBG007046.
InParanoidQ8BJ56.
KOK16816.
OMALVLREMC.
OrthoDBEOG7J9VQR.
PhylomeDBQ8BJ56.
TreeFamTF314272.

Enzyme and pathway databases

UniPathwayUPA00256.

Gene expression databases

ArrayExpressQ8BJ56.
BgeeQ8BJ56.
CleanExMM_PNPLA2.
GenevestigatorQ8BJ56.

Family and domain databases

InterProIPR016035. Acyl_Trfase/lysoPLipase.
IPR002641. Patatin/PLipase_A2-rel.
[Graphical view]
PfamPF01734. Patatin. 1 hit.
[Graphical view]
SUPFAMSSF52151. SSF52151. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPNPLA2. mouse.
NextBio322819.
PROQ8BJ56.
SOURCESearch...

Entry information

Entry namePLPL2_MOUSE
AccessionPrimary (citable) accession number: Q8BJ56
Secondary accession number(s): O89080 expand/collapse secondary AC list , Q05BJ0, Q3UD97, Q643S0, Q6P234, Q9D1Q9, Q9DCF6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot