Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Phosphatidate phosphatase LPIN1

Gene

Lpin1

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

Functioni

Plays important roles in controlling the metabolism of fatty acids at differents levels. Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis. Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression. Is involved in adipocyte differentiation. Isoform 1 is recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol.1 Publication

Catalytic activityi

A 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Inhibited by N-ethylmaleimide treatment.1 Publication

GO - Molecular functioni

  • histone deacetylase binding Source: MGI
  • peroxisome proliferator activated receptor binding Source: UniProtKB
  • phosphatidate phosphatase activity Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: MGI
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: MGI
  • cellular response to insulin stimulus Source: MGI
  • fat cell differentiation Source: UniProtKB
  • fatty acid catabolic process Source: UniProtKB
  • lipid metabolic process Source: MGI
  • mitochondrial fission Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of histone deacetylation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of fat cell differentiation Source: MGI
  • ruffle organization Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • triglyceride biosynthetic process Source: GO_Central
  • triglyceride mobilization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

BRENDAi3.1.3.4. 3474.

Chemistry databases

SwissLipidsiSLP:000000601.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidate phosphatase LPIN1 (EC:3.1.3.4)
Alternative name(s):
Fatty liver dystrophy protein
Lipin-1
Gene namesi
Name:Lpin1
Synonyms:Fld
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1891340. Lpin1.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Nucleus
  • Cytoplasm
  • Endoplasmic reticulum membrane

  • Note: Nuclear localization requires both CNEP1R1 and CTDNEP1. In neuronals cells, localized in both the cytoplasm and the nucleus. In 3T3-L1 pre-adipocytes, it is predominantly nuclear.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • mitochondrial outer membrane Source: UniProtKB
  • nuclear membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Lpin1 are the cause of the fatty liver dystrophy phenotype (fld). Fld mutant mices are characterized by neonatal fatty liver and hypertriglyceridemia that resolve at weaning, and neuropathy affecting peripheral nerve in adulthood. Adipose tissue deficiency, glucose intolerance and increased susceptibility to atherosclerosis are associated with this mutation too. Two independent mutant alleles are characterized in this phenotype, fld and fld2j.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106S → A: Abolishes phosphorylation in response to insulin but has no effect on cellular location. 1 Publication1
Mutagenesisi599K → R: Reduces sumoylation. Abolishes sumoylation and nuclear localization; when associated with R-629. 1 Publication1
Mutagenesisi629K → R: Reduces sumoylation. Abolishes sumoylation and nuclear localization; when associated with R-599. 1 Publication1
Mutagenesisi712D → A or E: Abolishes phosphatidate phosphatase activity. No effect on interaction or coactivation with PPARA. 2 Publications1
Mutagenesisi726I → F: Diminishes significantly the interaction and coactivation OF PPARA; when associated with F-727. 1 Publication1
Mutagenesisi727L → F: Diminishes significantly the interaction and coactivation OF PPARA; when associated with F-726. 1 Publication1

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002098801 – 924Phosphatidate phosphatase LPIN1Add BLAST924

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei106Phosphoserine1 Publication1
Modified residuei150Phosphoserine1 Publication1
Modified residuei285Phosphoserine1 Publication1
Modified residuei287Phosphoserine1 Publication1
Modified residuei293Phosphoserine1 Publication1
Modified residuei298Phosphothreonine1 Publication1
Modified residuei328PhosphoserineCombined sources1 Publication1
Modified residuei392Phosphoserine1 Publication1
Modified residuei468Phosphoserine1 Publication1
Modified residuei472Phosphoserine1 Publication1
Modified residuei483Phosphoserine1 Publication1
Cross-linki599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki629Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei634Phosphoserine1 Publication1
Modified residuei635Phosphoserine1 Publication1
Modified residuei921Phosphoserine1 Publication1
Modified residuei923Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated at multiple sites in response to insulin. Phosphorylation is controlled by the mTOR signaling pathway. Phosphorylation is decreased by epinephrine. Phosphorylation may not directly affect the catalytic activity but may regulate the localization. Dephosphorylated by the CTDNEP1-CNEP1R1 complex.1 Publication
Sumoylation is important in brain and is marginal in other tissues. Sumoylation facilitates nuclear localization of isoform 2 in neuronals cells and its transcriptional coactivator activity.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ91ZP3.
PRIDEiQ91ZP3.

PTM databases

iPTMnetiQ91ZP3.
PhosphoSitePlusiQ91ZP3.

Expressioni

Tissue specificityi

Specifically expressed in skeletal muscle. Also expressed prominently in adipose tissue, and testis. Lower expression also detected in kidney, lung, brain and liver. Isoform 1 is the predominant isoform in the liver. Isoform 2 is the major form in the brain.4 Publications

Inductioni

By fasting, glucocorticoids and diabetes in the liver in a PPARGC1A-dependent manner. Up-regulated during differentiation of 3T3-L1 pre-adipocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000020593.
CleanExiMM_LPIN1.

Interactioni

Subunit structurei

Interacts (via LXXIL motif) with PPARA. Interacts with PPARGC1A. Interaction with PPARA and PPARGC1A leads to the formation of a complex that modulates gene transcription. Interacts with MEF2C.2 Publications

GO - Molecular functioni

  • histone deacetylase binding Source: MGI
  • peroxisome proliferator activated receptor binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi199700. 1 interactor.
IntActiQ91ZP3. 2 interactors.
MINTiMINT-4610704.
STRINGi10090.ENSMUSP00000070583.

Structurei

3D structure databases

ProteinModelPortaliQ91ZP3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 108N-LIPAdd BLAST108
Regioni658 – 864C-LIPAdd BLAST207

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi153 – 158Nuclear localization signalSequence analysis6
Motifi712 – 716DXDXT motif5
Motifi723 – 727LXXIL motif5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi632 – 635Poly-Ser4

Domaini

Contains one Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif essential for phosphatidate phosphatase activity.
Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL), a transcriptional binding motif, which mediates interaction with PPARA.

Sequence similaritiesi

Belongs to the lipin family.Curated

Phylogenomic databases

eggNOGiKOG2116. Eukaryota.
COG5083. LUCA.
HOGENOMiHOG000230954.
HOVERGENiHBG052338.
InParanoidiQ91ZP3.
KOiK15728.
PhylomeDBiQ91ZP3.
TreeFamiTF314095.

Family and domain databases

Gene3Di3.40.50.1000. 1 hit.
InterProiIPR023214. HAD-like_dom.
IPR031703. Lipin_mid.
IPR007651. Lipin_N.
IPR013209. LNS2.
IPR031315. LNS2/PITP.
IPR028794. LPIN1.
[Graphical view]
PANTHERiPTHR12181:SF10. PTHR12181:SF10. 1 hit.
PfamiPF16876. Lipin_mid. 1 hit.
PF04571. Lipin_N. 1 hit.
PF08235. LNS2. 1 hit.
[Graphical view]
SMARTiSM00775. LNS2. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q91ZP3-1) [UniParc]FASTAAdd to basket
Also known as: Lipin-beta

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
MNYVGQLAGQ VFVTVKELYK GLNPATLSGC IDIIVIRQPN GSLQCSPFHV
60 70 80 90 100
RFGKMGVLRS REKVVDIEIN GESVDLHMKL GDNGEAFFVQ ETDNDQEIIP
110 120 130 140 150
MYLATSPILS EGAARMESQL KRNSVDRIRC LDPTTAAQGL PPSDTPSTGS
160 170 180 190 200
LGKKRRKRRR KAQLDNLKRD DNVNSSEDED MFPIEMSSDE DTAPMDGSRT
210 220 230 240 250
LPNDVPPFQD DIPKENFPSI STHPQSASYP SSDREWSPSP SSLVDCQRTP
260 270 280 290 300
PHLAEGVLSS SCPLQSCHFH ASESPSGSRP STPKSDSELV SKSADRLTPK
310 320 330 340 350
NNLEMLWLWG ELPQAAKSSS PHKMKESSPL GSRKTPDKMN FQAIHSESSD
360 370 380 390 400
TFSDQSPTMA RGLLIHQSKA QTEMQFVNEE DLESLGAAAP PSPVAEELKA
410 420 430 440 450
PYPNTAQSSS KTDSPSRKKD KRSRHLGADG VYLDDLTDMD PEVAALYFPK
460 470 480 490 500
NGDPGGLPKQ ASDNGARSAN QSPQSVGGSG IDSGVESTSD SLRDLPSIAI
510 520 530 540 550
SLCGGLSDHR EITKDAFLEQ AVSYQQFADN PAIIDDPNLV VKVGNKYYNW
560 570 580 590 600
TTAAPLLLAM QAFQKPLPKA TVESIMRDKM PKKGGRWWFS WRGRNATIKE
610 620 630 640 650
ESKPEQCLTG KGHNTGEQPA QLGLATRIKH ESSSSDEEHA AAKPSGSSHL
660 670 680 690 700
SLLSNVSYKK TLRLTSEQLK SLKLKNGPND VVFSVTTQYQ GTCRCEGTIY
710 720 730 740 750
LWNWDDKVII SDIDGTITRS DTLGHILPTL GKDWTHQGIA KLYHKVSQNG
760 770 780 790 800
YKFLYCSARA IGMADMTRGY LHWVNERGTV LPQGPLLLSP SSLFSALHRE
810 820 830 840 850
VIEKKPEKFK VQCLTDIKNL FFPNTEPFYA AFGNRPADVY SYKQVGVSLN
860 870 880 890 900
RIFTVNPKGE LVQEHAKTNI SSYVRLCEVV DHVFPLLKRS HSCDFPCSDT
910 920
FSNFTFWREP LPPFENQDMH SASA
Length:924
Mass (Da):102,002
Last modified:December 1, 2001 - v1
Checksum:i175F90E9159A216A
GO
Isoform 2 (identifier: Q91ZP3-2) [UniParc]FASTAAdd to basket
Also known as: Lipin-alpha

The sequence of this isoform differs from the canonical sequence as follows:
     241-273: Missing.

Note: Mutagenesis of 724:Ser->Leu abolishes phosphatidate phosphatase activity but does not prevent membrane association.
Show »
Length:891
Mass (Da):98,496
Checksum:i52303A406C235957
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti175S → T in BAB31786 (PubMed:16141072).Curated1
Sequence conflicti175S → T in BAB29412 (PubMed:16141072).Curated1
Sequence conflicti223H → Y in BAB31786 (PubMed:16141072).Curated1
Sequence conflicti223H → Y in BAB29412 (PubMed:16141072).Curated1
Sequence conflicti465G → V in AAF44296 (PubMed:11138012).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti84G → R in allele FLD2J. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003134241 – 273Missing in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF412811 mRNA. Translation: AAL07798.1.
AF180471 mRNA. Translation: AAF44296.1.
AK019539 mRNA. Translation: BAB31786.1.
AK014526 mRNA. Translation: BAB29412.1.
CCDSiCCDS25822.1. [Q91ZP3-1]
CCDS25823.1. [Q91ZP3-2]
RefSeqiNP_001123884.1. NM_001130412.1.
NP_056578.2. NM_015763.4.
NP_766538.2. NM_172950.3.
XP_006515051.1. XM_006514988.3.
UniGeneiMm.153625.

Genome annotation databases

GeneIDi14245.
KEGGimmu:14245.
UCSCiuc007nbs.2. mouse. [Q91ZP3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF412811 mRNA. Translation: AAL07798.1.
AF180471 mRNA. Translation: AAF44296.1.
AK019539 mRNA. Translation: BAB31786.1.
AK014526 mRNA. Translation: BAB29412.1.
CCDSiCCDS25822.1. [Q91ZP3-1]
CCDS25823.1. [Q91ZP3-2]
RefSeqiNP_001123884.1. NM_001130412.1.
NP_056578.2. NM_015763.4.
NP_766538.2. NM_172950.3.
XP_006515051.1. XM_006514988.3.
UniGeneiMm.153625.

3D structure databases

ProteinModelPortaliQ91ZP3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199700. 1 interactor.
IntActiQ91ZP3. 2 interactors.
MINTiMINT-4610704.
STRINGi10090.ENSMUSP00000070583.

Chemistry databases

SwissLipidsiSLP:000000601.

PTM databases

iPTMnetiQ91ZP3.
PhosphoSitePlusiQ91ZP3.

Proteomic databases

PaxDbiQ91ZP3.
PRIDEiQ91ZP3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi14245.
KEGGimmu:14245.
UCSCiuc007nbs.2. mouse. [Q91ZP3-1]

Organism-specific databases

CTDi23175.
MGIiMGI:1891340. Lpin1.

Phylogenomic databases

eggNOGiKOG2116. Eukaryota.
COG5083. LUCA.
HOGENOMiHOG000230954.
HOVERGENiHBG052338.
InParanoidiQ91ZP3.
KOiK15728.
PhylomeDBiQ91ZP3.
TreeFamiTF314095.

Enzyme and pathway databases

BRENDAi3.1.3.4. 3474.

Miscellaneous databases

ChiTaRSiLpin1. mouse.
PROiQ91ZP3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020593.
CleanExiMM_LPIN1.

Family and domain databases

Gene3Di3.40.50.1000. 1 hit.
InterProiIPR023214. HAD-like_dom.
IPR031703. Lipin_mid.
IPR007651. Lipin_N.
IPR013209. LNS2.
IPR031315. LNS2/PITP.
IPR028794. LPIN1.
[Graphical view]
PANTHERiPTHR12181:SF10. PTHR12181:SF10. 1 hit.
PfamiPF16876. Lipin_mid. 1 hit.
PF04571. Lipin_N. 1 hit.
PF08235. LNS2. 1 hit.
[Graphical view]
SMARTiSM00775. LNS2. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiLPIN1_MOUSE
AccessioniPrimary (citable) accession number: Q91ZP3
Secondary accession number(s): Q9CQI2, Q9JLG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 135 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, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.