LPIN2_MOUSE
ID LPIN2_MOUSE Reviewed; 893 AA.
AC Q99PI5; Q8C357; Q8C7I8; Q8CC85; Q8CHR7;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Phosphatidate phosphatase LPIN2 {ECO:0000305};
DE EC=3.1.3.4 {ECO:0000269|PubMed:17158099};
DE AltName: Full=Lipin-2 {ECO:0000303|PubMed:19717560};
GN Name=Lpin2 {ECO:0000312|MGI:MGI:1891341};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11138012; DOI=10.1038/83685;
RA Peterfy M., Phan J., Xu P., Reue K.;
RT "Lipodystrophy in the fld mouse results from mutation of a new gene
RT encoding a nuclear protein, lipin.";
RL Nat. Genet. 27:121-124(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-276 AND 659-893 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cecum, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP FUNCTION.
RX PubMed=17158099; DOI=10.1074/jbc.m610745200;
RA Donkor J., Sariahmetoglu M., Dewald J., Brindley D.N., Reue K.;
RT "Three mammalian lipins act as phosphatidate phosphatases with distinct
RT tissue expression patterns.";
RL J. Biol. Chem. 282:3450-3457(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP SUBCELLULAR LOCATION, FUNCTION, PHOSPHORYLATION AT SER-106, AND INDUCTION.
RX PubMed=19136718; DOI=10.1074/jbc.m807882200;
RA Gropler M.C., Harris T.E., Hall A.M., Wolins N.E., Gross R.W., Han X.,
RA Chen Z., Finck B.N.;
RT "Lipin 2 is a liver-enriched phosphatidate phosphohydrolase enzyme that is
RT dynamically regulated by fasting and obesity in mice.";
RL J. Biol. Chem. 284:6763-6772(2009).
RN [7]
RP SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP MUTAGENESIS OF SER-731.
RX PubMed=19717560; DOI=10.1074/jbc.m109.023663;
RA Donkor J., Zhang P., Wong S., O'Loughlin L., Dewald J., Kok B.P.,
RA Brindley D.N., Reue K.;
RT "A conserved serine residue is required for the phosphatidate phosphatase
RT activity but not the transcriptional coactivator functions of lipin-1 and
RT lipin-2.";
RL J. Biol. Chem. 284:29968-29978(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174; SER-186 AND SER-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as a magnesium-dependent phosphatidate phosphatase
CC enzyme which catalyzes the conversion of phosphatidic acid to
CC diacylglycerol during triglyceride, phosphatidylcholine and
CC phosphatidylethanolamine biosynthesis in the reticulum endoplasmic
CC membrane (PubMed:17158099). Plays important roles in controlling the
CC metabolism of fatty acids at different levels. Acts also as a nuclear
CC transcriptional coactivator for PPARGC1A to modulate lipid metabolism.
CC {ECO:0000269|PubMed:17158099, ECO:0000269|PubMed:19136718,
CC ECO:0000269|PubMed:19717560}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:27429, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:43474, ChEBI:CHEBI:58608; EC=3.1.3.4;
CC Evidence={ECO:0000269|PubMed:17158099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000269|PubMed:17158099};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17158099};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide.
CC {ECO:0000269|PubMed:17158099}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytosol. Endoplasmic
CC reticulum membrane. Note=Translocates from cytosol to endoplasmic
CC reticulum membrane with increasing levels of oleate.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99PI5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99PI5-2; Sequence=VSP_010387, VSP_010388;
CC -!- TISSUE SPECIFICITY: Expressed at high level in liver and to some extend
CC in lung, kidney, placenta, spleen, thymus, lymph node, prostate,
CC testes, small intestine, and colon. Expressed also in circulating red
CC blood cells and site of lymphopoiesis. {ECO:0000269|PubMed:17158099,
CC ECO:0000269|PubMed:19717560}.
CC -!- INDUCTION: By fasting in hepatocytes. Up-regulated in fld/fld (defect
CC in LPIN1) mice. Up-regulated at protein level but not at transcript
CC level in ob/ob and db/db mice, two obese mice models.
CC {ECO:0000269|PubMed:19136718, ECO:0000269|PubMed:19717560}.
CC -!- DOMAIN: Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif
CC known to be essential for phosphatidate phosphatase activity.
CC {ECO:0000250}.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known
CC to be a transcriptional binding motif. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lipin family. {ECO:0000305}.
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DR EMBL; AF286723; AAG52761.1; -; mRNA.
DR EMBL; AK033662; BAC28415.1; -; mRNA.
DR EMBL; AK050138; BAC34088.1; -; mRNA.
DR EMBL; AK086834; BAC39754.1; -; mRNA.
DR EMBL; BC039698; AAH39698.1; -; mRNA.
DR CCDS; CCDS28956.1; -. [Q99PI5-1]
DR RefSeq; NP_075020.2; NM_022882.4. [Q99PI5-1]
DR RefSeq; XP_006524850.1; XM_006524787.3.
DR RefSeq; XP_006524851.1; XM_006524788.2. [Q99PI5-1]
DR PDB; 7KIQ; X-ray; 2.52 A; A/B/C/D/E/F/G/H/I/J=459-549.
DR PDBsum; 7KIQ; -.
DR AlphaFoldDB; Q99PI5; -.
DR SMR; Q99PI5; -.
DR BioGRID; 211110; 4.
DR STRING; 10090.ENSMUSP00000118610; -.
DR SwissLipids; SLP:000000602; -.
DR iPTMnet; Q99PI5; -.
DR PhosphoSitePlus; Q99PI5; -.
DR jPOST; Q99PI5; -.
DR MaxQB; Q99PI5; -.
DR PaxDb; Q99PI5; -.
DR PRIDE; Q99PI5; -.
DR ProteomicsDB; 291962; -. [Q99PI5-1]
DR ProteomicsDB; 291963; -. [Q99PI5-2]
DR Antibodypedia; 2826; 197 antibodies from 33 providers.
DR DNASU; 64898; -.
DR Ensembl; ENSMUST00000129635; ENSMUSP00000119282; ENSMUSG00000024052. [Q99PI5-1]
DR Ensembl; ENSMUST00000156570; ENSMUSP00000120634; ENSMUSG00000024052. [Q99PI5-2]
DR GeneID; 64898; -.
DR KEGG; mmu:64898; -.
DR UCSC; uc008dmc.1; mouse. [Q99PI5-2]
DR UCSC; uc012awp.1; mouse. [Q99PI5-1]
DR CTD; 9663; -.
DR MGI; MGI:1891341; Lpin2.
DR VEuPathDB; HostDB:ENSMUSG00000024052; -.
DR eggNOG; KOG2116; Eukaryota.
DR GeneTree; ENSGT00940000156313; -.
DR HOGENOM; CLU_595744_0_0_1; -.
DR InParanoid; Q99PI5; -.
DR OMA; NFCTEHI; -.
DR Reactome; R-MMU-1483191; Synthesis of PC.
DR Reactome; R-MMU-1483213; Synthesis of PE.
DR Reactome; R-MMU-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-MMU-75109; Triglyceride biosynthesis.
DR BioGRID-ORCS; 64898; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Lpin2; mouse.
DR PRO; PR:Q99PI5; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q99PI5; protein.
DR Bgee; ENSMUSG00000024052; Expressed in renal corpuscle and 252 other tissues.
DR ExpressionAtlas; Q99PI5; baseline and differential.
DR Genevisible; Q99PI5; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0044255; P:cellular lipid metabolic process; IBA:GO_Central.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0009062; P:fatty acid catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IBA:GO_Central.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR026058; LIPIN.
DR InterPro; IPR031703; Lipin_mid.
DR InterPro; IPR007651; Lipin_N.
DR InterPro; IPR013209; LNS2.
DR InterPro; IPR031315; LNS2/PITP.
DR PANTHER; PTHR12181; PTHR12181; 1.
DR Pfam; PF16876; Lipin_mid; 1.
DR Pfam; PF04571; Lipin_N; 1.
DR Pfam; PF08235; LNS2; 1.
DR SMART; SM00775; LNS2; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Endoplasmic reticulum;
KW Fatty acid metabolism; Hydrolase; Lipid metabolism; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..893
FT /note="Phosphatidate phosphatase LPIN2"
FT /id="PRO_0000209882"
FT REGION 1..108
FT /note="N-LIP"
FT REGION 122..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 568..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..834
FT /note="C-LIP"
FT MOTIF 153..158
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 686..690
FT /note="DXDXT motif"
FT MOTIF 697..701
FT /note="LXXIL motif"
FT COMPBIAS 126..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..603
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19136718"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92539"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92539"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92539"
FT VAR_SEQ 388..459
FT /note="VHKRSQHQGPDDIYLDDLKALEPEVAALYFPKSDTDPGSRQWPESDTFSGSQ
FT SPQSVGSAAADSGTECLSDS -> LVWLKNNCLLGDRCISGYDHGCVSRGPTWQLMTDS
FT SARGPNALFWPLWAPGTQPYIRQNMHIPKMNRNKNTF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010387"
FT VAR_SEQ 460..893
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010388"
FT MUTAGEN 731
FT /note="S->D: Abolishes phosphatidate phosphatase activity
FT but does not prevent membrane association."
FT /evidence="ECO:0000269|PubMed:19717560"
FT MUTAGEN 731
FT /note="S->L: Abolishes phosphatidate phosphatase activity
FT but does not prevent membrane association nor coactivator
FT activity."
FT /evidence="ECO:0000269|PubMed:19717560"
FT CONFLICT 839
FT /note="R -> S (in Ref. 2; BAC34088)"
FT /evidence="ECO:0000305"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:7KIQ"
FT HELIX 482..487
FT /evidence="ECO:0007829|PDB:7KIQ"
FT HELIX 492..497
FT /evidence="ECO:0007829|PDB:7KIQ"
FT HELIX 499..503
FT /evidence="ECO:0007829|PDB:7KIQ"
FT STRAND 508..511
FT /evidence="ECO:0007829|PDB:7KIQ"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:7KIQ"
FT HELIX 518..530
FT /evidence="ECO:0007829|PDB:7KIQ"
FT STRAND 531..533
FT /evidence="ECO:0007829|PDB:7KIQ"
FT HELIX 537..544
FT /evidence="ECO:0007829|PDB:7KIQ"
SQ SEQUENCE 893 AA; 99613 MW; 8C7FD7881946F8EA CRC64;
MNYVGQLAGQ VLVTVKELYK GINQATLSGC IDVVVVRQQD GSYQCSPFHV RFGKLGVLRS
KEKVIDIEIN GSAVDLHMKL GDNGEAFFVE ETEEEYEKLP AYLATSPIPT EDQFFKHIET
PLVKSSGNER PAQSSDVSHT LESEAVFTQS SVKKKKRRRK KCKQDNRKEE QAASPVAEDV
GDVGVSSDDE KRAQAARGSS NASLKEEDYK EPSLFHSGDN YPLSDGDWSP LETTYPQAVC
PKSDSELEVK PSESLLRSEP HMEWTWGGFP ESTKVTKRER YDYHPRTATI TPSENTHFRV
IPSEDSLIRE VEKDATVEDT TCTIVKPKPR ALCKQLSDAA STELPESPLE APQISSLLDA
DPVPSPSAEA PSEPKPAAKD SPTKKKGVHK RSQHQGPDDI YLDDLKALEP EVAALYFPKS
DTDPGSRQWP ESDTFSGSQS PQSVGSAAAD SGTECLSDSA MDLPDVTLSL CGGLSENGEI
SKEKFMEHII TYHEFAENPG LIDNPNLVIR IYNRYYNWAL AAPMILSLQV FQKSLPKATV
ESWVKDKMPK KSGRWWFWRK KESMIKQLPE TKEGKSEVPP ANDLPSNAEE PTSARPAEND
TSSDEGSQEL EESIKVDPIT VETLSHCGTA SYKKSLRLSS DQIAKLKLHD GPNDVVFSIT
TQYQGTCRCA GTIYLWNWND KVIISDIDGT ITKSDALGQI LPQLGKDWTH QGIARLYHSI
NENGYKFLYC SARAIGMADM TRGYLHWVND KGTILPRGPL MLSPSSLFSA FHREVIEKKP
EKFKIECLND IKNLFAPSRQ PFYAAFGNRP NDVYAYTQVG VPDCRIFTVN PKGELIQERT
KGNKSSYHRL SELVEHVFPL LSKEQNSAFP CPEFSSFCYW RDPIPDLDLD DLA
