LPIN3_HUMAN
ID LPIN3_HUMAN Reviewed; 851 AA.
AC Q9BQK8; B2RTT5; Q5TDB9; Q9NPY8; Q9UJE5;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Phosphatidate phosphatase LPIN3 {ECO:0000305};
DE EC=3.1.3.4 {ECO:0000250|UniProtKB:Q99PI4};
DE AltName: Full=Lipin-3;
DE AltName: Full=Lipin-3-like;
GN Name=LPIN3 {ECO:0000312|HGNC:HGNC:14451}; Synonyms=LIPN3L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP TISSUE SPECIFICITY.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-159; SER-161 AND SER-162, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Magnesium-dependent phosphatidate phosphatase enzyme which
CC catalyzes the conversion of phosphatidic acid to diacylglycerol during
CC triglyceride, phosphatidylcholine and phosphatidylethanolamine
CC biosynthesis therefore regulates fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q99PI4}.
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:0000250|UniProtKB:Q99PI4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000250|UniProtKB:Q99PI4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BQK8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQK8-2; Sequence=VSP_036885;
CC -!- TISSUE SPECIFICITY: Significant expression in intestine and other
CC regions of the gastrointestinal tract. {ECO:0000269|PubMed:17158099}.
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; AL132654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031667; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140806; AAI40807.1; -; mRNA.
DR CCDS; CCDS33469.2; -. [Q9BQK8-2]
DR RefSeq; NP_001288789.1; NM_001301860.1. [Q9BQK8-2]
DR RefSeq; XP_016883509.1; XM_017028020.1.
DR AlphaFoldDB; Q9BQK8; -.
DR SMR; Q9BQK8; -.
DR BioGRID; 122340; 67.
DR IntAct; Q9BQK8; 15.
DR STRING; 9606.ENSP00000362354; -.
DR DEPOD; LPIN3; -.
DR iPTMnet; Q9BQK8; -.
DR PhosphoSitePlus; Q9BQK8; -.
DR BioMuta; LPIN3; -.
DR DMDM; 71153524; -.
DR EPD; Q9BQK8; -.
DR jPOST; Q9BQK8; -.
DR MassIVE; Q9BQK8; -.
DR MaxQB; Q9BQK8; -.
DR PaxDb; Q9BQK8; -.
DR PeptideAtlas; Q9BQK8; -.
DR PRIDE; Q9BQK8; -.
DR ProteomicsDB; 78695; -. [Q9BQK8-1]
DR ProteomicsDB; 78696; -. [Q9BQK8-2]
DR Antibodypedia; 27036; 166 antibodies from 26 providers.
DR DNASU; 64900; -.
DR Ensembl; ENST00000373257.8; ENSP00000362354.3; ENSG00000132793.12. [Q9BQK8-1]
DR Ensembl; ENST00000632009.1; ENSP00000487971.1; ENSG00000132793.12. [Q9BQK8-2]
DR GeneID; 64900; -.
DR KEGG; hsa:64900; -.
DR MANE-Select; ENST00000373257.8; ENSP00000362354.3; NM_022896.3; NP_075047.1.
DR UCSC; uc002xjx.3; human. [Q9BQK8-1]
DR CTD; 64900; -.
DR DisGeNET; 64900; -.
DR GeneCards; LPIN3; -.
DR HGNC; HGNC:14451; LPIN3.
DR HPA; ENSG00000132793; Low tissue specificity.
DR MIM; 605520; gene.
DR neXtProt; NX_Q9BQK8; -.
DR OpenTargets; ENSG00000132793; -.
DR PharmGKB; PA30438; -.
DR VEuPathDB; HostDB:ENSG00000132793; -.
DR eggNOG; KOG2116; Eukaryota.
DR GeneTree; ENSGT00940000160046; -.
DR HOGENOM; CLU_002546_0_1_1; -.
DR InParanoid; Q9BQK8; -.
DR OMA; TWSSINP; -.
DR OrthoDB; 866929at2759; -.
DR PhylomeDB; Q9BQK8; -.
DR TreeFam; TF314095; -.
DR PathwayCommons; Q9BQK8; -.
DR Reactome; R-HSA-1483191; Synthesis of PC.
DR Reactome; R-HSA-1483213; Synthesis of PE.
DR Reactome; R-HSA-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-75109; Triglyceride biosynthesis.
DR SignaLink; Q9BQK8; -.
DR BioGRID-ORCS; 64900; 13 hits in 1077 CRISPR screens.
DR ChiTaRS; LPIN3; human.
DR GenomeRNAi; 64900; -.
DR Pharos; Q9BQK8; Tbio.
DR PRO; PR:Q9BQK8; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BQK8; protein.
DR Bgee; ENSG00000132793; Expressed in lower esophagus mucosa and 91 other tissues.
DR ExpressionAtlas; Q9BQK8; baseline and differential.
DR Genevisible; Q9BQK8; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IBA:GO_Central.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
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:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 Alternative splicing; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..851
FT /note="Phosphatidate phosphatase LPIN3"
FT /id="PRO_0000209883"
FT REGION 1..108
FT /note="N-LIP"
FT REGION 114..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..792
FT /note="C-LIP"
FT MOTIF 141..148
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 644..648
FT /note="DXDXT motif"
FT MOTIF 655..659
FT /note="LXXIL motif"
FT COMPBIAS 325..340
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..564
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 159
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PI4"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 186
FT /note="G -> GS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036885"
FT VARIANT 679
FT /note="Q -> H (in dbSNP:rs12625565)"
FT /id="VAR_053489"
SQ SEQUENCE 851 AA; 93614 MW; BBDFDA0A53722625 CRC64;
MNYVGQLAET VFGTVKELYR GLNPATLSGG IDVLVVKQVD GSFRCSPFHV RFGKLGVLRS
REKVVDIELN GEPVDLHMKL GDSGEAFFVQ ELESDDEHVP PGLCTSPIPW GGLSGFPSDS
QLGTASEPEG LVMAGTASTG RRKRRRRRKP KQKEDAVATD SSPEELEAGA ESELSLPEKL
RPEPPGVQLE EKSSLQPKDI YPYSDGEWPP QASLSAGELT SPKSDSELEV RTPEPSPLRA
ESHMQWAWGR LPKVARAERP ESSVVLEGRA GATSPPRGGP STPSTSVAGG VDPLGLPIQQ
TEAGADLQPD TEDPTLVGPP LHTPETEESK TQSSGDMGLP PASKSWSWAT LEVPVPTGQP
ERVSRGKGSP KRSQHLGPSD IYLDDLPSLD SENAALYFPQ SDSGLGARRW SEPSSQKSLR
DPNPEHEPEP TLDTVDTIAL SLCGGLADSR DISLEKFNQH SVSYQDLTKN PGLLDDPNLV
VKINGKHYNW AVAAPMILSL QAFQKNLPKS TMDKLEREKM PRKGGRWWFS WRRRDFLAEE
RSAQKEKTAA KEQQGEKTEV LSSDDDAPDS PVILEIPSLP PSTPPSTPTY KKSLRLSSDQ
IRRLNLQEGA NDVVFSVTTQ YQGTCRCKAT IYLWKWDDKV VISDIDGTIT KSDALGHILP
QLGKDWTHQG ITSLYHKIQL NGYKFLYCSA RAIGMADLTK GYLQWVSEGG CSLPKGPILL
SPSSLFSALH REVIEKKPEV FKVACLSDIQ QLFLPHGQPF YAAFGNRPND VFAYRQVGLP
ESRIFTVNPR GELIQELIKN HKSTYERLGE VVELLFPPVA RGPSTDLANP EYSNFCYWRE
PLPAVDLDTL D
