LPIN2_HUMAN
ID LPIN2_HUMAN Reviewed; 896 AA.
AC Q92539; A7MD25; D3DUH3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Phosphatidate phosphatase LPIN2 {ECO:0000305};
DE EC=3.1.3.4 {ECO:0000250|UniProtKB:Q99PI5};
DE AltName: Full=Lipin-2 {ECO:0000250|UniProtKB:Q99PI5};
GN Name=LPIN2 {ECO:0000312|HGNC:HGNC:14450}; Synonyms=KIAA0249;
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 MRNA].
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106; SER-243 AND SER-303, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-566, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP VARIANT MJDS LEU-734, AND TISSUE SPECIFICITY.
RX PubMed=15994876; DOI=10.1136/jmg.2005.030759;
RA Ferguson P.J., Chen S., Tayeh M.K., Ochoa L., Leal S.M., Pelet A.,
RA Munnich A., Lyonnet S., Majeed H.A., El-Shanti H.;
RT "Homozygous mutations in LPIN2 are responsible for the syndrome of chronic
RT recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia
RT (Majeed syndrome).";
RL J. Med. Genet. 42:551-557(2005).
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. Plays important roles in controlling the metabolism of fatty
CC acids at different levels. Acts also as a nuclear transcriptional
CC coactivator for PPARGC1A to modulate lipid metabolism.
CC {ECO:0000250|UniProtKB:Q99PI5}.
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:Q99PI5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000250|UniProtKB:Q99PI5};
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:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}. Endoplasmic reticulum membrane {ECO:0000250}.
CC Note=Translocates to endoplasmic reticulum membrane with increasing
CC levels of oleate. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, lung, kidney, placenta, spleen,
CC thymus, lymph node, prostate, testes, small intestine, and colon.
CC {ECO:0000269|PubMed:15994876, 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 -!- DISEASE: Majeed syndrome (MJDS) [MIM:609628]: An autosomal recessive
CC syndrome characterized by chronic recurrent multifocal osteomyelitis
CC that is of early onset with a lifelong course, congenital
CC dyserythropoietic anemia that presents as hypochromic, microcytic
CC anemia during the first year of life and ranges from mild to
CC transfusion-dependent, and transient inflammatory dermatosis, often
CC manifesting as Sweet syndrome (neutrophilic skin infiltration).
CC {ECO:0000269|PubMed:15994876}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the lipin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13380.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary
CC autoinflammatory disorders mutations;
CC URL="https://infevers.umai-montpellier.fr/web/search.php?n=7";
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DR EMBL; D87436; BAA13380.2; ALT_INIT; mRNA.
DR EMBL; CH471113; EAX01686.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01687.1; -; Genomic_DNA.
DR EMBL; BC152448; AAI52449.1; -; mRNA.
DR CCDS; CCDS11829.1; -.
DR RefSeq; NP_055461.1; NM_014646.2.
DR RefSeq; XP_005258235.1; XM_005258178.3.
DR RefSeq; XP_005258236.1; XM_005258179.4.
DR RefSeq; XP_016881587.1; XM_017026098.1.
DR RefSeq; XP_016881588.1; XM_017026099.1.
DR AlphaFoldDB; Q92539; -.
DR SMR; Q92539; -.
DR BioGRID; 115019; 19.
DR IntAct; Q92539; 6.
DR STRING; 9606.ENSP00000261596; -.
DR DEPOD; LPIN2; -.
DR iPTMnet; Q92539; -.
DR PhosphoSitePlus; Q92539; -.
DR BioMuta; LPIN2; -.
DR DMDM; 2495724; -.
DR EPD; Q92539; -.
DR jPOST; Q92539; -.
DR MassIVE; Q92539; -.
DR MaxQB; Q92539; -.
DR PaxDb; Q92539; -.
DR PeptideAtlas; Q92539; -.
DR PRIDE; Q92539; -.
DR ProteomicsDB; 75297; -.
DR Antibodypedia; 2826; 197 antibodies from 33 providers.
DR DNASU; 9663; -.
DR Ensembl; ENST00000261596.8; ENSP00000261596.4; ENSG00000101577.10.
DR Ensembl; ENST00000677752.1; ENSP00000504857.1; ENSG00000101577.10.
DR GeneID; 9663; -.
DR KEGG; hsa:9663; -.
DR MANE-Select; ENST00000677752.1; ENSP00000504857.1; NM_001375808.2; NP_001362737.1.
DR UCSC; uc002klo.3; human.
DR CTD; 9663; -.
DR DisGeNET; 9663; -.
DR GeneCards; LPIN2; -.
DR HGNC; HGNC:14450; LPIN2.
DR HPA; ENSG00000101577; Group enriched (intestine, liver).
DR MalaCards; LPIN2; -.
DR MIM; 605519; gene.
DR MIM; 609628; phenotype.
DR neXtProt; NX_Q92539; -.
DR OpenTargets; ENSG00000101577; -.
DR Orphanet; 77297; Majeed syndrome.
DR PharmGKB; PA30437; -.
DR VEuPathDB; HostDB:ENSG00000101577; -.
DR eggNOG; KOG2116; Eukaryota.
DR GeneTree; ENSGT00940000156313; -.
DR HOGENOM; CLU_002546_0_1_1; -.
DR InParanoid; Q92539; -.
DR OMA; NFCTEHI; -.
DR OrthoDB; 866929at2759; -.
DR PhylomeDB; Q92539; -.
DR TreeFam; TF314095; -.
DR PathwayCommons; Q92539; -.
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; Q92539; -.
DR BioGRID-ORCS; 9663; 10 hits in 1081 CRISPR screens.
DR ChiTaRS; LPIN2; human.
DR GenomeRNAi; 9663; -.
DR Pharos; Q92539; Tbio.
DR PRO; PR:Q92539; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q92539; protein.
DR Bgee; ENSG00000101577; Expressed in jejunal mucosa and 193 other tissues.
DR ExpressionAtlas; Q92539; baseline and differential.
DR Genevisible; Q92539; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; EXP:Reactome.
DR GO; GO:0003713; F:transcription coactivator activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS: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 Congenital dyserythropoietic anemia; Cytoplasm; Disease variant;
KW Endoplasmic reticulum; Fatty acid metabolism; Hereditary hemolytic anemia;
KW Hydrolase; Lipid metabolism; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..896
FT /note="Phosphatidate phosphatase LPIN2"
FT /id="PRO_0000209881"
FT REGION 1..108
FT /note="N-LIP"
FT REGION 120..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 420..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 569..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..837
FT /note="C-LIP"
FT MOTIF 153..158
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 689..693
FT /note="DXDXT motif"
FT MOTIF 700..704
FT /note="LXXIL motif"
FT COMPBIAS 126..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PI5"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PI5"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PI5"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 566
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 734
FT /note="S -> L (in MJDS; dbSNP:rs80338807)"
FT /evidence="ECO:0000269|PubMed:15994876"
FT /id="VAR_023817"
SQ SEQUENCE 896 AA; 99399 MW; 080113FCCA533272 CRC64;
MNYVGQLAGQ VIVTVKELYK GINQATLSGC IDVIVVQQQD GSYQCSPFHV RFGKLGVLRS
KEKVIDIEIN GSAVDLHMKL GDNGEAFFVE ETEEEYEKLP AYLATSPIPT EDQFFKDIDT
PLVKSGGDET PSQSSDISHV LETETIFTPS SVKKKKRRRK KYKQDSKKEE QAASAAAEDT
CDVGVSSDDD KGAQAARGSS NASLKEEECK EPLLFHSGDH YPLSDGDWSP LETTYPQTAC
PKSDSELEVK PAESLLRSES HMEWTWGGFP ESTKVSKRER SDHHPRTATI TPSENTHFRV
IPSEDNLISE VEKDASMEDT VCTIVKPKPR ALGTQMSDPT SVAELLEPPL ESTQISSMLD
ADHLPNAALA EAPSESKPAA KVDSPSKKKG VHKRSQHQGP DDIYLDDLKG LEPEVAALYF
PKSESEPGSR QWPESDTLSG SQSPQSVGSA AADSGTECLS DSAMDLPDVT LSLCGGLSEN
GEISKEKFME HIITYHEFAE NPGLIDNPNL VIRIYNRYYN WALAAPMILS LQVFQKSLPK
ATVESWVKDK MPKKSGRWWF WRKRESMTKQ LPESKEGKSE APPASDLPSS SKEPAGARPA
ENDSSSDEGS QELEESITVD PIPTEPLSHG STTSYKKSLR LSSDQIAKLK LHDGPNDVVF
SITTQYQGTC RCAGTIYLWN WNDKIIISDI DGTITKSDAL GQILPQLGKD WTHQGIAKLY
HSINENGYKF LYCSARAIGM ADMTRGYLHW VNDKGTILPR GPLMLSPSSL FSAFHREVIE
KKPEKFKIEC LNDIKNLFAP SKQPFYAAFG NRPNDVYAYT QVGVPDCRIF TVNPKGELIQ
ERTKGNKSSY HRLSELVEHV FPLLSKEQNS AFPCPEFSSF CYWRDPIPEV DLDDLS
