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   27-MAR-2024, entry version 166.
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; 28.
DR   IntAct; Q92539; 5.
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; 9606-ENSP00000261596; -.
DR   PeptideAtlas; Q92539; -.
DR   ProteomicsDB; 75297; -.
DR   Pumba; Q92539; -.
DR   Antibodypedia; 2826; 225 antibodies from 33 providers.
DR   DNASU; 9663; -.
DR   Ensembl; ENST00000261596.9; ENSP00000261596.4; ENSG00000101577.11.
DR   Ensembl; ENST00000677752.1; ENSP00000504857.1; ENSG00000101577.11.
DR   Ensembl; ENST00000697040.1; ENSP00000513062.1; ENSG00000101577.11.
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   AGR; HGNC:14450; -.
DR   CTD; 9663; -.
DR   DisGeNET; 9663; -.
DR   GeneCards; LPIN2; -.
DR   GeneReviews; LPIN2; -.
DR   HGNC; HGNC:14450; LPIN2.
DR   HPA; ENSG00000101577; Tissue enhanced (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; TEDIFEM; -.
DR   OrthoDB; 599098at2759; -.
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; Depolymerization of the Nuclear Lamina.
DR   Reactome; R-HSA-75109; Triglyceride biosynthesis.
DR   SignaLink; Q92539; -.
DR   BioGRID-ORCS; 9663; 11 hits in 1171 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 194 other cell types or tissues.
DR   ExpressionAtlas; Q92539; baseline and differential.
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: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; LIPIN; 1.
DR   PANTHER; PTHR12181:SF11; PHOSPHATIDATE PHOSPHATASE LPIN2; 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; HAD-like; 1.
DR   Genevisible; Q92539; HS.
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
//