LIPI_HUMAN
ID LIPI_HUMAN Reviewed; 460 AA.
AC Q6XZB0; G1JSG3; G1JSG4; G1JSG5; G1JSG6; G1JSG7; G1JSG8; G1JSG9;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Lipase member I;
DE Short=LIPI;
DE EC=3.1.1.-;
DE AltName: Full=Cancer/testis antigen 17;
DE Short=CT17;
DE AltName: Full=LPD lipase;
DE AltName: Full=Membrane-associated phosphatidic acid-selective phospholipase A1-beta;
DE Short=mPA-PLA1 beta;
DE Flags: Precursor;
GN Name=LIPI; Synonyms=LPDL; ORFNames=PRED5;
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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP SER-159.
RX PubMed=12963729; DOI=10.1074/jbc.m213018200;
RA Hiramatsu T., Sonoda H., Takanezawa Y., Morikawa R., Ishida M.,
RA Kasahara K., Sanai Y., Taguchi R., Aoki J., Arai H.;
RT "Biochemical and molecular characterization of two phosphatidic acid-
RT selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta.";
RL J. Biol. Chem. 278:49438-49447(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS
RP GLU-364; LYS-431 AND GLU-444, INVOLVEMENT IN FHTR, AND VARIANT FHTR TYR-55.
RX PubMed=12719377; DOI=10.1093/hmg/ddg124;
RA Wen X.-Y., Hegele R.A., Wang J., Wang D.Y., Cheung J., Wilson M.,
RA Yahyapour M., Bai Y., Zhuang L., Skaug J., Young T.K., Connelly P.W.,
RA Koop B.F., Tsui L.-C., Stewart A.K.;
RT "Identification of a novel lipase gene mutated in lpd mice with
RT hypertriglyceridemia and associated with dyslipidemia in humans.";
RL Hum. Mol. Genet. 12:1131-1143(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4; 5; 6; 7 AND 8), AND
RP ALTERNATIVE SPLICING.
RX PubMed=21132378; DOI=10.1007/s11033-010-0595-z;
RA Schmiedel B.J., Hutter C., Hesse M., Staege M.S.;
RT "Expression of multiple membrane-associated phospholipase A1 beta
RT transcript variants and lysophosphatidic acid receptors in Ewing tumor
RT cells.";
RL Mol. Biol. Rep. 38:4619-4628(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
CC -!- FUNCTION: Hydrolyzes specifically phosphatidic acid (PA) to produce 2-
CC acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and
CC fatty acid. Does not hydrolyze other phospholipids, like
CC phosphatidylserine (PS), phosphatidylcholine (PC) and
CC phosphatidylethanolamine (PE) or triacylglycerol (TG).
CC {ECO:0000269|PubMed:12963729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:40943, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64839,
CC ChEBI:CHEBI:77593; Evidence={ECO:0000269|PubMed:12963729};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40944;
CC Evidence={ECO:0000305|PubMed:12963729};
CC -!- ACTIVITY REGULATION: Inhibited by sodium vanadate.
CC {ECO:0000269|PubMed:12963729}.
CC -!- SUBUNIT: Interacts with heparin with a high affinity.
CC {ECO:0000269|PubMed:12963729}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:12963729}. Secreted {ECO:0000269|PubMed:12963729}.
CC Note=May associate with lipid draft. {ECO:0000269|PubMed:12963729}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:12963729}. Secreted {ECO:0000269|PubMed:12963729}.
CC Note=May associate with lipid draft. {ECO:0000269|PubMed:12963729}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=mPA-PLA1beta {ECO:0000303|PubMed:12963729};
CC IsoId=Q6XZB0-1; Sequence=Displayed;
CC Name=2; Synonyms=mPA-PLA1alpha {ECO:0000303|PubMed:12963729};
CC IsoId=Q6XZB0-2; Sequence=VSP_016090;
CC Name=3; Synonyms=deltaE7.2;
CC IsoId=Q6XZB0-3; Sequence=VSP_053899;
CC Name=4; Synonyms=deltaE6.1;
CC IsoId=Q6XZB0-4; Sequence=VSP_053898;
CC Name=5; Synonyms=deltaE5;
CC IsoId=Q6XZB0-5; Sequence=VSP_053897;
CC Name=6; Synonyms=deltaE8-9;
CC IsoId=Q6XZB0-6; Sequence=VSP_053900, VSP_053903;
CC Name=7; Synonyms=7B+;
CC IsoId=Q6XZB0-7; Sequence=VSP_053901, VSP_053902;
CC Name=8; Synonyms=deltaE2-3;
CC IsoId=Q6XZB0-8; Sequence=VSP_053896;
CC -!- TISSUE SPECIFICITY: Expressed in testis. Expressed exclusively at the
CC connecting piece of the sperm. {ECO:0000269|PubMed:12719377,
CC ECO:0000269|PubMed:12963729}.
CC -!- DISEASE: Hypertriglyceridemia, familial (FHTR) [MIM:145750]: A common
CC inherited disorder in which the concentration of very low density
CC lipoprotein (VLDL) is elevated in the plasma. This leads to increased
CC risk of heart disease, obesity, and pancreatitis.
CC {ECO:0000269|PubMed:12719377}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; AY197607; AAP37476.1; -; mRNA.
DR EMBL; JN387910; AEL12688.1; -; mRNA.
DR EMBL; JN387911; AEL12689.1; -; mRNA.
DR EMBL; JN387912; AEL12690.1; -; mRNA.
DR EMBL; JN387913; AEL12691.1; -; mRNA.
DR EMBL; JN387914; AEL12692.1; -; mRNA.
DR EMBL; JN387915; AEL12693.1; -; mRNA.
DR EMBL; JN387916; AEL12694.1; -; mRNA.
DR EMBL; AF130358; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL078615; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001347; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001289927.1; NM_001302998.1. [Q6XZB0-1]
DR RefSeq; NP_001289928.1; NM_001302999.1. [Q6XZB0-5]
DR RefSeq; NP_001289929.1; NM_001303000.1. [Q6XZB0-3]
DR RefSeq; NP_001289930.1; NM_001303001.1.
DR RefSeq; NP_945347.2; NM_198996.3.
DR AlphaFoldDB; Q6XZB0; -.
DR SMR; Q6XZB0; -.
DR BioGRID; 127254; 2.
DR STRING; 9606.ENSP00000343331; -.
DR SwissLipids; SLP:000000626; -.
DR ESTHER; human-LIPI; Phospholipase.
DR GlyGen; Q6XZB0; 2 sites.
DR iPTMnet; Q6XZB0; -.
DR PhosphoSitePlus; Q6XZB0; -.
DR BioMuta; LIPI; -.
DR DMDM; 81170675; -.
DR MassIVE; Q6XZB0; -.
DR PaxDb; Q6XZB0; -.
DR PeptideAtlas; Q6XZB0; -.
DR PRIDE; Q6XZB0; -.
DR ProteomicsDB; 67826; -. [Q6XZB0-1]
DR ProteomicsDB; 67827; -. [Q6XZB0-2]
DR Antibodypedia; 22161; 103 antibodies from 25 providers.
DR DNASU; 149998; -.
DR Ensembl; ENST00000536861.6; ENSP00000440381.3; ENSG00000188992.12. [Q6XZB0-3]
DR Ensembl; ENST00000614229.5; ENSP00000482652.2; ENSG00000188992.12. [Q6XZB0-5]
DR Ensembl; ENST00000679868.1; ENSP00000506458.1; ENSG00000188992.12. [Q6XZB0-8]
DR Ensembl; ENST00000680487.1; ENSP00000506194.1; ENSG00000188992.12. [Q6XZB0-7]
DR Ensembl; ENST00000680801.1; ENSP00000505904.1; ENSG00000188992.12. [Q6XZB0-4]
DR Ensembl; ENST00000681601.1; ENSP00000505323.1; ENSG00000188992.12. [Q6XZB0-1]
DR GeneID; 149998; -.
DR KEGG; hsa:149998; -.
DR MANE-Select; ENST00000681601.1; ENSP00000505323.1; NM_001302998.2; NP_001289927.1.
DR UCSC; uc002yjm.4; human. [Q6XZB0-1]
DR CTD; 149998; -.
DR DisGeNET; 149998; -.
DR GeneCards; LIPI; -.
DR HGNC; HGNC:18821; LIPI.
DR HPA; ENSG00000188992; Tissue enriched (epididymis).
DR MalaCards; LIPI; -.
DR MIM; 145750; phenotype.
DR MIM; 609252; gene.
DR neXtProt; NX_Q6XZB0; -.
DR OpenTargets; ENSG00000188992; -.
DR Orphanet; 413; NON RARE IN EUROPE: Hyperlipoproteinemia type 4.
DR PharmGKB; PA38695; -.
DR VEuPathDB; HostDB:ENSG00000188992; -.
DR eggNOG; ENOG502QUQT; Eukaryota.
DR GeneTree; ENSGT00940000161940; -.
DR HOGENOM; CLU_027171_3_0_1; -.
DR InParanoid; Q6XZB0; -.
DR OMA; CAYYFVL; -.
DR PhylomeDB; Q6XZB0; -.
DR TreeFam; TF324997; -.
DR BRENDA; 3.1.1.111; 2681.
DR BRENDA; 3.1.1.32; 2681.
DR PathwayCommons; Q6XZB0; -.
DR Reactome; R-HSA-1483166; Synthesis of PA.
DR BioGRID-ORCS; 149998; 3 hits in 1066 CRISPR screens.
DR ChiTaRS; LIPI; human.
DR GenomeRNAi; 149998; -.
DR Pharos; Q6XZB0; Tbio.
DR PRO; PR:Q6XZB0; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q6XZB0; protein.
DR Bgee; ENSG00000188992; Expressed in corpus epididymis and 71 other tissues.
DR ExpressionAtlas; Q6XZB0; baseline and differential.
DR Genevisible; Q6XZB0; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; IBA:GO_Central.
DR GO; GO:0004620; F:phospholipase activity; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IDA:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; TAS:Reactome.
DR GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
DR CDD; cd00707; Pancreat_lipase_like; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013818; Lipase.
DR InterPro; IPR016272; Lipase_LIPH.
DR InterPro; IPR033906; Lipase_N.
DR InterPro; IPR000734; TAG_lipase.
DR PANTHER; PTHR11610; PTHR11610; 1.
DR Pfam; PF00151; Lipase; 1.
DR PIRSF; PIRSF000865; Lipoprotein_lipase_LIPH; 1.
DR PRINTS; PR00821; TAGLIPASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Heparin-binding; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..460
FT /note="Lipase member I"
FT /id="PRO_0000042779"
FT ACT_SITE 159
FT /note="Nucleophile"
FT ACT_SITE 183
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 253
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 238..251
FT /evidence="ECO:0000250"
FT DISULFID 275..286
FT /evidence="ECO:0000250"
FT DISULFID 289..297
FT /evidence="ECO:0000250"
FT DISULFID 436..455
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..13
FT /note="MRVYIFLCLMCWV -> MLLKCLHNNLCQKYSAHAFQFSPRNVLWLLVVCL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12963729"
FT /id="VSP_016090"
FT VAR_SEQ 16..180
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053896"
FT VAR_SEQ 215..244
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053897"
FT VAR_SEQ 245..279
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053898"
FT VAR_SEQ 330..336
FT /note="GTYPFCT -> A (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053899"
FT VAR_SEQ 336..375
FT /note="TYYFVLSIIVPDKTMMDGSFSFKLLNQLGMIEEPRLYEKN -> NHHFAGII
FT LYLKNERKCFLIQTHVHQRTHKMPSSIKCTCL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053900"
FT VAR_SEQ 336..368
FT /note="TYYFVLSIIVPDKTMMDGSFSFKLLNQLGMIEE -> NKPVFRIYLFNTSPY
FT PLLAGRLFHLSCLRVVKN (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053901"
FT VAR_SEQ 369..460
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053902"
FT VAR_SEQ 376..460
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:21132378"
FT /id="VSP_053903"
FT VARIANT 55
FT /note="C -> Y (in FHTR; dbSNP:rs11909217)"
FT /evidence="ECO:0000269|PubMed:12719377"
FT /id="VAR_023760"
FT VARIANT 364
FT /note="G -> E (in dbSNP:rs74369337)"
FT /evidence="ECO:0000269|PubMed:12719377"
FT /id="VAR_023761"
FT VARIANT 431
FT /note="E -> K (in dbSNP:rs2822432)"
FT /evidence="ECO:0000269|PubMed:12719377"
FT /id="VAR_023762"
FT VARIANT 444
FT /note="D -> E (in dbSNP:rs7278737)"
FT /evidence="ECO:0000269|PubMed:12719377"
FT /id="VAR_023763"
FT MUTAGEN 159
FT /note="S->A: No activity."
FT /evidence="ECO:0000269|PubMed:12963729"
FT CONFLICT 421
FT /note="S -> R (in Ref. 1; AAP37476)"
SQ SEQUENCE 460 AA; 52922 MW; D83A76050DBB6D24 CRC64;
MRVYIFLCLM CWVRSDNKRP CLEFSQLSVK DSFRDLFIPR IETILMMYTR NNLNCAEPLF
EQNNSLNVNF NTQKKTVWLI HGYRPVGSIP LWLQNFVRIL LNEEDMNVIV VDWSRGATTF
IYNRAVKNTR KVAVSLSVHI KNLLKHGASL DNFHFIGVSL GAHISGFVGK IFHGQLGRIT
GLDPAGPRFS RKPPYSRLDY TDAKFVDVIH SDSNGLGIQE PLGHIDFYPN GGNKQPGCPK
SIFSGIQFIK CNHQRAVHLF MASLETNCNF ISFPCRSYKD YKTSLCVDCD CFKEKSCPRL
GYQAKLFKGV LKERMEGRPL RTTVFLDTSG TYPFCTYYFV LSIIVPDKTM MDGSFSFKLL
NQLGMIEEPR LYEKNKPFYK LQEVKILAQF YNDFVNISSI GLTYFQSSNL QCSTCTYKIQ
SLMLKSLTYP ERPPLCRYNI VLKDREEVFL NPNTCTPKNT
