LIPR1_HUMAN
ID LIPR1_HUMAN Reviewed; 467 AA.
AC P54315; Q68D83; Q68DR6; Q8TAU2; Q9BS82;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Inactive pancreatic lipase-related protein 1;
DE Short=PL-RP1;
DE Flags: Precursor;
GN Name=PNLIPRP1; Synonyms=PLRP1;
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] (ISOFORM 1), ABSENCE OF LIPASE ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Pancreas;
RX PubMed=1379598; DOI=10.1016/s0021-9258(18)42032-7;
RA Giller T., Buchwald P., Blum-Kaelin D., Hunziker W.;
RT "Two novel human pancreatic lipase related proteins, hPLRP1 and hPLRP2.
RT Differences in colipase dependence and in lipase activity.";
RL J. Biol. Chem. 267:16509-16516(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Liver;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ASP-414.
RC TISSUE=Pancreas;
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 FUNCTION, SUBCELLULAR LOCATION, AND ABSENCE OF CATALYTIC ACTIVITY.
RX PubMed=19824014; DOI=10.1002/mnfr.200800563;
RA Berton A., Sebban-Kreuzer C., Rouvellac S., Lopez C., Crenon I.;
RT "Individual and combined action of pancreatic lipase and pancreatic lipase-
RT related proteins 1 and 2 on native versus homogenized milk fat globules.";
RL Mol. Nutr. Food Res. 53:1592-1602(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 18-467 IN COMPLEX WITH CALCIUM
RP IONS, AND DISULFIDE BONDS.
RG Structural genomics consortium (SGC);
RT "Structure of the human pancreatic lipase-related protein 1.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [6]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-129.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May function as inhibitor of dietary triglyceride digestion.
CC Lacks detectable lipase activity towards triglycerides, diglycerides,
CC phosphatidylcholine, galactolipids or cholesterol esters (in vitro) (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:19824014}.
CC -!- INTERACTION:
CC P54315; P41181: AQP2; NbExp=3; IntAct=EBI-8652812, EBI-12701138;
CC P54315; Q8NFU1: BEST2; NbExp=3; IntAct=EBI-8652812, EBI-19947314;
CC P54315; P11912: CD79A; NbExp=3; IntAct=EBI-8652812, EBI-7797864;
CC P54315; Q9HA82: CERS4; NbExp=3; IntAct=EBI-8652812, EBI-2622997;
CC P54315; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-8652812, EBI-18013275;
CC P54315; P00387: CYB5R3; NbExp=3; IntAct=EBI-8652812, EBI-1046040;
CC P54315; Q15125: EBP; NbExp=3; IntAct=EBI-8652812, EBI-3915253;
CC P54315; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-8652812, EBI-18304435;
CC P54315; O15552: FFAR2; NbExp=3; IntAct=EBI-8652812, EBI-2833872;
CC P54315; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-8652812, EBI-11110431;
CC P54315; P48165: GJA8; NbExp=3; IntAct=EBI-8652812, EBI-17458373;
CC P54315; O95377: GJB5; NbExp=3; IntAct=EBI-8652812, EBI-3909454;
CC P54315; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-8652812, EBI-13345167;
CC P54315; O15529: GPR42; NbExp=3; IntAct=EBI-8652812, EBI-18076404;
CC P54315; Q8TED1: GPX8; NbExp=3; IntAct=EBI-8652812, EBI-11721746;
CC P54315; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-8652812, EBI-18053395;
CC P54315; P48051: KCNJ6; NbExp=3; IntAct=EBI-8652812, EBI-12017638;
CC P54315; A8MZ59: LEUTX; NbExp=3; IntAct=EBI-8652812, EBI-17490413;
CC P54315; Q8N386: LRRC25; NbExp=3; IntAct=EBI-8652812, EBI-11304917;
CC P54315; Q8NI22: MCFD2; NbExp=3; IntAct=EBI-8652812, EBI-2689785;
CC P54315; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-8652812, EBI-16439278;
CC P54315; P15941-11: MUC1; NbExp=3; IntAct=EBI-8652812, EBI-17263240;
CC P54315; Q9Y375: NDUFAF1; NbExp=3; IntAct=EBI-8652812, EBI-741874;
CC P54315; O14524-2: NEMP1; NbExp=3; IntAct=EBI-8652812, EBI-10969203;
CC P54315; O00623: PEX12; NbExp=3; IntAct=EBI-8652812, EBI-594836;
CC P54315; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-8652812, EBI-10192441;
CC P54315; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-8652812, EBI-18159983;
CC P54315; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-8652812, EBI-17595455;
CC P54315; O95436-2: SLC34A2; NbExp=3; IntAct=EBI-8652812, EBI-12811757;
CC P54315; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-8652812, EBI-17295964;
CC P54315; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-8652812, EBI-12898013;
CC P54315; P30825: SLC7A1; NbExp=3; IntAct=EBI-8652812, EBI-4289564;
CC P54315; Q16623: STX1A; NbExp=3; IntAct=EBI-8652812, EBI-712466;
CC P54315; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-8652812, EBI-8638294;
CC P54315; Q96Q45-2: TMEM237; NbExp=5; IntAct=EBI-8652812, EBI-10982110;
CC P54315; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-8652812, EBI-11724433;
CC P54315; Q9Y320: TMX2; NbExp=3; IntAct=EBI-8652812, EBI-6447886;
CC P54315; P19075: TSPAN8; NbExp=3; IntAct=EBI-8652812, EBI-4289938;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1379598,
CC ECO:0000269|PubMed:19824014}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P54315-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54315-2; Sequence=VSP_014097, VSP_014100;
CC Name=3;
CC IsoId=P54315-3; Sequence=VSP_014098, VSP_014099;
CC -!- TISSUE SPECIFICITY: Pancreas. {ECO:0000269|PubMed:1379598}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; M93283; AAA59532.1; -; mRNA.
DR EMBL; CR749299; CAH18154.1; -; mRNA.
DR EMBL; CR749524; CAH18337.1; -; mRNA.
DR EMBL; BC005233; AAH05233.1; -; mRNA.
DR EMBL; BC025784; AAH25784.1; -; mRNA.
DR CCDS; CCDS7595.1; -. [P54315-1]
DR PIR; A43357; A43357.
DR RefSeq; NP_001290064.1; NM_001303135.1. [P54315-1]
DR RefSeq; NP_006220.1; NM_006229.3. [P54315-1]
DR RefSeq; XP_011538170.1; XM_011539868.1.
DR PDB; 2PPL; X-ray; 2.20 A; A=18-467.
DR PDBsum; 2PPL; -.
DR AlphaFoldDB; P54315; -.
DR SMR; P54315; -.
DR BioGRID; 111408; 167.
DR IntAct; P54315; 48.
DR MINT; P54315; -.
DR STRING; 9606.ENSP00000433933; -.
DR ESTHER; human-PNLIPRP1; Pancreatic_lipase.
DR PhosphoSitePlus; P54315; -.
DR BioMuta; PNLIPRP1; -.
DR DMDM; 1708837; -.
DR MassIVE; P54315; -.
DR PaxDb; P54315; -.
DR PeptideAtlas; P54315; -.
DR PRIDE; P54315; -.
DR ProteomicsDB; 56681; -. [P54315-1]
DR ProteomicsDB; 56682; -. [P54315-2]
DR ProteomicsDB; 56683; -. [P54315-3]
DR Antibodypedia; 35303; 76 antibodies from 15 providers.
DR DNASU; 5407; -.
DR Ensembl; ENST00000358834.9; ENSP00000351695.4; ENSG00000187021.15. [P54315-1]
DR Ensembl; ENST00000528052.5; ENSP00000433933.1; ENSG00000187021.15. [P54315-1]
DR GeneID; 5407; -.
DR KEGG; hsa:5407; -.
DR MANE-Select; ENST00000358834.9; ENSP00000351695.4; NM_006229.4; NP_006220.1.
DR UCSC; uc001lco.2; human. [P54315-1]
DR CTD; 5407; -.
DR DisGeNET; 5407; -.
DR GeneCards; PNLIPRP1; -.
DR HGNC; HGNC:9156; PNLIPRP1.
DR HPA; ENSG00000187021; Tissue enriched (pancreas).
DR MIM; 604422; gene.
DR neXtProt; NX_P54315; -.
DR OpenTargets; ENSG00000187021; -.
DR PharmGKB; PA33479; -.
DR VEuPathDB; HostDB:ENSG00000187021; -.
DR eggNOG; ENOG502QUK7; Eukaryota.
DR GeneTree; ENSGT00940000162375; -.
DR HOGENOM; CLU_027171_0_2_1; -.
DR InParanoid; P54315; -.
DR OMA; NMFKVEE; -.
DR OrthoDB; 534956at2759; -.
DR PhylomeDB; P54315; -.
DR TreeFam; TF324997; -.
DR BRENDA; 3.1.1.26; 2681.
DR PathwayCommons; P54315; -.
DR Reactome; R-HSA-192456; Digestion of dietary lipid.
DR SignaLink; P54315; -.
DR BioGRID-ORCS; 5407; 9 hits in 1069 CRISPR screens.
DR ChiTaRS; PNLIPRP1; human.
DR EvolutionaryTrace; P54315; -.
DR GenomeRNAi; 5407; -.
DR Pharos; P54315; Tbio.
DR PRO; PR:P54315; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P54315; protein.
DR Bgee; ENSG00000187021; Expressed in body of pancreas and 98 other tissues.
DR ExpressionAtlas; P54315; baseline and differential.
DR Genevisible; P54315; HS.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; TAS:ProtInc.
DR GO; GO:0006629; P:lipid metabolic process; IEA:InterPro.
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; IPR002331; Lipase_panc.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR000734; TAG_lipase.
DR PANTHER; PTHR11610; PTHR11610; 1.
DR Pfam; PF00151; Lipase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PIRSF; PIRSF000865; Lipoprotein_lipase_LIPH; 1.
DR PRINTS; PR00823; PANCLIPASE.
DR PRINTS; PR00821; TAGLIPASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Disulfide bond; Metal-binding;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..467
FT /note="Inactive pancreatic lipase-related protein 1"
FT /id="PRO_0000017790"
FT DOMAIN 356..467
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT ACT_SITE 171
FT /note="Nucleophile"
FT ACT_SITE 194
FT /note="Charge relay system"
FT ACT_SITE 281
FT /note="Charge relay system"
FT BINDING 205
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT DISULFID 21..27
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT DISULFID 109..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT DISULFID 255..279
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT DISULFID 303..314
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT DISULFID 317..322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT DISULFID 451..467
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152,
FT ECO:0000269|Ref.5"
FT VAR_SEQ 111..186
FT /note="KLFEVEEVNCICVDWKKGSQATYTQAANNVRVVGAQVAQMLDILLTEYSYPP
FT SKVHLIGHSLGAHVAGEAGSKTPG -> VGASSDPCGQLRPTLLLTSLHHFMHSRNLYI
FT LGNFMQLKCFSSQKLKCLSMFPHYICTLKQPHLLLEKYSYYLISG (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014097"
FT VAR_SEQ 111..117
FT /note="KLFEVEE -> PGASPRA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_014098"
FT VAR_SEQ 118..467
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_014099"
FT VAR_SEQ 187..467
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014100"
FT VARIANT 61
FT /note="N -> D (in dbSNP:rs11197744)"
FT /id="VAR_049820"
FT VARIANT 129
FT /note="S -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036379"
FT VARIANT 271
FT /note="A -> V (in dbSNP:rs2305205)"
FT /id="VAR_022082"
FT VARIANT 414
FT /note="E -> D (in dbSNP:rs2305204)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_022659"
FT VARIANT 461
FT /note="L -> P (in dbSNP:rs1049125)"
FT /id="VAR_014915"
FT STRAND 19..22
FT /evidence="ECO:0007829|PDB:2PPL"
FT TURN 23..25
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:2PPL"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 133..158
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 173..182
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:2PPL"
FT TURN 198..202
FT /evidence="ECO:0007829|PDB:2PPL"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 240..246
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 266..270
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 279..293
FT /evidence="ECO:0007829|PDB:2PPL"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 306..310
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:2PPL"
FT HELIX 327..331
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 356..367
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 369..379
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 387..394
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 399..408
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 412..421
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 432..441
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 447..451
FT /evidence="ECO:0007829|PDB:2PPL"
FT STRAND 462..466
FT /evidence="ECO:0007829|PDB:2PPL"
SQ SEQUENCE 467 AA; 51848 MW; 2781EA1E22E39E78 CRC64;
MLIFWTITLF LLGAAKGKEV CYEDLGCFSD TEPWGGTAIR PLKILPWSPE KIGTRFLLYT
NENPNNFQIL LLSDPSTIEA SNFQMDRKTR FIIHGFIDKG DESWVTDMCK KLFEVEEVNC
ICVDWKKGSQ ATYTQAANNV RVVGAQVAQM LDILLTEYSY PPSKVHLIGH SLGAHVAGEA
GSKTPGLSRI TGLDPVEASF ESTPEEVRLD PSDADFVDVI HTDAAPLIPF LGFGTNQQMG
HLDFFPNGGE SMPGCKKNAL SQIVDLDGIW AGTRDFVACN HLRSYKYYLE SILNPDGFAA
YPCTSYKSFE SDKCFPCPDQ GCPQMGHYAD KFAGRTSEEQ QKFFLNTGEA SNFARWRYGV
SITLSGRTAT GQIKVALFGN KGNTHQYSIF RGILKPGSTH SYEFDAKLDV GTIEKVKFLW
NNNVINPTLP KVGATKITVQ KGEEKTVYNF CSEDTVREDT LLTLTPC
