ID   PLPL6_PONAB             Reviewed;        1365 AA.
AC   Q5RDS0;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   22-FEB-2023, entry version 83.
DE   RecName: Full=Patatin-like phospholipase domain-containing protein 6 {ECO:0000305};
DE   AltName: Full=Neuropathy target esterase;
DE            EC=3.1.1.5 {ECO:0000250|UniProtKB:Q8IY17};
GN   Name=PNPLA6; Synonyms=NTE;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Phospholipase B that deacylates intracellular
CC       phosphatidylcholine (PtdCho), generating glycerophosphocholine
CC       (GroPtdCho). This deacylation occurs at both sn-2 and sn-1 positions of
CC       PtdCho. Catalyzes the hydrolysis of several naturally occurring
CC       membrane-associated lipids. Hydrolyzes lysophospholipids and
CC       monoacylglycerols, preferring the 1-acyl to the 2-acyl isomer. Does not
CC       catalyze hydrolysis of di- or triacylglycerols or fatty acid amides.
CC       {ECO:0000250|UniProtKB:Q8IY17}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid +
CC         H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870,
CC         ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC         hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC         ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4,
CC         ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4,
CC         ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-
CC         octadecenoate + H(+) + sn-glycerol 3-phosphocholine;
CC         Xref=Rhea:RHEA:40807, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:28610, ChEBI:CHEBI:30823;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40808;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC         hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC         ChEBI:CHEBI:69081; Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC         hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC         ChEBI:CHEBI:75455; Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC         glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC         ChEBI:CHEBI:75342; Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC         glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC         ChEBI:CHEBI:73990; Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC         (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC         Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC         Evidence={ECO:0000250|UniProtKB:Q8IY17};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-hexadecanoyl-sn-glycero-3-phosphate + H2O = H(+) +
CC         hexadecanoate + sn-glycerol 3-phosphate; Xref=Rhea:RHEA:49092,
CC         ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57518, ChEBI:CHEBI:57597;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49093;
CC         Evidence={ECO:0000250|UniProtKB:Q3TRM4};
CC   -!- ACTIVITY REGULATION: Inhibited by a series a OPs such as mipafox (MPX),
CC       phenyl saligenin phosphate (PSP), phenyl dipentyl phosphinate (PDPP),
CC       diisopropyl fluorophosphate and paraoxon.
CC       {ECO:0000250|UniProtKB:Q8IY17}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q8IY17}; Single-pass type III membrane protein
CC       {ECO:0000250|UniProtKB:Q8IY17}.
CC   -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q8IY17}.
CC   -!- SIMILARITY: Belongs to the NTE family. {ECO:0000305}.
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DR   EMBL; CR857832; CAH90087.1; -; mRNA.
DR   RefSeq; NP_001124999.1; NM_001131527.1.
DR   AlphaFoldDB; Q5RDS0; -.
DR   SMR; Q5RDS0; -.
DR   STRING; 9601.ENSPPYP00000010625; -.
DR   GlyCosmos; Q5RDS0; 1 site, No reported glycans.
DR   GeneID; 100453292; -.
DR   KEGG; pon:100453292; -.
DR   CTD; 10908; -.
DR   eggNOG; KOG2968; Eukaryota.
DR   InParanoid; Q5RDS0; -.
DR   OrthoDB; 5303733at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004622; F:lysophospholipase activity; ISS:UniProtKB.
DR   GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR   GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0046470; P:phosphatidylcholine metabolic process; IEA:InterPro.
DR   CDD; cd00038; CAP_ED; 3.
DR   CDD; cd07225; Pat_PNPLA6_PNPLA7; 1.
DR   Gene3D; 3.40.1090.10; Cytosolic phospholipase A2 catalytic domain; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 3.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
DR   InterPro; IPR001423; LysoPLipase_patatin_CS.
DR   InterPro; IPR002641; PNPLA_dom.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   PANTHER; PTHR14226; NEUROPATHY TARGET ESTERASE/SWISS CHEESE D.MELANOGASTER; 1.
DR   PANTHER; PTHR14226:SF26; PATATIN-LIKE PHOSPHOLIPASE DOMAIN-CONTAINING PROTEIN 6; 1.
DR   Pfam; PF00027; cNMP_binding; 3.
DR   Pfam; PF01734; Patatin; 1.
DR   SMART; SM00100; cNMP; 3.
DR   SUPFAM; SSF51206; cAMP-binding domain-like; 3.
DR   SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 3.
DR   PROSITE; PS51635; PNPLA; 1.
DR   PROSITE; PS01237; UPF0028; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid degradation;
KW   Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..1365
FT                   /note="Patatin-like phospholipase domain-containing protein
FT                   6"
FT                   /id="PRO_0000292201"
FT   TOPO_DOM        1..50
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        51..71
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        72..1365
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          971..1137
FT                   /note="PNPLA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   REGION          343..427
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          441..463
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1296..1365
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           975..980
FT                   /note="GXGXXG"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   MOTIF           1002..1006
FT                   /note="GXSXG"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   MOTIF           1124..1126
FT                   /note="DGA/G"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   COMPBIAS        356..370
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        376..391
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1004
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   ACT_SITE        1124
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT   BINDING         186..313
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /ligand_label="1"
FT   BINDING         502..624
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /ligand_label="2"
FT   BINDING         620..740
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /ligand_label="3"
FT   MOD_RES         345
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   MOD_RES         352
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   MOD_RES         353
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   MOD_RES         363
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   MOD_RES         411
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   MOD_RES         455
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IY17"
FT   CARBOHYD        11
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1365 AA;  149750 MW;  A700733C7A74EB39 CRC64;
     MGTSSHGLAT NSSGAKVAER DGFQDVPAPG EGAAGRICGA QPVPFVPQVL GVMIGAGVAV
     VVTAVLILLV VRRLRVPKTP APDGPRYRFR KRDKVLFYGR KIMRKVSQST SSLVDTSVSA
     TSRPRMKKKL KMLNIAKKIL RIQKETPTLQ RKEPPPAVLE ADLTEGDLAN SHLPSEVLYM
     FKNVRVLGHF EKPLFLELCR HMVFQRLGQG DYVFRPGQPD ASIYVVQDGL LELCLPGPDG
     KECVVKEVVP GDSVNSLLSI LDVITGHQHP QRTVSARAAR DSTVLRLPVE AFSAVFAKYP
     ESLVRVVQII MVRLQRVTFL ALHNYLGLTN ELFSHEIQPL RLFPSPGLPT RTSPVRGSKR
     MVSTSATDEP RETPGRPPDP TGAPLPGPTG DPVKPTSLET PSAPLLSRCV SMPGDISGLQ
     GGPRSDFDMA YERGRISVSL QEGASGGSLA APARTPTQEP REQPAGACEY SYCEDESATG
     GCPFGPYQGR QTSSIFEAAK RELAKLMRIE DPSLLNSRVL LHHAKAGTII ARQGDQDVSL
     HFVLWGCLHV YQHMIDKAED VCLFVAQPGE LVGQLAVLTG EPLIFTLRAQ RDCTFLRISK
     SDFYEIMRAQ PSVVLSAAHT VAARMSPFVR QMDFAIDWTA VEAGRALYRQ GDRSDCTYIV
     LNGRLRSVIQ RGSGKKELVG EYGRGDLIGV VEALTRQPRA TTVHAVRDTE LAKLPEGTLG
     HIKRRHPQVV TRLIHLLSQK ILGNLQQLQG PFPGSGLGVP PHSELTNPAS NLATVAVLPV
     CAEVPMVAFT LELQHALQAI GPTLLLNSDI IRARLGASAL DSIQEFRLSG WLAQQEDAHR
     IVLYQTDASL TPWTVRCLRQ ADCILIVGLG DQEPTLGQLE QMLENTAVRA LKQLVLLHRE
     EGAGPTRTVE WLNMRSWCSG HPHLRCPRRL FSRRSPAKLH ELYEKVFSRR ADRHSDFSRL
     ARVLTGNTIA LVLGGGGARG CSHIGVLKAL EEAGVPVDLV GGTSIGSFIG ALYAEERSAS
     RTKQRAREWA KSMTSVLEPV LDLTYPVTSM FTGSAFNRSI HRVFQDKQIE DLWLPYFNVT
     TDITASAMRV HKDGSLWRYV RASMTLSGYL PPLCDPKDGH LLMDGGYINN LPADIARSMG
     AKTVIAIDVG SQDETDLSTY GDSLSGWWLL WKRLNPWADK VKVPDMAEIQ SRLAYVSCVR
     QLEVVKSSSY CEYLRPPIDC FKTMDFGKFD QVYDVGYQYG KAVFGGWSRG NVIEKMLTDR
     RSTDLNESRR ADVLAYPSSG FTDLAEIVSR IEPPTSYVSD GCADGEESDC LTEYEEDAGP
     DCSRDEGGSP EGASPSTASE MEEEKSILRQ RRCLPQEPPG SATDA
//