ID PLPL6_HUMAN Reviewed; 1375 AA.
AC Q8IY17; A6NGQ0; B4DFB9; B7Z7T2; F5H5K9; J3KQS3; O60859; Q86W58; Q9UG58;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 27-MAR-2024, entry version 164.
DE RecName: Full=Patatin-like phospholipase domain-containing protein 6 {ECO:0000305};
DE EC=3.1.1.5 {ECO:0000269|PubMed:15044461};
DE AltName: Full=Neuropathy target esterase {ECO:0000303|PubMed:9576844};
GN Name=PNPLA6 {ECO:0000312|HGNC:HGNC:16268}; Synonyms=NTE;
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 2), GLYCOSYLATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9576844; DOI=10.1042/bj3320001;
RA Lush M.J., Li Y., Read D.J., Willis A.C., Glynn P.;
RT "Neuropathy target esterase and a homologous Drosophila neurodegeneration-
RT associated mutant protein contain a novel domain conserved from bacteria to
RT man.";
RL Biochem. J. 332:1-4(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), AND VARIANT
RP PRO-412.
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 43-1375 (ISOFORM 3), AND VARIANTS PRO-412 AND
RP ARG-1033.
RC TISSUE=Brain, Duodenum, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 994-1375 (ISOFORMS 2/3/4/5).
RC TISSUE=Brain;
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 [7]
RP REVIEW ON ACTIVITY REGULATION.
RX PubMed=1666291; DOI=10.3109/10408449209089884;
RA Lotti M.;
RT "The pathogenesis of organophosphate polyneuropathy.";
RL Crit. Rev. Toxicol. 21:465-487(1991).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11927584; DOI=10.1074/jbc.m200330200;
RA van Tienhoven M., Atkins J., Li Y., Glynn P.;
RT "Human neuropathy target esterase catalyzes hydrolysis of membrane
RT lipids.";
RL J. Biol. Chem. 277:20942-20948(2002).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15044461; DOI=10.1074/jbc.m400830200;
RA Zaccheo O., Dinsdale D., Meacock P.A., Glynn P.;
RT "Neuropathy target esterase and its yeast homologue degrade
RT phosphatidylcholine to glycerophosphocholine in living cells.";
RL J. Biol. Chem. 279:24024-24033(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354; THR-361 AND SER-362, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, AND IDENTIFICATION BY
RP 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354; SER-362; SER-372 AND
RP SER-420, AND 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 [15]
RP INVOLVEMENT IN BNHS, AND VARIANTS BNHS CYS-1147; CYS-1175 AND TRP-1359.
RX PubMed=25033069; DOI=10.1210/jc.2014-1836;
RA Topaloglu A.K., Lomniczi A., Kretzschmar D., Dissen G.A., Kotan L.D.,
RA McArdle C.A., Koc A.F., Hamel B.C., Guclu M., Papatya E.D., Eren E.,
RA Mengen E., Gurbuz F., Cook M., Castellano J.M., Kekil M.B., Mungan N.O.,
RA Yuksel B., Ojeda S.R.;
RT "Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase
RT underlie pubertal failure and neurological deficits in Gordon Holmes
RT syndrome.";
RL J. Clin. Endocrinol. Metab. 99:E2067-E2075(2014).
RN [16]
RP INVOLVEMENT IN SPG39, AND VARIANTS SPG39 HIS-938 AND VAL-1060.
RX PubMed=18313024; DOI=10.1016/j.ajhg.2007.12.018;
RA Rainier S., Bui M., Mark E., Thomas D., Tokarz D., Ming L., Delaney C.,
RA Richardson R.J., Albers J.W., Matsunami N., Stevens J., Coon H.,
RA Leppert M., Fink J.K.;
RT "Neuropathy target esterase gene mutations cause motor neuron disease.";
RL Am. J. Hum. Genet. 82:780-785(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420 AND THR-464, AND
RP IDENTIFICATION BY 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 [18]
RP TISSUE SPECIFICITY, INVOLVEMENT IN LNMS, INVOLVEMENT IN OMCS, VARIANT LNMS
RP ARG-726, AND VARIANTS OMCS GLN-1099; ARG-1129; SER-1176 AND ALA-1215.
RX PubMed=25480986; DOI=10.1136/jmedgenet-2014-102856;
RA Hufnagel R.B., Arno G., Hein N.D., Hersheson J., Prasad M., Anderson Y.,
RA Krueger L.A., Gregory L.C., Stoetzel C., Jaworek T.J., Hull S., Li A.,
RA Plagnol V., Willen C.M., Morgan T.M., Prows C.A., Hegde R.S., Riazuddin S.,
RA Grabowski G.A., Richardson R.J., Dieterich K., Huang T., Revesz T.,
RA Martinez-Barbera J.P., Sisk R.A., Jefferies C., Houlden H., Dattani M.T.,
RA Fink J.K., Dollfus H., Moore A.T., Ahmed Z.M.;
RT "Neuropathy target esterase impairments cause Oliver-McFarlane and
RT Laurence-Moon syndromes.";
RL J. Med. Genet. 52:85-94(2015).
RN [19]
RP VARIANTS SPG39 ILE-263 AND GLU-840, VARIANTS BNHS TRP-578; LEU-1045;
RP ILE-1058; SER-1066; MET-1110 AND LEU-1122, AND VARIANTS GLY-1100 AND
RP GLY-1362.
RX PubMed=24355708; DOI=10.1093/brain/awt326;
RA Synofzik M., Gonzalez M.A., Lourenco C.M., Coutelier M., Haack T.B.,
RA Rebelo A., Hannequin D., Strom T.M., Prokisch H., Kernstock C., Durr A.,
RA Schols L., Lima-Martinez M.M., Farooq A., Schule R., Stevanin G.,
RA Marques W. Jr., Zuchner S.;
RT "PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as
RT part of a broad neurodegenerative spectrum.";
RL Brain 137:69-77(2014).
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 (PubMed:11927584). Hydrolyzes
CC lysophospholipids and monoacylglycerols, preferring the 1-acyl to the
CC 2-acyl isomer. Does not catalyze hydrolysis of di- or triacylglycerols
CC or fatty acid amides (PubMed:11927584). {ECO:0000269|PubMed:11927584,
CC ECO:0000269|PubMed:15044461}.
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:0000269|PubMed:15044461};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC Evidence={ECO:0000269|PubMed:15044461};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40808;
CC Evidence={ECO:0000305|PubMed:11927584};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960;
CC Evidence={ECO:0000305|PubMed:11927584};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964;
CC Evidence={ECO:0000305|PubMed:11927584};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000305|PubMed:11927584};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000305|PubMed:11927584};
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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000305|PubMed:11927584};
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 -!- 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:0000269|PubMed:11927584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:11927584};
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. {ECO:0000269|PubMed:15044461,
CC ECO:0000305|PubMed:1666291}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.05 mM for 1-palmitoyl-lysophosphatidylcholine
CC {ECO:0000269|PubMed:11927584};
CC KM=0.4 mM for 1-palmitoylglycerol {ECO:0000269|PubMed:11927584};
CC Vmax=20 umol/min/mg enzyme towards 1-palmitoyl-
CC lysophosphatidylcholine {ECO:0000269|PubMed:11927584};
CC Vmax=1 umol/min/mg enzyme towards 1-palmitoylglycerol
CC {ECO:0000269|PubMed:11927584};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15044461}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:15044461}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=4;
CC IsoId=Q8IY17-4; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IY17-2; Sequence=VSP_059668;
CC Name=3;
CC IsoId=Q8IY17-3; Sequence=VSP_059670;
CC Name=5;
CC IsoId=Q8IY17-5; Sequence=VSP_059668, VSP_059669, VSP_059670;
CC -!- TISSUE SPECIFICITY: Expressed in brain, placenta, kidney, neuron and
CC skeletal muscle. Expressed in the developing eye, pituitary and brain.
CC {ECO:0000269|PubMed:25480986, ECO:0000269|PubMed:9576844}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:9576844}.
CC -!- DISEASE: Spastic paraplegia 39, autosomal recessive (SPG39)
CC [MIM:612020]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body. SPG39 is associated
CC with a motor axonopathy affecting upper and lower limbs and resulting
CC in progressive wasting of distal upper and lower extremity muscles.
CC {ECO:0000269|PubMed:18313024, ECO:0000269|PubMed:24355708}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Boucher-Neuhauser syndrome (BNHS) [MIM:215470]: An autosomal
CC recessive disorder characterized by spinocerebellar ataxia,
CC hypogonadotropic hypogonadism, and visual impairment due to
CC chorioretinal dystrophy. The age at onset is variable, but most
CC patients develop 1 or more symptoms in the first decade of life.
CC Chorioretinal dystrophy may not always be present.
CC {ECO:0000269|PubMed:24355708, ECO:0000269|PubMed:25033069}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Laurence-Moon syndrome (LNMS) [MIM:245800]: An autosomal
CC recessive syndrome characterized by progressive spinocerebellar
CC degeneration, spastic paraplegia, intellectual disability,
CC hypogonadism, dwarfism, and chorioretinopathy. Trichomegaly is absent.
CC {ECO:0000269|PubMed:25480986}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Oliver-McFarlane syndrome (OMCS) [MIM:275400]: A rare
CC autosomal recessive, congenital syndrome characterized by trichomegaly,
CC severe chorioretinal atrophy and multiple pituitary hormone
CC deficiencies. It results in intellectual impairment and dwarfism, if
CC untreated. Clinical features include hypogonadotropic hypogonadism
CC during puberty, pigmentary retinal degeneration, ataxia, spastic
CC paraplegia, and peripheral neuropathy. {ECO:0000269|PubMed:25480986}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Its specific chemical modification by certain
CC organophosphorus (OP) compounds leads to distal axonopathy.
CC {ECO:0000303|PubMed:1666291}.
CC -!- SIMILARITY: Belongs to the NTE family. {ECO:0000305}.
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DR EMBL; AJ004832; CAA06164.1; -; mRNA.
DR EMBL; AK294021; BAG57380.1; -; mRNA.
DR EMBL; AK302462; BAH13718.1; -; mRNA.
DR EMBL; AC008878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69029.1; -; Genomic_DNA.
DR EMBL; BC038229; AAH38229.1; -; mRNA.
DR EMBL; BC050553; AAH50553.1; -; mRNA.
DR EMBL; BC051768; AAH51768.1; -; mRNA.
DR EMBL; AL050362; CAB43674.1; -; mRNA.
DR CCDS; CCDS32891.1; -. [Q8IY17-2]
DR CCDS; CCDS54206.1; -. [Q8IY17-4]
DR CCDS; CCDS54207.1; -. [Q8IY17-5]
DR RefSeq; NP_001159583.1; NM_001166111.1. [Q8IY17-4]
DR RefSeq; NP_001159584.1; NM_001166112.1. [Q8IY17-5]
DR RefSeq; NP_001159585.1; NM_001166113.1. [Q8IY17-2]
DR RefSeq; NP_001159586.1; NM_001166114.1.
DR RefSeq; NP_006693.3; NM_006702.4. [Q8IY17-2]
DR AlphaFoldDB; Q8IY17; -.
DR SMR; Q8IY17; -.
DR BioGRID; 116114; 117.
DR IntAct; Q8IY17; 41.
DR MINT; Q8IY17; -.
DR STRING; 9606.ENSP00000407509; -.
DR ChEMBL; CHEMBL2189129; -.
DR SwissLipids; SLP:000000615; -.
DR GlyCosmos; Q8IY17; 2 sites, 1 glycan.
DR GlyGen; Q8IY17; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IY17; -.
DR PhosphoSitePlus; Q8IY17; -.
DR SwissPalm; Q8IY17; -.
DR BioMuta; PNPLA6; -.
DR DMDM; 150403921; -.
DR EPD; Q8IY17; -.
DR jPOST; Q8IY17; -.
DR MassIVE; Q8IY17; -.
DR MaxQB; Q8IY17; -.
DR PaxDb; 9606-ENSP00000407509; -.
DR PeptideAtlas; Q8IY17; -.
DR ProteomicsDB; 26908; -.
DR ProteomicsDB; 71085; -. [Q8IY17-2]
DR ProteomicsDB; 71086; -. [Q8IY17-3]
DR Pumba; Q8IY17; -.
DR Antibodypedia; 2222; 285 antibodies from 30 providers.
DR DNASU; 10908; -.
DR Ensembl; ENST00000221249.10; ENSP00000221249.5; ENSG00000032444.17. [Q8IY17-2]
DR Ensembl; ENST00000414982.7; ENSP00000407509.2; ENSG00000032444.17. [Q8IY17-4]
DR Ensembl; ENST00000450331.7; ENSP00000394348.2; ENSG00000032444.17. [Q8IY17-2]
DR Ensembl; ENST00000545201.6; ENSP00000443323.1; ENSG00000032444.17. [Q8IY17-5]
DR GeneID; 10908; -.
DR KEGG; hsa:10908; -.
DR UCSC; uc002mgq.3; human. [Q8IY17-4]
DR AGR; HGNC:16268; -.
DR CTD; 10908; -.
DR DisGeNET; 10908; -.
DR GeneCards; PNPLA6; -.
DR GeneReviews; PNPLA6; -.
DR HGNC; HGNC:16268; PNPLA6.
DR HPA; ENSG00000032444; Low tissue specificity.
DR MalaCards; PNPLA6; -.
DR MIM; 215470; phenotype.
DR MIM; 245800; phenotype.
DR MIM; 275400; phenotype.
DR MIM; 603197; gene.
DR MIM; 612020; phenotype.
DR neXtProt; NX_Q8IY17; -.
DR OpenTargets; ENSG00000032444; -.
DR Orphanet; 1180; Ataxia-hypogonadism-choroidal dystrophy syndrome.
DR Orphanet; 139480; Autosomal recessive spastic paraplegia type 39.
DR Orphanet; 1173; Cerebellar ataxia-hypogonadism syndrome.
DR Orphanet; 2377; Laurence-Moon syndrome.
DR Orphanet; 3363; Trichomegaly-retina pigmentary degeneration-dwarfism syndrome.
DR PharmGKB; PA145148268; -.
DR VEuPathDB; HostDB:ENSG00000032444; -.
DR eggNOG; KOG2968; Eukaryota.
DR GeneTree; ENSGT00940000159130; -.
DR HOGENOM; CLU_000960_1_0_1; -.
DR InParanoid; Q8IY17; -.
DR OMA; CIEDLWI; -.
DR OrthoDB; 5303733at2759; -.
DR PhylomeDB; Q8IY17; -.
DR TreeFam; TF300519; -.
DR PathwayCommons; Q8IY17; -.
DR Reactome; R-HSA-6814848; Glycerophospholipid catabolism.
DR SignaLink; Q8IY17; -.
DR SIGNOR; Q8IY17; -.
DR BioGRID-ORCS; 10908; 21 hits in 1158 CRISPR screens.
DR ChiTaRS; PNPLA6; human.
DR GeneWiki; Neuropathy_target_esterase; -.
DR GenomeRNAi; 10908; -.
DR Pharos; Q8IY17; Tbio.
DR PRO; PR:Q8IY17; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IY17; Protein.
DR Bgee; ENSG00000032444; Expressed in granulocyte and 188 other cell types or tissues.
DR ExpressionAtlas; Q8IY17; baseline and differential.
DR Genevisible; Q8IY17; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; EXP:Reactome.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; TAS:Reactome.
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 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Dwarfism; Endoplasmic reticulum;
KW Glycoprotein; Hereditary spastic paraplegia; Hydrolase;
KW Hypogonadotropic hypogonadism; Intellectual disability; Lipid degradation;
KW Lipid metabolism; Membrane; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Repeat; Retinitis pigmentosa; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1375
FT /note="Patatin-like phospholipase domain-containing protein
FT 6"
FT /id="PRO_0000292199"
FT TOPO_DOM 1..59
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..1375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 981..1147
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 352..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1306..1375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 985..990
FT /note="GXGXXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 1012..1016
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 1134..1136
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT COMPBIAS 365..379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..400
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1014
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 1134
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT BINDING 195..322
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /ligand_label="1"
FT BINDING 511..633
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /ligand_label="2"
FT BINDING 629..749
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT /ligand_label="3"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 361
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 464
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 10..57
FT /note="Missing (in isoform 2 and isoform 5)"
FT /id="VSP_059668"
FT VAR_SEQ 521..546
FT /note="Missing (in isoform 5)"
FT /id="VSP_059669"
FT VAR_SEQ 763
FT /note="Missing (in isoform 3 and isoform 5)"
FT /id="VSP_059670"
FT VARIANT 263
FT /note="V -> I (in SPG39; dbSNP:rs587777184)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071091"
FT VARIANT 412
FT /note="A -> P (in dbSNP:rs17854645)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_032949"
FT VARIANT 578
FT /note="G -> W (in BNHS; dbSNP:rs587777615)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071092"
FT VARIANT 726
FT /note="G -> R (in LNMS)"
FT /evidence="ECO:0000269|PubMed:25480986"
FT /id="VAR_073409"
FT VARIANT 840
FT /note="G -> E (in SPG39; dbSNP:rs587777185)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071093"
FT VARIANT 938
FT /note="R -> H (in SPG39; dbSNP:rs121434416)"
FT /evidence="ECO:0000269|PubMed:18313024"
FT /id="VAR_044409"
FT VARIANT 1033
FT /note="K -> R (in dbSNP:rs17854647)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032950"
FT VARIANT 1045
FT /note="S -> L (in BNHS; dbSNP:rs541098659)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071094"
FT VARIANT 1058
FT /note="T -> I (in BNHS; dbSNP:rs587777181)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071095"
FT VARIANT 1060
FT /note="M -> V (in SPG39; dbSNP:rs121434415)"
FT /evidence="ECO:0000269|PubMed:18313024"
FT /id="VAR_044410"
FT VARIANT 1066
FT /note="F -> S (in BNHS; dbSNP:rs587777183)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071096"
FT VARIANT 1099
FT /note="R -> Q (in OMCS; dbSNP:rs786201037)"
FT /evidence="ECO:0000269|PubMed:25480986"
FT /id="VAR_073410"
FT VARIANT 1100
FT /note="V -> G (found in a patient with sporadic ataxia and
FT BNHS; uncertain significance; dbSNP:rs754429587)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071097"
FT VARIANT 1110
FT /note="V -> M (in BNHS; dbSNP:rs587777182)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071098"
FT VARIANT 1122
FT /note="P -> L (in BNHS; dbSNP:rs748506175)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071099"
FT VARIANT 1129
FT /note="G -> R (in OMCS; dbSNP:rs773955314)"
FT /evidence="ECO:0000269|PubMed:25480986"
FT /id="VAR_073411"
FT VARIANT 1147
FT /note="R -> C (in BNHS; dbSNP:rs587777854)"
FT /evidence="ECO:0000269|PubMed:25033069"
FT /id="VAR_073412"
FT VARIANT 1175
FT /note="S -> C (in BNHS; dbSNP:rs1555751592)"
FT /evidence="ECO:0000269|PubMed:25033069"
FT /id="VAR_073413"
FT VARIANT 1176
FT /note="G -> S (in OMCS; dbSNP:rs142422525)"
FT /evidence="ECO:0000269|PubMed:25480986"
FT /id="VAR_073414"
FT VARIANT 1215
FT /note="V -> A (in OMCS; dbSNP:rs1211079280)"
FT /evidence="ECO:0000269|PubMed:25480986"
FT /id="VAR_073415"
FT VARIANT 1359
FT /note="R -> W (in BNHS; dbSNP:rs374434303)"
FT /evidence="ECO:0000269|PubMed:25033069"
FT /id="VAR_073416"
FT VARIANT 1362
FT /note="R -> G (found in a patient with Gordon-Holmes
FT syndrome; uncertain significance; dbSNP:rs1204274988)"
FT /evidence="ECO:0000269|PubMed:24355708"
FT /id="VAR_071100"
FT CONFLICT 43..46
FT /note="AGRI -> TRPV (in Ref. 5; AAH38229)"
FT /evidence="ECO:0000305"
FT CONFLICT 648
FT /note="T -> A (in Ref. 2; BAG57380)"
FT /evidence="ECO:0000305"
FT CONFLICT 714
FT /note="A -> T (in Ref. 5; AAH38229)"
FT /evidence="ECO:0000305"
FT CONFLICT 994
FT /note="I -> W (in Ref. 6; CAB43674)"
FT /evidence="ECO:0000305"
FT CONFLICT 1178
FT /note="W -> V (in Ref. 6; CAB43674)"
FT /evidence="ECO:0000305"
FT CONFLICT 1296
FT /note="E -> G (in Ref. 6; CAB43674)"
FT /evidence="ECO:0000305"
FT CONFLICT 1302
FT /note="E -> K (in Ref. 2; BAH13718)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1375 AA; 150954 MW; 1C9F2797FB6D8612 CRC64;
MEAPLQTGMM GTSSHGLATN SSGAKVAERD GFQDVLAPGE GSAGRICGAQ PVPFVPQVLG
VMIGAGVAVV VTAVLILLVV RRLRVPKTPA PDGPRYRFRK RDKVLFYGRK IMRKVSQSTS
SLVDTSVSAT SRPRMRKKLK MLNIAKKILR IQKETPTLQR KEPPPAVLEA DLTEGDLANS
HLPSEVLYML KNVRVLGHFE KPLFLELCRH MVFQRLGQGD YVFRPGQPDA SIYVVQDGLL
ELCLPGPDGK ECVVKEVVPG DSVNSLLSIL DVITGHQHPQ RTVSARAARD STVLRLPVEA
FSAVFTKYPE SLVRVVQIIM VRLQRVTFLA LHNYLGLTNE LFSHEIQPLR LFPSPGLPTR
TSPVRGSKRM VSTSATDEPR ETPGRPPDPT GAPLPGPTGD PVKPTSLETP SAPLLSRCVS
MPGDISGLQG GPRSDFDMAY ERGRISVSLQ EEASGGSLAA PARTPTQEPR EQPAGACEYS
YCEDESATGG CPFGPYQGRQ TSSIFEAAKQ ELAKLMRIED PSLLNSRVLL HHAKAGTIIA
RQGDQDVSLH FVLWGCLHVY QRMIDKAEDV CLFVAQPGEL VGQLAVLTGE PLIFTLRAQR
DCTFLRISKS DFYEIMRAQP SVVLSAAHTV AARMSPFVRQ MDFAIDWTAV EAGRALYRQG
DRSDCTYIVL NGRLRSVIQR GSGKKELVGE YGRGDLIGVV EALTRQPRAT TVHAVRDTEL
AKLPEGTLGH IKRRYPQVVT RLIHLLSQKI LGNLQQLQGP FPAGSGLGVP PHSELTNPAS
NLATVAILPV CAEVPMVAFT LELQHALQAI GPTLLLNSDI IRARLGASAL DSIQEFRLSG
WLAQQEDAHR IVLYQTDASL TPWTVRCLRQ ADCILIVGLG DQEPTLGQLE QMLENTAVRA
LKQLVLLHRE EGAGPTRTVE WLNMRSWCSG HLHLRCPRRL 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 QIYDVGYQYG KAVFGGWSRG
NVIEKMLTDR RSTDLNESRR ADVLAFPSSG FTDLAEIVSR IEPPTSYVSD GCADGEESDC
LTEYEEDAGP DCSRDEGGSP EGASPSTASE MEEEKSILRQ RRCLPQEPPG SATDA
//
