PLPL1_HUMAN
ID PLPL1_HUMAN Reviewed; 532 AA.
AC Q8N8W4; A3RMU3; J3JS20; Q2A6N1; Q3SY95; Q3SY96; Q5R3L2;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Omega-hydroxyceramide transacylase {ECO:0000305|PubMed:27751867, ECO:0000305|PubMed:28248318};
DE EC=2.3.1.296 {ECO:0000269|PubMed:27751867, ECO:0000269|PubMed:28248318};
DE AltName: Full=Patatin-like phospholipase domain-containing protein 1 {ECO:0000312|HGNC:HGNC:21246};
GN Name=PNPLA1 {ECO:0000312|HGNC:HGNC:21246};
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), AND TISSUE SPECIFICITY.
RX PubMed=16799181; DOI=10.1194/jlr.m600185-jlr200;
RA Wilson P.A., Gardner S.D., Lambie N.M., Commans S.A., Crowther D.J.;
RT "Characterization of the human patatin-like phospholipase family.";
RL J. Lipid Res. 47:1940-1949(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT HIS-423.
RC TISSUE=Kidney;
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=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP HIS-423; MET-490 AND PRO-522.
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INVOLVEMENT IN ARCI10,
RP AND VARIANTS ARCI10 VAL-59 AND 131-GLU--GLN-532 DEL.
RX PubMed=22246504; DOI=10.1038/ng.1056;
RA Grall A., Guaguere E., Planchais S., Grond S., Bourrat E., Hausser I.,
RA Hitte C., Le Gallo M., Derbois C., Kim G.J., Lagoutte L.,
RA Degorce-Rubiales F., Radner F.P., Thomas A., Kuery S., Bensignor E.,
RA Fontaine J., Pin D., Zimmermann R., Zechner R., Lathrop M., Galibert F.,
RA Andre C., Fischer J.;
RT "PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden
RT retriever dogs and humans.";
RL Nat. Genet. 44:140-147(2012).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27751867; DOI=10.1016/j.jid.2016.08.036;
RA Grond S., Eichmann T.O., Dubrac S., Kolb D., Schmuth M., Fischer J.,
RA Crumrine D., Elias P.M., Haemmerle G., Zechner R., Lass A., Radner F.P.W.;
RT "PNPLA1 Deficiency in Mice and Humans Leads to a Defect in the Synthesis of
RT Omega-O-Acylceramides.";
RL J. Invest. Dermatol. 137:394-402(2017).
RN [7]
RP INDUCTION.
RX PubMed=28248300; DOI=10.1038/ncomms14609;
RA Hirabayashi T., Anjo T., Kaneko A., Senoo Y., Shibata A., Takama H.,
RA Yokoyama K., Nishito Y., Ono T., Taya C., Muramatsu K., Fukami K.,
RA Munoz-Garcia A., Brash A.R., Ikeda K., Arita M., Akiyama M., Murakami M.;
RT "PNPLA1 has a crucial role in skin barrier function by directing
RT acylceramide biosynthesis.";
RL Nat. Commun. 8:14609-14609(2017).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS ARCI10
RP THR-34; VAL-59 AND 131-GLU--GLN-532 DEL.
RX PubMed=28248318; DOI=10.1038/ncomms14610;
RA Ohno Y., Kamiyama N., Nakamichi S., Kihara A.;
RT "PNPLA1 is a transacylase essential for the generation of the skin barrier
RT lipid omega-O-acylceramide.";
RL Nat. Commun. 8:14610-14610(2017).
RN [9]
RP VARIANT ARCI10 THR-34.
RX PubMed=24344921; DOI=10.1111/bjd.12757;
RA Fachal L., Rodriguez-Pazos L., Ginarte M., Carracedo A., Toribio J.,
RA Vega A.;
RT "Identification of a novel PNPLA1 mutation in a Spanish family with
RT autosomal recessive congenital ichthyosis.";
RL Br. J. Dermatol. 170:980-982(2014).
CC -!- FUNCTION: Omega-hydroxyceramide transacylase involved in the synthesis
CC of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine;
CC EOS), which are extremely hydrophobic lipids involved in skin barrier
CC formation (PubMed:27751867, PubMed:28248318). Catalyzes the last step
CC of the synthesis of omega-O-acylceramides by transferring linoleic acid
CC from triglycerides to an omega-hydroxyceramide (PubMed:27751867,
CC PubMed:28248318). Omega-O-acylceramides, are required for the
CC biogenesis of lipid lamellae in the stratum corneum and the formation
CC of the cornified lipid envelope which are essential for the epidermis
CC barrier function (PubMed:22246504, PubMed:27751867, PubMed:28248318).
CC These lipids also play a role in keratinocyte differentiation (By
CC similarity). May also act on omega-hydroxylated ultra-long chain fatty
CC acids (omega-OH ULCFA) and acylglucosylceramides (GlcEOS) (By
CC similarity). {ECO:0000250|UniProtKB:Q3V1D5,
CC ECO:0000269|PubMed:22246504, ECO:0000269|PubMed:27751867,
CC ECO:0000269|PubMed:28248318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(omega-hydroxy-ultra-long chain fatty acyl)-sphingoid base = a
CC diacylglycerol + an N-[omega-(9Z,12Z-octadecadienoyloxy)-O-ultra-long
CC chain fatty acyl]-sphingoid base; Xref=Rhea:RHEA:61528,
CC ChEBI:CHEBI:18035, ChEBI:CHEBI:144774, ChEBI:CHEBI:144784,
CC ChEBI:CHEBI:144785; EC=2.3.1.296;
CC Evidence={ECO:0000269|PubMed:28248318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61529;
CC Evidence={ECO:0000305|PubMed:28248318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(omega-hydroxy-ultra-long chain fatty acyl)-sphing-4-enine = a
CC diacylglycerol + an N-(omega-(9Z,12Z-octadecadienoyloxy)-ultra-long
CC chain fatty acyl)-sphing-4-enine; Xref=Rhea:RHEA:65692,
CC ChEBI:CHEBI:18035, ChEBI:CHEBI:144774, ChEBI:CHEBI:157662,
CC ChEBI:CHEBI:157663; Evidence={ECO:0000305|PubMed:27751867,
CC ECO:0000305|PubMed:28248300};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65693;
CC Evidence={ECO:0000305|PubMed:27751867, ECO:0000305|PubMed:28248300};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + N-(30-
CC hydroxytriacontanoyl)-sphing-4-enine = di-(9Z,12Z)-
CC octadecadienoylglycerol + N-[30-(9Z,12Z-octadecadienoyloxy)-
CC triacontanoyl]-sphing-4-enine; Xref=Rhea:RHEA:55264,
CC ChEBI:CHEBI:34862, ChEBI:CHEBI:75844, ChEBI:CHEBI:138658,
CC ChEBI:CHEBI:138664; Evidence={ECO:0000269|PubMed:28248318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55265;
CC Evidence={ECO:0000305|PubMed:28248318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + N-
CC (28-hydroxyoctacosanoyl)-sphing-4-enine = a diacylglycerol + N-(28-
CC (9Z,12Z-octadecadienoyloxy)-octacosanoyl)-sphing-4-enine;
CC Xref=Rhea:RHEA:65648, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157643, ChEBI:CHEBI:157652;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65649;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + N-
CC (32-hydroxydotriacontanoyl)-sphing-4-enine = a diacylglycerol + N-
CC (32-(9Z,12Z-octadecadienoyloxy)-dotricontanoyl)-sphing-4-enine;
CC Xref=Rhea:RHEA:65652, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157644, ChEBI:CHEBI:157653;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65653;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + N-
CC (32-hydroxydotriacontenoyl)-sphing-4-enine = a diacylglycerol + an N-
CC (32-(9Z,12Z-octadecadienoyloxy)-dotriacontenoyl)-sphing-4-enine;
CC Xref=Rhea:RHEA:65668, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157645, ChEBI:CHEBI:157657;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65669;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(34-hydroxytetratriacontenoyl)-sphing-4-enine = a diacylglycerol +
CC an N-(34-(9Z,12Z-octadecadienoyloxy)-tetratriacontenoyl)-sphing-4-
CC enine; Xref=Rhea:RHEA:65672, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157646, ChEBI:CHEBI:157656;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65673;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(34-hydroxytetratriacontadienoyl)-sphing-4-enine = a diacylglycerol
CC + an N-(34-(9Z,12Z-octadecadienoyloxy)-tetratriacontadienoyl)-sphing-
CC 4-enine; Xref=Rhea:RHEA:65676, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157647, ChEBI:CHEBI:157658;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65677;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(36-hydroxyhexatriacontenoyl)-sphing-4-enine = a diacylglycerol +
CC an N-(36-(9Z,12Z-octadecadienoyloxy)-hexatriacontenoyl)-sphing-4-
CC enine; Xref=Rhea:RHEA:65680, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157648, ChEBI:CHEBI:157659;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65681;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(36-hydroxyhexatriacontadienoyl)-sphing-4-enine = a diacylglycerol
CC + an N-(36-(9Z,12Z-octadecadienoyloxy)-hexatriacontadienoyl)-sphing-
CC 4-enine; Xref=Rhea:RHEA:65684, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157649, ChEBI:CHEBI:157660;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65685;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an
CC N-(38-hydroxyoctatriacontenoyl)-sphing-4-enine = a diacylglycerol +
CC an N-(38-(9Z,12Z-octadecadienoyloxy)-octatriacontenoyl)-sphing-4-
CC enine; Xref=Rhea:RHEA:65688, ChEBI:CHEBI:18035, ChEBI:CHEBI:144774,
CC ChEBI:CHEBI:157650, ChEBI:CHEBI:157661;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65689;
CC Evidence={ECO:0000250|UniProtKB:Q3V1D5};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22246504}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N8W4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N8W4-2; Sequence=VSP_026371;
CC Name=3;
CC IsoId=Q8N8W4-3; Sequence=VSP_026371, VSP_026372;
CC -!- TISSUE SPECIFICITY: Expressed in the digestive system. Expressed in the
CC epidermis of skin keratinocytes. Strongly expressed in the granular
CC layer. Expressed in the upper epidermis and eccrine sweat glands of the
CC dermis and in the region of keratin filament bundles, which is more
CC pronounced in upper epidermal layers and in the lower cornified layers.
CC {ECO:0000269|PubMed:16799181, ECO:0000269|PubMed:22246504}.
CC -!- INDUCTION: Up-regulated upon induced differentiation of keratinocytes.
CC {ECO:0000269|PubMed:28248300}.
CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 10 (ARCI10)
CC [MIM:615024]: A form of autosomal recessive congenital ichthyosis, a
CC disorder of keratinization with abnormal differentiation and
CC desquamation of the epidermis, resulting in abnormal skin scaling over
CC the whole body. The main skin phenotypes are lamellar ichthyosis (LI)
CC and non-bullous congenital ichthyosiform erythroderma (NCIE), although
CC phenotypic overlap within the same patient or among patients from the
CC same family can occur. Lamellar ichthyosis is a condition often
CC associated with an embedment in a collodion-like membrane at birth;
CC skin scales later develop, covering the entire body surface. Non-
CC bullous congenital ichthyosiform erythroderma characterized by fine
CC whitish scaling on an erythrodermal background; larger brownish scales
CC are present on the buttocks, neck and legs.
CC {ECO:0000269|PubMed:22246504, ECO:0000269|PubMed:24344921,
CC ECO:0000269|PubMed:28248318}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Inactive. {ECO:0000305}.
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DR EMBL; AM182887; CAJ58679.1; -; mRNA.
DR EMBL; AK096074; BAC04697.1; -; mRNA.
DR EMBL; Z84484; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC103905; AAI03906.1; -; mRNA.
DR EMBL; BC103906; AAI03907.1; -; mRNA.
DR EMBL; BC103907; AAI03908.1; -; mRNA.
DR CCDS; CCDS34438.1; -. [Q8N8W4-2]
DR CCDS; CCDS47416.1; -. [Q8N8W4-3]
DR CCDS; CCDS54997.1; -. [Q8N8W4-1]
DR RefSeq; NP_001139188.1; NM_001145716.2. [Q8N8W4-3]
DR RefSeq; NP_001139189.2; NM_001145717.1. [Q8N8W4-1]
DR RefSeq; NP_775947.2; NM_173676.2. [Q8N8W4-2]
DR AlphaFoldDB; Q8N8W4; -.
DR SMR; Q8N8W4; -.
DR BioGRID; 130231; 24.
DR IntAct; Q8N8W4; 8.
DR STRING; 9606.ENSP00000378072; -.
DR SwissLipids; SLP:000001823; -.
DR iPTMnet; Q8N8W4; -.
DR PhosphoSitePlus; Q8N8W4; -.
DR BioMuta; PNPLA1; -.
DR DMDM; 296452995; -.
DR MassIVE; Q8N8W4; -.
DR PaxDb; Q8N8W4; -.
DR PeptideAtlas; Q8N8W4; -.
DR PRIDE; Q8N8W4; -.
DR Antibodypedia; 29651; 130 antibodies from 17 providers.
DR DNASU; 285848; -.
DR Ensembl; ENST00000312917.9; ENSP00000321116.5; ENSG00000180316.13. [Q8N8W4-3]
DR Ensembl; ENST00000388715.7; ENSP00000373367.3; ENSG00000180316.13. [Q8N8W4-2]
DR Ensembl; ENST00000394571.3; ENSP00000378072.2; ENSG00000180316.13. [Q8N8W4-1]
DR GeneID; 285848; -.
DR KEGG; hsa:285848; -.
DR UCSC; uc003olw.2; human. [Q8N8W4-1]
DR CTD; 285848; -.
DR DisGeNET; 285848; -.
DR GeneCards; PNPLA1; -.
DR GeneReviews; PNPLA1; -.
DR HGNC; HGNC:21246; PNPLA1.
DR HPA; ENSG00000180316; Tissue enriched (skin).
DR MalaCards; PNPLA1; -.
DR MIM; 612121; gene.
DR MIM; 615024; phenotype.
DR neXtProt; NX_Q8N8W4; -.
DR OpenTargets; ENSG00000180316; -.
DR Orphanet; 79394; Congenital non-bullous ichthyosiform erythroderma.
DR PharmGKB; PA134887192; -.
DR VEuPathDB; HostDB:ENSG00000180316; -.
DR eggNOG; KOG3773; Eukaryota.
DR GeneTree; ENSGT00940000160828; -.
DR InParanoid; Q8N8W4; -.
DR OrthoDB; 1204225at2759; -.
DR PhylomeDB; Q8N8W4; -.
DR TreeFam; TF314272; -.
DR BioCyc; MetaCyc:ENSG00000180316-MON; -.
DR BRENDA; 2.3.1.296; 2681.
DR PathwayCommons; Q8N8W4; -.
DR SignaLink; Q8N8W4; -.
DR BioGRID-ORCS; 285848; 15 hits in 1066 CRISPR screens.
DR ChiTaRS; PNPLA1; human.
DR GenomeRNAi; 285848; -.
DR Pharos; Q8N8W4; Tbio.
DR PRO; PR:Q8N8W4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8N8W4; protein.
DR Bgee; ENSG00000180316; Expressed in skin of abdomen and 72 other tissues.
DR ExpressionAtlas; Q8N8W4; baseline and differential.
DR Genevisible; Q8N8W4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IMP:UniProtKB.
DR GO; GO:0106341; F:omega-hydroxyceramide transacylase activity; IDA:UniProtKB.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IC:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0106342; P:omega-hydroxyceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
DR CDD; cd07219; Pat_PNPLA1; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR033562; PLPL.
DR InterPro; IPR039180; PNPLA1.
DR InterPro; IPR002641; PNPLA_dom.
DR PANTHER; PTHR12406; PTHR12406; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR PROSITE; PS51635; PNPLA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Disease variant; Ichthyosis;
KW Lipid biosynthesis; Lipid metabolism; Reference proteome; Transferase.
FT CHAIN 1..532
FT /note="Omega-hydroxyceramide transacylase"
FT /id="PRO_0000292019"
FT DOMAIN 16..185
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 290..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 51..55
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 172..174
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT COMPBIAS 327..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..368
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 COMPBIAS 401..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..523
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 53
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 172
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT VAR_SEQ 1..95
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026371"
FT VAR_SEQ 168
FT /note="V -> VWAFLTLPPQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026372"
FT VARIANT 34
FT /note="A -> T (in ARCI10; decreased omega-hydroxyceramide
FT transacylase activity; dbSNP:rs1182312612)"
FT /evidence="ECO:0000269|PubMed:24344921,
FT ECO:0000269|PubMed:28248318"
FT /id="VAR_084012"
FT VARIANT 59
FT /note="A -> V (in ARCI10; decreased omega-hydroxyceramide
FT transacylase activity; dbSNP:rs1561853847)"
FT /evidence="ECO:0000269|PubMed:22246504,
FT ECO:0000269|PubMed:28248318"
FT /id="VAR_069566"
FT VARIANT 131..532
FT /note="Missing (in ARCI10; loss of omega-hydroxyceramide
FT transacylase activity; dbSNP:rs1561864453)"
FT /evidence="ECO:0000269|PubMed:22246504,
FT ECO:0000269|PubMed:28248318"
FT /id="VAR_084013"
FT VARIANT 423
FT /note="P -> H (in dbSNP:rs12199580)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_032929"
FT VARIANT 490
FT /note="T -> M (in dbSNP:rs12197079)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032930"
FT VARIANT 522
FT /note="S -> P (in dbSNP:rs4713956)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032931"
FT CONFLICT 147
FT /note="A -> AA (in Ref. 1; CAJ58679)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 532 AA; 57875 MW; 175852A0FFABE035 CRC64;
MEEQVFKGDP DTPHSISFSG SGFLSFYQAG AVDALRDLAP RMLETAHRFA GTSAGAVIAA
LAICGIEMDE YLRVLNVGVA EVKKSFLGPL SPSCKMVQMM RQFLYRVLPE DSYKVTTGKL
HVSLTRLTDG ENVVVSEFTS KEELIEALYC SCFVPVYCGL IPPTYRGVRY IDGGFTGMQP
CAFWTDAITI STFSGQQDIC PRDCPAIFHD FRMFNCSFQF SLENIARMTH ALFPPDLVIL
HDYYYRGYED AVLYLRRLNA VYLNSSSKRV IFPRVEVYCQ IELALGNECP ERSQPSLRAR
QASLEGATQP HKEWVPKGDG RGSHGPPVSQ PVQTLEFTCE SPVSAPVSPL EQPPAQPLAS
STPLSLSGMP PVSFPAVHKP PSSTPGSSLP TPPPGLSPLS PQQQVQPSGS PARSLHSQAP
TSPRPSLGPS TVGAPQTLPR SSLSAFPAQP PVEELGQEQP QAVALLVSSK PKSAVPLVHV
KETVSKPYVT ESPAEDSNWV NKVFKKNKQK TSGTRKGFPR HSGSKKPSSK VQ
