UniProtKB - Q8N8W4 (PLPL1_HUMAN)
Protein
Omega-hydroxyceramide transacylase
Gene
PNPLA1
Organism
Homo sapiens (Human)
Status
Functioni
Omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation (PubMed:27751867, PubMed:28248318). Catalyzes the last step of the synthesis of omega-O-acylceramides by transferring linoleic acid from triglycerides to an omega-hydroxyceramide (PubMed:27751867, PubMed:28248318). Omega-O-acylceramides, are required for the biogenesis of lipid lamellae in the stratum corneum and the formation of the cornified lipid envelope which are essential for the epidermis barrier function (PubMed:22246504, PubMed:27751867, PubMed:28248318). These lipids also play a role in keratinocyte differentiation (By similarity). May also act on omega-hydroxylated ultra-long chain fatty acids (omega-OH ULCFA) and acylglucosylceramides (GlcEOS) (By similarity).By similarity3 Publications
Catalytic activityi
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(ω-hydroxy-ultra-long chain fatty acyl)-sphingoid base = a diacylglycerol + an N-[ω-(9Z,12Z-octadecadienoyloxy)-O-ultra-long chain fatty acyl]-sphingoid base1 PublicationEC:2.3.1.2961 PublicationThis reaction proceeds in the forward1 Publication direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(ω-hydroxy-ultra-long chain fatty acyl)-sphing-4-enine = a diacylglycerol + an N-(ω-(9Z,12Z-octadecadienoyloxy)-ultra-long chain fatty acyl)-sphing-4-enine2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + N-(30-hydroxytriacontanoyl)-sphing-4-enine = di-(9Z,12Z)-octadecadienoylglycerol + N-[30-(9Z,12Z-octadecadienoyloxy)-triacontanoyl]-sphing-4-enine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + N-(28-hydroxyoctacosanoyl)-sphing-4-enine = a diacylglycerol + N-(28-(9Z,12Z-octadecadienoyloxy)-octacosanoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + N-(32-hydroxydotriacontanoyl)-sphing-4-enine = a diacylglycerol + N-(32-(9Z,12Z-octadecadienoyloxy)-dotricontanoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(32-hydroxydotriacontenoyl)-sphing-4-enine = a diacylglycerol + an N-(32-(9Z,12Z-octadecadienoyloxy)-dotriacontenoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(34-hydroxytetratriacontenoyl)-sphing-4-enine = a diacylglycerol + an N-(34-(9Z,12Z-octadecadienoyloxy)-tetratriacontenoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(34-hydroxytetratriacontadienoyl)-sphing-4-enine = a diacylglycerol + an N-(34-(9Z,12Z-octadecadienoyloxy)-tetratriacontadienoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(36-hydroxyhexatriacontenoyl)-sphing-4-enine = a diacylglycerol + an N-(36-(9Z,12Z-octadecadienoyloxy)-hexatriacontenoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(36-hydroxyhexatriacontadienoyl)-sphing-4-enine = a diacylglycerol + an N-(36-(9Z,12Z-octadecadienoyloxy)-hexatriacontadienoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol + an N-(38-hydroxyoctatriacontenoyl)-sphing-4-enine = a diacylglycerol + an N-(38-(9Z,12Z-octadecadienoyloxy)-octatriacontenoyl)-sphing-4-enineBy similarityThis reaction proceeds in the forwardBy similarity direction.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 53 | NucleophilePROSITE-ProRule annotation | 1 | |
Active sitei | 172 | Proton acceptorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- omega-hydroxyceramide transacylase activity Source: UniProtKB
- structural constituent of skin epidermis Source: UniProtKB
- transferase activity, transferring acyl groups other than amino-acyl groups Source: UniProtKB
- triglyceride lipase activity Source: GO_Central
GO - Biological processi
- ceramide biosynthetic process Source: UniProtKB
- lipid homeostasis Source: GO_Central
- omega-hydroxyceramide biosynthetic process Source: UniProtKB
- triglyceride catabolic process Source: GO_Central
Keywordsi
Molecular function | Transferase |
Biological process | Lipid biosynthesis, Lipid metabolism |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000180316-MONOMER |
PathwayCommonsi | Q8N8W4 |
Chemistry databases
SwissLipidsi | SLP:000001823 |
Names & Taxonomyi
Protein namesi | Recommended name: Omega-hydroxyceramide transacylase2 Publications (EC:2.3.1.2962 Publications)Alternative name(s): Patatin-like phospholipase domain-containing protein 1Imported |
Gene namesi | Name:PNPLA1Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21246, PNPLA1 |
MIMi | 612121, gene |
neXtProti | NX_Q8N8W4 |
VEuPathDBi | HostDB:ENSG00000180316.11 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- cytoplasm Source: UniProtKB
- lipid droplet Source: GO_Central
- membrane Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Ichthyosis, congenital, autosomal recessive 10 (ARCI10)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_084012 | 34 | A → T in ARCI10; decreased omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1182312612Ensembl. | 1 | |
Natural variantiVAR_069566 | 59 | A → V in ARCI10; decreased omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1561853847Ensembl. | 1 | |
Natural variantiVAR_084013 | 131 – 532 | Missing in ARCI10; loss of omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1561864453Add BLAST | 402 |
Keywords - Diseasei
Disease variant, IchthyosisOrganism-specific databases
DisGeNETi | 285848 |
GeneReviewsi | PNPLA1 |
MalaCardsi | PNPLA1 |
MIMi | 615024, phenotype |
OpenTargetsi | ENSG00000180316 |
Orphaneti | 79394, Congenital non-bullous ichthyosiform erythroderma |
PharmGKBi | PA134887192 |
Miscellaneous databases
Pharosi | Q8N8W4, Tbio |
Genetic variation databases
BioMutai | PNPLA1 |
DMDMi | 296452995 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000292019 | 1 – 532 | Omega-hydroxyceramide transacylaseAdd BLAST | 532 |
Proteomic databases
PaxDbi | Q8N8W4 |
PRIDEi | Q8N8W4 |
ProteomicsDBi | 72466 [Q8N8W4-1] 72467 [Q8N8W4-2] 72468 [Q8N8W4-3] |
PTM databases
iPTMneti | Q8N8W4 |
PhosphoSitePlusi | Q8N8W4 |
Expressioni
Tissue specificityi
Expressed in the digestive system. Expressed in the epidermis of skin keratinocytes. Strongly expressed in the granular layer. Expressed in the upper epidermis and eccrine sweat glands of the dermis and in the region of keratin filament bundles, which is more pronounced in upper epidermal layers and in the lower cornified layers.2 Publications
Inductioni
Up-regulated upon induced differentiation of keratinocytes.1 Publication
Gene expression databases
Bgeei | ENSG00000180316, Expressed in zone of skin and 69 other tissues |
ExpressionAtlasi | Q8N8W4, baseline and differential |
Genevisiblei | Q8N8W4, HS |
Organism-specific databases
HPAi | ENSG00000180316, Tissue enhanced (blood, skin) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 130231, 11 interactors |
IntActi | Q8N8W4, 8 interactors |
STRINGi | 9606.ENSP00000378072 |
Miscellaneous databases
RNActi | Q8N8W4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 16 – 185 | PNPLAPROSITE-ProRule annotationAdd BLAST | 170 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 51 – 55 | GXSXGPROSITE-ProRule annotation | 5 | |
Motifi | 172 – 174 | DGA/GPROSITE-ProRule annotation | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 326 – 451 | Pro-richAdd BLAST | 126 |
Phylogenomic databases
eggNOGi | KOG3773, Eukaryota |
GeneTreei | ENSGT00940000160828 |
InParanoidi | Q8N8W4 |
OrthoDBi | 1204225at2759 |
PhylomeDBi | Q8N8W4 |
TreeFami | TF314272 |
Family and domain databases
CDDi | cd07219, Pat_PNPLA1, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR039180, Pat_PNPLA1 IPR033562, PLPL IPR002641, PNPLA_dom |
PANTHERi | PTHR12406, PTHR12406, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS51635, PNPLA, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8N8W4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEEQVFKGDP DTPHSISFSG SGFLSFYQAG AVDALRDLAP RMLETAHRFA
60 70 80 90 100
GTSAGAVIAA LAICGIEMDE YLRVLNVGVA EVKKSFLGPL SPSCKMVQMM
110 120 130 140 150
RQFLYRVLPE DSYKVTTGKL HVSLTRLTDG ENVVVSEFTS KEELIEALYC
160 170 180 190 200
SCFVPVYCGL IPPTYRGVRY IDGGFTGMQP CAFWTDAITI STFSGQQDIC
210 220 230 240 250
PRDCPAIFHD FRMFNCSFQF SLENIARMTH ALFPPDLVIL HDYYYRGYED
260 270 280 290 300
AVLYLRRLNA VYLNSSSKRV IFPRVEVYCQ IELALGNECP ERSQPSLRAR
310 320 330 340 350
QASLEGATQP HKEWVPKGDG RGSHGPPVSQ PVQTLEFTCE SPVSAPVSPL
360 370 380 390 400
EQPPAQPLAS STPLSLSGMP PVSFPAVHKP PSSTPGSSLP TPPPGLSPLS
410 420 430 440 450
PQQQVQPSGS PARSLHSQAP TSPRPSLGPS TVGAPQTLPR SSLSAFPAQP
460 470 480 490 500
PVEELGQEQP QAVALLVSSK PKSAVPLVHV KETVSKPYVT ESPAEDSNWV
510 520 530
NKVFKKNKQK TSGTRKGFPR HSGSKKPSSK VQ
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1B0GW56 | A0A1B0GW56_HUMAN | Omega-hydroxyceramide transacylase | PNPLA1 | 481 | Annotation score: | ||
A0A0C4DG24 | A0A0C4DG24_HUMAN | Omega-hydroxyceramide transacylase | PNPLA1 | 533 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 147 | A → AA in CAJ58679 (PubMed:16799181).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_084012 | 34 | A → T in ARCI10; decreased omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1182312612Ensembl. | 1 | |
Natural variantiVAR_069566 | 59 | A → V in ARCI10; decreased omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1561853847Ensembl. | 1 | |
Natural variantiVAR_084013 | 131 – 532 | Missing in ARCI10; loss of omega-hydroxyceramide transacylase activity. 2 PublicationsCorresponds to variant dbSNP:rs1561864453Add BLAST | 402 | |
Natural variantiVAR_032929 | 423 | P → H2 PublicationsCorresponds to variant dbSNP:rs12199580Ensembl. | 1 | |
Natural variantiVAR_032930 | 490 | T → M1 PublicationCorresponds to variant dbSNP:rs12197079Ensembl. | 1 | |
Natural variantiVAR_032931 | 522 | S → P1 PublicationCorresponds to variant dbSNP:rs4713956Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026371 | 1 – 95 | Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST | 95 | |
Alternative sequenceiVSP_026372 | 168 | V → VWAFLTLPPQ in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AM182887 mRNA Translation: CAJ58679.1 AK096074 mRNA Translation: BAC04697.1 Z84484 Genomic DNA No translation available. BC103905 mRNA Translation: AAI03906.1 BC103906 mRNA Translation: AAI03907.1 BC103907 mRNA Translation: AAI03908.1 |
CCDSi | CCDS34438.1 [Q8N8W4-2] CCDS47416.1 [Q8N8W4-3] CCDS54997.1 [Q8N8W4-1] |
RefSeqi | NP_001139188.1, NM_001145716.2 [Q8N8W4-3] NP_001139189.2, NM_001145717.1 [Q8N8W4-1] NP_775947.2, NM_173676.2 [Q8N8W4-2] |
Genome annotation databases
Ensembli | ENST00000312917; ENSP00000321116; ENSG00000180316 [Q8N8W4-3] ENST00000388715; ENSP00000373367; ENSG00000180316 [Q8N8W4-2] ENST00000394571; ENSP00000378072; ENSG00000180316 [Q8N8W4-1] |
GeneIDi | 285848 |
KEGGi | hsa:285848 |
UCSCi | uc003olw.2, human [Q8N8W4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AM182887 mRNA Translation: CAJ58679.1 AK096074 mRNA Translation: BAC04697.1 Z84484 Genomic DNA No translation available. BC103905 mRNA Translation: AAI03906.1 BC103906 mRNA Translation: AAI03907.1 BC103907 mRNA Translation: AAI03908.1 |
CCDSi | CCDS34438.1 [Q8N8W4-2] CCDS47416.1 [Q8N8W4-3] CCDS54997.1 [Q8N8W4-1] |
RefSeqi | NP_001139188.1, NM_001145716.2 [Q8N8W4-3] NP_001139189.2, NM_001145717.1 [Q8N8W4-1] NP_775947.2, NM_173676.2 [Q8N8W4-2] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 130231, 11 interactors |
IntActi | Q8N8W4, 8 interactors |
STRINGi | 9606.ENSP00000378072 |
Chemistry databases
SwissLipidsi | SLP:000001823 |
PTM databases
iPTMneti | Q8N8W4 |
PhosphoSitePlusi | Q8N8W4 |
Genetic variation databases
BioMutai | PNPLA1 |
DMDMi | 296452995 |
Proteomic databases
PaxDbi | Q8N8W4 |
PRIDEi | Q8N8W4 |
ProteomicsDBi | 72466 [Q8N8W4-1] 72467 [Q8N8W4-2] 72468 [Q8N8W4-3] |
Protocols and materials databases
Antibodypediai | 29651, 125 antibodies |
Genome annotation databases
Ensembli | ENST00000312917; ENSP00000321116; ENSG00000180316 [Q8N8W4-3] ENST00000388715; ENSP00000373367; ENSG00000180316 [Q8N8W4-2] ENST00000394571; ENSP00000378072; ENSG00000180316 [Q8N8W4-1] |
GeneIDi | 285848 |
KEGGi | hsa:285848 |
UCSCi | uc003olw.2, human [Q8N8W4-1] |
Organism-specific databases
CTDi | 285848 |
DisGeNETi | 285848 |
GeneCardsi | PNPLA1 |
GeneReviewsi | PNPLA1 |
HGNCi | HGNC:21246, PNPLA1 |
HPAi | ENSG00000180316, Tissue enhanced (blood, skin) |
MalaCardsi | PNPLA1 |
MIMi | 612121, gene 615024, phenotype |
neXtProti | NX_Q8N8W4 |
OpenTargetsi | ENSG00000180316 |
Orphaneti | 79394, Congenital non-bullous ichthyosiform erythroderma |
PharmGKBi | PA134887192 |
VEuPathDBi | HostDB:ENSG00000180316.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3773, Eukaryota |
GeneTreei | ENSGT00940000160828 |
InParanoidi | Q8N8W4 |
OrthoDBi | 1204225at2759 |
PhylomeDBi | Q8N8W4 |
TreeFami | TF314272 |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000180316-MONOMER |
PathwayCommonsi | Q8N8W4 |
Miscellaneous databases
BioGRID-ORCSi | 285848, 5 hits in 984 CRISPR screens |
ChiTaRSi | PNPLA1, human |
GenomeRNAii | 285848 |
Pharosi | Q8N8W4, Tbio |
PROi | PR:Q8N8W4 |
RNActi | Q8N8W4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180316, Expressed in zone of skin and 69 other tissues |
ExpressionAtlasi | Q8N8W4, baseline and differential |
Genevisiblei | Q8N8W4, HS |
Family and domain databases
CDDi | cd07219, Pat_PNPLA1, 1 hit |
InterProi | View protein in InterPro IPR016035, Acyl_Trfase/lysoPLipase IPR039180, Pat_PNPLA1 IPR033562, PLPL IPR002641, PNPLA_dom |
PANTHERi | PTHR12406, PTHR12406, 1 hit |
SUPFAMi | SSF52151, SSF52151, 1 hit |
PROSITEi | View protein in PROSITE PS51635, PNPLA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PLPL1_HUMAN | |
Accessioni | Q8N8W4Primary (citable) accession number: Q8N8W4 Secondary accession number(s): A3RMU3 Q5R3L2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 26, 2007 |
Last sequence update: | May 18, 2010 | |
Last modified: | April 7, 2021 | |
This is version 133 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot