2024-04-25 13:24:10, GGRNA : RefSeq release 60 (20130726)
LOCUS NM_001256126 6868 bp mRNA linear PRI 15-JUL-2013 DEFINITION Homo sapiens ceramide synthase 6 (CERS6), transcript variant 1, mRNA. ACCESSION NM_001256126 VERSION NM_001256126.1 GI:371122598 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 6868) AUTHORS Hoeferlin,L.A., Fekry,B., Ogretmen,B., Krupenko,S.A. and Krupenko,N.I. TITLE Folate stress induces apoptosis via p53-dependent de novo ceramide synthesis and up-regulation of ceramide synthase 6 JOURNAL J. Biol. Chem. 288 (18), 12880-12890 (2013) PUBMED 23519469 REMARK GeneRIF: folate withdrawal also induced CerS6/C16-ceramide elevation accompanied by p53 accumulation. Overall, these novel findings link folate and de novo ceramide pathways in cellular stress response. REFERENCE 2 (bases 1 to 6868) AUTHORS Schiffmann,S., Ferreiros,N., Birod,K., Eberle,M., Schreiber,Y., Pfeilschifter,W., Ziemann,U., Pierre,S., Scholich,K., Grosch,S. and Geisslinger,G. TITLE Ceramide synthase 6 plays a critical role in the development of experimental autoimmune encephalomyelitis JOURNAL J. Immunol. 188 (11), 5723-5733 (2012) PUBMED 22544924 REMARK GeneRIF: The transiently increased expression of ceramide synthase (CerS6) correlates to the clinical finding that C(16:0)-Cer levels are increased 1.9-fold in cerebrospinal fluid of multiple sclerosis patients. REFERENCE 3 (bases 1 to 6868) AUTHORS Senkal,C.E., Ponnusamy,S., Manevich,Y., Meyers-Needham,M., Saddoughi,S.A., Mukhopadyay,A., Dent,P., Bielawski,J. and Ogretmen,B. TITLE Alteration of ceramide synthase 6/C16-ceramide induces activating transcription factor 6-mediated endoplasmic reticulum (ER) stress and apoptosis via perturbation of cellular Ca2+ and ER/Golgi membrane network JOURNAL J. Biol. Chem. 286 (49), 42446-42458 (2011) PUBMED 22013072 REMARK GeneRIF: Alteration of ceramide synthase 6/C16-ceramide induces activating transcription factor 6-mediated endoplasmic reticulum (ER) stress and apoptosis via perturbation of cellular Ca2+ and ER/Golgi membrane network REFERENCE 4 (bases 1 to 6868) AUTHORS Mesicek,J., Lee,H., Feldman,T., Jiang,X., Skobeleva,A., Berdyshev,E.V., Haimovitz-Friedman,A., Fuks,Z. and Kolesnick,R. TITLE Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells JOURNAL Cell. Signal. 22 (9), 1300-1307 (2010) PUBMED 20406683 REMARK GeneRIF: ionizing radiation induces de novo synthesis of ceramide to influence HeLa cell apoptosis by specifically activating CerS isoforms 2, 5, and 6 that generate opposing anti- and pro-apoptotic ceramides in mitochondrial membranes. REFERENCE 5 (bases 1 to 6868) AUTHORS Yacoub,A., Hamed,H.A., Allegood,J., Mitchell,C., Spiegel,S., Lesniak,M.S., Ogretmen,B., Dash,R., Sarkar,D., Broaddus,W.C., Grant,S., Curiel,D.T., Fisher,P.B. and Dent,P. TITLE PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells JOURNAL Cancer Res. 70 (3), 1120-1129 (2010) PUBMED 20103619 REMARK GeneRIF: Findings indicate that mda-7/IL-24 induces PERK activation that triggers production of ceramide, ceramide synthase 6 and thioredoxin, which in turn promote glioma cell autophagy and cell death. REFERENCE 6 (bases 1 to 6868) AUTHORS Erez-Roman,R., Pienik,R. and Futerman,A.H. TITLE Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression JOURNAL Biochem. Biophys. Res. Commun. 391 (1), 219-223 (2010) PUBMED 19912991 REMARK GeneRIF: CerS2 and CerS6 mRNA was significantly elevated in breast cancer tissue compared to paired normal tissue, with approximately half of the individuals showing elevated CerS2 and CerS6 mRNA. REFERENCE 7 (bases 1 to 6868) AUTHORS Senkal,C.E., Ponnusamy,S., Bielawski,J., Hannun,Y.A. and Ogretmen,B. TITLE Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways JOURNAL FASEB J. 24 (1), 296-308 (2010) PUBMED 19723703 REMARK GeneRIF: Mechanistically, regulation of ER-stress-induced apoptosis by CerS6/C(16)-ceramide was linked to the activation of a specific arm, ATF6/CHOP, of the unfolded protein response pathway. COMMENT VALIDATED REFSEQ: This record has undergone validation or preliminary review. The reference sequence was derived from AK172775.1, BC109284.1, AC009475.5 and BM968545.1. Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1). Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. ##Evidence-Data-START## Transcript exon combination :: BC109284.1 [ECO:0000332] RNAseq introns :: single sample supports all introns ERS025082, ERS025083 [ECO:0000348] ##Evidence-Data-END## COMPLETENESS: complete on the 3' end. PRIMARY REFSEQ_SPAN PRIMARY_IDENTIFIER PRIMARY_SPAN COMP 1-150 AK172775.1 1-150 151-1429 BC109284.1 1-1279 1430-6269 AC009475.5 127714-132553 6270-6868 BM968545.1 1-599 c FEATURES Location/Qualifiers source 1..6868 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /chromosome="2" /map="2q24.3" gene 1..6868 /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="ceramide synthase 6" /db_xref="GeneID:253782" /db_xref="HGNC:23826" exon 1..370 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" STS 151..1429 /gene="CERS6" /gene_synonym="CERS5; LASS6" /db_xref="UniSTS:490081" CDS 201..1379 /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="isoform 1 is encoded by transcript variant 1; LAG1 homolog, ceramide synthase 6; longevity assurance homolog 6" /codon_start=1 /product="ceramide synthase 6 isoform 1" /protein_id="NP_001243055.1" /db_xref="GI:371122599" /db_xref="CCDS:CCDS58734.1" /db_xref="GeneID:253782" /db_xref="HGNC:23826" /translation="
MAGILAWFWNERFWLPHNVTWADLKNTEEATFPQAEDLYLAFPLAFCIFMVRLIFERFVAKPCAIALNIQANGPQIAPPNAILEKVFTAITKHPDEKRLEGLSKQLDWDVRSIQRWFRQRRNQEKPSTLTRFCESMWRFSFYLYVFTYGVRFLKKTPWLWNTRHCWYNYPYQPLTTDLHYYYILELSFYWSLMFSQFTDIKRKDFGIMFLHHLVSIFLITFSYVNNMARVGTLVLCLHDSADALLEAAKMANYAKFQKMCDLLFVMFAVVFITTRLGIFPLWVLNTTLFESWEIVGPYPSWWVFNLLLLLVQGLNCFWSYLIVKIACKAVSRGKAGKWNPLHVSKDDRSDIESSSDEEDSEPPGKNPHTATTTNGTSGTNGYLLTGSCSMDD
" misc_feature 438..581 /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner; Region: homeodomain; cd00086" /db_xref="CDD:28970" misc_feature order(477..479,495..497,534..536,540..545,552..557, 561..569,573..578) /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="DNA binding site [nucleotide binding]" /db_xref="CDD:28970" misc_feature order(543..545,552..557,564..566) /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="specific DNA base contacts [nucleotide binding]; other site" /db_xref="CDD:28970" misc_feature 588..1193 /gene="CERS6" /gene_synonym="CERS5; LASS6" /note="TRAM, LAG1 and CLN8 homology domains; Region: TLC; smart00724" /db_xref="CDD:128963" exon 371..476 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 477..607 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 608..665 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 666..716 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 717..809 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 810..938 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 939..1045 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 1046..1202 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 1203..1226 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" exon 1227..6851 /gene="CERS6" /gene_synonym="CERS5; LASS6" /inference="alignment:Splign:1.39.8" STS 1795..1916 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="RH91148" /db_xref="UniSTS:87635" STS 1814..1930 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="SHGC-61991" /db_xref="UniSTS:69314" STS 1851..1923 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="D2S2127" /db_xref="UniSTS:60130" STS 2331..2468 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="WI-13837" /db_xref="UniSTS:73569" STS 3800..3933 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="RH16666" /db_xref="UniSTS:26584" STS 3825..3973 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="D2S1544E" /db_xref="UniSTS:150630" STS 4675..4858 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="HUM0S12B10" /db_xref="UniSTS:44987" STS 4864..4966 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="WI-15844" /db_xref="UniSTS:22511" variation complement(5699) /gene="CERS6" /gene_synonym="CERS5; LASS6" /replace="a" /replace="c" /db_xref="dbSNP:3814378" STS 6081..6359 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="D2S2660" /db_xref="UniSTS:47670" STS 6098..6354 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="A005N32" /db_xref="UniSTS:60974" STS 6098..6354 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="G20356" /db_xref="UniSTS:60973" STS 6106..6244 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="D2S1648E" /db_xref="UniSTS:67815" STS 6541..6699 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="RH68290" /db_xref="UniSTS:53184" STS 6650..6785 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="RH35853" /db_xref="UniSTS:80041" STS 6650..6783 /gene="CERS6" /gene_synonym="CERS5; LASS6" /standard_name="LOC253782" /db_xref="UniSTS:266383" ORIGIN
gcggccagagggaggagagaaccggggctcgccgcgagccttcgagagcagcggccgcggaggaggcggcggcggcgggcgggagcagcggcggcggcggcacaggctcggggccagccgggcgcgcatccccgggcgccctgcgcggtggagagcttggcgggctgcgggtgccgcaggacaggagtggacaaagcaagatggcagggatcttagcctggttctggaacgagaggttttggctcccgcacaatgtcacctgggcggacctgaagaacacggaggaggccaccttcccgcaggctgaggacctctatctcgcttttcccctggccttctgtatcttcatggtgcggctcatcttcgagagatttgtagccaaaccgtgcgccatagccctcaacattcaggccaatggaccacaaattgctccgcccaatgccattctggaaaaggtcttcactgcaattacaaagcatcctgatgaaaagagattggaaggcctctccaagcaactggactgggatgttcgaagcattcagcgctggtttcgacaaagacgcaatcaggagaagccaagcacgctgacgaggttctgtgagagcatgtggagattttcattttacctttatgtatttacctacggagtcagattcctgaaaaagaccccctggttgtggaatacgaggcattgctggtacaactacccctatcagccactcacaactgaccttcactactattacatcctggagctgtcgttttattggtctttgatgttttctcagttcactgatatcaaaagaaaggactttggcattatgttcctgcaccaccttgtatctattttcttgattaccttttcatatgtcaacaatatggcccgagtaggaacgctggtcctttgtcttcatgattcagctgatgctcttctggaggctgccaaaatggcaaattatgccaagtttcagaaaatgtgtgatctcctgtttgttatgtttgccgtggtttttatcaccacacgactgggtatatttcctctctgggtgttaaataccacattatttgaaagctgggagatcgttggaccttacccttcctggtgggtttttaacctactgctattgctagtacaagggttgaactgcttctggtcttacttgattgtgaaaatagcttgcaaagctgtttcaagaggcaaggctgggaagtggaaccctttacatgtgtccaaggatgatcgaagtgatattgagtctagctcagatgaggaggactcagaacctccgggaaagaatccccacactgcgacaaccaccaatgggaccagtggtaccaacgggtatctcctgactggctcctgctccatggatgattaattactcaaaactacaagtcccaagcaaagtgaactatttgttcctggaagtatttaataagttgcaaatgcagttcctttcataatatctcagcaccagaaacaaaaattaagattatcaaagcattttgaatagtgcactgccatgtgtcctgtctgtgaatgaagaagaattaccattctctctttgtaggcatgctgtatgtaattgacacaagggaacagtatttgcatttgtactgtcttagaatattatttatttttttgtatttgtaaatctgtggacaaaagagggtttcctcactccttttactcactgggctcatgacagtgaaggagatgctccatctgcttctccccctttctcttgctgtagtccaatgtgctatgagcatcagcttactttgtcacttagagcaagcaaaacccagtgcaagagtctcgttcagctctaaataggtttgctttcttttagttacagtgcccattttgaaattgcctatacagtcttagtgaccatttaaaccggacgaactaggtgtttaattttcactcttcatgttcaattagcagttcaaattaaagaagatggttattggagaacttttttgaatggttttgtattaaattgctttgaaatagatttcatttcttgtgcacacagccaagatttcttcaatgggtgtgagctagttgagggttaaccttgtaggttgcagagtgtatttgtttgtttgtttgtttttctctgtgatgaggtcagtgctctgattttgaaggaggatattcactgaagctcatagttataaacaaggaaatcactgttaagaatgggaatttgtcctgtgttctgggaataacataaagagagcaactgatttcagccaggttttgccactaccctataattagtgcagtcttatgttataaaagaaagaagttaactatatttggggacaaaaaaatatttcaagagttgataaagattacctgtgcagtgcagagcactttaatgcaaccagctttcaagaaaaagccctatctagtacttgatgttgatgtttttattttgctgagcaaaataaagccaatgggagaaagactattttaccctttgcttttctccttaaacgtaatccagatgactttcctgttactaaacactgagcagcattacactacaatgcttctttggtttccaggaatttttttcaaatggggctgtttctggaaaaatgaaaaattctattggacaatggcaatatcaacaatgaggaaaattactgaagaataagtttccataagtctcctacatagcagtgttatttatgtacagataagaaaaccatatgtcagccaaagattttatctcttcttctaacttttagtaagaggaaaaagggattataaaacccttcataaatcaagaaggccatcacttagaacgaaccccaaacaaaaatgccataatataaatgtgtgaatcagggctgtgaagacaacagcagaaatgctaacaagcgtgcagaaacaccagagagtgcgtatcctgctcagaaccattcacatttaattcaattcttggaaaaaattaaagctttttgcccacaatttgcaatctgtgggttaatagttaaaagaatgttcccaaccaaaaaattcttaccgtaatattatatcttgccctacttatttacaaaataatatgtttctgttatggtccttagtaataattgaagaggcttagaaatacatctgcttgtttattgagaaaacgatgcaaataattctgcttttagagccttgttattttatttcacaaaacaggcatatgtctaggagtgtaatttgtggatggttgagtttgtaagaacaatcataaaaggacttgttagtctccagaacatctgctaaaatgcaagtatatgtataaggtaatagcatattacagctgaaaattttgagaaggtaaaagtttcttaattaaaatatgaacatatttagcttgctttagtgtctggggcaagtcctctcaatggctaaaattaactttagagatccatgtgttcaggtttagatcatatgacactcgagcacagaagaataatttcaaggaggtcatcttgtaaattaaaggtttagaagaattgcataaaacgtagtaaatggggtctgtcattagcaaaggcaaatctaagcaatcatttttccccccagaagttacttagaaggagaactgggaacacttggggtctctctaactgatggcattcacttcacacagtcgtctatgttatccagagatttttatttcattttacattttagggcacagttctttggggctaattaaaatggggtttgcaggctttttatggtgaagaataatatatctctgtctatagctttcccatggtagcctgataaggctgagagagaaaaatatgtgcagtatctcatcctccccctgtaccaggccatagctttgaagtgtattttgtaaattcaactataggttagtcagaatgctgtttttcgttaattaacttagcctgtgttgatatctcctccttcctggtcacattcaaaccttcccagagtacaaaggggtatgtagaaaggattccagaagaagtaatactttattctctaatgttaatagcttttctggatctcttagtagggggaaagtagaaaatcgagtagaatttggcctcaggtcaataaatgatataaaaacatgtgttctatttatgtatatatatgtatgtttctccaaaaagtgataaaaccaaaatatcactgactcatccctacccatattcttttcataaaacccactcaccaggtacaatagaaacttccctccttgtttgtcagcctcctgttcatgttccccacacacctgaaggtggtagaatcttttcagcctcttagccagtgagctaaatatggctaagcacaggtcataagagcacctaaggccagcatataagccaactacagttcacctttccaaatttggtcctatggatgttgagcatagggaagcaactctcagtattttggattattcaagtgtatgtggtaaaaatgcagatgattgctgctttaccccagggtttattagcatcctacttctgctgggctgcatcattatataatgccacaggcatctagtcaaggtaaagaagccagaaaggttaggcaagaagtgagataaaatcagatcacctttgatcaaaatggttggtgaacctccacatgtccagttctgttgccaaactttccattcagagtatttggtggagtttgaatttgagcaaactaaatgccttcatcttaggtagaaagggcctgaatcttccattttatattcaaacctcattgttatttggcctaagtaaaaagtcagatttcatttccatttacctgagttcgctttaaagagcttttcaaagagagctttatagacacccacaattgtccccaatctcttcatgatgttgcattaatagttgtttttgtccctttcttggaaatgttaatgccaaagttgcctgaacattgggcggttttcttaatttgaagtataaaaattataaagagtaattccaaaggtattaaaagattgtttaacagtatgtgtggtgatgtcattatctccagagaggcttcaagaaatcctttggaaataaaaagttaaatgtttacatttcatgtggtatttcaggtcttcaggttctgattagcttacttttttcctttgtctttggctgatttctgctttgtagataaataataatagccctgagatgtttctaacatttaaataagaaaaaaatcaaatcgaagtcagcctgctggaaaagtgatcacatggcagttgcagtaacttgtatggaaagagaaaatgcaatgagcccagttactgcacttgccactaccatgctgtccatggaaggaataatcagcagttcagttgtcacaagccgcccttgaagaaaacgcagcaaaatattttaaaatgaagatattgcagtccccagagccagtgaaggtttcttttggtaaaatgaaattgtgccattgtcaaagtaccccgtagtgatgagcactgactggttcactggccacattttagttcttcataataataggccacaaaagggctctgtggtttgcctccatgtgcactggcccctccccacccctagggggcactcagtagctgctgagaaggcctgtccacgaggctgttggaacccctccaataaatacttagaggtagtgtatctgatgcttgttttcgtggagaaaattgtattggagaacttaaaacatcacgaatatttttaataggatccgcagacacccaaaggagaagcttggtcttttccaggtatttccaacttgagttcaacccaaagcctttgaaaggaatgcattaccacatgaccacatgctgagaccccatggggtctaacacgggacctaagaaagtctctgcagccagatagtacatggtgtctccacaaaactaggcattctggagattgcccagaaagggatgtgaggggaccgttaagatctgtcttgcttatctcatgcactcacattccttcagcctcctggagttcctgataaaaggaagccagggtgtggacattttttagctattgatttcccaatagcttgtggatcagttgtacacccacacttccttctctgcctaattccgtttttctggaaaaagtagtatgcccatgtatgtgtgtttttcttaacacaggtccatgaaagtttggcttcctggtttgatgtctgttgcgtggcctggaaaccagggagcagcaactattgagatggtttctgtgttcagtgaaaaattctatttcattgagacaattttttctttatccacagtaattttttgacactgtcatcatgaaactacccttaggaaaataagattacctgcaaaaaaaaaaaagaaatgagttatggaataggaacagttatgtgatgattctgaaactttaacttagagcttcattactttaagaatggaaaacaacctctgagtttgatttcccaaagtttcataaagcccctaagctcatgattttcatcaactctttgcccacatagtcatttacctccacagccgtttgttgtcatagaaggggtggtggtgtttggatttgatttttttcaacttgcagtgagaaataggataggtgacaaaaccttacttgttttcttaagacaattcagtgcttgagcatctctgtcagaaatggaatgaaatactgttagccaattagaattattttatgtattgttattgtgttttgctgatttttatatgaaaatataattattcattcttgatctctggaagcaatcattattatgaggatcattttactttggaaacactttcataataaagataagtattaagagtgcaaaaaaaaaaaaaaaaaa
//
ANNOTATIONS from NCBI Entrez Gene (20130726): GeneID:253782 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: IEA GeneID:253782 -> Molecular function: GO:0043565 [sequence-specific DNA binding] evidence: IEA GeneID:253782 -> Molecular function: GO:0050291 [sphingosine N-acyltransferase activity] evidence: IEA GeneID:253782 -> Biological process: GO:0006665 [sphingolipid metabolic process] evidence: TAS GeneID:253782 -> Biological process: GO:0030148 [sphingolipid biosynthetic process] evidence: TAS GeneID:253782 -> Biological process: GO:0044281 [small molecule metabolic process] evidence: TAS GeneID:253782 -> Biological process: GO:0046513 [ceramide biosynthetic process] evidence: IEA GeneID:253782 -> Cellular component: GO:0005789 [endoplasmic reticulum membrane] evidence: TAS GeneID:253782 -> Cellular component: GO:0016021 [integral to membrane] evidence: IEA GeneID:253782 -> Cellular component: GO:0031965 [nuclear membrane] evidence: IEA
by
@meso_cacase at
DBCLS
This page is licensed under a Creative Commons Attribution 2.1 Japan License.