LAG1/YHL003C Summary Help

Standard Name LAG1 1
Systematic Name YHL003C
Feature Type ORF, Verified
Description Ceramide synthase component; involved in synthesis of ceramide from C26(acyl)-coenzyme A and dihydrosphingosine or phytosphingosine, functionally equivalent to Lac1p; forms ER foci upon DNA replication stress; homolog of human CERS2, a tumor metastasis suppressor gene whose silencing enahnces invasion/metastasis of prostate cancer cells; LAG1 has a paralog, LAC1, that arose from the whole genome duplication (2, 3, 4, 5 and see Summary Paragraph)
Name Description Longevity Assurance Gene 1
Chromosomal Location
ChrVIII:101883 to 100648 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All LAG1 GO evidence and references
  View Computational GO annotations for LAG1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
94 total interaction(s) for 50 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 4
  • Biochemical Activity: 2
  • PCA: 14
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 4
  • Negative Genetic: 21
  • Phenotypic Enhancement: 3
  • Positive Genetic: 26
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 4
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 411
Molecular Weight (Da) 48,454
Isoelectric Point (pI) 9.56
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:101883 to 100648 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1236 101883..100648 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000995
SUMMARY PARAGRAPH for LAG1

LAG1 was identified as a gene whose expression decreases with increasing age of yeast cells (1). Deletion of LAG1 results in a 50% increase in the lifespan of the mutated yeast cells (1). LAC1 was identified as a close homolog of LAG1, and a double deletion of the two genes has been reported as lethal (6) or poor-growing (7). Human and C. elegans homologs of LAG1 have been cloned, and each is able to complement a lag1 lac1 double deletion (6). Lag1p and Lac1p have been localized to the endoplasmic reticulum, and are thought to play a role in the transport from the ER to the Golgi of glycosylphosphatidylinositol (GPI)-anchored proteins (7).

About sphingolipid metabolism

Sphingolipids are essential components of the plasma membrane in all eukaryotic cells. S. cerevisiae cells make three complex sphingolipids: inositol-phosphoceramide (IPC), mannose-inositol-phosphoceramide (MIPC), and mannose-(inositol phosphate)2-ceramide (M(IP)2C)(8). In the yeast plasma membrane sphingolipids concentrate with ergosterol to form lipid rafts, specialized membrane microdomains implicated in a variety of cellular processes, including sorting of membrane proteins and lipids, as well as organizing and regulating signaling cascades (9). Intermediates in sphingolipid biosynthesis have been shown to play important roles as signaling molecules and growth regulators. Sphingolipid long chain bases (LCBs), dihydrosphingosine (DHS) and phytosphingosine (PHS), have been implicated as secondary messengers in signaling pathways that regulate the heat stress response (10, 11). Other intermediates, phytoceramide and long-chain base phosphates (LCBPs), have been shown to be components of the tightly-controlled ceramide/LCBP rheostat, which regulates cell growth (12). Since phosphoinositol-containing sphingolipids are unique to fungi, the sphingolipid biosynthesis pathway is considered a target for antifungal drugs (13, 14).

Last updated: 2000-03-01 Contact SGD

References cited on this page View Complete Literature Guide for LAG1
1) D'mello NP, et al.  (1994) Cloning and characterization of LAG1, a longevity-assurance gene in yeast. J Biol Chem 269(22):15451-9
2) Jazwinski SM  (2002) Growing old: metabolic control and yeast aging. Annu Rev Microbiol 56:769-92
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
5) Xu X, et al.  (2014) Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell. J Cell Biochem 115(4):731-43
6) Jiang JC, et al.  (1998) Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res 8(12):1259-72
7) Barz WP and Walter P  (1999) Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins. Mol Biol Cell 10(4):1043-59
8) Dickson RC and Lester RL  (2002) Sphingolipid functions in Saccharomyces cerevisiae. Biochim Biophys Acta 1583(1):13-25
9) Bagnat M and Simons K  (2002) Lipid rafts in protein sorting and cell polarity in budding yeast Saccharomyces cerevisiae. Biol Chem 383(10):1475-80
10) Jenkins GM, et al.  (1997) Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J Biol Chem 272(51):32566-72
11) Ferguson-Yankey SR, et al.  (2002) Mutant analysis reveals complex regulation of sphingolipid long chain base phosphates and long chain bases during heat stress in yeast. Yeast 19(7):573-86
12) Kobayashi SD and Nagiec MM  (2003) Ceramide/long-chain base phosphate rheostat in Saccharomyces cerevisiae: regulation of ceramide synthesis by Elo3p and Cka2p. Eukaryot Cell 2(2):284-94
13) Nagiec MM, et al.  (1997) Sphingolipid synthesis as a target for antifungal drugs. Complementation of the inositol phosphorylceramide synthase defect in a mutant strain of Saccharomyces cerevisiae by the AUR1 gene. J Biol Chem 272(15):9809-17
14) Sugimoto Y, et al.  (2004) IPC synthase as a useful target for antifungal drugs. Curr Drug Targets Infect Disord 4(4):311-22