Use of the ND evidence code for Gene Ontology (GO) terms
Annotation inferences using phylogenetic trees
Combined Automated Annotation using Multiple IEA Methods
Sequence and analysis of chromosome 2 of Dictyostelium discoideum
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Initial identification of the tlcd4b gene (DDB_G0277029) as part of the D. discoideum chromosome 2 sequencing project.
"the chromosome codes for 2,799 predicted protein coding genes and 73 transfer RNA genes"
The genome of the social amoeba Dictyostelium discoideum
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Complete genome sequence of D. discoideum strain AX4, providing the genomic context for tlcd4b on chromosome 2.
"The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins"
TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?
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Original identification of the TLC domain family shared across TRAM, LAG1/ceramide synthases, and CLN8, with predicted functions in lipid synthesis, transport, or sensing.
"A family of membrane-associated proteins related to yeast Lag1p and mammalian TRAM has been identified"
Acyl chain specificity of ceramide synthases is determined within a region of 150 residues in the Tram-Lag-CLN8 (TLC) domain
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CerS acyl chain specificity maps to 150 residues within the TLC domain. This work defined the functional architecture of ceramide synthases, but TLCD4 lacks the Lag1p motif characteristic of CerS enzymes.
"a minimal region of 150 residues is sufficient for retaining CerS specificity"
TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition
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Key paper demonstrating that non-CerS TLCD proteins are phospholipid acyltransferases, not ceramidases. TLCD1 is a lysophosphatidylethanolamine acyltransferase; CLN8 is a lysophosphatidylglycerol acyltransferase.
"poorly understood TRAM-LAG1-CLN8 domain (TLCD)-containing proteins are phospholipid remodeling enzymes"
Ceramide synthase homolog Tlc4 maintains nuclear envelope integrity via its Golgi translocation
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S. pombe Tlc4 is a CerS homolog with a TLC domain that functions through non-catalytic activity at the ER, NE, and Golgi. Demonstrates that TLC domain proteins can have structural/regulatory roles beyond enzymatic activity.
"Tlc4 was localized at the NE and endoplasmic reticulum, similar to CerS proteins"
Identification of TRAMs as sphingolipid-binding proteins using a photoactivatable and clickable short-chain ceramide analog
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TRAM1 and TRAM2, TLC domain proteins involved in ER translocation, bind ceramide. This demonstrates that TLC domains can interact with sphingolipids without necessarily being ceramide synthases.
"translocating chain-associated membrane protein 2 (TRAM2), a protein known to control RAT of transmembrane 4 L6 subfamily member 20, and TRAM1, a homolog of TRAM2, interacted with molecules derived from pac-C7-Cer"
Complex sphingolipid profiling and identification of an inositol-phosphorylceramide synthase in Dictyostelium discoideum
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D. discoideum produces phosphoinositol-containing sphingolipids with phytoceramide backbones. An IPC synthase was identified in the Golgi and contractile vacuole. Provides context for sphingolipid biology in D. discoideum but does not directly involve tlcd4b.
"produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones"