SCS7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000038 very long-chain fatty acid metabolic process	IMP PMID:9353282 Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion prote...	ACCEPT	Summary: Mitchell & Martin 1997: fah1 (scs7) deletion causes ~40-fold loss of alpha-hydroxy C26:0 and accumulation of C26:0 in sphingolipid-derived fatty acids. Scs7 modifies sphingolipid-bound VLCFA. Supporting Evidence: PMID:9353282 Analysis of sphingolipid-derived very long chain fatty acids revealed an approximately 40-fold reduction of alpha-HO 26:0 and a complementary increase in 26:0 in the gene-disrupted fah1Delta strain.
GO:0005783 endoplasmic reticulum	HDA PMID:14562095 Global analysis of protein localization in budding yeast.	ACCEPT	Summary: ER localisation in the Huh et al. 2003 GFP collection (cited by UniProt for ER membrane). Supporting Evidence: PMID:14562095 Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion file:yeast/SCS7/SCS7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005783 endoplasmic reticulum	HDA PMID:26928762 One library to make them all: streamlining the creation of y...	ACCEPT	Summary: ER localisation in the SWAT N-terminal GFP endomembrane library (Yofe et al. 2016). Supporting Evidence: PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: PANTHER IBA (PTN000304948, FA2H clade incl. Arabidopsis FAH1/FAH2 and mouse Fa2h). ER is the conserved location of these membrane hydroxylases; the Scs7 crystal structure shows four TM helices anchoring it in the ER. Supporting Evidence: PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt SubCell mapping (SL-0097) to ER membrane; most precise location. Supporting Evidence: file:yeast/SCS7/SCS7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum.
GO:0005829 cytosol	RCA GO_REF:0000123	REMOVE	Summary: YeastPathways RCA compartment default (cytosol). Scs7 is a four-TM integral ER membrane enzyme; its catalytic cap faces the cytosol but GO places membrane enzymes in the membrane, not the cytosol. Supporting Evidence: PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum. PMID:26515067 The structure contains two zinc atoms coordinated by the side chains of 10 highly conserved histidines within a dimetal center located near the plane of the cytosolic membrane.
GO:0006629 lipid metabolic process	IEA GO_REF:0000002	TOO GENERAL	Summary: InterPro IPR014430 (Scs7 family) mapping to lipid metabolic process. Correct but broad. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0006673 inositol phosphoceramide metabolic process	IGI PMID:9559540 Synthesis of monohydroxylated inositolphosphorylceramide (IP...	ACCEPT	Summary: Dunn et al. 1998 (IGI): deleting SCS7 suppresses the Ca2+-sensitivity of csg mutants that over-accumulate IPC-C; scs7 cells make unhydroxylated IPC-B instead of IPC-C. Scs7 carries out the hydroxylation that defines the IPC-C species, so participation is genuine. Supporting Evidence: PMID:9559540 Elimination of the SCS7 gene suppresses the Ca(2+)-sensitive phenotype of csg1 and csg2 mutants. PMID:9559540 Saccharomyces cerevisiae mutants lacking Scs7p fail to accumulate the inositolphosphorylceramide (IPC) species.
GO:0006673 inositol phosphoceramide metabolic process	IGI PMID:9559540 Synthesis of monohydroxylated inositolphosphorylceramide (IP...	ACCEPT	Summary: Same IGI (second csg partner) from Dunn et al. 1998. Supporting Evidence: PMID:9559540 Elimination of the SCS7 gene suppresses the Ca(2+)-sensitive phenotype of csg1 and csg2 mutants.
GO:0006673 inositol phosphoceramide metabolic process	IMP PMID:16652392 Mass spectrometry-based profiling of phospholipids and sphin...	ACCEPT	Summary: Guan & Wenk 2006 lipidomic profiling of scs7 mutants (IMP) shows altered sphingolipid species consistent with loss of fatty acyl alpha-hydroxylation. Supporting Evidence: PMID:16652392 Mutants of SCS7, a lipid hydroxylase, and SLC1, a putative acyl transferase with unknown substrate specificity, were profiled for their phospholipid and sphingolipid content.
GO:0006673 inositol phosphoceramide metabolic process	IMP PMID:9353282 Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion prote...	ACCEPT	Summary: Mitchell & Martin 1997 (IMP): loss of alpha-hydroxylated C26 in sphingolipids of fah1/scs7 cells; IPC species are the main carriers. Supporting Evidence: PMID:9353282 Analysis of sphingolipid-derived very long chain fatty acids revealed an approximately 40-fold reduction of alpha-HO 26:0 and a complementary increase in 26:0 in the gene-disrupted fah1Delta strain.
GO:0006673 inositol phosphoceramide metabolic process	IMP PMID:9368039 Hydroxylation of Saccharomyces cerevisiae ceramides requires...	ACCEPT	Summary: Haak et al. 1997 (IMP): Scs7p is required for hydroxylation of the VLCFA of ceramide; scs7 suppresses csg2 Ca2+ sensitivity, which stems from IPC-C over-accumulation. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0006673 inositol phosphoceramide metabolic process	IMP PMID:9559540 Synthesis of monohydroxylated inositolphosphorylceramide (IP...	ACCEPT	Summary: Dunn et al. 1998 (IMP): scs7 mutants fail to accumulate IPC-C and instead accumulate IPC-B. Supporting Evidence: PMID:9559540 Saccharomyces cerevisiae mutants lacking Scs7p fail to accumulate the inositolphosphorylceramide (IPC) species. PMID:9559540 Scs7p is therefore likely to be the enzyme that hydroxylates the C26-fatty acid of IPC-C.
GO:0008270 zinc ion binding	IDA PMID:26515067 The Crystal Structure of an Integral Membrane Fatty Acid α-H...	ACCEPT	Summary: Zhu et al. 2015 crystal structure: two Zn atoms coordinated by ten conserved histidines in a dimetal centre required for catalysis. Supporting Evidence: PMID:26515067 The structure contains two zinc atoms coordinated by the side chains of 10 highly conserved histidines within a dimetal center located near the plane of the cytosolic membrane.
GO:0008610 lipid biosynthetic process	IEA GO_REF:0000117	TOO GENERAL	Summary: ARBA rule mapping to lipid biosynthetic process; correct but broad (Scs7 produces alpha-hydroxyceramides). Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: InterPro IPR014430 mapping to membrane; correct, ER membrane also annotated. Supporting Evidence: PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum.
GO:0016020 membrane	ISM PMID:9353282 Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion prote...	ACCEPT	Summary: ISM from Mitchell & Martin 1997: hydropathy predicts two hydrophobic domains each spanning the membrane twice; confirmed by the four-TM crystal structure. Supporting Evidence: PMID:9353282 Both proteins are predicted to have two hydrophobic domains, each capable of spanning the membrane twice PMID:26515067 The Scs7p core is composed of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum.
GO:0020037 heme binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro IPR018506 (cytochrome b5 heme-binding site) mapping to heme binding. Scs7 has an N-terminal cytochrome b5 domain; expressed in E. coli it gives the oxidised/reduced spectra of a heme-containing cytochrome b5. Supporting Evidence: PMID:9353282 Expression of the S. cerevisiae FAH1 cytochrome b5 domain in Escherichia coli produces a soluble protein that exhibits the typical oxidized versus reduced differential absorbance spectra of cytochrome b5.
GO:0030148 sphingolipid biosynthetic process	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways RCA for sphingolipid biosynthesis; Scs7 hydroxylates the ceramide fatty acyl chain en route to IPC/MIPC/M(IP)2C. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0046513 ceramide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: PANTHER IBA (PTN000304948) for ceramide biosynthetic process: FA2H-family enzymes generate 2-hydroxy ceramides. Scs7 performs that hydroxylation step itself. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0046513 ceramide biosynthetic process	IMP PMID:26977056 Following the flux of long-chain bases through the sphingoli...	ACCEPT	Summary: Curator IMP from Martinez-Montanes & Schneiter 2016 C17-LCB flux assay (abstract does not mention Scs7; full text not cached). Consistent with Scs7's established role in hydroxyceramide formation; deferring to curator. Supporting Evidence: PMID:26977056 Here we describe an in vivo assay to monitor the flux of LCB through the sphingolipid pathway in yeast. PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0046513 ceramide biosynthetic process	IMP PMID:9368039 Hydroxylation of Saccharomyces cerevisiae ceramides requires...	ACCEPT	Summary: Haak et al. 1997 (IMP): Scs7p required for hydroxylation of the very long chain fatty acid of ceramide. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0080132 fatty acid 2-hydroxylase activity	IBA GO_REF:0000033	ACCEPT	Summary: PANTHER IBA (PTN000304948, FA2H clade). Core activity; more specific children (GO:0120521, GO:0102771) also annotated. Reason: Broad specificity. No single child term asserted here covers this activity, which acts on dihydroceramide and phytoceramide acyl chains; this term is the lowest common ancestor of those child terms and so states the range of the activity. Supporting Evidence: PMID:9353282 Analysis of sphingolipid-derived very long chain fatty acids revealed an approximately 40-fold reduction of alpha-HO 26:0 and a complementary increase in 26:0 in the gene-disrupted fah1Delta strain. PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0080132 fatty acid 2-hydroxylase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro IPR014430 (Scs7) mapping to fatty acid 2-hydroxylase activity; correct. Reason: Broad specificity. No single child term asserted here covers this activity, which acts on dihydroceramide and phytoceramide acyl chains; this term is the lowest common ancestor of those child terms and so states the range of the activity. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0080132 fatty acid 2-hydroxylase activity	IMP PMID:9353282 Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion prote...	ACCEPT	Summary: Mitchell & Martin 1997 (IMP): alpha-hydroxylation of sphingolipid VLCFA lost in fah1/scs7, restored by FAH1 expression. Reason: Broad specificity. No single child term asserted here covers this activity, which acts on dihydroceramide and phytoceramide acyl chains; this term is the lowest common ancestor of those child terms and so states the range of the activity. Supporting Evidence: PMID:9353282 Analysis of sphingolipid-derived very long chain fatty acids revealed an approximately 40-fold reduction of alpha-HO 26:0 and a complementary increase in 26:0 in the gene-disrupted fah1Delta strain.
GO:0080132 fatty acid 2-hydroxylase activity	IMP PMID:9559540 Synthesis of monohydroxylated inositolphosphorylceramide (IP...	ACCEPT	Summary: Dunn et al. 1998 (IMP): Scs7p likely hydroxylates the C26 fatty acid of IPC-C. Reason: Broad specificity. No single child term asserted here covers this activity, which acts on dihydroceramide and phytoceramide acyl chains; this term is the lowest common ancestor of those child terms and so states the range of the activity. Supporting Evidence: PMID:9559540 Scs7p is therefore likely to be the enzyme that hydroxylates the C26-fatty acid of IPC-C.
GO:0102771 dihydroceramide fatty acyl 2-hydroxylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Rhea mapping (RHEA:46512, EC 1.14.18.7) from UniProt catalytic activity for dihydroceramide substrates. Plausible (UniProt evidence is author-inferred, ECO:0000305); a valid alternative-substrate activity alongside the main phytoceramide reaction. Supporting Evidence: file:yeast/SCS7/SCS7-uniprot.txt Reaction=an N-(1,2-saturated acyl)sphinganine + 2 Fe(II)-[cytochrome PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0102772 sphingolipid C4-monooxygenase activity	IMP PMID:9353282 Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion prote...	MODIFY	Summary: IMP from Mitchell & Martin 1997 to sphingolipid C4-monooxygenase activity. GO:0102772 sphingolipid C4-monooxygenase activity (EC 1.14.18.5) is the dihydroceramide -> phytoceramide C-4 hydroxylation of the sphingoid base, catalysed in yeast by Sur2, not Scs7. Haak et al. 1997 assign C-4 hydroxylation to Sur2p and very-long-chain fatty acid hydroxylation to Scs7p, and the cited Mitchell & Martin 1997 paper shows loss of alpha-hydroxy C26:0 fatty acid in fah1/scs7 cells. The essence (ceramide hydroxylase) is right but the position/term is wrong; replace with the phytoceramide fatty acyl 2-hydroxylase term (EC 1.14.18.6), which is the YeastPathways reaction assigned to SCS7. Proposed replacements: 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid. PMID:9353282 Analysis of sphingolipid-derived very long chain fatty acids revealed an approximately 40-fold reduction of alpha-HO 26:0 and a complementary increase in 26:0 in the gene-disrupted fah1Delta strain.
GO:0102772 sphingolipid C4-monooxygenase activity	RCA GO_REF:0000123	MODIFY	Summary: YeastPathways RCA for 'a phytoceramide + 2 ferrocytochrome b5 + O2 -> (2'R)-2'-hydroxy-phytoceramide' mapped to sphingolipid C4-monooxygenase activity. GO:0102772 sphingolipid C4-monooxygenase activity (EC 1.14.18.5) is the dihydroceramide -> phytoceramide C-4 hydroxylation of the sphingoid base, catalysed in yeast by Sur2, not Scs7. Haak et al. 1997 assign C-4 hydroxylation to Sur2p and very-long-chain fatty acid hydroxylation to Scs7p, and the cited Mitchell & Martin 1997 paper shows loss of alpha-hydroxy C26:0 fatty acid in fah1/scs7 cells. The essence (ceramide hydroxylase) is right but the position/term is wrong; replace with the phytoceramide fatty acyl 2-hydroxylase term (EC 1.14.18.6), which is the YeastPathways reaction assigned to SCS7. Proposed replacements: 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.
GO:0120521 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Rhea mapping (RHEA:46520, EC 1.14.18.6) for phytoceramide fatty acyl 2-hydroxylation. Most specific correct description of Scs7's main reaction in yeast (phytoceramides predominate). Core. Supporting Evidence: file:yeast/SCS7/SCS7-uniprot.txt Reaction=an N-(1,2 saturated acyl)-(4R)-hydroxysphinganine + 2 Fe(II)- PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid.

Gene Description

Existing Annotations Review

Core Functions

ER-membrane cytochrome b5-fused, di-zinc fatty acid hydroxylase that alpha(C-2)-hydroxylates the C26 very-long-chain fatty acyl moiety of phytoceramide (and dihydroceramide), producing the 2-hydroxy ceramides that give rise to IPC-C and downstream mannosylated sphingolipids.

References

Suggested Questions for Experts

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Deep Research

SGD

SGD gene description for SCS7 (yeast)

📚 Additional Documentation

Notes

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