De novo sphingolipid biosynthesis (ceramide core, with fungal inositol-phosphorylceramide head groups)

De novo sphingolipid synthesis builds ceramide, the hydrophobic backbone of all complex sphingolipids, from serine and fatty acyl-CoA on the endoplasmic-reticulum membrane. The committed, rate-limiting first step is catalysed by serine palmitoyltransferase (SPT), a pyridoxal-5'-phosphate-dependent membrane complex built on a heterodimer of two homologous subunits (SPTLC1/LCB1 and SPTLC2/LCB2). A small, lineage-specific activating subunit is also required: SPTSSA/B in animals, which sets acyl-CoA specificity, and the unrelated Tsc3 in fungi. SPT condenses L-serine with palmitoyl-CoA to 3-ketodihydrosphingosine. 3-ketodihydrosphingosine reductase (KDSR, yeast Tsc10) then reduces this, using NADPH, to dihydrosphingosine (sphinganine). Ceramide synthases of the TLC/Lag1 family N-acylate the sphingoid base with a fatty acyl-CoA. Each animal isoform prefers a different acyl chain length: CERS1 makes C18 ceramide (brain/muscle), CERS2 very-long-chain C22-C24 ceramide (broadly expressed), and CERS3 ultra-long-chain C26+ (acyl)ceramides for the skin barrier. Fungal Lag1 and Lac1 act with the accessory subunit Lip1 and use C26-CoA. The sphingoid base is then modified at C4 by one of two related di-iron enzymes. The dihydroceramide desaturase DEGS1 introduces the 4,5-trans double bond, an O2- and iron-dependent oxidation that converts dihydroceramide to ceramide; this is the predominant route in animals. The sphingoid-base C4-hydroxylase (yeast Sur2) instead converts sphinganine or dihydroceramide to the phyto (4-hydroxy) form, which is the predominant route in fungi and plants. Fungal ceramides are also hydroxylated at C2 of the very long acyl chain (Scs7). Fungi then build their characteristic complex sphingolipids in the Golgi. The Aur1-Kei1 inositol phosphorylceramide (IPC) synthase transfers inositol phosphate from phosphatidylinositol to ceramide. IPC is mannosylated by Csg1/Csh1-Csg2 complexes to MIPC, and in budding yeast Ipt1 adds a second inositol phosphate to make M(IP)2C. Animals instead make sphingomyelin and glycosphingolipids, which are covered by separate modules. Inherited defects of the human ceramide core include HSAN1 (SPTLC1/SPTLC2), spastic paraplegia (SPTSSA), erythrokeratodermia/thrombocytopenia (KDSR), progressive myoclonic epilepsy 8 (CERS1), congenital ichthyosis ARCI9 (CERS3) and hypomyelinating leukodystrophy 18 (DEGS1). The fungal IPC synthase is the target of the antifungal aureobasidin A.

MODULE:sphingolipid_de_novo_synthesisDRAFTMetabolic Pathwaymodules/sphingolipid_de_novo_synthesis.yaml

sphingolipid biosynthetic processGO:0030148 ceramide biosynthetic processGO:0046513

GO:0030148

sphingolipid biosynthetic process

The module is grounded in sphingolipid biosynthetic process (GO:0030148). It covers de novo synthesis of ceramide from serine and acyl-CoA, plus the fungal inositol-phosphate head groups.

GO:0046513

ceramide biosynthetic process

The ceramide core produces ceramide (ceramide biosynthetic process, GO:0046513).

GO:0051999

mannosyl-inositol phosphorylceramide biosynthetic process

The fungal head-group extension ends in MIPC (and M(IP)2C in budding yeast).

Reactome:R-HSA-1660661

Sphingolipid de novo biosynthesis

Step order and intermediates follow the human Reactome "Sphingolipid de novo biosynthesis" pathway (reactions R-HSA-428127 SPT, R-HSA-428123 KDSR, R-HSA-428185 CerS, R-HSA-428259 DEGS1).

YeastPathways:SPHINGOLIPID-SYN-PWY-1

sphingolipid biosynthesis (yeast) (S. cerevisiae, SGD YeastPathways)

YeastCyc lists SPT (LCB1, LCB2), TSC10, SUR2 C4-hydroxylation of sphinganine, CerS (LAG1, LAC1, LIP1), SCS7 alpha-hydroxylation, AUR1 IPC synthase, the MIPC mannosyltransferase (SUR1/CSG1, CSG2) and IPT1. These were all retained. Added: the SPT small subunit TSC3 (PMID:10713067), the essential IPC-synthase subunit KEI1 (PMID:19726565) and the redundant MIPC synthase CSH1 (PMID:12954640). Excluded as the long-chain-base phosphate / degradation branch: LCB4/LCB5 kinases, LCB3/YSR3 phosphatases, the DPL1 aldolase and the YPC1/YDC1 ceramidases. Compartments were corrected from cytosol to ER membrane for the ceramide core and Golgi membrane for the head-group enzymes.

file:human/SPTLC1/SPTLC1-ai-review.yaml

SPTLC1 gene review (human)

The SPT catalytic-subunit step (UniProtKB:O15269, GO:0004758) matches the completed human SPTLC1 review.

file:human/SPTLC2/SPTLC2-ai-review.yaml

SPTLC2 gene review (human)

The SPT PLP-binding catalytic-subunit step (UniProtKB:O15270, GO:0004758) matches the completed human SPTLC2 review.

file:human/SPTSSA/SPTSSA-ai-review.yaml

SPTSSA gene review (human)

The SPT small regulatory subunit (UniProtKB:Q969W0, SPT complex GO:0017059) matches the completed human SPTSSA review.

file:human/KDSR/KDSR-ai-review.yaml

KDSR gene review (human)

The 3-ketodihydrosphingosine reductase step (UniProtKB:Q06136, GO:0047560) matches the completed human KDSR review.

file:human/CERS1/CERS1-ai-review.yaml

CERS1 gene review (human)

The C18-specific ceramide-synthase step (UniProtKB:P27544, GO:0050291) matches the completed human CERS1 review.

file:human/CERS2/CERS2-ai-review.yaml

CERS2 gene review (human)

The very-long-chain ceramide-synthase step (UniProtKB:Q96G23, GO:0050291) matches the completed human CERS2 review.

file:human/CERS3/CERS3-ai-review.yaml

CERS3 gene review (human)

The ultra-long-chain ceramide-synthase step (UniProtKB:Q8IU89, GO:0050291) matches the completed human CERS3 review.

file:human/DEGS1/DEGS1-ai-review.yaml

DEGS1 gene review (human)

The dihydroceramide-desaturase step (UniProtKB:O15121, GO:0042284) matches the completed human DEGS1 review.

PMID:8058731

The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis.

Overproducing SPT in S. cerevisiae requires both LCB1 and LCB2, which encode related subunits of the enzyme.

PMID:10713067

Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity.

The 80-residue membrane protein Tsc3p co-immunoprecipitates with Lcb1p/Lcb2p. tsc3 cells have severely reduced SPT activity.

PMID:19416851

Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities.

Mammalian ssSPTa/ssSPTb share no homology with yeast Tsc3p but likewise enhance SPT activity, so the activating small subunit is analogous, not orthologous, between fungi and animals.

PMID:9804843

The Saccharomyces cerevisiae TSC10/YBR265w gene encoding 3-ketosphinganine reductase is identified in a screen for temperature-sensitive suppressors of the Ca2+-sensitive csg2Delta mutant.

Recombinant Tsc10p, a short-chain dehydrogenase/reductase, is necessary and sufficient for NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine.

PMID:11387200

C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p.

lag1 lac1 microsomes lack the activity that transfers C26 fatty acids from C26-CoA onto dihydrosphingosine or phytosphingosine.

PMID:15692566

Lip1p: a novel subunit of acyl-CoA ceramide synthase.

Purified Lac1p and Lag1p copurify with ceramide synthase activity together with Lip1p, a single-span ER membrane subunit required for ceramide synthesis in vivo and in vitro.

PMID:9368039

Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p.

Sur2p is required for C4-hydroxylation of the sphingoid base and Scs7p for hydroxylation of the very-long-chain fatty acid. Neither is essential, and M(IP)2C is still made without them.

PMID:15063729

Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation.

Human DES2 (DEGS2), a member of the DEGS family, is a dihydroceramide C4-hydroxylase, which shows that phyto-ceramide synthesis also occurs in mammalian tissues.

PMID:9092515

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.

AUR1 complements the IPC synthase defect and restores enzyme activity. Aureobasidin A inhibits IPC synthase with an IC50 of about 0.2 nM.

PMID:19726565

Kei1: a novel subunit of inositolphosphorylceramide synthase, essential for its enzyme activity and Golgi localization.

Kei1 forms a complex with Aur1 in the medial Golgi and is essential for both IPC synthase activity and Golgi localization.

PMID:12954640

Csg1p and newly identified Csh1p function in mannosylinositol phosphorylceramide synthesis by interacting with Csg2p.

Csg1p and Csh1p are redundant IPC mannosyltransferases, each in a complex with the regulatory Csg2p.

PMID:9368028

Synthesis of mannose-(inositol-P)2-ceramide, the major sphingolipid in Saccharomyces cerevisiae, requires the IPT1 (YDR072c) gene.

IPT1, an AUR1 homolog, is required for M(IP)2C synthase activity. ipt1 deletion strains accumulate MIPC.

PMID:20388730

Mannosylinositol phosphorylceramide is a major sphingolipid component and is required for proper localization of plasma-membrane proteins in Schizosaccharomyces pombe.

S. pombe has no Ipt1 equivalent, and MIPC is its terminal complex sphingolipid. The three SUR1 homologs imt1, imt2 and imt3 are jointly required for MIPC synthesis and localize to the Golgi.

16Nodes

9Parts

3Variant Sets

6Variants

15Annotons

7Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:sphingolipid_de_novo_synthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

spt_step → kdsr_step [NOT_CHECKED]
Palmitoyl-CoA is consumed by SPT; the intermediate passed on (3-ketosphinganine) is not a CoA ester.
kdsr_step → cers_step [NOT_CHECKED]
The shared intermediate is a free sphingoid base. The acyl-CoA used by CerS comes from fatty-acid elongation, not from KDSR.
cers_step → degs1_step [NOT_CHECKED]
Ceramide intermediates; CoA is released by CerS, not passed on.
degs1_step → ceramide_acyl_2_hydroxylation_step [NOT_CHECKED]
Ceramide intermediates; no CoA carrier.
ceramide_acyl_2_hydroxylation_step → fungal_ipc_head_group_extension [NOT_CHECKED]
Ceramide intermediates; no CoA carrier.

Function consistency and core coverage

28 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (51 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
sptlc1_activity	SPTLC1 (human) UniProtKB:O15269 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sptlc1_activity	LCB1 (Saccharomyces cerevisiae) UniProtKB:P25045 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
sptlc1_activity	lcb1 (Schizosaccharomyces pombe) UniProtKB:O59682 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
sptlc2_activity	SPTLC2 (human) UniProtKB:O15270 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sptlc2_activity	LCB2 (Saccharomyces cerevisiae) UniProtKB:P40970 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sptlc2_activity	lcb2 (Schizosaccharomyces pombe) UniProtKB:Q09925 Family Representative	serine C-palmitoyltransferase activity GO:0004758	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
sptssa_activity	SPTSSA (human) UniProtKB:Q969W0 Family Representative	enzyme activator activity GO:0008047	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tsc3_activity	TSC3 (Saccharomyces cerevisiae) UniProtKB:Q3E790 Family Representative	enzyme activator activity GO:0008047	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tsc3_activity	tsc3/SPAC23A1.05 (Schizosaccharomyces pombe) UniProtKB:O42843 Family Representative	enzyme activator activity GO:0008047	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kdsr_activity	KDSR (human) UniProtKB:Q06136 Family Representative	3-dehydrosphinganine reductase activity GO:0047560	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kdsr_activity	TSC10 (Saccharomyces cerevisiae) UniProtKB:P38342 Family Representative	3-dehydrosphinganine reductase activity GO:0047560	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kdsr_activity	SPCC1450.15 (Schizosaccharomyces pombe) UniProtKB:Q9Y7P2 Family Representative	3-dehydrosphinganine reductase activity GO:0047560	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cers_activity	CERS1 (human, C18-specific) UniProtKB:P27544 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cers_activity	CERS2 (human, C22-C24) UniProtKB:Q96G23 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cers_activity	CERS3 (human, C26+) UniProtKB:Q8IU89 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_cers_activity	PROTEIN_COMPLEX Gene	sphingosine N-acyltransferase activity GO:0050291	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
fungal_cers_activity/lag1_lac1_catalytic_unit	LAG1 (Saccharomyces cerevisiae) UniProtKB:P38703 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_cers_activity/lag1_lac1_catalytic_unit	LAC1 (Saccharomyces cerevisiae) UniProtKB:P28496 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_cers_activity/lag1_lac1_catalytic_unit	lag1 (Schizosaccharomyces pombe) UniProtKB:P78970 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_cers_activity/lag1_lac1_catalytic_unit	lac1 (Schizosaccharomyces pombe) UniProtKB:O59735 Family Representative	sphingosine N-acyltransferase activity GO:0050291	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
degs1_activity	DEGS1 (human) UniProtKB:O15121 Family Representative	sphingolipid delta-4 desaturase activity GO:0042284	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
degs1_activity	dsd1 (Schizosaccharomyces pombe) UniProtKB:O59715 Family Representative	sphingolipid delta-4 desaturase activity GO:0042284	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sur2_c4_hydroxylase_activity	SUR2 (Saccharomyces cerevisiae) UniProtKB:P38992 Family Representative	sphingolipid C4-monooxygenase activity GO:0102772	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sur2_c4_hydroxylase_activity	sur2 (Schizosaccharomyces pombe) UniProtKB:O94298 Family Representative	sphingolipid C4-monooxygenase activity GO:0102772	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
scs7_activity	SCS7 (Saccharomyces cerevisiae) UniProtKB:Q03529 Family Representative	4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity GO:0120521	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
scs7_activity	scs7 (Schizosaccharomyces pombe) UniProtKB:O13846 Family Representative	4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity GO:0120521	Function Unreviewed No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
aur1_activity	AUR1 (Saccharomyces cerevisiae) UniProtKB:P36107 Family Representative	inositol phosphoceramide synthase activity GO:0045140	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aur1_activity	aur1 (Schizosaccharomyces pombe) UniProtKB:Q10142 Family Representative	inositol phosphoceramide synthase activity GO:0045140	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kei1_activity	KEI1 (Saccharomyces cerevisiae) UniProtKB:Q06346 Family Representative	inositol phosphoceramide synthase regulator activity GO:0070917	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kei1_activity	kei1 (Schizosaccharomyces pombe) UniProtKB:O13994 Family Representative	inositol phosphoceramide synthase regulator activity GO:0070917	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ipc_mannosyltransferase_activity	SUR1/CSG1 (Saccharomyces cerevisiae) UniProtKB:P33300 Family Representative	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ipc_mannosyltransferase_activity	CSH1 (Saccharomyces cerevisiae) UniProtKB:P38287 Family Representative	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ipc_mannosyltransferase_activity	imt1 (Schizosaccharomyces pombe) UniProtKB:O14084 Family Representative	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
ipc_mannosyltransferase_activity	imt2/SPCC4F11.04c (Schizosaccharomyces pombe) UniProtKB:Q9UT67 Family Representative	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
ipc_mannosyltransferase_activity	imt3/SPAC17G8.11c (Schizosaccharomyces pombe) UniProtKB:Q10323 Family Representative	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
csg2_regulatory_activity	CSG2 (Saccharomyces cerevisiae) UniProtKB:P35206 Gene	enzyme regulator activity GO:0030234	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ipt1_activity	IPT1 (Saccharomyces cerevisiae) UniProtKB:P38954 Family Representative	transferase activity, transferring phosphorus-containing groups GO:0016772	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
sptlc1_activity	Serine palmitoyltransferase subunit 1 subfamily (SPTLC1/LCB1) PANTHER:PTHR13693:SF2 Family	serine C-palmitoyltransferase activity GO:0004758	Family Function Unreviewed Family review leaves GO:0004758 UNRESOLVED. Holds for the eukaryotic SPT subunits: enables for the PLP-binding LCB2/SPTLC2/SPTLC3, and contributes_to for the non-catalytic LCB1/SPTLC1 (SF2). It also holds for the bacterial SPTs of SF3. It must not reach BioF, ALAS, KBL or GCAT. The LCB2-type subunits are spread over SF79, SF56, SF54, SF104 and the mixed SF3, so the term follows PAINT nodes PTN000343811 and PTN000343996 rather than subfamilies. The sphingolipid_de_novo_synthesis module's SPTLC2/LCB2 annoton uses the whole family PTHR13693 as its selector, which also selects every BioF, ALAS and KBL/GCAT protein.
sptlc2_activity	Serine palmitoyltransferase / AOS family (SPTLC) PANTHER:PTHR13693 Family	serine C-palmitoyltransferase activity GO:0004758	Family Function Unreviewed Family review leaves GO:0004758 UNRESOLVED. Holds for the eukaryotic SPT subunits: enables for the PLP-binding LCB2/SPTLC2/SPTLC3, and contributes_to for the non-catalytic LCB1/SPTLC1 (SF2). It also holds for the bacterial SPTs of SF3. It must not reach BioF, ALAS, KBL or GCAT. The LCB2-type subunits are spread over SF79, SF56, SF54, SF104 and the mixed SF3, so the term follows PAINT nodes PTN000343811 and PTN000343996 rather than subfamilies. The sphingolipid_de_novo_synthesis module's SPTLC2/LCB2 annoton uses the whole family PTHR13693 as its selector, which also selects every BioF, ALAS and KBL/GCAT protein.
sptssa_activity	Small subunit of serine palmitoyltransferase family (SPTSS) PANTHER:PTHR47084 Family	enzyme activator activity GO:0008047	Family Review Missing No supported structured family review is available for PANTHER:PTHR47084.
tsc3_activity	Tsc3 fungal SPT small subunit Family	enzyme activator activity GO:0008047	Family Id Missing The family has no identifier linking it to a curated family review.
kdsr_activity	3-ketodihydrosphingosine reductase / SDR family (KDSR) PANTHER:PTHR43550 Family	3-dehydrosphinganine reductase activity GO:0047560	Family Supported Family review supports GO:0047560 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by KDSR, TSC10 and SPCC1450.15.
cers_activity	Ceramide synthase / TRAM-LAG-CLN8 (TLC) family (CERS) PANTHER:PTHR12560 Family	sphingosine N-acyltransferase activity GO:0050291	Family Supported Family review supports GO:0050291 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by LAG1, LAC1, lag1, lac1 and CERS1-3.
lag1_lac1_catalytic_unit	Ceramide synthase / TLC family (fungal Lag1/Lac1) PANTHER:PTHR12560 Family	sphingosine N-acyltransferase activity GO:0050291	Family Supported Family review supports GO:0050291 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by LAG1, LAC1, lag1, lac1 and CERS1-3.
degs1_activity	Sphingolipid delta-4 desaturase / fatty-acid-hydroxylase family (DEGS) PANTHER:PTHR12879 Family	sphingolipid delta-4 desaturase activity GO:0042284	Family Supported Family review supports GO:0042284 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by DEGS1 and dsd1.
sur2_c4_hydroxylase_activity	Sur2 sphingoid-base C4-hydroxylase (sterol-desaturase / fatty-acid-hydroxylase superfamily) PANTHER:PTHR11863 Family	sphingolipid C4-monooxygenase activity GO:0102772	Family Function Unreviewed Family review leaves GO:0102772 UNRESOLVED. Sphingolipid C4-hydroxylase is the activity of S. cerevisiae SUR2 and S. pombe sur2, as sphingolipid_de_novo_synthesis selects. Both sit in SF226 together with the sterol desaturases and oxidases ERG3, ERG25 and SC5D, so no subfamily is safe for it; it has to be applied per member. This differs from the SOD1/CCS case in PTHR10003, which is scoped family-wide with member exceptions: there the members that lack the activity (the CCS chaperones) form an enumerable, PAINT-negated set, whereas here the members that lack sphingolipid C4-hydroxylase activity are most of the subfamily.
scs7_activity	fatty acid 2-hydroxylase family (FA2H / Scs7) PANTHER:PTHR12863:SF1 Family	4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity GO:0120521	Family Supported Family review supports GO:0120521 for PANTHER:PTHR12863:SF1. Ceramide-acyl 2-hydroxylation by the fungal enzymes in SF1, as sphingolipid_de_novo_synthesis selects.
aur1_activity	Aur1 IPC synthase catalytic subfamily PANTHER:PTHR31310:SF11 Family	inositol phosphoceramide synthase activity GO:0045140	Family Supported Family review supports GO:0045140 for PANTHER:PTHR31310:SF11. Aur1 (SF11), as sphingolipid_de_novo_synthesis selects.
kei1_activity	Kei1 IPC synthase regulatory subunit family PANTHER:PTHR28077 Family	inositol phosphoceramide synthase regulator activity GO:0070917	Family Supported Family review supports GO:0070917 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by KEI1 and kei1.
ipc_mannosyltransferase_activity	Sur1/Csh1/Imt MIPC synthase family PANTHER:PTHR32385 Family	inositol phosphorylceramide mannosyltransferase activity GO:0103064	Family Supported Family review supports GO:0103064 FAMILY_WIDE. Asserted by sphingolipid_de_novo_synthesis; accepted by SUR1 and CSH1.
ipt1_activity	Ipt1 inositolphosphotransferase subfamily (Aur1-related) PANTHER:PTHR31310:SF8 Family	transferase activity, transferring phosphorus-containing groups GO:0016772	Family Supported Family review supports GO:0016772 for PANTHER:PTHR31310:SF8. The inositol-phosphotransferases: IPT1 (SF8, M(IP)2C synthase) and AUR1 (SF11, IPC synthase), as sphingolipid_de_novo_synthesis uses for IPT1. Not the PA-phosphatase- related SF7.

Gene-review completeness (37/37 grounded genes reviewed)

34 complete review(s) · 15 with deep research · 0 missing review · 22 reviewed but lacking deep research

Gene	Review	Complete	Deep research
AUR1 P36107	✓	✓	✓
aur1 Q10142	✓	✓	✗
CERS1 P27544	✓	✓	✗
CERS2 Q96G23	✓	42/43	✗
CERS3 Q8IU89	✓	✓	✗
CSG2 P35206	✓	✓	✓
CSH1 P38287	✓	✓	✓
DEGS1 O15121	✓	39/40	✗
dsd1 O59715	✓	✓	✗
imt1 O14084	✓	✓	✗
IPT1 P38954	✓	✓	✓
KDSR Q06136	✓	✓	✗
kei1 O13994	✓	✓	✗
KEI1 Q06346	✓	✓	✓
lac1 O59735	✓	✓	✗
LAC1 P28496	✓	✓	✓
LAG1 P38703	✓	✓	✓
lag1 P78970	✓	✓	✗
lcb1 O59682	✓	✓	✗
LCB1 P25045	✓	✓	✓
LCB2 P40970	✓	✓	✓
lcb2 Q09925	✓	✓	✗
LIP1 Q03579	✓	✓	✓
scs7 O13846	✓	✓	✗
SCS7 Q03529	✓	✓	✓
SPAC17G8.11c Q10323	✓	✓	✗
SPAC23A1.05 O42843	✓	✓	✗
SPCC1450.15 Q9Y7P2	✓	✓	✗
SPCC4F11.04c Q9UT67	✓	✓	✗
SPTLC1 O15269	✓	✓	✗
SPTLC2 O15270	✓	✓	✗
SPTSSA Q969W0	✓	✓	✗
SUR1 P33300	✓	✓	✓
sur2 O94298	✓	13/15	✗
SUR2 P38992	✓	✓	✓
TSC10 P38342	✓	✓	✓
TSC3 Q3E790	✓	✓	✓

Tree

De novo sphingolipid biosynthesisMetabolic Pathwaysphingolipid_de_novo_synthesis

Parts
1. 1. committed step (serine + palmitoyl-CoA condensation)
2. L-serine + palmitoyl-CoA to 3-ketodihydrosphingosineProtein Complexspt_step
  
  Annotons
  - SPTLC1/LCB1: serine palmitoyltransferase subunit Family: Serine palmitoyltransferase subunit 1 subfamily (SPTLC1/LCB1)
  - SPTLC2/LCB2: PLP-binding catalytic SPT subunit Family: Serine palmitoyltransferase / AOS family (SPTLC)
  Variants
  1. SPT small activating subunit by lineage (non-homologous small subunits) (Exactly One)
    
    Animal ssSPTa/b small subunitReactionanimal_ssspt_variant
    
    Annotons
    
    SPTSSA: small regulatory SPT subunit (ssSPTa) Family: Small subunit of serine palmitoyltransferase family (SPTSS)
    
    Fungal Tsc3 small subunitReactionfungal_tsc3_variant
    
    Annotons
    
    Tsc3: fungal SPT activating subunit Family: Tsc3 fungal SPT small subunit
3. 2. reduction to sphinganine
4. 3-ketodihydrosphingosine to dihydrosphingosine (sphinganine)Reactionkdsr_step
  
  Annotons
  - KDSR/Tsc10: 3-ketodihydrosphingosine reductase Family: 3-ketodihydrosphingosine reductase / SDR family (KDSR)
5. 3. N-acylation to dihydroceramide (ceramide synthase family)
6. sphinganine (or phytosphingosine) + acyl-CoA to (dihydro/phyto)ceramideReactioncers_step
  
  Variants
  1. Ceramide synthase subunit architecture by lineage / complex composition (Exactly One)
    
    Animal CERS1-6 isoformsReactionanimal_cers_variant
    
    Annotons
    
    CERS1/2/3: ceramide synthase (N-acyltransferase) Family: Ceramide synthase / TRAM-LAG-CLN8 (TLC) family (CERS)
    
    Fungal Lag1/Lac1-Lip1 acyl-CoA ceramide synthase complexProtein Complexfungal_lag1_lac1_lip1_variant
    
    Annotons
    
    Lag1/Lac1-Lip1: C26-CoA-dependent ceramide synthase Protein Complex: acyl-CoA ceramide synthase complex
7. 4. sphingoid-base C4 modification (desaturation or hydroxylation)
8. sphingoid-base C4 modification (dihydroceramide to ceramide or phytoceramide)Reactiondegs1_step
  
  Variants
  1. C4 modification route by chemistry / lineage (One Or More)
    
    Delta-4 desaturation (DEGS family)Reactiondelta4_desaturation_variant
    
    Annotons
    
    DEGS1: dihydroceramide desaturase Family: Sphingolipid delta-4 desaturase / fatty-acid-hydroxylase family (DEGS)
    
    Sphingoid-base C4-hydroxylation (Sur2 type)Reactionc4_hydroxylation_variant
    
    Annotons
    
    Sur2: sphingolipid C4-hydroxylase Family: Sur2 sphingoid-base C4-hydroxylase (sterol-desaturase / fatty-acid-hydroxylase superfamily)
9. 5. ceramide very-long-chain fatty acyl 2-hydroxylation optional
10. phytoceramide to alpha-hydroxy (2'-hydroxyacyl) phytoceramideReactionceramide_acyl_2_hydroxylation_step
  
  Annotons
  - Scs7: ceramide very-long-chain fatty acyl 2-hydroxylase Family: fatty acid 2-hydroxylase family (FA2H / Scs7)
11. 6. fungal inositol-phosphate head groups (IPC, MIPC, M(IP)2C) optional
12. Fungal inositol-phosphorylceramide head-group synthesisMetabolic Pathwayfungal_ipc_head_group_extension
  
  Parts
  1. 1. IPC synthase (inositol phosphate transfer to ceramide)
  2. ceramide + phosphatidylinositol to IPC + diacylglycerolProtein Complexipc_synthase_step
    
    Annotons
    
    Aur1: IPC synthase catalytic subunit Family: Aur1 IPC synthase catalytic subfamily
    
    Kei1: IPC synthase regulatory subunit Family: Kei1 IPC synthase regulatory subunit family
  3. 2. IPC mannosylation to MIPC
  4. IPC + GDP-mannose to MIPCReactionmipc_synthase_step
    
    Annotons
    
    Csg1(Sur1)/Csh1 (S. pombe Imt1-3): IPC mannosyltransferase Family: Sur1/Csh1/Imt MIPC synthase family
    
    Csg2: regulatory subunit of the Csg1/Csh1 mannosyltransferases Gene Product: CSG2 (Saccharomyces cerevisiae)
  5. 3. second inositol phosphate transfer (M(IP)2C) optional
  6. MIPC + phosphatidylinositol to M(IP)2C + diacylglycerolReactionmip2c_synthase_step
    
    Annotons
    
    Ipt1: M(IP)2C synthase (inositolphosphotransferase) Family: Ipt1 inositolphosphotransferase subfamily (Aur1-related)

Details

Context

endoplasmic reticulum membraneGO:0005789

De novo sphingolipid biosynthesisMetabolic Pathwaysphingolipid_de_novo_synthesis

sphingolipid biosynthetic processGO:0030148 ceramide biosynthetic processGO:0046513

Context

endoplasmic reticulum membraneGO:0005789

The module was generalized from a human-only ceramide module to a eukaryotic ceramide core with a fungal head-group extension. The human groundings are kept unchanged: the SPT complex (SPTLC1 O15269 + SPTLC2 O15270, GO:0004758, EC 2.3.1.50; small subunit SPTSSA Q969W0; complex GO:0017059), KDSR (Q06136, GO:0047560, EC 1.1.1.102), the ceramide synthases CERS1 (P27544), CERS2 (Q96G23) and CERS3 (Q8IU89) (all GO:0050291, EC 2.3.1.24) and DEGS1 (O15121, GO:0042284, EC 1.14.19.17). Two steps were restructured into variant sets because fungi and animals use different protein architectures: the SPT small subunit (non-homologous ssSPT vs Tsc3) and the ceramide synthase (single-subunit CERS vs the Lag1/Lac1-Lip1 complex). The DEGS1 step became the C4-modification node with desaturation (DEGS family) and C4-hydroxylation (Sur2, sterol-desaturase superfamily) variants. Its id degs1_step was kept for continuity. PANTHER membership was checked in the PANTHER 19.0 classification files: LCB1/lcb1 and LCB2/lcb2 are in PTHR13693 (SF2/SF3) with SPTLC1/SPTLC2; TSC10 and SPCC1450.15 are in PTHR43550:SF3 with KDSR; LAG1, LAC1, lag1 and lac1 are in PTHR12560; dsd1 is in PTHR12879 with DEGS1; SUR2/sur2 are in PTHR11863; SCS7/scs7 share PTHR12863:SF1 with human FA2H; AUR1/aur1 and IPT1 are in PTHR31310 (SF11 and SF8); KEI1/kei1 are in PTHR28077; and SUR1, CSH1 and imt1-3 are in PTHR32385. TSC3 and CSG2 have no PANTHER classification. Out of scope: the long-chain-base kinase / phosphatase / lyase branch (LCB4/LCB5, LCB3/YSR3, DPL1) and the ceramidases (YPC1/YDC1), which belong to sphingoid-base turnover (see sphingosine_1_phosphate_rheostat); ORM/ORMDL feedback regulators of SPT; VLCFA elongation, which supplies the acyl-CoA; ceramide transport to the Golgi; and animal sphingomyelin and glycosphingolipid synthesis (sphingomyelin_cycle and glycosphingolipid_biosynthesis modules). Substrate palmitoyl-CoA comes from fatty-acid synthesis.

Connections

spt_step -> kdsr_step Precedes

3-ketodihydrosphingosine from SPT is reduced by KDSR to sphinganine.

kdsr_step -> cers_step Precedes

Sphinganine from KDSR (or phytosphingosine, after Sur2 hydroxylation in S. cerevisiae) is N-acylated by the ceramide synthases.

cers_step -> degs1_step Precedes

Dihydroceramide from the ceramide synthases is desaturated by DEGS1 to ceramide or C4-hydroxylated to phytoceramide.

degs1_step -> ceramide_acyl_2_hydroxylation_step Precedes

Phytoceramide is alpha-hydroxylated on its acyl chain by Scs7 (fungi).

ceramide_acyl_2_hydroxylation_step -> fungal_ipc_head_group_extension Precedes

(Alpha-hydroxy) phytoceramide is transported to the Golgi and receives the inositol-phosphate head group. Scs7 hydroxylation is not required for IPC synthesis.

Part 1: committed step (serine + palmitoyl-CoA condensation)

L-serine + palmitoyl-CoA to 3-ketodihydrosphingosineProtein Complexspt_step

The SPT heterodimer of two homologous large subunits is conserved across eukaryotes. A small activating subunit is required in both animals and fungi, but the two lineages use unrelated proteins for it, so it is modelled as a variant set.

Annotons

SPTLC1/LCB1: serine palmitoyltransferase subunit

sptlc1_activity

Participant: Family: Serine palmitoyltransferase subunit 1 subfamily (SPTLC1/LCB1)

Family:

Serine palmitoyltransferase subunit 1 subfamily (SPTLC1/LCB1)PANTHER:PTHR13693:SF2

Representative Members: SPTLC1 (human)UniProtKB:O15269 LCB1 (Saccharomyces cerevisiae)UniProtKB:P25045 lcb1 (Schizosaccharomyces pombe)UniProtKB:O59682

Function

serine C-palmitoyltransferase activityGO:0004758

Substrates: L-serine palmitoyl-CoA

Products: 3-ketodihydrosphingosine (3-ketosphinganine) CoA CO2

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic subunit of SPT; deficiency = HSAN1 (toxic 1-deoxysphingolipids).

SPTLC2/LCB2: PLP-binding catalytic SPT subunit

sptlc2_activity

Participant: Family: Serine palmitoyltransferase / AOS family (SPTLC)

Family:

Serine palmitoyltransferase / AOS family (SPTLC)PANTHER:PTHR13693

Representative Members: SPTLC2 (human)UniProtKB:O15270 LCB2 (Saccharomyces cerevisiae)UniProtKB:P40970 lcb2 (Schizosaccharomyces pombe)UniProtKB:Q09925

Function

serine C-palmitoyltransferase activityGO:0004758

Substrates: L-serine palmitoyl-CoA

Products: 3-ketodihydrosphingosine

Locations

endoplasmic reticulum membraneGO:0005789

PLP-binding catalytic subunit of SPT.

Variant set: SPT small activating subunit by lineage (non-homologous small subunits) (Exactly One)

Animal ssSPTs and fungal Tsc3 are functional analogs with no detectable sequence homology (PMID:19416851). Tsc3 has no PANTHER classification.

Animal ssSPTa/b small subunitReactionanimal_ssspt_variant

Annotons

SPTSSA: small regulatory SPT subunit (ssSPTa)

sptssa_activity

Participant: Family: Small subunit of serine palmitoyltransferase family (SPTSS)

Family:

Small subunit of serine palmitoyltransferase family (SPTSS)PANTHER:PTHR47084

Representative Members: SPTSSA (human)UniProtKB:Q969W0

Function

enzyme activator activityGO:0008047

Substrates: SPTLC1-SPTLC2 catalytic core

Products: activated, C16-specific SPT complex

Locations

endoplasmic reticulum membraneGO:0005789

Small accessory subunit that activates SPT and sets C16 acyl-CoA specificity.

Fungal Tsc3 small subunitReactionfungal_tsc3_variant

Annotons

Tsc3: fungal SPT activating subunit

tsc3_activity

Participant: Family: Tsc3 fungal SPT small subunit

Family:

Tsc3 fungal SPT small subunit No PANTHER family; not homologous to animal SPTSS.

Representative Members: TSC3 (Saccharomyces cerevisiae)UniProtKB:Q3E790 tsc3/SPAC23A1.05 (Schizosaccharomyces pombe)UniProtKB:O42843

Function

enzyme activator activityGO:0008047

Locations

endoplasmic reticulum membraneGO:0005789

An 80-residue membrane protein required for full SPT activity and for growth at high temperature. Missing from the YeastCyc gene list.

Part 2: reduction to sphinganine

3-ketodihydrosphingosine to dihydrosphingosine (sphinganine)Reactionkdsr_step

Annotons

KDSR/Tsc10: 3-ketodihydrosphingosine reductase

kdsr_activity

Participant: Family: 3-ketodihydrosphingosine reductase / SDR family (KDSR)

Family:

3-ketodihydrosphingosine reductase / SDR family (KDSR)PANTHER:PTHR43550

Representative Members: KDSR (human)UniProtKB:Q06136 TSC10 (Saccharomyces cerevisiae)UniProtKB:P38342 SPCC1450.15 (Schizosaccharomyces pombe)UniProtKB:Q9Y7P2

Function

3-dehydrosphinganine reductase activityGO:0047560

Substrates: 3-ketodihydrosphingosine NADPH

Products: dihydrosphingosine (sphinganine) NADP+

Locations

endoplasmic reticulum membraneGO:0005789

Reduces 3-ketodihydrosphingosine to sphinganine; deficiency = erythrokeratodermia variabilis / thrombocytopenia.

Part 3: N-acylation to dihydroceramide (ceramide synthase family)

sphinganine (or phytosphingosine) + acyl-CoA to (dihydro/phyto)ceramideReactioncers_step

Variant set: Ceramide synthase subunit architecture by lineage / complex composition (Exactly One)

The catalytic TLC-domain CerS subunits of animals and fungi are homologous (PANTHER PTHR12560). Fungal CerS also needs the accessory subunit Lip1, and the cached literature reports no animal counterpart.

Animal CERS1-6 isoformsReactionanimal_cers_variant

Annotons

CERS1/2/3: ceramide synthase (N-acyltransferase)

cers_activity

Participant: Family: Ceramide synthase / TRAM-LAG-CLN8 (TLC) family (CERS)

Family:

Ceramide synthase / TRAM-LAG-CLN8 (TLC) family (CERS)PANTHER:PTHR12560

Representative Members: CERS1 (human, C18-specific)UniProtKB:P27544 CERS2 (human, C22-C24)UniProtKB:Q96G23 CERS3 (human, C26+)UniProtKB:Q8IU89

Function

sphingosine N-acyltransferase activityGO:0050291

Substrates: dihydrosphingosine (sphinganine) fatty acyl-CoA (chain length set by CerS isoform)

Products: dihydroceramide CoA

Locations

endoplasmic reticulum membraneGO:0005789

N-acylation step; the six ceramide synthases produce ceramides of distinct chain lengths. Disorders: EPM8 (CERS1), ARCI9 (CERS3).

Fungal Lag1/Lac1-Lip1 acyl-CoA ceramide synthase complexProtein Complexfungal_lag1_lac1_lip1_variant

Annotons

Lag1/Lac1-Lip1: C26-CoA-dependent ceramide synthase

fungal_cers_activity

Participant: Protein Complex: acyl-CoA ceramide synthase complex

Protein Complex:

acyl-CoA ceramide synthase complexGO:0061576

Active units:

Lag1/Lac1 catalytic TLC subunit (redundant paralogs)

Participant: Family: Ceramide synthase / TLC family (fungal Lag1/Lac1)

Family:

Ceramide synthase / TLC family (fungal Lag1/Lac1)PANTHER:PTHR12560

Representative Members: LAG1 (Saccharomyces cerevisiae)UniProtKB:P38703 LAC1 (Saccharomyces cerevisiae)UniProtKB:P28496 lag1 (Schizosaccharomyces pombe)UniProtKB:P78970 lac1 (Schizosaccharomyces pombe)UniProtKB:O59735

Role: Catalytic N-acyltransferase subunit; Lag1 and Lac1 are redundant.

Function:

sphingosine N-acyltransferase activityGO:0050291

Lip1 accessory subunit

Participant: Gene Product: LIP1 (Saccharomyces cerevisiae)

Gene Product:

LIP1 (Saccharomyces cerevisiae)UniProtKB:Q03579

Role: Single-span ER membrane subunit required for ceramide synthase activity in vivo and in vitro.

Function

sphingosine N-acyltransferase activityGO:0050291

Substrates: phytosphingosine or dihydrosphingosine C26 very-long-chain fatty acyl-CoA

Products: phytoceramide or dihydroceramide CoA

Locations

endoplasmic reticulum membraneGO:0005789

In S. cerevisiae the main substrate is phytosphingosine made by Sur2 (see part 4), giving C26 phytoceramide.

Part 4: sphingoid-base C4 modification (desaturation or hydroxylation)

sphingoid-base C4 modification (dihydroceramide to ceramide or phytoceramide)Reactiondegs1_step

Two related O2- and cytochrome-b5-dependent di-iron activities modify C4 of the sphinganine backbone. Delta-4 desaturation gives ceramide (sphingosine backbone). C4 hydroxylation gives phyto (4-hydroxysphinganine) sphingolipids. Desaturation acts on dihydroceramide. The C4-hydroxylase can act on free sphinganine before N-acylation, as in the S. cerevisiae route listed by YeastCyc, or on dihydroceramide. The node therefore follows CerS in the generic chain, and each variant records the substrate order.

Variant set: C4 modification route by chemistry / lineage (One Or More)

S. pombe encodes both activities (dsd1 desaturase and sur2 hydroxylase). Mammals mainly desaturate (DEGS1) but make phyto-ceramides in some tissues with the DEGS-family bifunctional DES2 (PMID:15063729). S. cerevisiae makes only phyto-sphingolipids.

Delta-4 desaturation (DEGS family)Reactiondelta4_desaturation_variant

Annotons

DEGS1: dihydroceramide desaturase

degs1_activity

Participant: Family: Sphingolipid delta-4 desaturase / fatty-acid-hydroxylase family (DEGS)

Family:

Sphingolipid delta-4 desaturase / fatty-acid-hydroxylase family (DEGS)PANTHER:PTHR12879

Representative Members: DEGS1 (human)UniProtKB:O15121 dsd1 (Schizosaccharomyces pombe)UniProtKB:O59715

Function

sphingolipid delta-4 desaturase activityGO:0042284

Substrates: dihydroceramide O2 NAD(P)H / reduced electron donor

Products: ceramide H2O

Locations

endoplasmic reticulum membraneGO:0005789

Final step; converts dihydroceramide to ceramide. Deficiency = hypomyelinating leukodystrophy 18 (HLD18).

Sphingoid-base C4-hydroxylation (Sur2 type)Reactionc4_hydroxylation_variant

Annotons

Sur2: sphingolipid C4-hydroxylase

sur2_c4_hydroxylase_activity

Participant: Family: Sur2 sphingoid-base C4-hydroxylase (sterol-desaturase / fatty-acid-hydroxylase superfamily)

Family:

Sur2 sphingoid-base C4-hydroxylase (sterol-desaturase / fatty-acid-hydroxylase superfamily)PANTHER:PTHR11863

Representative Members: SUR2 (Saccharomyces cerevisiae)UniProtKB:P38992 sur2 (Schizosaccharomyces pombe)UniProtKB:O94298

Function

sphingolipid C4-monooxygenase activityGO:0102772

Substrates: sphinganine (S. cerevisiae main route) or dihydroceramide O2 reduced cytochrome b5

Products: phytosphingosine or phytoceramide H2O

Locations

endoplasmic reticulum membraneGO:0005789

Makes the phyto (4-hydroxy) sphingoid backbone. It belongs to the sterol-desaturase / fatty-acid-hydroxylase superfamily and is not homologous to the DEGS desaturases. sur2 deletion is viable (PMID:9368039).

Part 5: ceramide very-long-chain fatty acyl 2-hydroxylation (optional)

phytoceramide to alpha-hydroxy (2'-hydroxyacyl) phytoceramideReactionceramide_acyl_2_hydroxylation_step

Annotons

Scs7: ceramide very-long-chain fatty acyl 2-hydroxylase

scs7_activity

Participant: Family: fatty acid 2-hydroxylase family (FA2H / Scs7)

Family:

fatty acid 2-hydroxylase family (FA2H / Scs7)PANTHER:PTHR12863:SF1

Representative Members: SCS7 (Saccharomyces cerevisiae)UniProtKB:Q03529 scs7 (Schizosaccharomyces pombe)UniProtKB:O13846

Function

4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activityGO:0120521

Substrates: N-(very-long-chain acyl)-4-hydroxysphinganine (phytoceramide) O2 reduced cytochrome b5

Products: N-(2R-hydroxy very-long-chain acyl)-4-hydroxysphinganine H2O

Locations

endoplasmic reticulum membraneGO:0005789

Optional in fungi (scs7 deletion is viable). The cytochrome-b5-domain fungal enzyme hydroxylates the acyl chain within ceramide. Its animal homolog FA2H (same PANTHER subfamily) mainly hydroxylates free fatty acids and is not a representative here.

Part 6: fungal inositol-phosphate head groups (IPC, MIPC, M(IP)2C) (optional)

Fungal inositol-phosphorylceramide head-group synthesisMetabolic Pathwayfungal_ipc_head_group_extension

Fungi, and also plants and some protists, transfer inositol phosphate from phosphatidylinositol onto ceramide instead of making sphingomyelin. The Golgi IPC synthase is essential in fungi and is the target of aureobasidin A. IPC is then mannosylated to MIPC, and in S. cerevisiae a second inositol phosphate is added to form M(IP)2C. This extension is optional at the module level because animals do not use it; animal ceramide-to-sphingomyelin and glycosphingolipid synthesis are covered by separate modules.

mannosyl-inositol phosphorylceramide biosynthetic processGO:0051999 inositol phosphoceramide metabolic processGO:0006673

Context

FungiNCBITaxon:4751

Golgi membraneGO:0000139

Connections

ipc_synthase_step -> mipc_synthase_step Precedes

IPC is the mannosyl acceptor for the Csg1/Csh1/Imt enzymes.

mipc_synthase_step -> mip2c_synthase_step Precedes

MIPC is the acceptor for the second inositol phosphate added by Ipt1.

Part 1: IPC synthase (inositol phosphate transfer to ceramide)

ceramide + phosphatidylinositol to IPC + diacylglycerolProtein Complexipc_synthase_step

inositol phosphoceramide synthase complexGO:0070916

Annotons

Aur1: IPC synthase catalytic subunit

aur1_activity

Participant: Family: Aur1 IPC synthase catalytic subfamily

Family:

Aur1 IPC synthase catalytic subfamilyPANTHER:PTHR31310:SF11

Representative Members: AUR1 (Saccharomyces cerevisiae)UniProtKB:P36107 aur1 (Schizosaccharomyces pombe)UniProtKB:Q10142

Function

inositol phosphoceramide synthase activityGO:0045140

Substrates: (alpha-hydroxy) phytoceramide 1-phosphatidyl-1D-myo-inositol

Products: inositol phosphorylceramide (IPC) 1,2-diacyl-sn-glycerol

Locations

Golgi membraneGO:0000139

Essential catalytic subunit; target of aureobasidin A.

Kei1: IPC synthase regulatory subunit

kei1_activity

Participant: Family: Kei1 IPC synthase regulatory subunit family

Family:

Kei1 IPC synthase regulatory subunit familyPANTHER:PTHR28077

Representative Members: KEI1 (Saccharomyces cerevisiae)UniProtKB:Q06346 kei1 (Schizosaccharomyces pombe)UniProtKB:O13994

Function

inositol phosphoceramide synthase regulator activityGO:0070917

Locations

Golgi membraneGO:0000139

Essential non-catalytic subunit, missing from the YeastCyc gene list.

Part 2: IPC mannosylation to MIPC

IPC + GDP-mannose to MIPCReactionmipc_synthase_step

Annotons

Csg1(Sur1)/Csh1 (S. pombe Imt1-3): IPC mannosyltransferase

ipc_mannosyltransferase_activity

Participant: Family: Sur1/Csh1/Imt MIPC synthase family

Family:

Sur1/Csh1/Imt MIPC synthase familyPANTHER:PTHR32385

Representative Members: SUR1/CSG1 (Saccharomyces cerevisiae)UniProtKB:P33300 CSH1 (Saccharomyces cerevisiae)UniProtKB:P38287 imt1 (Schizosaccharomyces pombe)UniProtKB:O14084 imt2/SPCC4F11.04c (Schizosaccharomyces pombe)UniProtKB:Q9UT67 imt3/SPAC17G8.11c (Schizosaccharomyces pombe)UniProtKB:Q10323

Function

inositol phosphorylceramide mannosyltransferase activityGO:0103064

Substrates: inositol phosphorylceramide GDP-alpha-D-mannose

Products: mannosyl-inositol phosphorylceramide (MIPC) GDP

Locations

Golgi membraneGO:0000139

Catalytic mannosyltransferase. S. cerevisiae CSH1 is missing from the YeastCyc gene list.

Csg2: regulatory subunit of the Csg1/Csh1 mannosyltransferases

csg2_regulatory_activity

Participant: Gene Product: CSG2 (Saccharomyces cerevisiae)

Gene Product:

CSG2 (Saccharomyces cerevisiae)UniProtKB:P35206

Function

enzyme regulator activityGO:0030234

Locations

Golgi membraneGO:0000139

Budding-yeast regulatory subunit. No S. pombe ortholog is included in the PomBase model, and none is established in the cached literature.

Part 3: second inositol phosphate transfer (M(IP)2C) (optional)

MIPC + phosphatidylinositol to M(IP)2C + diacylglycerolReactionmip2c_synthase_step

Annotons

Ipt1: M(IP)2C synthase (inositolphosphotransferase)

ipt1_activity

Participant: Family: Ipt1 inositolphosphotransferase subfamily (Aur1-related)

Family:

Ipt1 inositolphosphotransferase subfamily (Aur1-related)PANTHER:PTHR31310:SF8

Representative Members: IPT1 (Saccharomyces cerevisiae)UniProtKB:P38954

Function

transferase activity, transferring phosphorus-containing groupsGO:0016772 Mannosyl-inositol-phosphoceramide inositolphosphotransferase (EC 2.7.1.228). GO has no specific term for this activity, so the generic parent used by SGD is asserted.

Substrates: mannosyl-inositol phosphorylceramide (MIPC) 1-phosphatidyl-1D-myo-inositol

Products: mannosyl-diinositol phosphorylceramide (M(IP)2C) 1,2-diacyl-sn-glycerol

Locations

Golgi membraneGO:0000139

Lineage-restricted: present in S. cerevisiae and absent from S. pombe, whose terminal complex sphingolipid is MIPC (PMID:20388730).