View original ARBA rule on UniProt
ARBA rule that assigned GO:0046467 membrane lipid biosynthetic process through 51 alternative condition sets built from InterPro, CATH FunFam and taxon conditions. GO has made the term obsolete and UniProt no longer serves the rule.
Condition-set counts describe the sets recorded in this review, which may omit the full rule.
No domain overlap table is shown: the cached overlap analysis for this version of the review is not available.
Run just analyze-rule ARBA00028538 and re-render to add it.
GO:0046467 is obsolete in GO, and UniProt returned 404 for this rule on 2026-11-09. The 51 condition sets recorded are those of the last version reviewed. Nine of them (sets 2, 5, 12, 15, 19, 26, 31, 37 and 45) were checked against Swiss-Prot members and their GO annotations. In each case a matched protein carries a curated annotation to a lipid biosynthetic process: the ceramidases, sphingomyelinase and glucosylceramidase are annotated to biosynthesis of their products ceramide and sphingosine; protein kinase D and the chloroplast phosphoglycerate kinases are annotated to sphingolipid and galactolipid biosynthesis; and the Bacteroidota set selects serine palmitoyltransferases. So these sets reflect existing annotations rather than fold-level errors. The other 42 sets were not checked.
The rule has been withdrawn by UniProt and its only consequent is an obsolete GO term.
QuickGO, 2026-11-09: GO:0046467 isObsolete = true, so the consequent itself cannot be assessed. The examples are reviewed proteins that match a checked condition set and carry a curated annotation under GO:0008610 lipid biosynthetic process: P17405 GO:0046513 IDA PMID:17303575; Q9NR71 GO:0046513 IDA PMID:17475390; Q8TDN7 GO:0046512 IDA PMID:17713573; P04062 GO:0046513 IMP PMID:19279011; Q9NRA0 GO:0006669 IDA PMID:10751414; Q9LD57 and P50318 GO:0019375 IGI PMID:30834637; Q15139 and Q9BZL6 GO:0030148 TAS Reactome:R-HSA-1660661. Q8A9E5 is a reviewed serine palmitoyltransferase (EC 2.3.1.50).
Alkaline ceramidase family. Human ACER1 (Q8TDN7) has IPR008901 and is annotated to GO:0046512 sphingosine biosynthetic process (IDA, PMID:17713573 and PMID:20628055) and GO:0030148 sphingolipid biosynthetic process (IDA, PMID:17713573).
Acid sphingomyelinase architecture. Human SMPD1 (P17405) has all three signatures and is annotated to GO:0046513 ceramide biosynthetic process (IDA, PMID:17303575, PMID:18815062, PMID:20807762, PMID:33163980; IMP, PMID:19279011, PMID:8706124).
Human PRKD1 (Q15139) and PRKD2 (Q9BZL6) carry both FunFams and are annotated to GO:0030148 sphingolipid biosynthetic process as a Reactome traceable author statement (R-HSA-1660661).
Human ASAH2 (Q9NR71) carries this FunFam and is annotated to GO:0046513 ceramide biosynthetic process (IDA, PMID:17475390; IMP, PMID:11278489) and GO:0046512 sphingosine biosynthetic process (IMP, PMID:30154232).
Human SMPD1 (P17405) carries this FunFam; see set 5 for its annotations.
Arabidopsis chloroplast phosphoglycerate kinases PGKH1 (Q9LD57) and PGKH2 (P50318) carry both FunFams and are annotated to GO:0019375 galactolipid biosynthetic process (IGI, PMID:30834637).
Human SPHK2 (Q9NRA0) carries this FunFam and is annotated to GO:0006669 sphinganine-1-phosphate biosynthetic process (IDA, PMID:10751414, PMID:19729656) and GO:0046512 sphingosine biosynthetic process (IGI and IMP, PMID:23106337).
The two reviewed Bacteroidota members of this FunFam are serine palmitoyltransferases: Bacteroides thetaiotaomicron SPT (Q8A9E5) and Bacteroides ovatus SPT (A7LXM2). Of 1958 Bacteroidota members in UniProtKB, 52 are named serine palmitoyltransferase and none is named aminolevulinate synthase; many unreviewed ones are named 2-amino-3-ketobutyrate coenzyme A ligase.
Human GBA1 (P04062) carries this FunFam and is annotated to GO:0046513 ceramide biosynthetic process (IMP, PMID:19279011) and GO:0009247 glycolipid biosynthetic process (IDA, PMID:24211208, PMID:26724485).
The consequent GO:0046467 is obsolete.
The paper states: "sphingolipids of mammalian cells are degraded in a stepwise manner without an effective bypass in human lysosomal catabolism"
The paper states: "The recessively inherited ASMD mainly leads to impaired cellular SM catabolism causing progressive SM accumulation in the cellular membranes."
The paper states: "The essential enzyme LpxC catalyzes the first committed step of LPS synthesis and thus represents a promising antibiotic target"
The paper states: "Instead of the first enzyme LpxA, which catalyzes a reversible reaction, the second enzyme, LpxC, is the main driver in this process as it catalyzes the first committed step"
The paper states: "ethanolamine phosphate (EtNP), three mannoses (Mans), one non-N-acetylated glucosamine, and inositol phospholipid"
The paper states: "Fatty chains of inositol phospholipids are inserted into the outer leaflet of the plasma membrane"
The paper states: "the functional annotations provided by FunFams are found to be more precise compared with those generated by other domain-based resources"
The paper states: "ceramidases catalyze the degradation of ceramide to sphingosine"
The paper states: "alkaline ceramidases (encoded by ACER1, ACER2 and ACER3), acidic ceramidase (encoded by ASAH1) and neutral ceramidase (encoded by ASAH2)"
The paper states: "Lipid A, the conserved, lipid component of LPS, anchors LPS to the outer membrane"
The paper states: "E. coli acyl transferases are chain length specific, orthologs from other Gram-negative bacteria are more tolerant, yielding a heterogeneous Lipid A composition of the outer membrane."
id: ARBA00028538
description: >-
ARBA rule that assigned GO:0046467 membrane lipid biosynthetic process through 51 alternative condition
sets built from InterPro, CATH FunFam and taxon conditions. GO has made the term obsolete and UniProt
no longer serves the rule.
status: COMPLETE
rule_type: ARBA
rule:
rule_id: ARBA00028538
condition_sets:
- number: 1
conditions:
- condition_type: INTERPRO
value: IPR006634
curie: InterPro:IPR006634
label: TRAM/LAG1/CLN8 homology domain
negated: false
- condition_type: INTERPRO
value: IPR016439
curie: InterPro:IPR016439
label: Sphingosine N-acyltransferase Lag1/Lac1-like
negated: false
- condition_type: TAXON
value: Chordata
curie: NCBITaxon:7711
label: Chordata
negated: false
- number: 2
conditions:
- condition_type: INTERPRO
value: IPR008901
curie: InterPro:IPR008901
label: Alkaline ceramidase
negated: false
- condition_type: TAXON
value: Craniata
curie: NCBITaxon:89593
label: Craniata
negated: false
notes: >-
Alkaline ceramidase family. Human ACER1 (Q8TDN7) has IPR008901 and is annotated to GO:0046512
sphingosine biosynthetic process (IDA, PMID:17713573 and PMID:20628055) and GO:0030148 sphingolipid
biosynthetic process (IDA, PMID:17713573).
- number: 3
conditions:
- condition_type: INTERPRO
value: IPR001675
curie: InterPro:IPR001675
label: Glycosyl transferase family 29
negated: false
- condition_type: INTERPRO
value: IPR051757
curie: InterPro:IPR051757
label: Beta-galactoside alpha2-3 sialyltransferases
negated: false
- condition_type: TAXON
value: Euarchontoglires
curie: NCBITaxon:314146
label: Euarchontoglires
negated: false
- number: 4
conditions:
- condition_type: INTERPRO
value: IPR002347
curie: InterPro:IPR002347
label: Short-chain dehydrogenase/reductase SDR
negated: false
- condition_type: INTERPRO
value: IPR020904
curie: InterPro:IPR020904
label: Short-chain dehydrogenase/reductase, conserved site
negated: false
- condition_type: INTERPRO
value: IPR045022
curie: InterPro:IPR045022
label: 3-ketodihydrosphingosine reductase KDSR-like
negated: false
- number: 5
conditions:
- condition_type: INTERPRO
value: IPR004843
curie: InterPro:IPR004843
label: Calcineurin-like, phosphoesterase domain
negated: false
- condition_type: INTERPRO
value: IPR008139
curie: InterPro:IPR008139
label: Saposin B type domain
negated: false
- condition_type: INTERPRO
value: IPR045473
curie: InterPro:IPR045473
label: Sphingomyelin phosphodiesterase, C-terminal domain
negated: false
notes: >-
Acid sphingomyelinase architecture. Human SMPD1 (P17405) has all three signatures and is annotated
to GO:0046513 ceramide biosynthetic process (IDA, PMID:17303575, PMID:18815062, PMID:20807762,
PMID:33163980; IMP, PMID:19279011, PMID:8706124).
- number: 6
conditions:
- condition_type: INTERPRO
value: IPR007577
curie: InterPro:IPR007577
label: Glycosyltransferase, DXD sugar-binding motif
negated: false
- condition_type: INTERPRO
value: IPR051706
curie: InterPro:IPR051706
negated: false
- condition_type: TAXON
value: Eukaryota
curie: NCBITaxon:2759
label: Eukaryota
negated: false
- number: 7
conditions:
- condition_type: INTERPRO
value: IPR004960
curie: InterPro:IPR004960
label: Bacterial lipid A biosynthesis acyltransferase
negated: false
- condition_type: TAXON
value: Bacteria
curie: NCBITaxon:2
label: Bacteria
negated: false
- number: 8
conditions:
- condition_type: FUNFAM
value: 1.10.10.60:FF:000020
curie: CATH.FunFam:1.10.10.60:FF:000020
label: Ceramide synthase 5
negated: false
- condition_type: TAXON
value: Metazoa
curie: NCBITaxon:33208
label: Metazoa
negated: false
- number: 9
conditions:
- condition_type: FUNFAM
value: 3.40.50.720:FF:000165
curie: CATH.FunFam:3.40.50.720:FF:000165
label: 3-ketodihydrosphingosine reductase
negated: false
- condition_type: TAXON
value: Eukaryota
curie: NCBITaxon:2759
label: Eukaryota
negated: false
- number: 10
conditions:
- condition_type: FUNFAM
value: 2.40.160.20:FF:000002
curie: CATH.FunFam:2.40.160.20:FF:000002
label: Lipid A palmitoyltransferase PagP
negated: false
- condition_type: TAXON
value: Bacteria
curie: NCBITaxon:2
label: Bacteria
negated: false
- number: 11
conditions:
- condition_type: FUNFAM
value: 3.90.550.20:FF:000001
curie: CATH.FunFam:3.90.550.20:FF:000001
label: MIPC synthase subunit (SurA)
negated: false
- condition_type: TAXON
value: Fungi
curie: NCBITaxon:4751
label: Fungi
negated: false
- number: 12
conditions:
- condition_type: FUNFAM
value: 1.10.510.10:FF:000151
curie: CATH.FunFam:1.10.510.10:FF:000151
label: Serine/threonine-protein kinase
negated: false
- condition_type: FUNFAM
value: 2.30.29.30:FF:000056
curie: CATH.FunFam:2.30.29.30:FF:000056
label: Serine/threonine-protein kinase
negated: false
- condition_type: TAXON
value: Primates
curie: NCBITaxon:9443
label: Primates
negated: false
notes: >-
Human PRKD1 (Q15139) and PRKD2 (Q9BZL6) carry both FunFams and are annotated to GO:0030148 sphingolipid
biosynthetic process as a Reactome traceable author statement (R-HSA-1660661).
- number: 13
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000001
curie: CATH.FunFam:3.40.50.2000:FF:000001
label: UDP-glucuronosyltransferase
negated: false
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000033
curie: CATH.FunFam:3.40.50.2000:FF:000033
label: 2-hydroxyacylsphingosine 1-beta-galactosyltransferase
negated: false
- condition_type: TAXON
value: Chordata
curie: NCBITaxon:7711
label: Chordata
negated: false
- number: 14
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000069
curie: CATH.FunFam:3.40.50.2000:FF:000069
label: Alpha-(1-6)-phosphatidylinositol monomannoside mannosyltransferase
negated: false
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000115
curie: CATH.FunFam:3.40.50.2000:FF:000115
label: Alpha-(1-6)-phosphatidylinositol monomannoside mannosyltransferase
negated: false
- condition_type: TAXON
value: Bacillati
curie: NCBITaxon:1783272
label: Bacillati
negated: false
- number: 15
conditions:
- condition_type: FUNFAM
value: 2.60.40.2300:FF:000001
curie: CATH.FunFam:2.60.40.2300:FF:000001
label: N-acylsphingosine amidohydrolase 2
negated: false
- condition_type: TAXON
value: Mammalia
curie: NCBITaxon:40674
label: Mammalia
negated: false
notes: >-
Human ASAH2 (Q9NR71) carries this FunFam and is annotated to GO:0046513 ceramide biosynthetic
process (IDA, PMID:17475390; IMP, PMID:11278489) and GO:0046512 sphingosine biosynthetic process
(IMP, PMID:30154232).
- number: 16
conditions:
- condition_type: FUNFAM
value: 3.10.120.10:FF:000011
curie: CATH.FunFam:3.10.120.10:FF:000011
label: Fatty acid 2-hydroxylase
negated: false
- condition_type: TAXON
value: Craniata
curie: NCBITaxon:89593
label: Craniata
negated: false
- number: 17
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000111
curie: CATH.FunFam:3.40.50.2000:FF:000111
label: Monogalactosyldiacylglycerol synthase 3, chloroplastic
negated: false
- condition_type: TAXON
value: Viridiplantae
curie: NCBITaxon:33090
label: Viridiplantae
negated: false
- number: 18
conditions:
- condition_type: FUNFAM
value: 3.40.640.10:FF:000049
curie: CATH.FunFam:3.40.640.10:FF:000049
label: serine palmitoyltransferase 1 isoform X1
negated: false
- condition_type: TAXON
value: Vertebrata
curie: NCBITaxon:7742
label: Vertebrata
negated: false
- number: 19
conditions:
- condition_type: FUNFAM
value: 3.60.21.10:FF:000045
curie: CATH.FunFam:3.60.21.10:FF:000045
label: Sphingomyelin phosphodiesterase
negated: false
- condition_type: TAXON
value: Euteleostomi
curie: NCBITaxon:117571
label: Euteleostomi
negated: false
notes: Human SMPD1 (P17405) carries this FunFam; see set 5 for its annotations.
- number: 20
conditions:
- condition_type: FUNFAM
value: 3.90.1480.20:FF:000002
curie: CATH.FunFam:3.90.1480.20:FF:000002
label: CMP-N-acetylneuraminate-beta-galactosamide- alpha-2,3-sialyltransferase 2
negated: false
- condition_type: TAXON
value: Eutheria
curie: NCBITaxon:9347
label: Eutheria
negated: false
- number: 21
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000037
curie: CATH.FunFam:3.90.550.10:FF:000037
label: Beta-1,4-galactosyltransferase 6
negated: false
- condition_type: TAXON
value: Glires
curie: NCBITaxon:314147
label: Glires
negated: false
- number: 22
conditions:
- condition_type: FUNFAM
value: 3.40.720.10:FF:000015
curie: CATH.FunFam:3.40.720.10:FF:000015
label: GPI ethanolamine phosphate transferase 1
negated: false
- number: 23
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000119
curie: CATH.FunFam:3.90.550.10:FF:000119
label: Dolichol-phosphate mannosyltransferase subunit 1
negated: false
- number: 24
conditions:
- condition_type: FUNFAM
value: 3.30.1700.10:FF:000001
curie: CATH.FunFam:3.30.1700.10:FF:000001
label: UDP-3-O-acyl-N-acetylglucosamine deacetylase
negated: false
- condition_type: FUNFAM
value: 3.30.230.20:FF:000001
curie: CATH.FunFam:3.30.230.20:FF:000001
label: UDP-3-O-acyl-N-acetylglucosamine deacetylase
negated: false
- condition_type: TAXON
value: Pseudomonadati
curie: NCBITaxon:3379134
label: Pseudomonadati
negated: false
- number: 25
conditions:
- condition_type: FUNFAM
value: 3.40.1090.10:FF:000014
curie: CATH.FunFam:3.40.1090.10:FF:000014
label: Patatin like phospholipase domain containing 1
negated: false
- condition_type: FUNFAM
value: 3.40.1090.10:FF:000016
curie: CATH.FunFam:3.40.1090.10:FF:000016
label: Patatin like phospholipase domain containing 1
negated: false
- condition_type: TAXON
value: Euarchontoglires
curie: NCBITaxon:314146
label: Euarchontoglires
negated: false
- number: 26
conditions:
- condition_type: FUNFAM
value: 3.40.50.1260:FF:000007
curie: CATH.FunFam:3.40.50.1260:FF:000007
label: Phosphoglycerate kinase
negated: false
- condition_type: FUNFAM
value: 3.40.50.1260:FF:000014
curie: CATH.FunFam:3.40.50.1260:FF:000014
label: Phosphoglycerate kinase
negated: false
- condition_type: TAXON
value: Streptophyta
curie: NCBITaxon:35493
label: Streptophyta
negated: false
notes: >-
Arabidopsis chloroplast phosphoglycerate kinases PGKH1 (Q9LD57) and PGKH2 (P50318) carry both
FunFams and are annotated to GO:0019375 galactolipid biosynthetic process (IGI, PMID:30834637).
- number: 27
conditions:
- condition_type: FUNFAM
value: 3.40.640.10:FF:000047
curie: CATH.FunFam:3.40.640.10:FF:000047
label: serine palmitoyltransferase 2 isoform X1
negated: false
- condition_type: FUNFAM
value: 3.90.1150.10:FF:000004
curie: CATH.FunFam:3.90.1150.10:FF:000004
label: 2-amino-3-ketobutyrate coenzyme A ligase
negated: false
- condition_type: TAXON
value: Hominidae
curie: NCBITaxon:9604
label: Hominidae
negated: false
- number: 28
conditions:
- condition_type: FUNFAM
value: 1.20.144.10:FF:000034
curie: CATH.FunFam:1.20.144.10:FF:000034
label: Dihydrosphingosine-1-phosphate phosphatase
negated: false
- condition_type: TAXON
value: Dikarya
curie: NCBITaxon:451864
label: Dikarya
negated: false
- number: 29
conditions:
- condition_type: FUNFAM
value: 1.20.144.10:FF:000044
curie: CATH.FunFam:1.20.144.10:FF:000044
label: Lipid A 1-phosphatase
negated: false
- condition_type: TAXON
value: Campylobacterota
curie: NCBITaxon:29547
label: Campylobacterota
negated: false
- number: 30
conditions:
- condition_type: FUNFAM
value: 3.10.120.10:FF:000021
curie: CATH.FunFam:3.10.120.10:FF:000021
label: Delta(8)-fatty-acid desaturase 2
negated: false
- condition_type: TAXON
value: Embryophyta
curie: NCBITaxon:3193
label: Embryophyta
negated: false
- number: 31
conditions:
- condition_type: FUNFAM
value: 3.40.50.10330:FF:000005
curie: CATH.FunFam:3.40.50.10330:FF:000005
label: Sphingosine kinase 2
negated: false
- condition_type: TAXON
value: Homo
curie: NCBITaxon:9605
label: Homo
negated: false
notes: >-
Human SPHK2 (Q9NRA0) carries this FunFam and is annotated to GO:0006669 sphinganine-1-phosphate
biosynthetic process (IDA, PMID:10751414, PMID:19729656) and GO:0046512 sphingosine biosynthetic
process (IGI and IMP, PMID:23106337).
- number: 32
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000072
curie: CATH.FunFam:3.40.50.2000:FF:000072
label: Glycosyl transferase
negated: false
- condition_type: TAXON
value: Mycobacteriales
curie: NCBITaxon:85007
label: Mycobacteriales
negated: false
- number: 33
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000145
curie: CATH.FunFam:3.40.50.2000:FF:000145
label: Probable glycosyl transferase
negated: false
- condition_type: TAXON
value: Actinomycetota
curie: NCBITaxon:201174
label: Actinomycetota
negated: false
- number: 34
conditions:
- condition_type: FUNFAM
value: 3.40.50.2000:FF:000207
curie: CATH.FunFam:3.40.50.2000:FF:000207
label: Phosphatidyl-myo-inositol mannosyltransferase
negated: false
- condition_type: TAXON
value: Actinomycetes
curie: NCBITaxon:1760
label: Actinomycetes
negated: false
- number: 35
conditions:
- condition_type: FUNFAM
value: 3.40.50.720:FF:000317
curie: CATH.FunFam:3.40.50.720:FF:000317
label: Very-long-chain 3-oxoacyl-CoA reductase
negated: false
- condition_type: TAXON
value: Ascomycota
curie: NCBITaxon:4890
label: Ascomycota
negated: false
- number: 36
conditions:
- condition_type: FUNFAM
value: 3.40.50.720:FF:000578
curie: CATH.FunFam:3.40.50.720:FF:000578
label: 3-ketodihydrosphingosine reductase
negated: false
- condition_type: TAXON
value: Saccharomycotina
curie: NCBITaxon:147537
label: Saccharomycotina
negated: false
- number: 37
conditions:
- condition_type: FUNFAM
value: 3.40.640.10:FF:000006
curie: CATH.FunFam:3.40.640.10:FF:000006
label: 5-aminolevulinate synthase, mitochondrial
negated: false
- condition_type: TAXON
value: Bacteroidota
curie: NCBITaxon:976
label: Bacteroidota
negated: false
notes: >-
The two reviewed Bacteroidota members of this FunFam are serine palmitoyltransferases: Bacteroides
thetaiotaomicron SPT (Q8A9E5) and Bacteroides ovatus SPT (A7LXM2). Of 1958 Bacteroidota members
in UniProtKB, 52 are named serine palmitoyltransferase and none is named aminolevulinate synthase;
many unreviewed ones are named 2-amino-3-ketobutyrate coenzyme A ligase.
- number: 38
conditions:
- condition_type: FUNFAM
value: 3.60.21.10:FF:000012
curie: CATH.FunFam:3.60.21.10:FF:000012
label: UDP-2,3-diacylglucosamine hydrolase
negated: false
- condition_type: TAXON
value: Pseudomonadota
curie: NCBITaxon:1224
label: Pseudomonadota
negated: false
- number: 39
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000164
curie: CATH.FunFam:3.90.550.10:FF:000164
label: Beta-(1-3)-glucosyl transferase
negated: false
- condition_type: TAXON
value: Cyanobacteriota
curie: NCBITaxon:1117
label: Cyanobacteriota
negated: false
- number: 40
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000207
curie: CATH.FunFam:3.90.550.10:FF:000207
label: Ceramide glucosyltransferase 1
negated: false
- condition_type: TAXON
value: Ecdysozoa
curie: NCBITaxon:1206794
label: Ecdysozoa
negated: false
- number: 41
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000323
curie: CATH.FunFam:3.90.550.10:FF:000323
label: Processive diacylglycerol beta-glycosyltransferase
negated: false
- condition_type: TAXON
value: Mycoplasmatota
curie: NCBITaxon:544448
label: Mycoplasmatota
negated: false
- number: 42
conditions:
- condition_type: FUNFAM
value: 3.90.550.20:FF:000013
curie: CATH.FunFam:3.90.550.20:FF:000013
label: Alpha1,4-N-acetylgalactosaminyltransferase
negated: false
- condition_type: TAXON
value: Arthropoda
curie: NCBITaxon:6656
label: Arthropoda
negated: false
- number: 43
conditions:
- condition_type: FUNFAM
value: 3.90.76.10:FF:000006
curie: CATH.FunFam:3.90.76.10:FF:000006
label: Monoacyl phosphatidylinositol tetramannoside-binding protein
negated: false
- condition_type: TAXON
value: Mycobacteriaceae
curie: NCBITaxon:1762
label: Mycobacteriaceae
negated: false
- number: 44
conditions:
- condition_type: FUNFAM
value: 1.10.150.50:FF:000037
curie: CATH.FunFam:1.10.150.50:FF:000037
label: sphingomyelin synthase-related protein 1 isoform X1
negated: false
- number: 45
conditions:
- condition_type: FUNFAM
value: 3.20.20.80:FF:000030
curie: CATH.FunFam:3.20.20.80:FF:000030
label: Lysosomal acid glucosylceramidase
negated: false
notes: >-
Human GBA1 (P04062) carries this FunFam and is annotated to GO:0046513 ceramide biosynthetic
process (IMP, PMID:19279011) and GO:0009247 glycolipid biosynthetic process (IDA, PMID:24211208,
PMID:26724485).
- number: 46
conditions:
- condition_type: FUNFAM
value: 3.40.50.10320:FF:000002
curie: CATH.FunFam:3.40.50.10320:FF:000002
label: Probable N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase
negated: false
- number: 47
conditions:
- condition_type: FUNFAM
value: 3.40.720.10:FF:000041
curie: CATH.FunFam:3.40.720.10:FF:000041
label: GPI ethanolamine phosphate transferase 3
negated: false
- number: 48
conditions:
- condition_type: FUNFAM
value: 3.60.21.10:FF:000022
curie: CATH.FunFam:3.60.21.10:FF:000022
label: Putative metallophosphoesterase 1
negated: false
- number: 49
conditions:
- condition_type: FUNFAM
value: 3.90.1480.20:FF:000009
curie: CATH.FunFam:3.90.1480.20:FF:000009
label: alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 isoform X2
negated: false
- number: 50
conditions:
- condition_type: FUNFAM
value: 3.90.550.10:FF:000036
curie: CATH.FunFam:3.90.550.10:FF:000036
label: Dolichol-phosphate mannosyltransferase subunit 1
negated: false
- number: 51
conditions:
- condition_type: FUNFAM
value: 3.90.550.50:FF:000019
curie: CATH.FunFam:3.90.550.50:FF:000019
label: Hexosyltransferase
negated: false
go_annotations:
- go_id: GO:0046467
go_label: obsolete membrane lipid biosynthetic process
aspect: BP
entries: []
reviewed_protein_count: 0
unreviewed_protein_count: 0
created_date: '2021-10-20'
modified_date: '2025-12-15'
retrieved_date: '2026-11-09'
withdrawn: true
review_summary: >-
GO:0046467 is obsolete in GO, and UniProt returned 404 for this rule on 2026-11-09. The 51 condition
sets recorded are those of the last version reviewed. Nine of them (sets 2, 5, 12, 15, 19, 26, 31,
37 and 45) were checked against Swiss-Prot members and their GO annotations. In each case a matched
protein carries a curated annotation to a lipid biosynthetic process: the ceramidases, sphingomyelinase
and glucosylceramidase are annotated to biosynthesis of their products ceramide and sphingosine;
protein kinase D and the chloroplast phosphoglycerate kinases are annotated to sphingolipid and
galactolipid biosynthesis; and the Bacteroidota set selects serine palmitoyltransferases. So these
sets reflect existing annotations rather than fold-level errors. The other 42 sets were not checked.
action: DEPRECATE
action_rationale: The rule has been withdrawn by UniProt and its only consequent is an obsolete GO
term.
suggested_modifications:
- 'No change to make: the rule is withdrawn.'
- >-
If rules for the same families are re-derived with current terms, do not exclude the hydrolase sets
(2, 5, 15, 19, 45) on the ground that hydrolysis is catabolic: their Swiss-Prot members are experimentally
annotated to ceramide or sphingosine biosynthetic process.
- >-
For set 37, check the unreviewed Bacteroidota members named 2-amino-3-ketobutyrate coenzyme A ligase
before propagating a sphingolipid term from the two reviewed serine palmitoyltransferases.
go_specificity:
assessment: MISMATCHED
notes: The consequent GO:0046467 is obsolete.
annotation_assessments:
- annotation_kind: GO_TERM
value: GO:0046467
label: obsolete membrane lipid biosynthetic process
assessment: UNDECIDED
consequent_obsolete: true
correct_examples:
- P17405
- Q9NR71
- Q8TDN7
- P04062
- Q9NRA0
- Q8A9E5
- Q9LD57
- P50318
- Q15139
- Q9BZL6
notes: >-
QuickGO, 2026-11-09: GO:0046467 isObsolete = true, so the consequent itself cannot be assessed.
The examples are reviewed proteins that match a checked condition set and carry a curated annotation
under GO:0008610 lipid biosynthetic process: P17405 GO:0046513 IDA PMID:17303575; Q9NR71 GO:0046513
IDA PMID:17475390; Q8TDN7 GO:0046512 IDA PMID:17713573; P04062 GO:0046513 IMP PMID:19279011; Q9NRA0
GO:0006669 IDA PMID:10751414; Q9LD57 and P50318 GO:0019375 IGI PMID:30834637; Q15139 and Q9BZL6
GO:0030148 TAS Reactome:R-HSA-1660661. Q8A9E5 is a reviewed serine palmitoyltransferase (EC 2.3.1.50).
confidence: 0.95
references:
- id: PMID:34445706
title: >-
Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid
Catabolism.
findings:
- statement: >-
The paper states: "sphingolipids of mammalian cells are degraded in a stepwise manner without
an effective bypass in human lysosomal catabolism"
- statement: >-
The paper states: "The recessively inherited ASMD mainly leads to impaired cellular SM catabolism
causing progressive SM accumulation in the cellular membranes."
- id: PMID:38458396
title: >-
Common and varied molecular responses of Escherichia coli to five different inhibitors of the
lipopolysaccharide biosynthetic enzyme LpxC.
findings:
- statement: >-
The paper states: "The essential enzyme LpxC catalyzes the first committed step of LPS synthesis
and thus represents a promising antibiotic target"
- statement: >-
The paper states: "Instead of the first enzyme LpxA, which catalyzes a reversible reaction,
the second enzyme, LpxC, is the main driver in this process as it catalyzes the first committed
step"
- id: PMID:26563290
title: 'Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.'
findings:
- statement: >-
The paper states: "ethanolamine phosphate (EtNP), three mannoses (Mans), one non-N-acetylated
glucosamine, and inositol phospholipid"
- statement: >-
The paper states: "Fatty chains of inositol phospholipids are inserted into the outer leaflet
of the plasma membrane"
- id: PMID:26139634
title: >-
Functional classification of CATH superfamilies: a domain-based approach for protein function
annotation.
findings:
- statement: >-
The paper states: "the functional annotations provided by FunFams are found to be more precise
compared with those generated by other domain-based resources"
- id: PMID:34357010
title: Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.
findings:
- statement: 'The paper states: "ceramidases catalyze the degradation of ceramide to sphingosine"'
- statement: >-
The paper states: "alkaline ceramidases (encoded by ACER1, ACER2 and ACER3), acidic ceramidase
(encoded by ASAH1) and neutral ceramidase (encoded by ASAH2)"
- id: PMID:28942130
title: Biosynthesis and structure-activity relationships of the lipid A family of glycolipids.
findings:
- statement: >-
The paper states: "Lipid A, the conserved, lipid component of LPS, anchors LPS to the outer
membrane"
- statement: >-
The paper states: "E. coli acyl transferases are chain length specific, orthologs from other
Gram-negative bacteria are more tolerant, yielding a heterogeneous Lipid A composition of the
outer membrane."
corrections:
- date: '2026-11-10'
withdrawn_claim: >-
Five condition sets (alkaline ceramidase, acid sphingomyelinase, neutral ceramidase, sphingomyelin
phosphodiesterase, lysosomal glucosylceramidase) are catabolic, so a lipid biosynthesis term on
them would be false.
correction: >-
GO curators annotate these hydrolases to biosynthesis of their lipid products, with experimental
evidence.
error_type: REFUTED_BY_CURATED_ANNOTATION
evidence:
- 'QuickGO: P17405 (SMPD1) GO:0046513 ceramide biosynthetic process, IDA, PMID:17303575'
- 'QuickGO: Q9NR71 (ASAH2) GO:0046513, IDA, PMID:17475390'
- 'QuickGO: Q8TDN7 (ACER1) GO:0046512 sphingosine biosynthetic process, IDA, PMID:17713573'
- 'QuickGO: P04062 (GBA1) GO:0046513, IMP, PMID:19279011'
- date: '2026-11-10'
withdrawn_claim: >-
Set 37 is 5-aminolevulinate synthase, a fold-level false positive that the Bacteroidota restriction
conceals.
correction: >-
With the taxon condition applied, the reviewed members are serine palmitoyltransferases, the first
enzyme of sphingolipid synthesis; the FunFam label alone was read.
error_type: CONJUNCTION_IGNORED
evidence:
- >-
UniProtKB query xref funfam-3.40.640.10:FF:000006 AND taxonomy 976 AND reviewed: SPT_BACTN (Q8A9E5),
SPT_BACO1 (A7LXM2)
- >-
Same query, all entries: 1958; with protein name aminolevulinate: 0; with protein name serine
palmitoyltransferase: 52
- date: '2026-11-10'
withdrawn_claim: Set 12 is a PH-domain protein kinase with no route to lipid biosynthesis.
correction: >-
The set matches protein kinase D1 and D2, which carry a curated sphingolipid biosynthesis annotation.
error_type: REFUTED_BY_CURATED_ANNOTATION
evidence:
- 'QuickGO: Q15139 (PRKD1) and Q9BZL6 (PRKD2) GO:0030148, TAS, Reactome:R-HSA-1660661'
- UniProtKB Q15139 and Q9BZL6 FunFams include 1.10.510.10:FF:000151 and 2.30.29.30:FF:000056
- date: '2026-11-10'
withdrawn_claim: >-
Set 26 is phosphoglycerate kinase, with no basis for a lipid biosynthetic annotation in Streptophyta
or anywhere else.
correction: >-
The Arabidopsis chloroplast phosphoglycerate kinases matched by the set are annotated to galactolipid
biosynthetic process from a genetic study.
error_type: REFUTED_BY_CURATED_ANNOTATION
evidence:
- 'QuickGO: Q9LD57 (PGKH1) and P50318 (PGKH2) GO:0019375, IGI, PMID:30834637'
- date: '2026-11-10'
withdrawn_claim: Set 31 (sphingosine kinase 2) is interconversion, not biosynthesis.
correction: SPHK2 is experimentally annotated to biosynthetic process terms for sphingoid bases.
error_type: REFUTED_BY_CURATED_ANNOTATION
evidence:
- >-
QuickGO: Q9NRA0 GO:0006669 sphinganine-1-phosphate biosynthetic process, IDA, PMID:10751414
- 'QuickGO: Q9NRA0 GO:0046512, IGI, PMID:23106337'
- date: '2026-11-10'
withdrawn_claim: >-
Four mechanistically unrelated sets reveal that the rule was built by following shared folds.
correction: >-
Three of the four (sets 12, 26 and 37) trace to curated annotations on the matched proteins; set
43 was not checked.
error_type: UNSUPPORTED_SOURCE
evidence:
- See the receipts for sets 12, 26 and 37 above
- date: '2026-11-10'
withdrawn_claim: >-
Per-set verdicts for the remaining sets (non-diagnostic, wrong pathway, annotation-bias taxon
scopes) and the count of at most 26 sound sets.
correction: >-
These rested on reading FunFam and superfamily labels without checking matched proteins, the method
that failed for the sets above; they are removed rather than kept unverified.
error_type: UNEXAMINED_RULE
evidence:
- 42 of 51 condition sets were not checked against Swiss-Prot members
- date: '2026-11-10'
withdrawn_claim: UniProt still serves the rule.
correction: UniProt returned 404 on 2026-11-09.
error_type: STALE_RULE_VERSION
evidence:
- 'rest.uniprot.org/arba/ARBA00028538: HTTP 404 on 2026-11-09'