DUFMech

All families / PF03781

PF03781: FGE-sulfatase

Sulfatase-modifying factor enzyme 1-like domain

Curation status
SEEDED
Seed status
EX DUF
Characterization
UNSCORED

Grounding

PF03781: Sulfatase-modifying factor enzyme 1-like domain
IPR005532: integrated entry for Sulfatase-modifying factor enzyme 1-like domain

Source description

This domain is found in eukaryotic proteins [InterPro reference PUB00019471] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [InterPro reference PUB00033658]. The protein product of the SUMF1 gene is FGE, formylglycine (FGly),-generating enzyme, which is a sulfatase. Sulfatases are enzymes essential for degradation and remodelling of sulfate esters, and formylglycine (FGly), the key catalytic in the active site, is unique to sulfatases [InterPro reference PUB00038408]. FGE is localised to the endoplasmic reticulum (ER) and interacts with and modifies the unfolded form of newly synthesised sulfatases. FGE is a single-domain monomer with a surprising paucity of secondary structure that adopts a unique fold which is stabilised by two Ca2+ ions. The effect of all mutations found in MSD patients is explained by the FGE structure, providing a molecular basis for MSD. A redox-active disulfide bond is present in the active site of FGE. An oxidised cysteine residue, possibly cysteine sulfenic acid, has been detected that may allow formulation of a structure-based mechanism for FGly formation from cysteine residues in all sulfatases [InterPro reference PUB00055960]. In Mycobacteria and Treponema denticola this enzyme functions as an iron(II)-dependent oxidoreductase [InterPro reference PUB00060032,InterPro reference PUB00066766]. This domain is also found in the Serine/threonine-protein kinase Pkn1 from Chlamydia trachomatis which is a multidomain protein. Pkn1 plays a role in specific interactions with host proteins during host intracellular growth.

Evidence and references

Source descriptions and links are provenance, not independent functional validation.

Evidence counts: not scored.

Curated functional assertions

No curated functional assertions supplied.

Protein sequence examples

11 verified sequence examples. FASTA

UniProtProtein / organismSequenceProvenance
A0R5N0Hercynine oxygenase
Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
428 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
G7CFI3Hercynine oxygenase
Mycolicibacterium thermoresistibile (strain ATCC 19527 / DSM 44167 / CIP 105390 / JCM 6362 / NCTC 10409 / 316)
446 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
O34722Uncharacterized protein YfmG
Bacillus subtilis (strain 168)
487 aa; version 1
UniProt 2026_03
PTM REGISTRY MIRROR
5 sibling references
Q4WZV3Ergothioneine biosynthesis protein A
Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293)
844 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
Q7RX33Ergothioneine biosynthesis protein 1
Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
876 aa; version 3
UniProt 2026_03
UNIPROT FETCH
1 sibling references
Q8BPG6Inactive C-alpha-formylglycine-generating enzyme 2
Mus musculus
308 aa; version 2
UniProt 2026_03
UNIPROT FETCH
3 sibling references
Q8NBJ7Inactive C-alpha-formylglycine-generating enzyme 2
Homo sapiens
301 aa; version 2
UniProt 2026_03
UNIPROT FETCH
4 sibling references
Q8NBK3Formylglycine-generating enzyme
Homo sapiens
374 aa; version 3
UniProt 2026_03
UNIPROT FETCH
7 sibling references
Q8R0F3Formylglycine-generating enzyme
Mus musculus
372 aa; version 2
UniProt 2026_03
UNIPROT FETCH
5 sibling references
Q9I185PvdO
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
284 aa; version 1
UniProt 2026_03
PTM REGISTRY MIRROR
1 sibling references

First 10 shown; the FASTA and family JSON contain all examples.

Pfam membership is not functional evidence. Whole-protein sequences do not establish domain boundaries. A coverage gap here is not absence from UniProt.

Sequences and metadata: UniProt Consortium, CC BY 4.0.

Domain matches

No residue-level domain match evidence is available in this build. Structure and AlphaFold counters do not supply coordinates or establish function.

Snapshot counters

proteins
38,188
matches
41,371
proteomes
14,430
taxa
23,526
structures
65
alphafold models
25,146
domain architectures
587

Classification basis

pfam previous unknown name

No scoring reasons supplied.

Related Mech records

This family joined the worklist after the frozen cross-Mech scan, so other Mechs were not searched for it. Missing links here are not evidence that other Mechs lack it; rows shown come from mentions of a former DUF/UPF name.

No cross-Mech examples are present in the supplied snapshot.

Curation history and reviews

No retained curation events supplied.

No retained review supplied.

Record source

data/families/PF03781.yaml
Family YAML in this build

Download this family (JSON)

Status and evidence

Seed status
A name-based classification of frozen InterPro/Pfam metadata. UNKNOWN CANDIDATE means the metadata explicitly says the function is unknown. KNOWN HISTORICAL DUF means a DUF name matched without that wording; this heuristic is not proof of a known function and does not establish experimental characterization. EX DUF means Pfam renamed the family away from a DUF/UPF name, as recorded in Pfam's previous identifiers; a rename usually follows published work on some members but is naming history, not proof of function for every member. Some EX DUF families' current names or descriptions still say the function is unknown; their classification basis lists this, and scoring does not treat them as characterized. FALSE POSITIVE TEXT HIT means the naming rules did not match.
Characterization
A separate evidence-scoring result. UNSCORED means no score has been calculated; it is not evidence that the family lacks a known function. Missing scores are not negative evidence. PARTIALLY CHARACTERIZED has partial support; KNOWN HISTORICAL DUF can inherit the seed label or reflect a known-function signal. Neither label implies experimental validation.
Evidence counts
Source-specific signals, not unique proteins, publications, or confidence scores. Known counts Rhea reactions and experimentally supported GO molecular-function annotations. Partial counts functional/domain assignments. Context counts structural, environmental, orthology, interaction and neighborhood signals; context alone does not assign function. Repeated annotations may not be independent.
Curation status
Reported separately from seed classification and characterization. SNAPSHOT ONLY means no curated metadata was supplied for this build. SEEDED denotes a source-derived record, not an expert-reviewed functional claim.
Missing counts
Not available means the source did not supply that counter. A zero is a reported count. Not scored means evidence counts are unavailable.