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36  structures 5113  species 1  interaction 14664  sequences 343  architectures

Family: FGE-sulfatase (PF03781)

Summary: Sulfatase-modifying factor enzyme 1

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This is the Wikipedia entry entitled "Formylglycine-generating sulfatase enzyme". More...

Formylglycine-generating sulfatase enzyme Edit Wikipedia article

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Sulfatase-modifying factor enzyme 1 Provide feedback

This domain is found in eukaryotic proteins [1] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [2]. 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 [3]. 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 [4]. In Mycobacteria and Treponema denticola this enzyme functions as an iron(II)-dependent oxidoreductase [5,6].

Literature references

  1. Landgrebe J, Dierks T, Schmidt B, von Figura K; , Gene 2003;316:47-56.: The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes. PUBMED:14563551 EPMC:14563551

  2. Cosma MP, Pepe S, Parenti G, Settembre C, Annunziata I, Wade-Martins R, Di Domenico C, Di Natale P, Mankad A, Cox B, Uziel G, Mancini GM, Zammarchi E, Donati MA, Kleijer WJ, Filocamo M, Carrozzo R, Carella M, Ballabio A; , Hum Mutat. 2004;23:576-581.: Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. PUBMED:15146462 EPMC:15146462

  3. Dierks T, Dickmanns A, Preusser-Kunze A, Schmidt B, Mariappan M, von Figura K, Ficner R, Rudolph MG; , Cell. 2005;121:541-552.: Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme. PUBMED:15907468 EPMC:15907468

  4. Schlotawa L, Steinfeld R, von Figura K, Dierks T, Gartner J; , Hum Mutat. 2008;29:205.: Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency. PUBMED:18157819 EPMC:18157819

  5. Seebeck FP;, J Am Chem Soc. 2010;132:6632-6633.: In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. PUBMED:20420449 EPMC:20420449

  6. Seshadri R, Myers GS, Tettelin H, Eisen JA, Heidelberg JF, Dodson RJ, Davidsen TM, DeBoy RT, Fouts DE, Haft DH, Selengut J, Ren Q, Brinkac LM, Madupu R, Kolonay J, Durkin SA, Daugherty SC, Shetty J, Shvartsbeyn A, Gebregeorgis E, Geer K, Tsegaye G, Malek J, Ayodeji B, Shatsman S, McLeod MP, Smajs D, Howell JK, Pal S, Amin A, Vashisth P, McNeill TZ, Xiang Q, Sodergren E, Baca E, Weinstock GM, Norris SJ, Fraser CM, Paulsen IT;, Proc Natl Acad Sci U S A. 2004;101:5646-5651.: Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. PUBMED:15064399 EPMC:15064399


This tab holds annotation information from the InterPro database.

InterPro entry IPR005532

This domain is found in sulfatase-modifying factors (SUMFs) [PUBMED:14563551] and Chlamydia serine/threonine-protein kinase pkn1 [PUBMED:14500499]. It is also found in iron(II)-dependent oxidoreductase from Mycobacterium [PUBMED:20420449, PUBMED:15064399].

The structure of this domain is homologous to the complex alpha/beta topology found in sulfatase-modifying factors (SUMF1). SUMF1 is a paralogue of oxoalanine-generating enzyme, also called C(alpha)-formylglycine generating enzyme (FGE). SUMF1 converts newly synthesized inactive sulfatases to their active form by modifying an active site cysteine residue to oxoalanine. Sulfatases are essential for the degradation of sulfate esters, whose catalytic activity is dependent upon an oxoalanine residue [PUBMED:16041070]. Defects in SUMF1 or FGE cause multiple sulfatase deficiency (MSD), which leads to the impairment of all sulfatases and to the accumulation of glycoaminoglycans or sulfolipids, causing early infant death [PUBMED:17206939, PUBMED:16124866, PUBMED:16174644] Known substrates for SUMF1 are: N-acetylgalactosamine-6-sulfate sulfatase (GALNS), arylsulfatase A (ARSA), steroid sulfatase (STS) and arylsulfatase E (ARSE). SUMF1 occurs in the endoplasmic reticulum or its lumen.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan C_Lectin (CL0056), which has the following description:

This clan contains domains that have a C-type lectin fold. Many of these are known or expected to mediate interactions with sugars.

The clan contains the following 12 members:

APT C4 Chordopox_A33R DUF1554 DUF5075 Endostatin FGE-sulfatase Intimin_C Lectin_C Ly49 UL45 Xlink

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(22)
Full
(14664)
Representative proteomes UniProt
(39739)
NCBI
(55145)
Meta
(2597)
RP15
(4132)
RP35
(10022)
RP55
(15006)
RP75
(20670)
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PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(22)
Full
(14664)
Representative proteomes UniProt
(39739)
NCBI
(55145)
Meta
(2597)
RP15
(4132)
RP35
(10022)
RP55
(15006)
RP75
(20670)
Alignment:
Format:
Order:
Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(22)
Full
(14664)
Representative proteomes UniProt
(39739)
NCBI
(55145)
Meta
(2597)
RP15
(4132)
RP35
(10022)
RP55
(15006)
RP75
(20670)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: COG1262
Previous IDs: DUF323;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Wood V , Mistry J
Number in seed: 22
Number in full: 14664
Average length of the domain: 231.20 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 54.95 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.3 23.3
Trusted cut-off 23.3 23.3
Noise cut-off 23.2 23.2
Model length: 260
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Interactions

There is 1 interaction for this family. More...

FGE-sulfatase

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FGE-sulfatase domain has been found. There are 36 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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