This domain is found in eukaryotic proteins [[cite:PUB00019471]] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [[cite: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 [[cite: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 [[cite:PUB00055960]]. In Mycobacteria and Treponema denticola this enzyme functions as an iron(II)-dependent oxidoreductase [[cite:PUB00060032],[cite: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.
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Formylglycine-generating_enzyme","extract":"Formylglycine-generating enzyme (FGE), located at 3p26.1 in humans, is the name for an enzyme present in the endoplasmic reticulum that catalyzes the conversion of cysteine to formylglycine (fGly). There are two main classes of FGE, aerobic and anaerobic. FGE activates sulfatases, which are essential for the degradation of sulfate esters. The catalytic activity of sulfatases is dependent upon a formylglycine residue in the active site.
","thumbnail":null}],"literature":{"PUB00019471":{"PMID":14563551,"ISBN":null,"volume":"316","issue":null,"year":2003,"title":"The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes.","URL":null,"raw_pages":"47-56","medline_journal":"Gene","ISO_journal":"Gene","authors":["Landgrebe J","Dierks T","Schmidt B","von Figura K."],"DOI_URL":"http://dx.doi.org/10.1016/S0378-1119(03)00746-7"},"PUB00060032":{"PMID":20420449,"ISBN":null,"volume":"132","issue":"19","year":2010,"title":"In vitro reconstitution of Mycobacterial ergothioneine biosynthesis.","URL":null,"raw_pages":"6632-3","medline_journal":"J Am Chem Soc","ISO_journal":"J. Am. Chem. Soc.","authors":["Seebeck FP."],"DOI_URL":"http://dx.doi.org/10.1021/ja101721e"},"PUB00033658":{"PMID":15146462,"ISBN":null,"volume":"23","issue":"6","year":2004,"title":"Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency.","URL":null,"raw_pages":"576-81","medline_journal":"Hum Mutat","ISO_journal":"Hum. Mutat.","authors":["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."],"DOI_URL":"http://dx.doi.org/10.1002/humu.20040"},"PUB00038408":{"PMID":15907468,"ISBN":null,"volume":"121","issue":"4","year":2005,"title":"Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme.","URL":null,"raw_pages":"541-52","medline_journal":"Cell","ISO_journal":"Cell","authors":["Dierks T","Dickmanns A","Preusser-Kunze A","Schmidt B","Mariappan M","von Figura K","Ficner R","Rudolph MG."],"DOI_URL":"http://dx.doi.org/10.1016/j.cell.2005.03.001"},"PUB00055960":{"PMID":18157819,"ISBN":null,"volume":"29","issue":"1","year":2008,"title":"Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency.","URL":null,"raw_pages":"205","medline_journal":"Hum Mutat","ISO_journal":"Hum. Mutat.","authors":["Schlotawa L","Steinfeld R","von Figura K","Dierks T","Gartner J."],"DOI_URL":"http://dx.doi.org/10.1002/humu.9515"},"PUB00066766":{"PMID":15064399,"ISBN":null,"volume":"101","issue":"15","year":2004,"title":"Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes.","URL":null,"raw_pages":"5646-51","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc. Natl. Acad. Sci. U.S.A.","authors":["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."],"DOI_URL":"http://dx.doi.org/10.1073/pnas.0307639101"}},"set_info":{"accession":"CL0056","name":"C_Lectin"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":587,"interactions":0,"matches":41371,"pathways":0,"proteins":38188,"proteomes":14430,"sets":1,"structural_models":{"alphafold":25146},"structures":65,"taxa":23526},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":17,"alignment:full":23072},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"2afy","name":"Formylglycine generating enzyme C341S mutant"}}}