SUMF1_HUMAN
ID SUMF1_HUMAN Reviewed; 374 AA.
AC Q8NBK3; B4DXK5; B7XD05; E9PGL0; G5E9B0; Q0VAC6; Q0VAC7; Q2NL78; Q53ZE4;
AC Q6UY39; Q96AK5; Q96DK8;
DT 25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Formylglycine-generating enzyme {ECO:0000303|PubMed:12757705};
DE Short=FGE {ECO:0000303|PubMed:12757705};
DE EC=1.8.3.7 {ECO:0000269|PubMed:15657036, ECO:0000269|PubMed:25931126};
DE AltName: Full=C-alpha-formylglycine-generating enzyme 1 {ECO:0000303|PubMed:12757705};
DE AltName: Full=Sulfatase-modifying factor 1 {ECO:0000303|PubMed:12757706};
DE Flags: Precursor;
GN Name=SUMF1 {ECO:0000303|PubMed:12757706, ECO:0000312|HGNC:HGNC:20376};
GN ORFNames=PSEC0152 {ECO:0000303|PubMed:16303743},
GN UNQ3037/PRO9852 {ECO:0000303|PubMed:12975309};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MSD VAL-279; ARG-336;
RP GLN-349 AND TRP-349, AND VARIANT ASN-63.
RX PubMed=12757705; DOI=10.1016/s0092-8674(03)00347-7;
RA Dierks T., Schmidt B., Borissenko L.V., Peng J., Preusser A., Mariappan M.,
RA von Figura K.;
RT "Multiple sulfatase deficiency is caused by mutations in the gene encoding
RT the Homo sapiens C-alpha-formyglycine-generating enzyme.";
RL Cell 113:435-444(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MSD PRO-155; TYR-218;
RP ARG-336; CYS-345; PRO-348; GLN-349 AND TRP-349, AND FUNCTION.
RX PubMed=12757706; DOI=10.1016/s0092-8674(03)00348-9;
RA Cosma M.P., Pepe S., Annunziata I., Newbold R.F., Grompe M., Parenti G.,
RA Ballabio A.;
RT "The multiple sulfatase deficiency gene encodes an essential and limiting
RT factor for the activity of sulfatases.";
RL Cell 113:445-456(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=19262745;
RA Oshikawa M., Usami R., Kato S.;
RT "Characterization of the arylsulfatase I (ARSI) gene preferentially
RT expressed in the human retinal pigment epithelium cell line ARPE-19.";
RL Mol. Vis. 15:482-494(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ASN-63.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Gastric mucosa, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Colon, and Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP SUBUNIT, INTERACTION WITH SUMF2, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15962010; DOI=10.1038/sj.embor.7400454;
RA Zito E., Fraldi A., Pepe S., Annunziata I., Kobinger G., Di Natale P.,
RA Ballabio A., Cosma M.P.;
RT "Sulphatase activities are regulated by the interaction of sulphatase-
RT modifying factor 1 with SUMF2.";
RL EMBO Rep. 6:655-660(2005).
RN [11]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY,
RP IDENTIFICATION BY MASS SPECTROMETRY, CALCIUM-BINDING, GLYCOSYLATION AT
RP ASN-141, SUBCELLULAR LOCATION, AND DISULFIDE BONDS.
RX PubMed=15657036; DOI=10.1074/jbc.m413383200;
RA Preusser-Kunze A., Mariappan M., Schmidt B., Gande S.L., Mutenda K.,
RA Wenzel D., von Figura K., Dierks T.;
RT "Molecular characterization of the human Calpha-formylglycine-generating
RT enzyme.";
RL J. Biol. Chem. 280:14900-14910(2005).
RN [12]
RP PARTIAL PROTEIN SEQUENCE, X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 73-374
RP IN COMPLEX WITH CALCIUM, FUNCTION, GLYCOSYLATION AT ASN-141, MUTAGENESIS OF
RP SER-333; CYS-336; HIS-337; TYR-340 AND CYS-341, AND DISULFIDE BONDS.
RX PubMed=15907468; DOI=10.1016/j.cell.2005.03.001;
RA Dierks T., Dickmanns A., Preusser-Kunze A., Schmidt B., Mariappan M.,
RA von Figura K., Ficner R., Rudolph M.G.;
RT "Molecular basis for multiple sulfatase deficiency and mechanism for
RT formylglycine generation of the human formylglycine-generating enzyme.";
RL Cell 121:541-552(2005).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=18266766; DOI=10.1111/j.1742-4658.2008.06271.x;
RA Gande S.L., Mariappan M., Schmidt B., Pringle T.H., von Figura K.,
RA Dierks T.;
RT "Paralog of the formylglycine-generating enzyme--retention in the
RT endoplasmic reticulum by canonical and noncanonical signals.";
RL FEBS J. 275:1118-1130(2008).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-141.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16]
RP FUNCTION, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND
RP COFACTOR.
RX PubMed=25931126; DOI=10.1074/jbc.m115.652669;
RA Holder P.G., Jones L.C., Drake P.M., Barfield R.M., Banas S., de Hart G.W.,
RA Baker J., Rabuka D.;
RT "Reconstitution of formylglycine-generating enzyme with copper(II) for
RT aldehyde tag conversion.";
RL J. Biol. Chem. 290:15730-15745(2015).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF MUTANTS SER-336 AND SER-341 IN
RP COMPLEX WITH SULFATASE PEPTIDE, AND FUNCTION.
RX PubMed=16368756; DOI=10.1073/pnas.0507592102;
RA Roeser D., Preusser-Kunze A., Schmidt B., Gasow K., Wittmann J.G.,
RA Dierks T., von Figura K., Rudolph M.G.;
RT "A general binding mechanism for all human sulfatases by the formylglycine-
RT generating enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:81-86(2006).
RN [18]
RP VARIANTS MSD PHE-20; PRO-177; TRP-224; ILE-259 AND LEU-266, AND
RP CHARACTERIZATION OF VARIANTS MSD PHE-20; PRO-155; PRO-177; TYR-218;
RP TRP-224; ILE-259; LEU-266; VAL-279; ARG-336; CYS-345; PRO-348; TRP-349 AND
RP GLN-349.
RX PubMed=15146462; DOI=10.1002/humu.20040;
RA Cosma M.P., Pepe S., Parenti G., Settembre C., Annunziata I.,
RA Wade-Martins R., Domenico C.D., Natale P.D., Mankad A., Cox B., Uziel G.,
RA Mancini G.M., Zammarchi E., Donati M.A., Kleijer W.J., Filocamo M.,
RA Carrozzo R., Carella M., Ballabio A.;
RT "Molecular and functional analysis of SUMF1 mutations in multiple sulfatase
RT deficiency.";
RL Hum. Mutat. 23:576-581(2004).
RN [19]
RP CHARACTERIZATION OF VARIANTS MSD PRO-177; SER-179; VAL-279 AND TRP-349.
RX PubMed=18157819; DOI=10.1002/humu.9515;
RA Schlotawa L., Steinfeld R., von Figura K., Dierks T., Gaertner J.;
RT "Molecular analysis of SUMF1 mutations: stability and residual activity of
RT mutant formylglycine-generating enzyme determine disease severity in
RT multiple sulfatase deficiency.";
RL Hum. Mutat. 29:205-205(2008).
RN [20]
RP VARIANTS MSD PRO-155; ARG-247; VAL-263; 327-ARG--ASP-374 DEL AND CYS-345,
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS MSD
RP PRO-155; VAL-263; 327-ARG--ASP-374 DEL AND CYS-345.
RX PubMed=21224894; DOI=10.1038/ejhg.2010.219;
RA Schlotawa L., Ennemann E.C., Radhakrishnan K., Schmidt B., Chakrapani A.,
RA Christen H.J., Moser H., Steinmann B., Dierks T., Gaertner J.;
RT "SUMF1 mutations affecting stability and activity of formylglycine
RT generating enzyme predict clinical outcome in multiple sulfatase
RT deficiency.";
RL Eur. J. Hum. Genet. 19:253-261(2011).
CC -!- FUNCTION: Oxidase that catalyzes the conversion of cysteine to 3-
CC oxoalanine on target proteins, using molecular oxygen and an
CC unidentified reducing agent (PubMed:12757706, PubMed:15657036,
CC PubMed:15907468, PubMed:25931126, PubMed:16368756, PubMed:21224894). 3-
CC oxoalanine modification, which is also named formylglycine (fGly),
CC occurs in the maturation of arylsulfatases and some alkaline
CC phosphatases that use the hydrated form of 3-oxoalanine as a catalytic
CC nucleophile (PubMed:12757706, PubMed:15657036, PubMed:15907468,
CC PubMed:25931126, PubMed:16368756). Known substrates include GALNS,
CC ARSA, STS and ARSE (PubMed:12757706, PubMed:15907468, PubMed:15657036).
CC {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15657036,
CC ECO:0000269|PubMed:15907468, ECO:0000269|PubMed:16368756,
CC ECO:0000269|PubMed:21224894, ECO:0000269|PubMed:25931126}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a thiol + L-cysteinyl-[sulfatase] + O2 = 3-oxo-L-alanyl-
CC [sulfatase] + an organic disulfide + H(+) + H2O + hydrogen sulfide;
CC Xref=Rhea:RHEA:51152, Rhea:RHEA-COMP:12900, Rhea:RHEA-COMP:12901,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29256, ChEBI:CHEBI:29919, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:35489, ChEBI:CHEBI:85621; EC=1.8.3.7;
CC Evidence={ECO:0000269|PubMed:15657036, ECO:0000269|PubMed:25931126};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000269|PubMed:25931126};
CC Note=The catalytic copper is required to activate oxygen and catalyze
CC oxidative C-H activation. {ECO:0000269|PubMed:25931126};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.34 uM for [sulfatase]-L-cysteine {ECO:0000269|PubMed:25931126};
CC Note=kcat is 6.06 min(-1) with [sulfatase]-L-cysteine as substrate.
CC {ECO:0000269|PubMed:25931126};
CC -!- PATHWAY: Protein modification; sulfatase oxidation.
CC {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15657036,
CC ECO:0000269|PubMed:15907468, ECO:0000269|PubMed:25931126}.
CC -!- SUBUNIT: Monomer, homodimer and heterodimer with SUMF2.
CC {ECO:0000269|PubMed:15907468, ECO:0000269|PubMed:15962010,
CC ECO:0000269|PubMed:16368756}.
CC -!- INTERACTION:
CC Q8NBK3; P51688: SGSH; NbExp=2; IntAct=EBI-2853497, EBI-2907521;
CC Q8NBK3; Q8NBK3: SUMF1; NbExp=3; IntAct=EBI-2853497, EBI-2853497;
CC Q8NBK3; Q8NBJ7: SUMF2; NbExp=9; IntAct=EBI-2853497, EBI-723091;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:15657036, ECO:0000269|PubMed:15962010,
CC ECO:0000269|PubMed:18266766, ECO:0000269|PubMed:21224894}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8NBK3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NBK3-2; Sequence=VSP_007877;
CC Name=3;
CC IsoId=Q8NBK3-3; Sequence=VSP_013185;
CC Name=4;
CC IsoId=Q8NBK3-4; Sequence=VSP_045414;
CC Name=5;
CC IsoId=Q8NBK3-5; Sequence=VSP_045415;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in kidney, pancreas
CC and liver. Detected at lower levels in leukocytes, lung, placenta,
CC small intestine, skeletal muscle and heart.
CC {ECO:0000269|PubMed:15962010}.
CC -!- PTM: N-glycosylated. Contains high-mannose-type oligosaccharides.
CC {ECO:0000269|PubMed:15657036, ECO:0000269|PubMed:15907468,
CC ECO:0000269|PubMed:19159218}.
CC -!- DISEASE: Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically
CC and biochemically heterogeneous disorder caused by the simultaneous
CC impairment of all sulfatases, due to defective post-translational
CC modification and activation. It combines features of individual
CC sulfatase deficiencies such as metachromatic leukodystrophy,
CC mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus,
CC ichthyosis, neurologic deterioration and developmental delay.
CC {ECO:0000269|PubMed:12757705, ECO:0000269|PubMed:12757706,
CC ECO:0000269|PubMed:15146462, ECO:0000269|PubMed:18157819,
CC ECO:0000269|PubMed:21224894}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. SUMF1 mutations result in
CC defective post-translational modification of sulfatases.
CC {ECO:0000269|PubMed:12757706}.
CC -!- MISCELLANEOUS: The resulting 3-oxoalanine in the substrate protein is
CC called C(alpha)-formylglycine by many authors. It should not be
CC confused with N-formylglycine.
CC -!- SIMILARITY: Belongs to the sulfatase-modifying factor family.
CC {ECO:0000305}.
CC -!- CAUTION: The disulfide bond observed in the structure does not exist in
CC vivo (PubMed:15907468). The enzyme reaction was initially thought to
CC act via a redox-active disulfide bond mechanism; however the disulfide
CC bond only takes place with inactive enzyme that lacks the copper
CC cofactor (PubMed:25931126). The catalytic copper is required to
CC activate oxygen and catalyze oxidative C-H activation
CC (PubMed:25931126). {ECO:0000269|PubMed:15907468,
CC ECO:0000269|PubMed:25931126}.
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DR EMBL; AY208752; AAO34683.1; -; mRNA.
DR EMBL; AY323910; AAP86217.1; -; mRNA.
DR EMBL; AB448737; BAH11168.1; -; mRNA.
DR EMBL; AY358092; AAQ88459.1; -; mRNA.
DR EMBL; AK057983; BAB71625.1; -; mRNA.
DR EMBL; AK302018; BAG63417.1; -; mRNA.
DR EMBL; AK075459; BAC11634.1; -; mRNA.
DR EMBL; AC018822; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023484; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC024168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW63906.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW63907.1; -; Genomic_DNA.
DR EMBL; BC017005; AAH17005.2; -; mRNA.
DR EMBL; BC110862; AAI10863.1; -; mRNA.
DR EMBL; BC121122; AAI21123.1; -; mRNA.
DR EMBL; BC121123; AAI21124.1; -; mRNA.
DR CCDS; CCDS2564.1; -. [Q8NBK3-1]
DR CCDS; CCDS54548.1; -. [Q8NBK3-4]
DR CCDS; CCDS54549.1; -. [Q8NBK3-5]
DR RefSeq; NP_001158146.1; NM_001164674.1. [Q8NBK3-4]
DR RefSeq; NP_001158147.1; NM_001164675.1. [Q8NBK3-5]
DR RefSeq; NP_877437.2; NM_182760.3. [Q8NBK3-1]
DR PDB; 1Y1E; X-ray; 1.73 A; X=73-374.
DR PDB; 1Y1F; X-ray; 1.80 A; X=73-374.
DR PDB; 1Y1G; X-ray; 1.67 A; X=73-374.
DR PDB; 1Y1H; X-ray; 1.67 A; X=73-374.
DR PDB; 1Y1I; X-ray; 2.61 A; X=73-374.
DR PDB; 1Y1J; X-ray; 1.55 A; X=73-374.
DR PDB; 1Z70; X-ray; 1.15 A; X=73-374.
DR PDB; 2AFT; X-ray; 1.66 A; X=86-371.
DR PDB; 2AFY; X-ray; 1.49 A; X=86-371.
DR PDB; 2AII; X-ray; 1.54 A; X=86-371.
DR PDB; 2AIJ; X-ray; 1.55 A; X=86-371.
DR PDB; 2AIK; X-ray; 1.73 A; X=86-371.
DR PDB; 2HI8; X-ray; 1.64 A; X=86-371.
DR PDB; 2HIB; X-ray; 2.00 A; X=86-371.
DR PDBsum; 1Y1E; -.
DR PDBsum; 1Y1F; -.
DR PDBsum; 1Y1G; -.
DR PDBsum; 1Y1H; -.
DR PDBsum; 1Y1I; -.
DR PDBsum; 1Y1J; -.
DR PDBsum; 1Z70; -.
DR PDBsum; 2AFT; -.
DR PDBsum; 2AFY; -.
DR PDBsum; 2AII; -.
DR PDBsum; 2AIJ; -.
DR PDBsum; 2AIK; -.
DR PDBsum; 2HI8; -.
DR PDBsum; 2HIB; -.
DR AlphaFoldDB; Q8NBK3; -.
DR SMR; Q8NBK3; -.
DR BioGRID; 130091; 74.
DR IntAct; Q8NBK3; 19.
DR MINT; Q8NBK3; -.
DR STRING; 9606.ENSP00000272902; -.
DR GlyConnect; 1772; 4 N-Linked glycans (1 site).
DR GlyGen; Q8NBK3; 1 site, 4 N-linked glycans (1 site).
DR iPTMnet; Q8NBK3; -.
DR PhosphoSitePlus; Q8NBK3; -.
DR BioMuta; SUMF1; -.
DR DMDM; 62298562; -.
DR EPD; Q8NBK3; -.
DR jPOST; Q8NBK3; -.
DR MassIVE; Q8NBK3; -.
DR MaxQB; Q8NBK3; -.
DR PaxDb; Q8NBK3; -.
DR PeptideAtlas; Q8NBK3; -.
DR PRIDE; Q8NBK3; -.
DR ProteomicsDB; 20338; -.
DR ProteomicsDB; 33885; -.
DR ProteomicsDB; 72786; -. [Q8NBK3-1]
DR ProteomicsDB; 72787; -. [Q8NBK3-2]
DR ProteomicsDB; 72788; -. [Q8NBK3-3]
DR Antibodypedia; 44604; 200 antibodies from 30 providers.
DR DNASU; 285362; -.
DR Ensembl; ENST00000272902.10; ENSP00000272902.5; ENSG00000144455.14. [Q8NBK3-1]
DR Ensembl; ENST00000383843.9; ENSP00000373355.5; ENSG00000144455.14. [Q8NBK3-4]
DR Ensembl; ENST00000405420.2; ENSP00000384977.2; ENSG00000144455.14. [Q8NBK3-5]
DR GeneID; 285362; -.
DR KEGG; hsa:285362; -.
DR MANE-Select; ENST00000272902.10; ENSP00000272902.5; NM_182760.4; NP_877437.2.
DR UCSC; uc003bpz.3; human. [Q8NBK3-1]
DR CTD; 285362; -.
DR DisGeNET; 285362; -.
DR GeneCards; SUMF1; -.
DR GeneReviews; SUMF1; -.
DR HGNC; HGNC:20376; SUMF1.
DR HPA; ENSG00000144455; Low tissue specificity.
DR MalaCards; SUMF1; -.
DR MIM; 272200; phenotype.
DR MIM; 607939; gene.
DR neXtProt; NX_Q8NBK3; -.
DR OpenTargets; ENSG00000144455; -.
DR Orphanet; 585; Multiple sulfatase deficiency.
DR PharmGKB; PA134977552; -.
DR VEuPathDB; HostDB:ENSG00000144455; -.
DR eggNOG; ENOG502QVDG; Eukaryota.
DR GeneTree; ENSGT00390000008983; -.
DR HOGENOM; CLU_012431_4_1_1; -.
DR InParanoid; Q8NBK3; -.
DR OMA; WTADLWD; -.
DR OrthoDB; 835112at2759; -.
DR PhylomeDB; Q8NBK3; -.
DR TreeFam; TF324027; -.
DR BioCyc; MetaCyc:ENSG00000144455-MON; -.
DR BRENDA; 1.8.3.7; 2681.
DR PathwayCommons; Q8NBK3; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR SignaLink; Q8NBK3; -.
DR UniPathway; UPA00910; -.
DR BioGRID-ORCS; 285362; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; SUMF1; human.
DR EvolutionaryTrace; Q8NBK3; -.
DR GeneWiki; SUMF1; -.
DR GenomeRNAi; 285362; -.
DR Pharos; Q8NBK3; Tbio.
DR PRO; PR:Q8NBK3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8NBK3; protein.
DR Bgee; ENSG00000144455; Expressed in kidney epithelium and 194 other tissues.
DR ExpressionAtlas; Q8NBK3; baseline and differential.
DR Genevisible; Q8NBK3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:1903135; F:cupric ion binding; IDA:UniProtKB.
DR GO; GO:0120147; F:Formylglycine-generating oxidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016491; F:oxidoreductase activity; TAS:Reactome.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0018158; P:protein oxidation; IDA:UniProtKB.
DR Gene3D; 3.90.1580.10; -; 1.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR005532; SUMF_dom.
DR InterPro; IPR042095; SUMF_sf.
DR Pfam; PF03781; FGE-sulfatase; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Copper;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Ichthyosis; Leukodystrophy;
KW Metachromatic leukodystrophy; Metal-binding; Mucopolysaccharidosis;
KW Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..33
FT /evidence="ECO:0000269|PubMed:15657036"
FT CHAIN 34..374
FT /note="Formylglycine-generating enzyme"
FT /id="PRO_0000033456"
FT REGION 61..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..360
FT /note="Interaction with sulfatases"
FT /evidence="ECO:0000269|PubMed:16368756"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 260
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 273
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 275
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 296
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 298
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 300
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15907468"
FT BINDING 336
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:25931126"
FT BINDING 341
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:25931126"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15657036,
FT ECO:0000269|PubMed:15907468, ECO:0000269|PubMed:19159218"
FT DISULFID 50..52
FT /evidence="ECO:0000269|PubMed:15657036,
FT ECO:0000269|PubMed:15907468"
FT DISULFID 218..365
FT /evidence="ECO:0000269|PubMed:15657036,
FT ECO:0000269|PubMed:15907468"
FT DISULFID 235..346
FT /evidence="ECO:0000269|PubMed:15657036,
FT ECO:0000269|PubMed:15907468"
FT VAR_SEQ 1..90
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_007877"
FT VAR_SEQ 149..173
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045414"
FT VAR_SEQ 319..338
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045415"
FT VAR_SEQ 340..374
FT /note="YCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMD -> QEYYDPYFQDVAS
FT EMLRRHTASRWKAFSSLEPCCSIRRHQQYAAIERLTCGKFELRCASLRKIDCLNTNIAC
FT SYSMRQHGPRLHCVD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013185"
FT VARIANT 20
FT /note="L -> F (in MSD; loss of activity;
FT dbSNP:rs200142963)"
FT /evidence="ECO:0000269|PubMed:15146462"
FT /id="VAR_019050"
FT VARIANT 63
FT /note="S -> N (in dbSNP:rs2819590)"
FT /evidence="ECO:0000269|PubMed:12757705,
FT ECO:0000269|PubMed:12975309"
FT /id="VAR_016052"
FT VARIANT 155
FT /note="S -> P (in MSD; loss of enzyme activity;
FT dbSNP:rs137852850)"
FT /evidence="ECO:0000269|PubMed:12757706,
FT ECO:0000269|PubMed:15146462, ECO:0000269|PubMed:21224894"
FT /id="VAR_016053"
FT VARIANT 177
FT /note="A -> P (in MSD; loss of activity; decreases its
FT specific enzyme activity to less than 1%; does not affect
FT localization of the protein in the endoplasmic reticulum of
FT MSD fibroblasts; protein stability is almost comparable to
FT wild-type)"
FT /evidence="ECO:0000269|PubMed:15146462,
FT ECO:0000269|PubMed:18157819"
FT /id="VAR_019051"
FT VARIANT 179
FT /note="W -> S (in MSD; decreases its specific enzyme
FT activity to less than 3%; does not affect localization of
FT the protein in the endoplasmic reticulum of MSD
FT fibroblasts; protein stability is almost comparable to
FT wild-type; dbSNP:rs757323641)"
FT /evidence="ECO:0000269|PubMed:18157819"
FT /id="VAR_042602"
FT VARIANT 218
FT /note="C -> Y (in MSD; loss of activity;
FT dbSNP:rs137852854)"
FT /evidence="ECO:0000269|PubMed:12757706,
FT ECO:0000269|PubMed:15146462"
FT /id="VAR_016054"
FT VARIANT 224
FT /note="R -> W (in MSD; loss of activity;
FT dbSNP:rs759888604)"
FT /evidence="ECO:0000269|PubMed:15146462"
FT /id="VAR_019052"
FT VARIANT 247
FT /note="G -> R (in MSD; dbSNP:rs1057517363)"
FT /evidence="ECO:0000269|PubMed:21224894"
FT /id="VAR_080468"
FT VARIANT 259
FT /note="N -> I (in MSD; loss of activity;
FT dbSNP:rs764215221)"
FT /evidence="ECO:0000269|PubMed:15146462"
FT /id="VAR_019053"
FT VARIANT 263
FT /note="G -> V (in MSD; mild phenotype; reduced but not
FT abolished activity; dbSNP:rs387906976)"
FT /evidence="ECO:0000269|PubMed:21224894"
FT /id="VAR_080469"
FT VARIANT 266
FT /note="P -> L (in MSD; retains some activity;
FT dbSNP:rs763243827)"
FT /evidence="ECO:0000269|PubMed:15146462"
FT /id="VAR_019054"
FT VARIANT 279
FT /note="A -> V (in MSD; loss of activity; decreases its
FT specific enzyme activity to about 23%; does not affect
FT localization of the protein in the endoplasmic reticulum of
FT MSD fibroblasts; protein stability is decreased;
FT dbSNP:rs137852849)"
FT /evidence="ECO:0000269|PubMed:12757705,
FT ECO:0000269|PubMed:15146462, ECO:0000269|PubMed:18157819"
FT /id="VAR_016055"
FT VARIANT 327..374
FT /note="Missing (in MSD; almost abolished enzyme activity)"
FT /evidence="ECO:0000269|PubMed:21224894"
FT /id="VAR_080470"
FT VARIANT 336
FT /note="C -> R (in MSD; loss of activity;
FT dbSNP:rs137852848)"
FT /evidence="ECO:0000269|PubMed:12757705,
FT ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15146462"
FT /id="VAR_016056"
FT VARIANT 345
FT /note="R -> C (in MSD; reduced but not abolished activity;
FT dbSNP:rs137852852)"
FT /evidence="ECO:0000269|PubMed:12757706,
FT ECO:0000269|PubMed:15146462, ECO:0000269|PubMed:21224894"
FT /id="VAR_016057"
FT VARIANT 348
FT /note="A -> P (in MSD; loss of activity;
FT dbSNP:rs137852853)"
FT /evidence="ECO:0000269|PubMed:12757706,
FT ECO:0000269|PubMed:15146462"
FT /id="VAR_016058"
FT VARIANT 349
FT /note="R -> Q (in MSD; loss of activity;
FT dbSNP:rs137852847)"
FT /evidence="ECO:0000269|PubMed:12757705,
FT ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15146462"
FT /id="VAR_016059"
FT VARIANT 349
FT /note="R -> W (in MSD; loss of activity; decreases its
FT specific enzyme activity to less than 1%; does not affect
FT localization of the protein in the endoplasmic reticulum of
FT MSD fibroblasts; protein stability is severely decreased;
FT dbSNP:rs137852846)"
FT /evidence="ECO:0000269|PubMed:12757705,
FT ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15146462,
FT ECO:0000269|PubMed:18157819"
FT /id="VAR_016060"
FT MUTAGEN 333
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15907468"
FT MUTAGEN 333
FT /note="S->T: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:15907468"
FT MUTAGEN 336
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15907468"
FT MUTAGEN 337
FT /note="H->A: Reduces activity 5-fold."
FT /evidence="ECO:0000269|PubMed:15907468"
FT MUTAGEN 340
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:15907468"
FT MUTAGEN 341
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15907468"
FT CONFLICT 112
FT /note="G -> E (in Ref. 5; BAG63417)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="V -> A (in Ref. 9; AAI21124)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="F -> L (in Ref. 6; BAC11634)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="E -> D (in Ref. 6; BAC11634)"
FT /evidence="ECO:0000305"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 148..152
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 211..220
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 228..236
FT /evidence="ECO:0007829|PDB:1Z70"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:1Z70"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 293..305
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:1Z70"
FT TURN 338..340
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:1Z70"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:1Z70"
SQ SEQUENCE 374 AA; 40556 MW; E64F2DF004C8CEA3 CRC64;
MAAPALGLVC GRCPELGLVL LLLLLSLLCG AAGSQEAGTG AGAGSLAGSC GCGTPQRPGA
HGSSAAAHRY SREANAPGPV PGERQLAHSK MVPIPAGVFT MGTDDPQIKQ DGEAPARRVT
IDAFYMDAYE VSNTEFEKFV NSTGYLTEAE KFGDSFVFEG MLSEQVKTNI QQAVAAAPWW
LPVKGANWRH PEGPDSTILH RPDHPVLHVS WNDAVAYCTW AGKRLPTEAE WEYSCRGGLH
NRLFPWGNKL QPKGQHYANI WQGEFPVTNT GEDGFQGTAP VDAFPPNGYG LYNIVGNAWE
WTSDWWTVHH SVEETLNPKG PPSGKDRVKK GGSYMCHRSY CYRYRCAARS QNTPDSSASN
LGFRCAADRL PTMD
