ID ARSB_HUMAN Reviewed; 533 AA. AC P15848; B2RC20; Q8N322; Q9UDI9; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 24-JAN-2024, entry version 220. DE RecName: Full=Arylsulfatase B; DE Short=ASB; DE EC=3.1.6.12; DE AltName: Full=N-acetylgalactosamine-4-sulfatase; DE Short=G4S; DE Flags: Precursor; GN Name=ARSB; 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), AND PROTEIN SEQUENCE OF 103-119; RP 135-158; 161-168; 286-295; 319-337; 379-387; 389-410; 440-450; 490-501; RP 508-520 AND 525-533. RC TISSUE=Placenta, and Testis; RX PubMed=2303452; DOI=10.1016/s0021-9258(19)39778-9; RA Peters C., Schmidt B., Rommerskirch W., Rupp K., Zuehlsdorf M., Vingron M., RA Meyer H.E., Pohlmann R., von Figura K.; RT "Phylogenetic conservation of arylsulfatases. cDNA cloning and expression RT of human arylsulfatase B."; RL J. Biol. Chem. 265:3374-3381(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1968043; DOI=10.1016/0888-7543(90)90460-c; RA Schuchman E.H., Jackson C.E., Desnick R.J.; RT "Human arylsulfatase B: MOPAC cloning, nucleotide sequence of a full-length RT cDNA, and regions of amino acid identity with arylsulfatases A and C."; RL Genomics 6:149-158(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-358. RX PubMed=7687847; DOI=10.1515/bchm3.1993.374.1-6.327; RA Modaressi S., Rupp K., von Figura K., Peters C.; RT "Structure of the human arylsulfatase B gene."; RL Biol. Chem. Hoppe-Seyler 374:327-335(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-358. RC TISSUE=Cerebellum; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon; 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-104. RX PubMed=1930244; RA Litjens T., Morris C.P., Gibson G.J., Beckmann K.R., Hopwood J.J.; RT "Human N-acetylgalactosamine-4-sulphatase: protein maturation and isolation RT of genomic clones."; RL Biochem. Int. 24:209-215(1991). RN [9] RP PROTEIN SEQUENCE OF 41-55; 424-454 AND 466-483. RC TISSUE=Placenta; RX PubMed=1390929; DOI=10.1016/0167-4838(92)90051-e; RA Kobayashi T., Honke K., Jin T., Gasa S., Miyazaki T., Makita A.; RT "Components and proteolytic processing sites of arylsulfatase B from human RT placenta."; RL Biochim. Biophys. Acta 1159:243-247(1992). RN [10] RP OXOALANINE AT CYS-91, IDENTIFICATION BY MASS SPECTROMETRY, AND ABSENCE OF RP OXOALANINE IN MSD. RX PubMed=7628016; DOI=10.1016/0092-8674(95)90314-3; RA Schmidt B., Selmer T., Ingendoh A., von Figura K.; RT "A novel amino acid modification in sulfatases that is defective in RT multiple sulfatase deficiency."; RL Cell 82:271-278(1995). RN [11] RP INVOLVEMENT IN MSD. 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 [12] RP FUNCTION. RX PubMed=19306108; DOI=10.1007/s10585-009-9253-z; RA Bhattacharyya S., Tobacman J.K.; RT "Arylsulfatase B regulates colonic epithelial cell migration by effects on RT MMP9 expression and RhoA activation."; RL Clin. Exp. Metastasis 26:535-545(2009). RN [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-366. 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 [14] 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX PubMed=9032078; DOI=10.1016/s0969-2126(97)00185-8; RA Bond C.S., Clements P.R., Ashby S.J., Collyer C.A., Harrop S.J., RA Hopwood J.J., Guss J.M.; RT "Structure of a human lysosomal sulfatase."; RL Structure 5:277-289(1997). RN [16] RP VARIANT MPS6 VAL-137, AND VARIANT MET-376. RX PubMed=1718978; DOI=10.1016/s0021-9258(18)54649-4; RA Wicker G., Prill V., Brooks D.A., Gibson G.J., Hopwood J.J., von Figura K., RA Peters C.; RT "Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). An intermediate RT clinical phenotype caused by substitution of valine for glycine at position RT 137 of arylsulfatase B."; RL J. Biol. Chem. 266:21386-21391(1991). RN [17] RP VARIANTS MPS6 ARG-117; PRO-236 AND TYR-405. RX PubMed=1550123; RA Jin W.-D., Jackson C.E., Desnick R.J., Schuchman E.H.; RT "Mucopolysaccharidosis type VI: identification of three mutations in the RT arylsulfatase B gene of patients with the severe and mild phenotypes RT provides molecular evidence for genetic heterogeneity."; RL Am. J. Hum. Genet. 50:795-800(1992). RN [18] RP VARIANTS MPS6 ARG-144; ARG-192; PRO-321 AND TYR-521, AND CHARACTERIZATION RP OF VARIANTS MPS6. RX PubMed=8116615; RA Isbrandt D., Arlt G., Brooks D.A., Hopwood J.J., von Figura K., Peters C.; RT "Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique RT arylsulfatase B gene alleles causing variable disease phenotypes."; RL Am. J. Hum. Genet. 54:454-463(1994). RN [19] RP VARIANTS MPS6 TRP-152 AND GLN-160. RX PubMed=8125475; DOI=10.1007/bf00212019; RA Voskoboeva E., Isbrandt D., von Figura K., Krasnopolskaya X., Peters C.; RT "Four novel mutant alleles of the arylsulfatase B gene in two patients with RT intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)."; RL Hum. Genet. 93:259-264(1994). RN [20] RP VARIANTS MPS6 ILE-142; ARG-146; LEU-146 AND SER-146. RX PubMed=8541342; DOI=10.1016/0925-4439(95)00070-4; RA Simonaro C.M., Schuchman E.H.; RT "N-acetylgalactosamine-4-sulfatase: identification of four new mutations RT within the conserved sulfatase region causing mucopolysaccharidosis type RT VI."; RL Biochim. Biophys. Acta 1272:129-132(1995). RN [21] RP VARIANTS MPS6 MET-92; GLN-95; CYS-210; PRO-393 AND PRO-498. RX PubMed=8651289; RA Litjens T., Brooks D.A., Peters C., Gibson G.J., Hopwood J.J.; RT "Identification, expression, and biochemical characterization of N- RT acetylgalactosamine-4-sulfatase mutations and relationship with clinical RT phenotype in MPS6 patients."; RL Am. J. Hum. Genet. 58:1127-1134(1996). RN [22] RP VARIANT MPS-IV ARG-302. RX PubMed=10206678; RX DOI=10.1002/(sici)1098-1004(1998)11:5<410::aid-humu9>3.0.co;2-q; RA Villani G.R.D., Balzano N., Di Natale P.; RT "Two novel mutations of the arylsulfatase B gene in two Italian patients RT with severe form of mucopolysaccharidosis."; RL Hum. Mutat. 11:410-410(1998). RN [23] RP VARIANT MET-358. RX PubMed=9582121; DOI=10.1126/science.280.5366.1077; RA Wang D.G., Fan J.-B., Siao C.-J., Berno A., Young P., Sapolsky R., RA Ghandour G., Perkins N., Winchester E., Spencer J., Kruglyak L., Stein L., RA Hsie L., Topaloglou T., Hubbell E., Robinson E., Mittmann M., Morris M.S., RA Shen N., Kilburn D., Rioux J., Nusbaum C., Rozen S., Hudson T.J., RA Lipshutz R., Chee M., Lander E.S.; RT "Large-scale identification, mapping, and genotyping of single-nucleotide RT polymorphisms in the human genome."; RL Science 280:1077-1082(1998). RN [24] RP VARIANTS MPS6 PHE-65; HIS-116; GLN-315 AND ARG-531, AND VARIANT MET-358. RX PubMed=10036316; DOI=10.1016/s0925-4439(98)00099-4; RA Villani G.R.D., Balzano N., Vitale D., Saviano M., Pavone V., Di Natale P.; RT "Maroteaux-Lamy syndrome: five novel mutations and their structural RT localization."; RL Biochim. Biophys. Acta 1453:185-192(1999). RN [25] RP VARIANTS MPS6 ARG-192 AND ARG-239. RX PubMed=10738004; RX DOI=10.1002/(sici)1098-1004(200004)15:4<389::aid-humu31>3.0.co;2-0; RA Wu J.-Y., Yang C.-F., Lee C.-C., Chang J.-G., Tsai F.-J.; RT "A novel mutation (Q239R) identified in a Taiwan Chinese patient with type RT VI mucopolysaccharidosis (Maroteaux-Lamy syndrome)."; RL Hum. Mutat. 15:389-390(2000). RN [26] RP VARIANTS MPS6 ARG-192; ARG-239 AND LEU-399, AND VARIANT MET-358. RX PubMed=11802522; RA Yang C.-F., Wu J.-Y., Lin S.-P., Tsai F.-J.; RT "Mucopolysaccharidosis type VI: report of two Taiwanese patients and RT identification of one novel mutation."; RL J. Formos. Med. Assoc. 100:820-823(2001). RN [27] RP VARIANTS MPS6 TYR-86 DEL; CYS-210; PRO-236; CYS-312; GLN-315; PRO-321 AND RP GLY-484, VARIANTS MET-358; MET-376 AND ASN-384, AND CHARACTERIZATION OF RP VARIANTS MPS6 TYR-86 DEL AND CYS-312. RX PubMed=14974081; DOI=10.1002/humu.10313; RA Karageorgos L., Harmatz P., Simon J., Pollard A., Clements P.R., RA Brooks D.A., Hopwood J.J.; RT "Mutational analysis of mucopolysaccharidosis type VI patients undergoing a RT trial of enzyme replacement therapy."; RL Hum. Mutat. 23:229-233(2004). RN [28] RP VARIANTS MPS6 ARG-82 AND GLN-315, AND VARIANT ASN-384. RX PubMed=19259130; DOI=10.1038/ejhg.2009.19; RA Zanetti A., Ferraresi E., Picci L., Filocamo M., Parini R., Rosano C., RA Tomanin R., Scarpa M.; RT "Segregation analysis in a family at risk for the Maroteaux-Lamy syndrome RT conclusively reveals c.1151G>A (p.S384N) as to be a polymorphism."; RL Eur. J. Hum. Genet. 17:1160-1164(2009). CC -!- FUNCTION: Removes sulfate groups from chondroitin-4-sulfate (C4S) and CC regulates its degradation (PubMed:19306108). Involved in the regulation CC of cell adhesion, cell migration and invasion in colonic epithelium CC (PubMed:19306108). In the central nervous system, is a regulator of CC neurite outgrowth and neuronal plasticity, acting through the control CC of sulfate glycosaminoglycans and neurocan levels (By similarity). CC {ECO:0000250|UniProtKB:P50430, ECO:0000269|PubMed:19306108}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of the 4-sulfate groups of the N-acetyl-D- CC galactosamine 4-sulfate units of chondroitin sulfate and dermatan CC sulfate.; EC=3.1.6.12; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Note=Binds 1 Ca(2+) ion per subunit.; CC -!- ACTIVITY REGULATION: Inhibited by ethanol (By similarity). CC {ECO:0000250|UniProtKB:P50430}. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P50429}. Cell CC surface {ECO:0000250|UniProtKB:P50429}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P15848-1; Sequence=Displayed; CC Name=2; CC IsoId=P15848-2; Sequence=VSP_042721; CC -!- PTM: The conversion to 3-oxoalanine (also known as C-formylglycine, CC FGly), of a serine or cysteine residue in prokaryotes and of a cysteine CC residue in eukaryotes, is critical for catalytic activity. This post- CC translational modification is severely defective in multiple sulfatase CC deficiency (MSD). {ECO:0000269|PubMed:7628016}. CC -!- DISEASE: Mucopolysaccharidosis 6 (MPS6) [MIM:253200]: A form of CC mucopolysaccharidosis, a group of lysosomal storage diseases CC characterized by defective degradation of glycosaminoglycans, resulting CC in their excessive accumulation and secretion. The diseases are CC progressive and often display a wide spectrum of clinical severity. CC MPS6 is an autosomal recessive form characterized by intracellular CC accumulation of dermatan sulfate. Clinical features can include CC abnormal growth, short stature, stiff joints, skeletal malformations, CC corneal clouding, hepatosplenomegaly, and cardiac abnormalities. CC {ECO:0000269|PubMed:10036316, ECO:0000269|PubMed:10738004, CC ECO:0000269|PubMed:11802522, ECO:0000269|PubMed:14974081, CC ECO:0000269|PubMed:1550123, ECO:0000269|PubMed:1718978, CC ECO:0000269|PubMed:19259130, ECO:0000269|PubMed:8116615, CC ECO:0000269|PubMed:8125475, ECO:0000269|PubMed:8541342, CC ECO:0000269|PubMed:8651289}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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:15146462}. Note=The protein represented in this CC entry is involved in disease pathogenesis. Arylsulfatase B activity is CC impaired in multiple sulfatase deficiency due to mutations in SUMF1. CC SUMF1 mutations result in defective post-translational modification of CC ARSB at residue Cys-91 that is not converted to 3-oxoalanine. CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J05225; AAA51784.1; -; mRNA. DR EMBL; M32373; AAA51779.1; -; mRNA. DR EMBL; X72735; CAA51272.1; -; Genomic_DNA. DR EMBL; X72736; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72737; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72738; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72739; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72740; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72741; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; X72742; CAA51272.1; JOINED; Genomic_DNA. DR EMBL; AK314903; BAG37417.1; -; mRNA. DR EMBL; AC020937; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025755; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC099485; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC114963; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471084; EAW95822.1; -; Genomic_DNA. DR EMBL; BC029051; AAH29051.1; -; mRNA. DR EMBL; S57777; AAB19988.1; -; Genomic_DNA. DR CCDS; CCDS4043.1; -. [P15848-1] DR CCDS; CCDS43334.1; -. [P15848-2] DR PIR; S35990; KJHUAB. DR RefSeq; NP_000037.2; NM_000046.3. [P15848-1] DR RefSeq; NP_942002.1; NM_198709.2. [P15848-2] DR RefSeq; XP_011541692.1; XM_011543390.1. [P15848-1] DR PDB; 1FSU; X-ray; 2.50 A; A=42-533. DR PDBsum; 1FSU; -. DR AlphaFoldDB; P15848; -. DR SMR; P15848; -. DR BioGRID; 106904; 45. DR IntAct; P15848; 14. DR STRING; 9606.ENSP00000264914; -. DR ChEMBL; CHEMBL2399; -. DR DrugBank; DB09301; Chondroitin sulfate. DR GlyConnect; 1016; 3 N-Linked glycans (3 sites). DR GlyCosmos; P15848; 7 sites, 4 glycans. DR GlyGen; P15848; 7 sites, 3 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P15848; -. DR PhosphoSitePlus; P15848; -. DR BioMuta; ARSB; -. DR EPD; P15848; -. DR jPOST; P15848; -. DR MassIVE; P15848; -. DR MaxQB; P15848; -. DR PaxDb; 9606-ENSP00000264914; -. DR PeptideAtlas; P15848; -. DR ProteomicsDB; 53228; -. [P15848-1] DR ProteomicsDB; 53229; -. [P15848-2] DR Pumba; P15848; -. DR Antibodypedia; 24535; 350 antibodies from 37 providers. DR DNASU; 411; -. DR Ensembl; ENST00000264914.10; ENSP00000264914.4; ENSG00000113273.17. [P15848-1] DR Ensembl; ENST00000396151.7; ENSP00000379455.3; ENSG00000113273.17. [P15848-2] DR GeneID; 411; -. DR KEGG; hsa:411; -. DR MANE-Select; ENST00000264914.10; ENSP00000264914.4; NM_000046.5; NP_000037.2. DR UCSC; uc003kfq.5; human. [P15848-1] DR AGR; HGNC:714; -. DR CTD; 411; -. DR DisGeNET; 411; -. DR GeneCards; ARSB; -. DR HGNC; HGNC:714; ARSB. DR HPA; ENSG00000113273; Low tissue specificity. DR MalaCards; ARSB; -. DR MIM; 253200; phenotype. DR MIM; 272200; phenotype. DR MIM; 611542; gene. DR neXtProt; NX_P15848; -. DR OpenTargets; ENSG00000113273; -. DR Orphanet; 276212; Mucopolysaccharidosis type 6, rapidly progressing. DR Orphanet; 276223; Mucopolysaccharidosis type 6, slowly progressing. DR PharmGKB; PA25006; -. DR VEuPathDB; HostDB:ENSG00000113273; -. DR eggNOG; KOG3867; Eukaryota. DR GeneTree; ENSGT00940000158270; -. DR HOGENOM; CLU_006332_10_1_1; -. DR InParanoid; P15848; -. DR OMA; HEHCVFI; -. DR OrthoDB; 2913702at2759; -. DR PhylomeDB; P15848; -. DR TreeFam; TF314186; -. DR BioCyc; MetaCyc:HS03665-MONOMER; -. DR BRENDA; 3.1.6.1; 2681. DR BRENDA; 3.1.6.12; 2681. DR PathwayCommons; P15848; -. DR Reactome; R-HSA-1663150; The activation of arylsulfatases. DR Reactome; R-HSA-2024101; CS/DS degradation. DR Reactome; R-HSA-2206285; MPS VI - Maroteaux-Lamy syndrome. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SABIO-RK; P15848; -. DR SignaLink; P15848; -. DR BioGRID-ORCS; 411; 17 hits in 1161 CRISPR screens. DR ChiTaRS; ARSB; human. DR EvolutionaryTrace; P15848; -. DR GenomeRNAi; 411; -. DR Pharos; P15848; Tbio. DR PRO; PR:P15848; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P15848; Protein. DR Bgee; ENSG00000113273; Expressed in calcaneal tendon and 120 other cell types or tissues. DR ExpressionAtlas; P15848; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0004065; F:arylsulfatase activity; TAS:ProtInc. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003943; F:N-acetylgalactosamine-4-sulfatase activity; IDA:UniProtKB. DR GO; GO:0006914; P:autophagy; IEA:Ensembl. DR GO; GO:0061580; P:colon epithelial cell migration; IMP:UniProtKB. DR GO; GO:0007041; P:lysosomal transport; TAS:ProtInc. DR GO; GO:0007040; P:lysosome organization; TAS:ProtInc. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0010632; P:regulation of epithelial cell migration; IMP:UniProtKB. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0051597; P:response to methylmercury; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0009268; P:response to pH; IEA:Ensembl. DR CDD; cd16029; 4-S; 1. DR DisProt; DP02670; -. DR Gene3D; 3.30.1120.10; -; 1. DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1. DR InterPro; IPR017850; Alkaline_phosphatase_core_sf. DR InterPro; IPR047115; ARSB. DR InterPro; IPR024607; Sulfatase_CS. DR InterPro; IPR000917; Sulfatase_N. DR PANTHER; PTHR10342; ARYLSULFATASE; 1. DR PANTHER; PTHR10342:SF272; ARYLSULFATASE B; 1. DR Pfam; PF00884; Sulfatase; 1. DR SUPFAM; SSF53649; Alkaline phosphatase-like; 1. DR PROSITE; PS00523; SULFATASE_1; 1. DR PROSITE; PS00149; SULFATASE_2; 1. DR Genevisible; P15848; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Ichthyosis; KW Leukodystrophy; Lysosome; Metachromatic leukodystrophy; Metal-binding; KW Mucopolysaccharidosis; Reference proteome; Signal. FT SIGNAL 1..36 FT /note="Or 38" FT /evidence="ECO:0000255" FT CHAIN 37..533 FT /note="Arylsulfatase B" FT /id="PRO_0000033421" FT ACT_SITE 91 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:7628016" FT ACT_SITE 147 FT BINDING 53 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 54 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 91 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /note="via 3-oxoalanine" FT /evidence="ECO:0000269|PubMed:7628016" FT BINDING 145 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 242 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 300 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 301 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT BINDING 318 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 91 FT /note="3-oxoalanine (Cys)" FT /evidence="ECO:0000269|PubMed:7628016" FT CARBOHYD 188 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 279 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 291 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT CARBOHYD 366 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 426 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 458 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 117..521 FT DISULFID 121..155 FT DISULFID 181..192 FT DISULFID 405..447 FT VAR_SEQ 405..533 FT /note="CPRNSMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQ FT YNVSEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSVPVYFP FT AQDPRCDPKATGVWGPWM -> YWPECSLLL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042721" FT VARIANT 65 FT /note="S -> F (in MPS6; intermediate form; FT dbSNP:rs1233331806)" FT /evidence="ECO:0000269|PubMed:10036316" FT /id="VAR_019017" FT VARIANT 82 FT /note="L -> R (in MPS6; dbSNP:rs749465732)" FT /evidence="ECO:0000269|PubMed:19259130" FT /id="VAR_080270" FT VARIANT 86 FT /note="Missing (in MPS6; severe form; low protein levels FT and activity; dbSNP:rs969231209)" FT /evidence="ECO:0000269|PubMed:14974081" FT /id="VAR_019018" FT VARIANT 92 FT /note="T -> M (in MPS6; mild form; dbSNP:rs751010538)" FT /evidence="ECO:0000269|PubMed:8651289" FT /id="VAR_007294" FT VARIANT 95 FT /note="R -> Q (in MPS6; mild/severe form; FT dbSNP:rs118203942)" FT /evidence="ECO:0000269|PubMed:8651289" FT /id="VAR_007295" FT VARIANT 116 FT /note="P -> H (in MPS6; severe form; dbSNP:rs775780931)" FT /evidence="ECO:0000269|PubMed:10036316" FT /id="VAR_019019" FT VARIANT 117 FT /note="C -> R (in MPS6; severe form; dbSNP:rs118203939)" FT /evidence="ECO:0000269|PubMed:1550123" FT /id="VAR_007296" FT VARIANT 137 FT /note="G -> V (in MPS6; intermediate form; FT dbSNP:rs118203938)" FT /evidence="ECO:0000269|PubMed:1718978" FT /id="VAR_007297" FT VARIANT 142 FT /note="M -> I (in MPS6; dbSNP:rs1554088053)" FT /evidence="ECO:0000269|PubMed:8541342" FT /id="VAR_019020" FT VARIANT 144 FT /note="G -> R (in MPS6; severe form; severe reduction of FT activity; dbSNP:rs746206847)" FT /evidence="ECO:0000269|PubMed:8116615" FT /id="VAR_019021" FT VARIANT 146 FT /note="W -> L (in MPS6; dbSNP:rs1554088034)" FT /evidence="ECO:0000269|PubMed:8541342" FT /id="VAR_019022" FT VARIANT 146 FT /note="W -> R (in MPS6; dbSNP:rs1554088037)" FT /evidence="ECO:0000269|PubMed:8541342" FT /id="VAR_019023" FT VARIANT 146 FT /note="W -> S (in MPS6; dbSNP:rs1554088034)" FT /evidence="ECO:0000269|PubMed:8541342" FT /id="VAR_019024" FT VARIANT 152 FT /note="R -> W (in MPS6; intermediate form; FT dbSNP:rs991104525)" FT /evidence="ECO:0000269|PubMed:8125475" FT /id="VAR_007298" FT VARIANT 160 FT /note="R -> Q (in MPS6; intermediate form; FT dbSNP:rs1196325597)" FT /evidence="ECO:0000269|PubMed:8125475" FT /id="VAR_007299" FT VARIANT 192 FT /note="C -> R (in MPS6; mild form; severe reduction of FT activity; dbSNP:rs1554087423)" FT /evidence="ECO:0000269|PubMed:10738004, FT ECO:0000269|PubMed:11802522, ECO:0000269|PubMed:8116615" FT /id="VAR_019025" FT VARIANT 210 FT /note="Y -> C (in MPS6; mild/intermediate; FT dbSNP:rs118203943)" FT /evidence="ECO:0000269|PubMed:14974081, FT ECO:0000269|PubMed:8651289" FT /id="VAR_007300" FT VARIANT 236 FT /note="L -> P (in MPS6; mild form; dbSNP:rs118203940)" FT /evidence="ECO:0000269|PubMed:14974081, FT ECO:0000269|PubMed:1550123" FT /id="VAR_007301" FT VARIANT 239 FT /note="Q -> R (in MPS6; dbSNP:rs1554086431)" FT /evidence="ECO:0000269|PubMed:10738004, FT ECO:0000269|PubMed:11802522" FT /id="VAR_019026" FT VARIANT 302 FT /note="G -> R (in MPS6; severe form; dbSNP:rs779378413)" FT /evidence="ECO:0000269|PubMed:10206678" FT /id="VAR_007302" FT VARIANT 312 FT /note="W -> C (in MPS6; severe form; loss of activity; FT dbSNP:rs759384989)" FT /evidence="ECO:0000269|PubMed:14974081" FT /id="VAR_019027" FT VARIANT 315 FT /note="R -> Q (in MPS6; intermediate form; FT dbSNP:rs727503809)" FT /evidence="ECO:0000269|PubMed:10036316, FT ECO:0000269|PubMed:14974081, ECO:0000269|PubMed:19259130" FT /id="VAR_019028" FT VARIANT 321 FT /note="L -> P (in MPS6; intermediate form; severe reduction FT of activity; dbSNP:rs1554079320)" FT /evidence="ECO:0000269|PubMed:14974081, FT ECO:0000269|PubMed:8116615" FT /id="VAR_019029" FT VARIANT 358 FT /note="V -> L (in dbSNP:rs1065757)" FT /id="VAR_061883" FT VARIANT 358 FT /note="V -> M (in dbSNP:rs1065757)" FT /evidence="ECO:0000269|PubMed:10036316, FT ECO:0000269|PubMed:11802522, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:14974081, ECO:0000269|PubMed:7687847, FT ECO:0000269|PubMed:9582121" FT /id="VAR_016061" FT VARIANT 376 FT /note="V -> M (in dbSNP:rs1071598)" FT /evidence="ECO:0000269|PubMed:14974081, FT ECO:0000269|PubMed:1718978" FT /id="VAR_007303" FT VARIANT 384 FT /note="S -> N (in dbSNP:rs25414)" FT /evidence="ECO:0000269|PubMed:14974081, FT ECO:0000269|PubMed:19259130" FT /id="VAR_019030" FT VARIANT 393 FT /note="H -> P (in MPS6; mild/severe form; FT dbSNP:rs118203944)" FT /evidence="ECO:0000269|PubMed:8651289" FT /id="VAR_007304" FT VARIANT 399 FT /note="F -> L (in MPS6; dbSNP:rs200793396)" FT /evidence="ECO:0000269|PubMed:11802522" FT /id="VAR_019031" FT VARIANT 405 FT /note="C -> Y (in MPS6; mild form; dbSNP:rs118203941)" FT /evidence="ECO:0000269|PubMed:1550123" FT /id="VAR_007305" FT VARIANT 484 FT /note="R -> G (in MPS6; dbSNP:rs201101343)" FT /evidence="ECO:0000269|PubMed:14974081" FT /id="VAR_019032" FT VARIANT 498 FT /note="L -> P (in MPS6; mild/severe form; FT dbSNP:rs774358117)" FT /evidence="ECO:0000269|PubMed:8651289" FT /id="VAR_007306" FT VARIANT 521 FT /note="C -> Y (in MPS6; severe form; severe reduction of FT activity; dbSNP:rs1554069661)" FT /evidence="ECO:0000269|PubMed:8116615" FT /id="VAR_019033" FT VARIANT 531 FT /note="P -> R (in MPS6; mild form; dbSNP:rs1554069659)" FT /evidence="ECO:0000269|PubMed:10036316" FT /id="VAR_019034" FT CONFLICT 153 FT /note="K -> F (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 408..410 FT /note="NSM -> SPC (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 46..54 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 70..77 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 91..100 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 104..107 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 129..135 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 139..144 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 163..167 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 179..184 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 185..188 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 189..194 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 211..224 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 232..237 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 261..286 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 290..292 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 293..301 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 323..326 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 330..333 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 353..360 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 377..382 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 390..396 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 429..435 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 438..443 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 454..456 FT /evidence="ECO:0007829|PDB:1FSU" FT STRAND 472..476 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 477..479 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 488..490 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 492..507 FT /evidence="ECO:0007829|PDB:1FSU" FT HELIX 519..521 FT /evidence="ECO:0007829|PDB:1FSU" FT TURN 524..526 FT /evidence="ECO:0007829|PDB:1FSU" SQ SEQUENCE 533 AA; 59687 MW; 5983FB6911C4789A CRC64; MGPRGAASLP RGPGPRRLLL PVVLPLLLLL LLAPPGSGAG ASRPPHLVFL LADDLGWNDV GFHGSRIRTP HLDALAAGGV LLDNYYTQPL CTPSRSQLLT GRYQIRTGLQ HQIIWPCQPS CVPLDEKLLP QLLKEAGYTT HMVGKWHLGM YRKECLPTRR GFDTYFGYLL GSEDYYSHER CTLIDALNVT RCALDFRDGE EVATGYKNMY STNIFTKRAI ALITNHPPEK PLFLYLALQS VHEPLQVPEE YLKPYDFIQD KNRHHYAGMV SLMDEAVGNV TAALKSSGLW NNTVFIFSTD NGGQTLAGGN NWPLRGRKWS LWEGGVRGVG FVASPLLKQK GVKNRELIHI SDWLPTLVKL ARGHTNGTKP LDGFDVWKTI SEGSPSPRIE LLHNIDPNFV DSSPCPRNSM APAKDDSSLP EYSAFNTSVH AAIRHGNWKL LTGYPGCGYW FPPPSQYNVS EIPSSDPPTK TLWLFDIDRD PEERHDLSRE YPHIVTKLLS RLQFYHKHSV PVYFPAQDPR CDPKATGVWG PWM //