ID   ARSA_MOUSE              Reviewed;         506 AA.
AC   P50428; Q9DC66;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 171.
DE   RecName: Full=Arylsulfatase A;
DE            Short=ASA;
DE            EC=3.1.6.8 {ECO:0000269|PubMed:24294900};
DE   AltName: Full=Cerebroside-sulfatase;
DE   Flags: Precursor;
GN   Name=Arsa; Synonyms=As2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   STRAIN=129/Sv, and C57BL/6J;
RX   PubMed=7910580; DOI=10.1006/geno.1994.1055;
RA   Kreysing J., Polten A., Hess B., von Figura K., Menz K., Steiner F.,
RA   Gieselmann V.;
RT   "Structure of the mouse arylsulfatase A gene and cDNA.";
RL   Genomics 19:249-256(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Lung, and Skin;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary tumor, and Trophoblast stem cell;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 32-66.
RX   PubMed=1572648; DOI=10.1016/0888-7543(92)90306-d;
RA   Grompe M., Pieretti M., Caskey C.T., Ballabio A.;
RT   "The sulfatase gene family: cross-species PCR cloning using the MOPAC
RT   technique.";
RL   Genomics 12:755-760(1992).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Lung, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=24294900; DOI=10.1021/ac4023555;
RA   Morena F., di Girolamo I., Emiliani C., Gritti A., Biffi A., Martino S.;
RT   "A new analytical bench assay for the determination of arylsulfatase a
RT   activity toward galactosyl-3-sulfate ceramide: implication for
RT   metachromatic leukodystrophy diagnosis.";
RL   Anal. Chem. 86:473-481(2014).
CC   -!- FUNCTION: Hydrolyzes cerebroside sulfate.
CC       {ECO:0000269|PubMed:24294900}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-acyl-1-beta-D-(3-O-sulfo)-galactosyl-sphing-4-enine =
CC         a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H(+) + sulfate;
CC         Xref=Rhea:RHEA:21300, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16189, ChEBI:CHEBI:18390, ChEBI:CHEBI:75956; EC=3.1.6.8;
CC         Evidence={ECO:0000269|PubMed:24294900};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21301;
CC         Evidence={ECO:0000269|PubMed:24294900};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P15289};
CC       Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P15289};
CC   -!- SUBUNIT: Homodimer at neutral pH and homooctamer at acidic pH. Exists
CC       both as a single chain of 58 kDa (component A) or as a chain of 50 kDa
CC       (component B) linked by disulfide bond(s) to a 7 kDa chain (component
CC       C). Interacts with SUMF1 (By similarity).
CC       {ECO:0000250|UniProtKB:P15289}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:P15289}. Lysosome
CC       {ECO:0000250|UniProtKB:P15289}.
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:0000250|UniProtKB:P15289}.
CC   -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR   EMBL; X73230; CAA51702.1; -; mRNA.
DR   EMBL; X73231; CAA51703.1; -; Genomic_DNA.
DR   EMBL; AK004540; BAB23356.1; -; mRNA.
DR   EMBL; AK132501; BAE21207.1; -; mRNA.
DR   EMBL; CH466550; EDL04336.1; -; Genomic_DNA.
DR   EMBL; BC011284; AAH11284.1; -; mRNA.
DR   EMBL; BC098075; AAH98075.1; -; mRNA.
DR   EMBL; M82876; AAA37260.1; -; mRNA.
DR   CCDS; CCDS27753.1; -.
DR   PIR; A54190; A54190.
DR   RefSeq; NP_033843.2; NM_009713.4.
DR   AlphaFoldDB; P50428; -.
DR   SMR; P50428; -.
DR   BioGRID; 198217; 2.
DR   IntAct; P50428; 1.
DR   STRING; 10090.ENSMUSP00000127646; -.
DR   SwissLipids; SLP:000000914; -.
DR   GlyConnect; 2133; 1 N-Linked glycan (1 site).
DR   GlyCosmos; P50428; 3 sites, 1 glycan.
DR   GlyGen; P50428; 3 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; P50428; -.
DR   PhosphoSitePlus; P50428; -.
DR   SwissPalm; P50428; -.
DR   EPD; P50428; -.
DR   MaxQB; P50428; -.
DR   PaxDb; 10090-ENSMUSP00000127646; -.
DR   PeptideAtlas; P50428; -.
DR   ProteomicsDB; 281905; -.
DR   Pumba; P50428; -.
DR   Antibodypedia; 215; 523 antibodies from 36 providers.
DR   DNASU; 11883; -.
DR   Ensembl; ENSMUST00000165199.8; ENSMUSP00000127646.2; ENSMUSG00000022620.15.
DR   GeneID; 11883; -.
DR   KEGG; mmu:11883; -.
DR   UCSC; uc007xgy.2; mouse.
DR   AGR; MGI:88077; -.
DR   CTD; 410; -.
DR   MGI; MGI:88077; Arsa.
DR   VEuPathDB; HostDB:ENSMUSG00000022620; -.
DR   eggNOG; KOG3867; Eukaryota.
DR   GeneTree; ENSGT00940000157610; -.
DR   HOGENOM; CLU_006332_13_7_1; -.
DR   InParanoid; P50428; -.
DR   OMA; YPAYPDE; -.
DR   OrthoDB; 2913702at2759; -.
DR   PhylomeDB; P50428; -.
DR   TreeFam; TF314186; -.
DR   Reactome; R-MMU-1663150; The activation of arylsulfatases.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
DR   SABIO-RK; P50428; -.
DR   BioGRID-ORCS; 11883; 4 hits in 80 CRISPR screens.
DR   ChiTaRS; Arsa; mouse.
DR   PRO; PR:P50428; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; P50428; Protein.
DR   Bgee; ENSMUSG00000022620; Expressed in spermatocyte and 265 other cell types or tissues.
DR   ExpressionAtlas; P50428; baseline and differential.
DR   GO; GO:0001669; C:acrosomal vesicle; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0031232; C:extrinsic component of external side of plasma membrane; ISO:MGI.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0004065; F:arylsulfatase activity; ISO:MGI.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0004098; F:cerebroside-sulfatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008484; F:sulfuric ester hydrolase activity; ISO:MGI.
DR   GO; GO:0006914; P:autophagy; ISO:MGI.
DR   GO; GO:0007339; P:binding of sperm to zona pellucida; IMP:MGI.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR   GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR   GO; GO:0051597; P:response to methylmercury; ISO:MGI.
DR   GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR   GO; GO:0009268; P:response to pH; ISO:MGI.
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; IPR024607; Sulfatase_CS.
DR   InterPro; IPR000917; Sulfatase_N.
DR   PANTHER; PTHR42693:SF11; ARYLSULFATASE A; 1.
DR   PANTHER; PTHR42693; ARYLSULFATASE FAMILY MEMBER; 1.
DR   Pfam; PF00884; Sulfatase; 1.
DR   Pfam; PF14707; Sulfatase_C; 1.
DR   SUPFAM; SSF53649; Alkaline phosphatase-like; 1.
DR   PROSITE; PS00523; SULFATASE_1; 1.
DR   PROSITE; PS00149; SULFATASE_2; 1.
DR   Genevisible; P50428; MM.
PE   1: Evidence at protein level;
KW   Calcium; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW   Lipid metabolism; Lysosome; Metal-binding; Reference proteome; Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CHAIN           18..506
FT                   /note="Arylsulfatase A"
FT                   /id="PRO_0000033420"
FT   ACT_SITE        68
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   ACT_SITE        124
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         28
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         29
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         68
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /note="via 3-oxoalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         122
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         149
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         228
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         280
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         281
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         301
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   MOD_RES         68
FT                   /note="3-oxoalanine (Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        349
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        155..171
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   DISULFID        160..167
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   DISULFID        299..413
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   DISULFID        487..499
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   DISULFID        488..501
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   DISULFID        492..498
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CONFLICT        85
FT                   /note="G -> A (in Ref. 1; CAA51702/CAA51703)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        104
FT                   /note="V -> L (in Ref. 1; CAA51702/CAA51703)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   506 AA;  53748 MW;  A12DFA369D65B1AD CRC64;
     MALGTLFLAL AAGLSTASPP NILLIFADDL GYGDLGSYGH PSSTTPNLDQ LAEGGLRFTD
     FYVPVSLCTP SRAALLTGRL PVRSGMYPGV LGPSSQGGLP LEEVTLAEVL AARGYLTGMA
     GKWHLGVGPE GAFLPPHQGF HRFLGIPYSH DQGPCQNLTC FPPDIPCKGG CDQGLVPIPL
     LANLTVEAQP PWLPGLEARY VSFSRDLMAD AQRQGRPFFL YYASHHTHYP QFSGQSFTKR
     SGRGPFGDSL MELDGAVGAL MTTVGDLGLL EETLVIFTAD NGPELMRMSN GGCSGLLRCG
     KGTTFEGGVR EPALVYWPGH ITPGVTHELA SSLDLLPTLA ALTGAPLPNV TLDGVDISPL
     LLGTGKSPRK SVFFYPPYPD EIHGVFAVRN GKYKAHFFTQ GSAHSDTTSD PACHAANRLT
     AHEPPLLYDL SQDPGENYNV LESIEGVSPE ALQALKHIQL LKAQYDAAMT FGPSQIAKGE
     DPALQICCQP SCTPHPVCCH CPGSQS
//