ARSA_MOUSE
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 03-AUG-2022, entry version 163.
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 GlyGen; P50428; 3 sites, 1 N-linked glycan (1 site).
DR PhosphoSitePlus; P50428; -.
DR EPD; P50428; -.
DR MaxQB; P50428; -.
DR PaxDb; P50428; -.
DR PeptideAtlas; P50428; -.
DR PRIDE; P50428; -.
DR ProteomicsDB; 281905; -.
DR Antibodypedia; 215; 490 antibodies from 36 providers.
DR DNASU; 11883; -.
DR Ensembl; ENSMUST00000165199; ENSMUSP00000127646; ENSMUSG00000022620.
DR GeneID; 11883; -.
DR KEGG; mmu:11883; -.
DR UCSC; uc007xgy.2; mouse.
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; PALEPCC; -.
DR OrthoDB; 515367at2759; -.
DR PhylomeDB; P50428; -.
DR TreeFam; TF314186; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-1663150; The activation of arylsulfatases.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR SABIO-RK; P50428; -.
DR BioGRID-ORCS; 11883; 3 hits in 75 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 262 other tissues.
DR ExpressionAtlas; P50428; baseline and differential.
DR Genevisible; P50428; MM.
DR GO; GO:0001669; C:acrosomal vesicle; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; 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:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005764; C:lysosome; ISO: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:0007417; P:central nervous system development; ISO: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; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR024607; Sulfatase_CS.
DR InterPro; IPR000917; Sulfatase_N.
DR Pfam; PF00884; Sulfatase; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
DR PROSITE; PS00523; SULFATASE_1; 1.
DR PROSITE; PS00149; SULFATASE_2; 1.
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
