ARSK_MOUSE
ID ARSK_MOUSE Reviewed; 553 AA.
AC Q9D2L1; Q6PE11; Q8BL50; Q8BUA1; Q9CYZ0;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Arylsulfatase K;
DE Short=ASK;
DE EC=3.1.6.1 {ECO:0000250|UniProtKB:Q6UWY0};
DE AltName: Full=Glucuronate-2-sulfatase;
DE EC=3.1.6.18 {ECO:0000269|PubMed:32856704};
DE Flags: Precursor;
GN Name=Arsk;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Corpora quadrigemina, Forelimb, Head, Hippocampus, Lung,
RC Spinal cord, Spinal ganglion, and Urinary bladder;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP IDENTIFICATION.
RX PubMed=16174644; DOI=10.1093/hmg/ddi351;
RA Sardiello M., Annunziata I., Roma G., Ballabio A.;
RT "Sulfatases and sulfatase modifying factors: an exclusive and promiscuous
RT relationship.";
RL Hum. Mol. Genet. 14:3203-3217(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32856704; DOI=10.1042/bcj20200546;
RA Trabszo C., Ramms B., Chopra P., Luellmann-Rauch R., Stroobants S.,
RA Spross J., Jeschke A., Schinke T., Boons G.J., Esko J.D., Luebke T.,
RA Dierks T.;
RT "Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient
RT glucuronate desulfation of heparan and chondroitin sulfate.";
RL Biochem. J. 477:3433-3451(2020).
CC -!- FUNCTION: Catalyzes the hydrolysis of pseudosubstrates such as p-
CC nitrocatechol sulfate and p-nitrophenyl sulfate (By similarity).
CC Catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-
CC glucuronate residues of chondroitin sulfate, heparin and heparitin
CC sulfate (PubMed:32856704). Acts selectively on 2-sulfoglucuronate and
CC lacks activity against 2-sulfoiduronate (By similarity).
CC {ECO:0000250|UniProtKB:Q6UWY0, ECO:0000269|PubMed:32856704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aryl sulfate + H2O = a phenol + H(+) + sulfate;
CC Xref=Rhea:RHEA:17261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16189, ChEBI:CHEBI:33853, ChEBI:CHEBI:140317; EC=3.1.6.1;
CC Evidence={ECO:0000250|UniProtKB:Q6UWY0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-
CC glucuronate residues of chondroitin sulfate, heparin and heparitin
CC sulfate.; EC=3.1.6.18; Evidence={ECO:0000269|PubMed:32856704};
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q6UWY0}. Lysosome
CC {ECO:0000250|UniProtKB:Q6UWY0}.
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.
CC {ECO:0000250|UniProtKB:Q6UWY0}.
CC -!- PTM: The 75-kDa precursor undergoes proteolytic processing to yield a
CC 23 kDa form. {ECO:0000250|UniProtKB:Q6UWY0}.
CC -!- PTM: N-glycosylated with both high mannose and complex type sugars.
CC {ECO:0000250|UniProtKB:Q6UWY0}.
CC -!- DISRUPTION PHENOTYPE: Mice accumulate significant amounts of heparan
CC sulfate, which exhibits glucuronate-2-O-sulfated non-reducing ends,
CC particularly in brain and kidney. {ECO:0000269|PubMed:32856704}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH46790.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH58351.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB28703.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB28703.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB31772.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC27279.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC28035.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC29070.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC30444.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC32696.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC38801.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC39115.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC39714.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE26079.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE38491.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAI84997.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK046378; BAC32696.1; ALT_INIT; mRNA.
DR EMBL; AK013194; BAB28703.1; ALT_SEQ; mRNA.
DR EMBL; AK086667; BAC39714.1; ALT_INIT; mRNA.
DR EMBL; AK019515; BAB31772.1; ALT_INIT; mRNA.
DR EMBL; AK031147; BAC27279.1; ALT_INIT; mRNA.
DR EMBL; AK032812; BAC28035.1; ALT_INIT; mRNA.
DR EMBL; AK035464; BAC29070.1; ALT_INIT; mRNA.
DR EMBL; AK039765; BAC30444.1; ALT_INIT; mRNA.
DR EMBL; AK083188; BAC38801.1; ALT_INIT; mRNA.
DR EMBL; AK084090; BAC39115.1; ALT_INIT; mRNA.
DR EMBL; AK144817; BAE26079.1; ALT_INIT; mRNA.
DR EMBL; AK165970; BAE38491.1; ALT_INIT; mRNA.
DR EMBL; BC046790; AAH46790.3; ALT_INIT; mRNA.
DR EMBL; BC058351; AAH58351.3; ALT_INIT; mRNA.
DR EMBL; BN000751; CAI84997.1; ALT_INIT; mRNA.
DR RefSeq; NP_084123.2; NM_029847.4.
DR AlphaFoldDB; Q9D2L1; -.
DR SMR; Q9D2L1; -.
DR BioGRID; 218477; 2.
DR STRING; 10090.ENSMUSP00000113274; -.
DR GlyGen; Q9D2L1; 6 sites.
DR PhosphoSitePlus; Q9D2L1; -.
DR MaxQB; Q9D2L1; -.
DR PaxDb; Q9D2L1; -.
DR PRIDE; Q9D2L1; -.
DR ProteomicsDB; 283177; -.
DR Antibodypedia; 25008; 118 antibodies from 23 providers.
DR DNASU; 77041; -.
DR Ensembl; ENSMUST00000239063; ENSMUSP00000158928; ENSMUSG00000021592.
DR GeneID; 77041; -.
DR KEGG; mmu:77041; -.
DR UCSC; uc007rgh.1; mouse.
DR CTD; 153642; -.
DR MGI; MGI:1924291; Arsk.
DR VEuPathDB; HostDB:ENSMUSG00000021592; -.
DR eggNOG; KOG3731; Eukaryota.
DR GeneTree; ENSGT00940000158982; -.
DR InParanoid; Q9D2L1; -.
DR OrthoDB; 349944at2759; -.
DR PhylomeDB; Q9D2L1; -.
DR TreeFam; TF313545; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-1663150; The activation of arylsulfatases.
DR BioGRID-ORCS; 77041; 5 hits in 74 CRISPR screens.
DR PRO; PR:Q9D2L1; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9D2L1; protein.
DR Bgee; ENSMUSG00000021592; Expressed in ciliary body and 201 other tissues.
DR ExpressionAtlas; Q9D2L1; baseline and differential.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0004065; F:arylsulfatase activity; ISO:MGI.
DR GO; GO:0015024; F:glucuronate-2-sulfatase activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR000917; Sulfatase_N.
DR Pfam; PF00884; Sulfatase; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Calcium; Glycoprotein; Hydrolase; Lysosome; Metal-binding;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..553
FT /note="Arylsulfatase K"
FT /id="PRO_0000356286"
FT REGION 530..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 80
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 80
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /note="via 3-oxoalanine"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 249
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 311
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 312
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT MOD_RES 80
FT /note="3-oxoalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:Q6UWY0"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 481
FT /note="Y -> H (in Ref. 1; BAC39714)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 62801 MW; 1C4C405D365EE507 CRC64;
MLLLLVSVVA ALALAAPAPR TQKKRMQVNQ APNVVLVASD SFDGRLTFQP GSQVVKLPFI
NFMRAHGTTF LNAYTNSPIC CPSRAAMWSG LFTHLTESWN NFKGLDPNYT TWMDIMEKHG
YQTQKFGKVD YTSGHHSISN RVEAWTRDVA FLLRQEGRPI INLIPDKNRR RVMTKDWQNT
DKAIEWLRQV NYTKPFVLYL GLNLPHPYPS PSSGENFGSS TFHTSLYWLE KVAYDAIKIP
KWLTLSQMHP VDFYSSYTKN CTGKFTENEI KNIRAFYYAM CAETDAMLGE IILALHKLDL
LQKTIVIYTS DHGEMAMEHR QFYKMSMYEA SVHVPLLMMG PGIKANLQVP SVVSLVDIYP
TMLDIAGIAL PPNLSGYSLL TLLSNASANE QAFKFHRPPW ILSEFHGCNA NASTYMLRTG
QWKYIAYADG ASVQPQLFDL SLDPDELTNI ATEFPEITYS LDQKLRSIVN YPKVSASVHQ
YNKEQFIMWK QSVGQNYSNV IAHLRWHQDW QRDPRKYENA IQHWLTAHSS PLASSPTQST
SGSQPTLPQS TSG
