ARSK_HUMAN
ID ARSK_HUMAN Reviewed; 536 AA.
AC Q6UWY0; A2BDE3; B4E1I4; Q3ZCW3; Q8N3Q8;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Arylsulfatase K;
DE Short=ASK;
DE EC=3.1.6.1 {ECO:0000269|PubMed:23986440};
DE AltName: Full=Glucuronate-2-sulfatase;
DE EC=3.1.6.18 {ECO:0000269|PubMed:28055182};
DE AltName: Full=Telethon sulfatase;
DE Flags: Precursor;
GN Name=ARSK; Synonyms=TSULF; ORFNames=UNQ630/PRO1246;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16500042; DOI=10.1016/j.gene.2005.12.023;
RA Obaya A.J.;
RT "Molecular cloning and initial characterization of three novel human
RT sulfatases.";
RL Gene 372:110-117(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-525.
RC TISSUE=Trachea;
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 MRNA].
RC TISSUE=Brain, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-536.
RC TISSUE=Heart;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-80, GLYCOSYLATION,
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND OXOALANINE AT CYS-80.
RX PubMed=23986440; DOI=10.1074/jbc.m113.499541;
RA Wiegmann E.M., Westendorf E., Kalus I., Pringle T.H., Luebke T., Dierks T.;
RT "Arylsulfatase K, a novel lysosomal sulfatase.";
RL J. Biol. Chem. 288:30019-30028(2013).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-80.
RX PubMed=28055182; DOI=10.1021/acschembio.6b01033;
RA Dhamale O.P., Lawrence R., Wiegmann E.M., Shah B.A., Al-Mafraji K.,
RA Lamanna W.C., Luebke T., Dierks T., Boons G.J., Esko J.D.;
RT "Arylsulfatase K is the Lysosomal 2-Sulfoglucuronate Sulfatase.";
RL ACS Chem. Biol. 12:367-373(2017).
CC -!- FUNCTION: Catalyzes the hydrolysis of pseudosubstrates such as p-
CC nitrocatechol sulfate and p-nitrophenyl sulfate (PubMed:23986440).
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:28055182). Acts selectively on 2-sulfoglucuronate and
CC lacks activity against 2-sulfoiduronate (PubMed:28055182).
CC {ECO:0000269|PubMed:23986440, ECO:0000269|PubMed:28055182}.
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:0000269|PubMed:23986440};
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:28055182};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.9 mM for p-nitrocatechol sulfate {ECO:0000269|PubMed:23986440};
CC KM=20.6 mM for p-nitrophenyl sulfate {ECO:0000269|PubMed:23986440};
CC Vmax=0.84 umol/min/mg enzyme for p-nitrocatechol sulfate
CC {ECO:0000269|PubMed:23986440};
CC Vmax=0.93 umol/min/mg enzyme for p-nitrophenyl sulfate
CC {ECO:0000269|PubMed:23986440};
CC pH dependence:
CC Optimum pH is 4.6. {ECO:0000269|PubMed:23986440};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23986440}. Lysosome
CC {ECO:0000269|PubMed:23986440}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the placenta and
CC pancreas (PubMed:23986440). Expressed at intermediate levels in the
CC lung, brain, heart, liver and kidney and at low levels in the muscle
CC (PubMed:23986440). {ECO:0000269|PubMed:23986440}.
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:0000269|PubMed:23986440}.
CC -!- PTM: The 75-kDa precursor undergoes proteolytic processing to yield a
CC 23 kDa form. {ECO:0000269|PubMed:23986440}.
CC -!- PTM: N-glycosylated with both high mannose and complex type sugars.
CC {ECO:0000269|PubMed:23986440}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH36047.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY875939; AAW66667.1; -; mRNA.
DR EMBL; AY358596; AAQ88959.1; -; mRNA.
DR EMBL; AK303855; BAG64796.1; -; mRNA.
DR EMBL; BC036047; AAH36047.1; ALT_INIT; mRNA.
DR EMBL; BC130329; AAI30330.1; -; mRNA.
DR EMBL; AL832711; CAD38634.1; -; mRNA.
DR CCDS; CCDS4073.1; -.
DR RefSeq; NP_937793.1; NM_198150.2.
DR AlphaFoldDB; Q6UWY0; -.
DR SMR; Q6UWY0; -.
DR BioGRID; 127507; 147.
DR IntAct; Q6UWY0; 23.
DR STRING; 9606.ENSP00000369346; -.
DR GlyGen; Q6UWY0; 7 sites.
DR iPTMnet; Q6UWY0; -.
DR PhosphoSitePlus; Q6UWY0; -.
DR BioMuta; ARSK; -.
DR DMDM; 74738157; -.
DR EPD; Q6UWY0; -.
DR jPOST; Q6UWY0; -.
DR MassIVE; Q6UWY0; -.
DR MaxQB; Q6UWY0; -.
DR PaxDb; Q6UWY0; -.
DR PeptideAtlas; Q6UWY0; -.
DR PRIDE; Q6UWY0; -.
DR ProteomicsDB; 67536; -.
DR Antibodypedia; 25008; 118 antibodies from 23 providers.
DR DNASU; 153642; -.
DR Ensembl; ENST00000380009.9; ENSP00000369346.4; ENSG00000164291.17.
DR GeneID; 153642; -.
DR KEGG; hsa:153642; -.
DR MANE-Select; ENST00000380009.9; ENSP00000369346.4; NM_198150.3; NP_937793.1.
DR UCSC; uc003kld.4; human.
DR CTD; 153642; -.
DR DisGeNET; 153642; -.
DR GeneCards; ARSK; -.
DR HGNC; HGNC:25239; ARSK.
DR HPA; ENSG00000164291; Tissue enhanced (parathyroid).
DR MIM; 610011; gene.
DR neXtProt; NX_Q6UWY0; -.
DR OpenTargets; ENSG00000164291; -.
DR PharmGKB; PA143485311; -.
DR VEuPathDB; HostDB:ENSG00000164291; -.
DR eggNOG; KOG3731; Eukaryota.
DR GeneTree; ENSGT00940000158982; -.
DR HOGENOM; CLU_006332_6_0_1; -.
DR InParanoid; Q6UWY0; -.
DR OMA; YGWAVNW; -.
DR OrthoDB; 349944at2759; -.
DR PhylomeDB; Q6UWY0; -.
DR TreeFam; TF313545; -.
DR BRENDA; 3.1.6.1; 2681.
DR BRENDA; 3.1.6.18; 2681.
DR PathwayCommons; Q6UWY0; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR SignaLink; Q6UWY0; -.
DR BioGRID-ORCS; 153642; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; ARSK; human.
DR GenomeRNAi; 153642; -.
DR Pharos; Q6UWY0; Tbio.
DR PRO; PR:Q6UWY0; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6UWY0; protein.
DR Bgee; ENSG00000164291; Expressed in kidney epithelium and 183 other tissues.
DR ExpressionAtlas; Q6UWY0; baseline and differential.
DR Genevisible; Q6UWY0; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0004065; F:arylsulfatase activity; IMP:UniProtKB.
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..22
FT /evidence="ECO:0000255"
FT CHAIN 23..536
FT /note="Arylsulfatase K"
FT /id="PRO_0000042219"
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 251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 313
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 314
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:0000269|PubMed:23986440"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 525
FT /note="Q -> R (in dbSNP:rs17084927)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_052516"
FT MUTAGEN 80
FT /note="C->A: Loss of arylsulfatase and glucuronate-2-
FT sulfatase activity."
FT /evidence="ECO:0000269|PubMed:23986440,
FT ECO:0000269|PubMed:28055182"
FT CONFLICT 380
FT /note="S -> P (in Ref. 6; CAD38634)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 61450 MW; 5A6D1B0FD8FCF386 CRC64;
MLLLWVSVVA ALALAVLAPG AGEQRRRAAK APNVVLVVSD SFDGRLTFHP GSQVVKLPFI
NFMKTRGTSF LNAYTNSPIC CPSRAAMWSG LFTHLTESWN NFKGLDPNYT TWMDVMERHG
YRTQKFGKLD YTSGHHSISN RVEAWTRDVA FLLRQEGRPM VNLIRNRTKV RVMERDWQNT
DKAVNWLRKE AINYTEPFVI YLGLNLPHPY PSPSSGENFG SSTFHTSLYW LEKVSHDAIK
IPKWSPLSEM HPVDYYSSYT KNCTGRFTKK EIKNIRAFYY AMCAETDAML GEIILALHQL
DLLQKTIVIY SSDHGELAME HRQFYKMSMY EASAHVPLLM MGPGIKAGLQ VSNVVSLVDI
YPTMLDIAGI PLPQNLSGYS LLPLSSETFK NEHKVKNLHP PWILSEFHGC NVNASTYMLR
TNHWKYIAYS DGASILPQLF DLSSDPDELT NVAVKFPEIT YSLDQKLHSI INYPKVSASV
HQYNKEQFIK WKQSIGQNYS NVIANLRWHQ DWQKEPRKYE NAIDQWLKTH MNPRAV
