ARSG_MOUSE
ID ARSG_MOUSE Reviewed; 525 AA.
AC Q3TYD4; B1AT67; B1AT68; Q5XFU5; Q69ZT6; Q8CHS3; Q8VBZ5; Q9D3B4;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Arylsulfatase G;
DE Short=ASG;
DE EC=3.1.6.1 {ECO:0000269|PubMed:25135642};
DE AltName: Full=N-sulfoglucosamine-3-sulfatase;
DE EC=3.1.6.15 {ECO:0000269|PubMed:22689975};
DE Flags: Precursor;
GN Name=Arsg; Synonyms=Kiaa1001;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata, and Visual cortex;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, Kidney, and Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-525 (ISOFORM 1).
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22689975; DOI=10.1073/pnas.1202071109;
RA Kowalewski B., Lamanna W.C., Lawrence R., Damme M., Stroobants S.,
RA Padva M., Kalus I., Frese M.A., Luebke T., Luellmann-Rauch R., D'Hooge R.,
RA Esko J.D., Dierks T.;
RT "Arylsulfatase G inactivation causes loss of heparan sulfate 3-O-sulfatase
RT activity and mucopolysaccharidosis in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:10310-10315(2012).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP GLYCOSYLATION AT ASN-117; ASN-215; ASN-356 AND ASN-497, AND MUTAGENESIS OF
RP ASN-117; ASN-215; ASN-356 AND ASN-497.
RX PubMed=25135642; DOI=10.1074/jbc.m114.584144;
RA Kowalewski B., Luebke T., Kollmann K., Braulke T., Reinheckel T.,
RA Dierks T., Damme M.;
RT "Molecular characterization of arylsulfatase G: expression, processing,
RT glycosylation, transport, and activity.";
RL J. Biol. Chem. 289:27992-28005(2014).
CC -!- FUNCTION: Displays arylsulfatase activity at acidic pH towards the
CC artificial substrate p-nitrocatechol sulfate (PubMed:25135642).
CC Catalyzes the hydrolysis of the 3-sulfate groups of the N-sulfo-D-
CC glucosamine 3-O-sulfate units of heparin (PubMed:22689975).
CC {ECO:0000269|PubMed:22689975, ECO:0000269|PubMed:25135642}.
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:25135642};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 3-sulfate groups of the N-sulfo-D-
CC glucosamine 3-O-sulfate units of heparin.; EC=3.1.6.15;
CC Evidence={ECO:0000269|PubMed:22689975};
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: Lysosome {ECO:0000269|PubMed:25135642}. Note=The
CC 63-kDa precursor protein localizes to pre-lysosomal compartments and
CC tightly associates with organelle membranes, most likely the
CC endoplasmic reticulum. In contrast, proteolytically processed fragments
CC of 34-, 18- and 10-kDa are found in lysosomal fractions and lose their
CC membrane association. {ECO:0000269|PubMed:25135642}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3TYD4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3TYD4-2; Sequence=VSP_018628, VSP_018629;
CC -!- TISSUE SPECIFICITY: Highly expressed in the spleen, kidney, liver,
CC brain, and testis (at protein level). {ECO:0000269|PubMed:25135642}.
CC -!- PTM: N-glycosylated with both high mannose and complex type sugars.
CC {ECO:0000269|PubMed:25135642}.
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:P15289}.
CC -!- PTM: The 63-kDa precursor undergoes proteolytic processing in two
CC steps, yielding two fragments in the first step (apparent molecular
CC masses of 44 and 18 kDa). In the second step, the 44-kDa fragment is
CC processed further to the 34- and 10-kDa chains. The 10-kDa chain is a
CC cleavage product of the 44-kDa fragment but linked to the 18-kDa chain
CC through a disulfide bridge. {ECO:0000269|PubMed:25135642}.
CC -!- DISRUPTION PHENOTYPE: Mice accumulate heparan sulfate in visceral
CC organs and the central nervous system and develop neuronal cell death
CC and behavioral deficits (PubMed:22689975). This accumulated heparan
CC sulfate exhibits unique non-reducing end structures with terminal N-
CC sulfoglucosamine-3-O-sulfate residues (PubMed:22689975).
CC {ECO:0000269|PubMed:22689975}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR EMBL; AK018132; BAB31086.1; -; mRNA.
DR EMBL; AK158726; BAE34629.1; -; mRNA.
DR EMBL; AL645791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022158; AAH22158.1; -; mRNA.
DR EMBL; BC039629; AAH39629.1; -; mRNA.
DR EMBL; BC084731; AAH84731.1; -; mRNA.
DR EMBL; AK173082; BAD32360.1; -; mRNA.
DR EMBL; BN000747; CAI84993.1; -; mRNA.
DR CCDS; CCDS25581.1; -. [Q3TYD4-1]
DR CCDS; CCDS48971.1; -. [Q3TYD4-2]
DR RefSeq; NP_001159649.1; NM_001166177.1. [Q3TYD4-2]
DR RefSeq; NP_082986.3; NM_028710.3. [Q3TYD4-1]
DR RefSeq; XP_006534411.1; XM_006534348.2. [Q3TYD4-1]
DR RefSeq; XP_006534412.1; XM_006534349.3. [Q3TYD4-1]
DR RefSeq; XP_006534413.1; XM_006534350.3. [Q3TYD4-1]
DR RefSeq; XP_017170289.1; XM_017314800.1. [Q3TYD4-1]
DR RefSeq; XP_017170290.1; XM_017314801.1.
DR AlphaFoldDB; Q3TYD4; -.
DR SMR; Q3TYD4; -.
DR BioGRID; 216419; 1.
DR STRING; 10090.ENSMUSP00000102307; -.
DR GlyConnect; 2135; 4 N-Linked glycans (1 site).
DR GlyGen; Q3TYD4; 2 sites, 4 N-linked glycans (1 site).
DR PhosphoSitePlus; Q3TYD4; -.
DR MaxQB; Q3TYD4; -.
DR PaxDb; Q3TYD4; -.
DR PeptideAtlas; Q3TYD4; -.
DR PRIDE; Q3TYD4; -.
DR ProteomicsDB; 265106; -. [Q3TYD4-1]
DR ProteomicsDB; 265107; -. [Q3TYD4-2]
DR Antibodypedia; 19259; 189 antibodies from 23 providers.
DR DNASU; 74008; -.
DR Ensembl; ENSMUST00000020928; ENSMUSP00000020928; ENSMUSG00000020604. [Q3TYD4-1]
DR Ensembl; ENSMUST00000106696; ENSMUSP00000102307; ENSMUSG00000020604. [Q3TYD4-2]
DR Ensembl; ENSMUST00000106697; ENSMUSP00000102308; ENSMUSG00000020604. [Q3TYD4-1]
DR GeneID; 74008; -.
DR KEGG; mmu:74008; -.
DR UCSC; uc007mcn.1; mouse. [Q3TYD4-1]
DR UCSC; uc007mcp.2; mouse. [Q3TYD4-2]
DR CTD; 22901; -.
DR MGI; MGI:1921258; Arsg.
DR VEuPathDB; HostDB:ENSMUSG00000020604; -.
DR eggNOG; KOG3867; Eukaryota.
DR GeneTree; ENSGT00940000159093; -.
DR HOGENOM; CLU_006332_13_6_1; -.
DR InParanoid; Q3TYD4; -.
DR OMA; PFTGLWQ; -.
DR OrthoDB; 515367at2759; -.
DR PhylomeDB; Q3TYD4; -.
DR BRENDA; 3.1.6.1; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-1663150; The activation of arylsulfatases.
DR BioGRID-ORCS; 74008; 3 hits in 69 CRISPR screens.
DR ChiTaRS; Arsg; mouse.
DR PRO; PR:Q3TYD4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3TYD4; protein.
DR Bgee; ENSMUSG00000020604; Expressed in lumbar subsegment of spinal cord and 153 other tissues.
DR Genevisible; Q3TYD4; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:HGNC-UCL.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0004065; F:arylsulfatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0033889; F:N-sulfoglucosamine-3-sulfatase activity; IMP:UniProtKB.
DR GO; GO:0006790; P:sulfur compound metabolic process; 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 Alternative splicing; Calcium; Disulfide bond; Glycoprotein; Hydrolase;
KW Lysosome; Metal-binding; Reference proteome; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..525
FT /note="Arylsulfatase G"
FT /id="PRO_0000238663"
FT ACT_SITE 84
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT ACT_SITE 139
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 44
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 84
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /note="via 3-oxoalanine"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 137
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 302
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT MOD_RES 84
FT /note="3-oxoalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25135642"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25135642"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25135642"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:25135642"
FT VAR_SEQ 1..323
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018628"
FT VAR_SEQ 324..327
FT /note="QTHQ -> MIKI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018629"
FT MUTAGEN 117
FT /note="N->Q: Faster electrophoretic migration typical of a
FT size reduction probably due to glycosylation loss."
FT /evidence="ECO:0000269|PubMed:25135642"
FT MUTAGEN 215
FT /note="N->Q: Faster electrophoretic migration typical of a
FT size reduction probably due to glycosylation loss."
FT /evidence="ECO:0000269|PubMed:25135642"
FT MUTAGEN 356
FT /note="N->Q: Faster electrophoretic migration typical of a
FT size reduction probably due to glycosylation loss."
FT /evidence="ECO:0000269|PubMed:25135642"
FT MUTAGEN 497
FT /note="N->Q: Faster electrophoretic migration typical of a
FT size reduction probably due to glycosylation loss.
FT Abolishes proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:25135642"
FT CONFLICT 122
FT /note="A -> V (in Ref. 3; AAH84731)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="L -> Q (in Ref. 1; BAB31086)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 57434 MW; FA319206459D1B2B CRC64;
MGWLFLKVLL VGMAFSGFFY PLVDFSISGK TRAPQPNIVI ILADDMGWGD LGANWAETKD
TTNLDKMASE GMRFVDFHAA ASTCSPSRAS LLTGRLGLRN GVTHNFAVTS VGGLPVNETT
LAEVLRQEGY VTAMIGKWHL GHHGSYHPNF RGFDYYFGIP YSNDMGCTDA PGYNYPPCPA
CPQRDGLWRN PGRDCYTDVA LPLYENLNIV EQPVNLSGLA QKYAERAVEF IEQASTSGRP
FLLYVGLAHM HVPLSVTPPL AHPQRQSLYR ASLREMDSLV GQIKDKVDHV ARENTLLWFT
GDNGPWAQKC ELAGSVGPFF GLWQTHQGGS PTKQTTWEGG HRVPALAYWP GRVPANVTST
ALLSLLDIFP TVIALAGASL PPNRKFDGRD VSEVLFGKSQ MGHRVLFHPN SGAAGEYGAL
QTVRLNHYKA FYITGGAKAC DGSVGPEQHH VAPLIFNLED AADEGMPLQK GSPEYQEVLQ
QVTRALADVL QDIADDNSSR ADYTQDPSVI PCCNPYQTTC RCQPV
