ID   ARSL_HUMAN              Reviewed;         589 AA.
AC   P51690; Q53FT2; Q53FU8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   02-SEP-2026, entry version 197.
DE   RecName: Full=Arylsulfatase L;
DE            EC=3.1.6.1 {ECO:0000269|PubMed:7720070, ECO:0000269|PubMed:9497243};
DE   AltName: Full=Arylsulfatase E;
DE            Short=ASE;
DE   Flags: Precursor;
GN   Name=ARSL {ECO:0000312|HGNC:HGNC:719}; Synonyms=ARSE;
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], VARIANTS CDPX1 SER-12; PRO-111; ARG-117;
RP   VAL-137 AND ARG-245, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC   TISSUE=Kidney;
RX   PubMed=7720070; DOI=10.1016/0092-8674(95)90367-4;
RA   Franco B., Meroni G., Parenti G., Levilliers J., Bernard L., Gebbia M.,
RA   Cox L., Maroteaux P., Sheffield L., Rappold G.A., Andria G., Petit C.,
RA   Ballabio A.;
RT   "A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia
RT   punctata (CDPX) and implications for warfarin embryopathy.";
RL   Cell 81:15-25(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-424.
RC   TISSUE=Kidney proximal tubule, and Pancreas;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   CHARACTERIZATION OF VARIANTS CDPX1 SER-12; PRO-111; VAL-137; ARG-245 AND
RP   TYR-492, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=9497243; DOI=10.1086/301746;
RA   Daniele A., Parenti G., D'Addio M., Andria G., Ballabio A., Meroni G.;
RT   "Biochemical characterization of arylsulfatase E and functional analysis of
RT   mutations found in patients with X-linked chondrodysplasia punctata.";
RL   Am. J. Hum. Genet. 62:562-572(1998).
RN   [4]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [5]
RP   VARIANT CDPX1 TYR-492.
RX   PubMed=9409863;
RX   DOI=10.1002/(sici)1096-8628(19971212)73:2<139::aid-ajmg7>3.0.co;2-p;
RA   Parenti G., Buttitta P., Meroni G., Franco B., Bernard L., Rizzolo M.G.,
RA   Brunetti-Pierri N., Ballabio A., Andria G.;
RT   "X-linked recessive chondrodysplasia punctata due to a new point mutation
RT   of the ARSE gene.";
RL   Am. J. Med. Genet. 73:139-143(1997).
RN   [6]
RP   VARIANTS CDPX1 ASN-80; MET-481 AND SER-578.
RX   PubMed=12567415; DOI=10.1002/ajmg.a.10950;
RA   Brunetti-Pierri N., Andreucci M.V., Tuzzi R., Vega G.R., Gray G.,
RA   McKeown C., Ballabio A., Andria G., Meroni G., Parenti G.;
RT   "X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E
RT   gene mutations and expanded clinical variability.";
RL   Am. J. Med. Genet. A 117:164-168(2003).
CC   -!- FUNCTION: Exhibits arylsulfatase activity towards the artificial
CC       substrate 4-methylumbelliferyl sulfate (PubMed:7720070,
CC       PubMed:9497243). May be essential for the correct composition of
CC       cartilage and bone matrix during development (PubMed:7720070). Has no
CC       activity toward steroid sulfates (PubMed:7720070).
CC       {ECO:0000269|PubMed:7720070, ECO:0000269|PubMed:9497243}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an aryl sulfate + H2O = a phenol + sulfate + H(+);
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:7720070, ECO:0000269|PubMed:9497243};
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   -!- ACTIVITY REGULATION: Inhibited by millimolar concentrations of
CC       warfarin. {ECO:0000269|PubMed:7720070}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7. {ECO:0000269|PubMed:7720070};
CC       Temperature dependence:
CC         Almost completely inactivated after 10 minutes at 50 degrees Celsius.
CC         {ECO:0000269|PubMed:7720070};
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack
CC       {ECO:0000269|PubMed:9497243}.
CC   -!- TISSUE SPECIFICITY: Expressed in the pancreas, liver and kidney.
CC       {ECO:0000269|PubMed:7720070}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19159218}.
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   -!- DISEASE: Chondrodysplasia punctata 1, X-linked recessive (CDPX1)
CC       [MIM:302950]: A clinically and genetically heterogeneous disorder
CC       characterized by punctiform calcification of the bones. CDPX1 is a
CC       congenital defect of bone and cartilage development characterized by
CC       aberrant bone mineralization, severe underdevelopment of nasal
CC       cartilage, and distal phalangeal hypoplasia. This disease can also be
CC       induced by inhibition with the drug warfarin.
CC       {ECO:0000269|PubMed:12567415, ECO:0000269|PubMed:7720070,
CC       ECO:0000269|PubMed:9409863, ECO:0000269|PubMed:9497243}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR   EMBL; X83573; CAA58556.1; -; mRNA.
DR   EMBL; AK223183; BAD96903.1; -; mRNA.
DR   EMBL; AK223199; BAD96919.1; -; mRNA.
DR   CCDS; CCDS14122.1; -.
DR   PIR; I37187; I37187.
DR   RefSeq; NP_000038.2; NM_000047.3.
DR   RefSeq; NP_001427680.1; NM_001440751.1.
DR   AlphaFoldDB; P51690; -.
DR   SMR; P51690; -.
DR   BioGRID; 106908; 40.
DR   FunCoup; P51690; 28.
DR   IntAct; P51690; 27.
DR   STRING; 9606.ENSP00000500220; -.
DR   GlyCosmos; P51690; 4 sites, No reported glycans.
DR   GlyGen; P51690; 4 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; P51690; -.
DR   PhosphoSitePlus; P51690; -.
DR   SwissPalm; P51690; -.
DR   BioMuta; ARSE; -.
DR   DMDM; 77416850; -.
DR   jPOST; P51690; -.
DR   MassIVE; P51690; -.
DR   PaxDb; 9606-ENSP00000500220; -.
DR   PeptideAtlas; P51690; -.
DR   ProteomicsDB; 56377; -.
DR   Antibodypedia; 23506; 132 antibodies from 27 providers.
DR   DNASU; 415; -.
DR   Ensembl; ENST00000381134.9; ENSP00000370526.3; ENSG00000157399.18.
DR   Ensembl; ENST00000540563.6; ENSP00000438198.2; ENSG00000157399.18.
DR   Ensembl; ENST00000879212.1; ENSP00000549271.1; ENSG00000157399.18.
DR   Ensembl; ENST00000879214.1; ENSP00000549273.1; ENSG00000157399.18.
DR   Ensembl; ENST00000879215.1; ENSP00000549274.1; ENSG00000157399.18.
DR   GeneID; 415; -.
DR   KEGG; hsa:415; -.
DR   MANE-Select; ENST00000381134.9; ENSP00000370526.3; NM_000047.3; NP_000038.2.
DR   UCSC; uc004crc.5; human.
DR   AGR; HGNC:719; -.
DR   ClinPGx; PA25010; -.
DR   CTD; 415; -.
DR   DisGeNET; 415; -.
DR   GeneCards; ARSL; -.
DR   GeneReviews; ARSL; -.
DR   HGNC; HGNC:719; ARSL.
DR   HPA; ENSG00000157399; Tissue enhanced (kidney, liver, pancreas).
DR   MalaCards; ARSL; -.
DR   MIM; 300180; gene.
DR   MIM; 302950; phenotype.
DR   OpenTargets; ENSG00000157399; -.
DR   Orphanet; 79345; Brachytelephalangic chondrodysplasia punctata.
DR   VEuPathDB; HostDB:ENSG00000157399; -.
DR   eggNOG; KOG3867; Eukaryota.
DR   GeneTree; ENSGT00940000163319; -.
DR   InParanoid; P51690; -.
DR   OMA; FSMMADC; -.
DR   OrthoDB; 103349at2759; -.
DR   PAN-GO; P51690; 1 GO annotation based on evolutionary models.
DR   PhylomeDB; P51690; -.
DR   PathwayCommons; P51690; -.
DR   Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR   Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR   SignaLink; P51690; -.
DR   Agora; ENSG00000157399; -.
DR   BioGRID-ORCS; 415; 10 hits in 772 CRISPR screens.
DR   GeneWiki; Arylsulfatase_E; -.
DR   GenomeRNAi; 415; -.
DR   Pharos; P51690; Tbio.
DR   PRO; PR:P51690; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P51690; protein.
DR   Bgee; ENSG00000157399; Expressed in body of pancreas and 107 other cell types or tissues.
DR   ExpressionAtlas; P51690; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR   GO; GO:0004065; F:arylsulfatase activity; IDA:UniProtKB.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   FunFam; 1.10.287.550:FF:000001; Arylsulfatase E; 1.
DR   FunFam; 3.30.1120.10:FF:000001; Arylsulfatase E; 1.
DR   FunFam; 3.40.720.10:FF:000233; Predicted protein; 1.
DR   Gene3D; 3.30.1120.10; -; 1.
DR   Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR   Gene3D; 1.10.287.550; Helix hairpin bin; 1.
DR   InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR   InterPro; IPR050738; Sulfatase.
DR   InterPro; IPR024607; Sulfatase_CS.
DR   InterPro; IPR000917; Sulfatase_N.
DR   PANTHER; PTHR42693; ARYLSULFATASE FAMILY MEMBER; 1.
DR   PANTHER; PTHR42693:SF48; ARYLSULFATASE L; 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.
PE   1: Evidence at protein level;
KW   Calcium; Disease variant; Glycoprotein; Golgi apparatus; Hydrolase;
KW   Metal-binding; Proteomics identification; Reference proteome; Signal.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255"
FT   CHAIN           32..589
FT                   /note="Arylsulfatase L"
FT                   /id="PRO_0000033425"
FT   ACT_SITE        86
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   ACT_SITE        147
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         46
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         47
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         86
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /note="via 3-oxoalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         145
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         301
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         353
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         354
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         378
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   MOD_RES         86
FT                   /note="3-oxoalanine (Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        258
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         12
FT                   /note="R -> S (in CDPX1; no effect on arylsulfatase
FT                   activity, protein stability and localization to the Golgi
FT                   apparatus; dbSNP:rs122460151)"
FT                   /evidence="ECO:0000269|PubMed:7720070,
FT                   ECO:0000269|PubMed:9497243"
FT                   /id="VAR_007307"
FT   VARIANT         80
FT                   /note="I -> N (in CDPX1)"
FT                   /evidence="ECO:0000269|PubMed:12567415"
FT                   /id="VAR_023570"
FT   VARIANT         111
FT                   /note="R -> P (in CDPX1; significant loss of arylsulfatase
FT                   activity; no effect on protein stability and localization
FT                   to the Golgi apparatus; dbSNP:rs122460153)"
FT                   /evidence="ECO:0000269|PubMed:7720070,
FT                   ECO:0000269|PubMed:9497243"
FT                   /id="VAR_007308"
FT   VARIANT         117
FT                   /note="G -> R (in CDPX1; dbSNP:rs122460152)"
FT                   /evidence="ECO:0000269|PubMed:7720070"
FT                   /id="VAR_007309"
FT   VARIANT         137
FT                   /note="G -> V (in CDPX1; significant loss of arylsulfatase
FT                   activity; no effect on protein stability and localization
FT                   to the Golgi apparatus; dbSNP:rs80338711)"
FT                   /evidence="ECO:0000269|PubMed:7720070,
FT                   ECO:0000269|PubMed:9497243"
FT                   /id="VAR_007310"
FT   VARIANT         183
FT                   /note="R -> H (in dbSNP:rs34412194)"
FT                   /id="VAR_037974"
FT   VARIANT         245
FT                   /note="G -> R (in CDPX1; significant loss of arylsulfatase
FT                   activity; no effect on protein stability and localization
FT                   to the Golgi apparatus; dbSNP:rs122460154)"
FT                   /evidence="ECO:0000269|PubMed:7720070,
FT                   ECO:0000269|PubMed:9497243"
FT                   /id="VAR_007311"
FT   VARIANT         424
FT                   /note="G -> S (in dbSNP:rs35143646)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_037975"
FT   VARIANT         481
FT                   /note="T -> M (in CDPX1; dbSNP:rs80338713)"
FT                   /evidence="ECO:0000269|PubMed:12567415"
FT                   /id="VAR_023571"
FT   VARIANT         492
FT                   /note="C -> Y (in CDPX1; significant loss of arylsulfatase
FT                   activity; no effect on protein stability and localization
FT                   to the Golgi apparatus; dbSNP:rs122460155)"
FT                   /evidence="ECO:0000269|PubMed:9409863,
FT                   ECO:0000269|PubMed:9497243"
FT                   /id="VAR_007312"
FT   VARIANT         578
FT                   /note="P -> S (in CDPX1; dbSNP:rs28935474)"
FT                   /evidence="ECO:0000269|PubMed:12567415"
FT                   /id="VAR_023572"
FT   CONFLICT        168
FT                   /note="D -> E (in Ref. 1; CAA58556)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   589 AA;  65669 MW;  37A941EF4A44027A CRC64;
     MLHLHHSCLC FRSWLPAMLA VLLSLAPSAS SDISASRPNI LLLMADDLGI GDIGCYGNNT
     MRTPNIDRLA EDGVKLTQHI SAASLCTPSR AAFLTGRYPV RSGMVSSIGY RVLQWTGASG
     GLPTNETTFA KILKEKGYAT GLIGKWHLGL NCESASDHCH HPLHHGFDHF YGMPFSLMGD
     CARWELSEKR VNLEQKLNFL FQVLALVALT LVAGKLTHLI PVSWMPVIWS ALSAVLLLAS
     SYFVGALIVH ADCFLMRNHT ITEQPMCFQR TTPLILQEVA SFLKRNKHGP FLLFVSFLHV
     HIPLITMENF LGKSLHGLYG DNVEEMDWMV GRILDTLDVE GLSNSTLIYF TSDHGGSLEN
     QLGNTQYGGW NGIYKGGKGM GGWEGGIRVP GIFRWPGVLP AGRVIGEPTS LMDVFPTVVR
     LAGGEVPQDR VIDGQDLLPL LLGTAQHSDH EFLMHYCERF LHAARWHQRD RGTMWKVHFV
     TPVFQPEGAG ACYGRKVCPC FGEKVVHHDP PLLFDLSRDP SETHILTPAS EPVFYQVMER
     VQQAVWEHQR TLSPVPLQLD RLGNIWRPWL QPCCGPFPLC WCLREDDPQ
//