ARSL_HUMAN
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 03-AUG-2022, entry version 178.
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 + 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: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_000047.2.
DR RefSeq; XP_005274576.1; XM_005274519.4.
DR AlphaFoldDB; P51690; -.
DR SMR; P51690; -.
DR BioGRID; 106908; 37.
DR IntAct; P51690; 5.
DR STRING; 9606.ENSP00000441417; -.
DR GlyGen; P51690; 4 sites.
DR iPTMnet; P51690; -.
DR PhosphoSitePlus; P51690; -.
DR BioMuta; ARSE; -.
DR DMDM; 77416850; -.
DR EPD; P51690; -.
DR jPOST; P51690; -.
DR MassIVE; P51690; -.
DR MaxQB; P51690; -.
DR PaxDb; P51690; -.
DR PeptideAtlas; P51690; -.
DR PRIDE; P51690; -.
DR ProteomicsDB; 56377; -.
DR Antibodypedia; 23506; 137 antibodies from 26 providers.
DR DNASU; 415; -.
DR Ensembl; ENST00000381134.9; ENSP00000370526.3; ENSG00000157399.17.
DR Ensembl; ENST00000540563.6; ENSP00000438198.2; ENSG00000157399.17.
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 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 neXtProt; NX_P51690; -.
DR OpenTargets; ENSG00000157399; -.
DR Orphanet; 79345; Brachytelephalangic chondrodysplasia punctata.
DR PharmGKB; PA25010; -.
DR VEuPathDB; HostDB:ENSG00000157399; -.
DR eggNOG; KOG3867; Eukaryota.
DR GeneTree; ENSGT00940000163319; -.
DR InParanoid; P51690; -.
DR OMA; FHGEKNT; -.
DR PhylomeDB; P51690; -.
DR TreeFam; TF314186; -.
DR PathwayCommons; P51690; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR SignaLink; P51690; -.
DR BioGRID-ORCS; 415; 8 hits in 698 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 106 other tissues.
DR ExpressionAtlas; P51690; baseline and differential.
DR Genevisible; P51690; HS.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
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; Disease variant; Glycoprotein; Golgi apparatus; Hydrolase;
KW Metal-binding; 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
