ID   ARSI_HUMAN              Reviewed;         569 AA.
AC   Q5FYB1; A1L3B0; B3KV22; B7XD03;
DT   11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2005, sequence version 1.
DT   29-MAY-2024, entry version 151.
DE   RecName: Full=Arylsulfatase I;
DE            Short=ASI;
DE            EC=3.1.6.-;
DE   Flags: Precursor;
GN   Name=ARSI;
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] (ISOFORM 1).
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] (ISOFORM 1), TISSUE SPECIFICITY, AND ABSENCE OF
RP   ARYLSULFATASE ACTIVITY.
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 [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP   MUTAGENESIS OF CYS-93, OXOALANINE AT CYS-93, AND TISSUE SPECIFICITY.
RX   PubMed=19262745;
RA   Oshikawa M., Usami R., Kato S.;
RT   "Characterization of the arylsulfatase I (ARSI) gene preferentially
RT   expressed in the human retinal pigment epithelium cell line ARPE-19.";
RL   Mol. Vis. 15:482-494(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lung;
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] (ISOFORM 1).
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).
CC   -!- FUNCTION: Displays arylsulfatase activity at neutral pH, when co-
CC       expressed with SUMF1; arylsulfatase activity is measured in the
CC       secretion medium of retinal cell line, but no activity is recorded when
CC       measured in cell extracts (PubMed:19262745). Lacks arylsulfatase
CC       activity (PubMed:16500042). {ECO:0000269|PubMed:16500042,
CC       ECO:0000269|PubMed:19262745}.
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   -!- INTERACTION:
CC       Q5FYB1; Q6A162: KRT40; NbExp=3; IntAct=EBI-10243706, EBI-10171697;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19262745}.
CC       Endoplasmic reticulum {ECO:0000269|PubMed:19262745}. Note=Localized in
CC       the intracellular granular structures.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q5FYB1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5FYB1-2; Sequence=VSP_036022;
CC   -!- TISSUE SPECIFICITY: Expressed in placenta, in embryonic stem cells,
CC       fetal eyes and lens. {ECO:0000269|PubMed:16500042,
CC       ECO:0000269|PubMed:19262745}.
CC   -!- PTM: The oxidation of Cys-93 residue to 3-oxoalanine (also known as
CC       C(alpha)-formylglycine) by SUMF1/Sulfatase-modifying factor 1, seems
CC       critical for catalytic activity. {ECO:0000269|PubMed:19262745}.
CC   -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR   EMBL; AY875937; AAW66665.1; -; mRNA.
DR   EMBL; AB448735; BAH11166.1; -; mRNA.
DR   EMBL; AK122641; BAG53634.1; -; mRNA.
DR   EMBL; BC129995; AAI29996.1; -; mRNA.
DR   EMBL; BC129996; AAI29997.1; -; mRNA.
DR   CCDS; CCDS34275.1; -. [Q5FYB1-1]
DR   RefSeq; NP_001012301.1; NM_001012301.3. [Q5FYB1-1]
DR   AlphaFoldDB; Q5FYB1; -.
DR   SMR; Q5FYB1; -.
DR   BioGRID; 130992; 12.
DR   IntAct; Q5FYB1; 4.
DR   STRING; 9606.ENSP00000333395; -.
DR   GlyCosmos; Q5FYB1; 4 sites, No reported glycans.
DR   GlyGen; Q5FYB1; 4 sites.
DR   iPTMnet; Q5FYB1; -.
DR   PhosphoSitePlus; Q5FYB1; -.
DR   BioMuta; ARSI; -.
DR   DMDM; 74722581; -.
DR   MassIVE; Q5FYB1; -.
DR   PaxDb; 9606-ENSP00000333395; -.
DR   PeptideAtlas; Q5FYB1; -.
DR   Antibodypedia; 50254; 207 antibodies from 26 providers.
DR   DNASU; 340075; -.
DR   Ensembl; ENST00000328668.8; ENSP00000333395.7; ENSG00000183876.9. [Q5FYB1-1]
DR   Ensembl; ENST00000515301.2; ENSP00000426879.2; ENSG00000183876.9. [Q5FYB1-2]
DR   GeneID; 340075; -.
DR   KEGG; hsa:340075; -.
DR   MANE-Select; ENST00000328668.8; ENSP00000333395.7; NM_001012301.4; NP_001012301.1.
DR   UCSC; uc003lrv.3; human. [Q5FYB1-1]
DR   AGR; HGNC:32521; -.
DR   CTD; 340075; -.
DR   DisGeNET; 340075; -.
DR   GeneCards; ARSI; -.
DR   HGNC; HGNC:32521; ARSI.
DR   HPA; ENSG00000183876; Low tissue specificity.
DR   MalaCards; ARSI; -.
DR   MIM; 610009; gene.
DR   neXtProt; NX_Q5FYB1; -.
DR   OpenTargets; ENSG00000183876; -.
DR   Orphanet; 401815; Autosomal recessive spastic paraplegia type 66.
DR   PharmGKB; PA143485309; -.
DR   VEuPathDB; HostDB:ENSG00000183876; -.
DR   eggNOG; KOG3867; Eukaryota.
DR   GeneTree; ENSGT00940000157656; -.
DR   HOGENOM; CLU_006332_10_1_1; -.
DR   InParanoid; Q5FYB1; -.
DR   OMA; WDWMKPS; -.
DR   OrthoDB; 2913702at2759; -.
DR   PhylomeDB; Q5FYB1; -.
DR   TreeFam; TF314186; -.
DR   PathwayCommons; Q5FYB1; -.
DR   Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR   Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR   SignaLink; Q5FYB1; -.
DR   BioGRID-ORCS; 340075; 13 hits in 1139 CRISPR screens.
DR   GenomeRNAi; 340075; -.
DR   Pharos; Q5FYB1; Tbio.
DR   PRO; PR:Q5FYB1; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q5FYB1; Protein.
DR   Bgee; ENSG00000183876; Expressed in stromal cell of endometrium and 102 other cell types or tissues.
DR   ExpressionAtlas; Q5FYB1; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004065; F:arylsulfatase activity; TAS:HGNC-UCL.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   CDD; cd16029; 4-S; 1.
DR   Gene3D; 3.30.1120.10; -; 1.
DR   Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR   InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR   InterPro; IPR047115; ARSB.
DR   InterPro; IPR024607; Sulfatase_CS.
DR   InterPro; IPR000917; Sulfatase_N.
DR   PANTHER; PTHR10342; ARYLSULFATASE; 1.
DR   PANTHER; PTHR10342:SF68; ARYLSULFATASE I; 1.
DR   Pfam; PF00884; Sulfatase; 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   Alternative splicing; Calcium; Endoplasmic reticulum; Glycoprotein;
KW   Hydrolase; Metal-binding; Oxidation; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..569
FT                   /note="Arylsulfatase I"
FT                   /id="PRO_0000042216"
FT   REGION          510..539
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        93
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000269|PubMed:19262745"
FT   ACT_SITE        149
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         55
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         56
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         93
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /note="via 3-oxoalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         147
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         239
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         297
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         298
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         315
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   MOD_RES         93
FT                   /note="3-oxoalanine (Cys)"
FT                   /evidence="ECO:0000269|PubMed:19262745"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        288
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        466
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        496
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..143
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036022"
FT   MUTAGEN         93
FT                   /note="C->S: No arylsulfatase activity in the media of
FT                   retinal epithelium cell."
FT                   /evidence="ECO:0000269|PubMed:19262745"
FT   CONFLICT        171
FT                   /note="L -> F (in Ref. 4; BAG53634)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        211
FT                   /note="L -> P (in Ref. 4; BAG53634)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   569 AA;  64030 MW;  D2F33EDD33ED211C CRC64;
     MHTLTGFSLV SLLSFGYLSW DWAKPSFVAD GPGEAGEQPS AAPPQPPHII FILTDDQGYH
     DVGYHGSDIE TPTLDRLAAK GVKLENYYIQ PICTPSRSQL LTGRYQIHTG LQHSIIRPQQ
     PNCLPLDQVT LPQKLQEAGY STHMVGKWHL GFYRKECLPT RRGFDTFLGS LTGNVDYYTY
     DNCDGPGVCG FDLHEGENVA WGLSGQYSTM LYAQRASHIL ASHSPQRPLF LYVAFQAVHT
     PLQSPREYLY RYRTMGNVAR RKYAAMVTCM DEAVRNITWA LKRYGFYNNS VIIFSSDNGG
     QTFSGGSNWP LRGRKGTYWE GGVRGLGFVH SPLLKRKQRT SRALMHITDW YPTLVGLAGG
     TTSAADGLDG YDVWPAISEG RASPRTEILH NIDPLYNHAQ HGSLEGGFGI WNTAVQAAIR
     VGEWKLLTGD PGYGDWIPPQ TLATFPGSWW NLERMASVRQ AVWLFNISAD PYEREDLAGQ
     RPDVVRTLLA RLAEYNRTAI PVRYPAENPR AHPDFNGGAW GPWASDEEEE EEEGRARSFS
     RGRRKKKCKI CKLRSFFRKL NTRLMSQRI
//