ARSI_HUMAN
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 03-AUG-2022, entry version 142.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q5FYB1; 4 sites.
DR iPTMnet; Q5FYB1; -.
DR PhosphoSitePlus; Q5FYB1; -.
DR BioMuta; ARSI; -.
DR DMDM; 74722581; -.
DR MassIVE; Q5FYB1; -.
DR PaxDb; Q5FYB1; -.
DR PeptideAtlas; Q5FYB1; -.
DR PRIDE; Q5FYB1; -.
DR Antibodypedia; 50254; 188 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 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; WGPWASE; -.
DR OrthoDB; 515367at2759; -.
DR PhylomeDB; Q5FYB1; -.
DR TreeFam; TF314186; -.
DR PathwayCommons; Q5FYB1; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR SignaLink; Q5FYB1; -.
DR BioGRID-ORCS; 340075; 11 hits in 1061 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 101 other tissues.
DR ExpressionAtlas; Q5FYB1; baseline and differential.
DR Genevisible; Q5FYB1; HS.
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 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; 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
