ID   ARSF_HUMAN              Reviewed;         590 AA.
AC   P54793; Q8TCC5;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 4.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Arylsulfatase F;
DE            Short=ASF;
DE            EC=3.1.6.1 {ECO:0000269|PubMed:9192838};
DE   Flags: Precursor;
GN   Name=ARSF;
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], VARIANT TYR-527, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC   TISSUE=Fetal brain;
RX   PubMed=9192838; DOI=10.1006/geno.1997.4716;
RA   Puca A.A., Zollo M., Repetto M., Andolfi G., Guffanti A., Simon G.,
RA   Ballabio A., Franco B.;
RT   "Identification by shotgun sequencing, genomic organization, and functional
RT   analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.";
RL   Genomics 42:192-199(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-527.
RC   TISSUE=Kidney;
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 [MRNA] OF 369-422.
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).
CC   -!- FUNCTION: Exhibits arylsulfatase activity towards the artificial
CC       substrate 4-methylumbelliferyl sulfate. {ECO:0000269|PubMed:9192838}.
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:9192838};
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: Not inhibited by DHEAS or warfarin.
CC       {ECO:0000269|PubMed:9192838}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 8. {ECO:0000269|PubMed:9192838};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
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   -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
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DR   EMBL; X97868; CAA66462.1; -; mRNA.
DR   EMBL; AC112653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC022389; AAH22389.1; -; mRNA.
DR   CCDS; CCDS14123.1; -.
DR   PIR; A56217; A56217.
DR   RefSeq; NP_001188467.1; NM_001201538.1.
DR   RefSeq; NP_001188468.1; NM_001201539.1.
DR   RefSeq; NP_004033.2; NM_004042.4.
DR   AlphaFoldDB; P54793; -.
DR   SMR; P54793; -.
DR   BioGRID; 106909; 77.
DR   IntAct; P54793; 3.
DR   STRING; 9606.ENSP00000370519; -.
DR   GlyCosmos; P54793; 3 sites, No reported glycans.
DR   GlyGen; P54793; 3 sites.
DR   iPTMnet; P54793; -.
DR   PhosphoSitePlus; P54793; -.
DR   BioMuta; ARSF; -.
DR   DMDM; 259016386; -.
DR   jPOST; P54793; -.
DR   MassIVE; P54793; -.
DR   PaxDb; 9606-ENSP00000370519; -.
DR   PeptideAtlas; P54793; -.
DR   ProteomicsDB; 56720; -.
DR   Antibodypedia; 406; 218 antibodies from 22 providers.
DR   DNASU; 416; -.
DR   Ensembl; ENST00000359361.2; ENSP00000352319.2; ENSG00000062096.15.
DR   Ensembl; ENST00000381127.6; ENSP00000370519.1; ENSG00000062096.15.
DR   GeneID; 416; -.
DR   KEGG; hsa:416; -.
DR   MANE-Select; ENST00000381127.6; ENSP00000370519.1; NM_001201539.2; NP_001188468.1.
DR   UCSC; uc004cre.3; human.
DR   AGR; HGNC:721; -.
DR   CTD; 416; -.
DR   DisGeNET; 416; -.
DR   GeneCards; ARSF; -.
DR   HGNC; HGNC:721; ARSF.
DR   HPA; ENSG00000062096; Tissue enhanced (brain, kidney, skin).
DR   MIM; 300003; gene.
DR   neXtProt; NX_P54793; -.
DR   OpenTargets; ENSG00000062096; -.
DR   PharmGKB; PA25012; -.
DR   VEuPathDB; HostDB:ENSG00000062096; -.
DR   eggNOG; KOG3867; Eukaryota.
DR   GeneTree; ENSGT00940000163432; -.
DR   HOGENOM; CLU_006332_13_4_1; -.
DR   InParanoid; P54793; -.
DR   OMA; HSQRGGW; -.
DR   OrthoDB; 2913702at2759; -.
DR   PhylomeDB; P54793; -.
DR   TreeFam; TF314186; -.
DR   PathwayCommons; P54793; -.
DR   Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR   Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR   SignaLink; P54793; -.
DR   BioGRID-ORCS; 416; 21 hits in 768 CRISPR screens.
DR   ChiTaRS; ARSF; human.
DR   GenomeRNAi; 416; -.
DR   Pharos; P54793; Tbio.
DR   PRO; PR:P54793; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P54793; Protein.
DR   Bgee; ENSG00000062096; Expressed in mammalian vulva and 71 other cell types or tissues.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0004065; F:arylsulfatase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IPR024607; Sulfatase_CS.
DR   InterPro; IPR000917; Sulfatase_N.
DR   PANTHER; PTHR42693:SF2; ARYLSULFATASE F; 1.
DR   PANTHER; PTHR42693; ARYLSULFATASE FAMILY MEMBER; 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.
DR   Genevisible; P54793; HS.
PE   1: Evidence at protein level;
KW   Calcium; Glycoprotein; Hydrolase; Metal-binding; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..590
FT                   /note="Arylsulfatase F"
FT                   /id="PRO_0000033427"
FT   ACT_SITE        78
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   ACT_SITE        139
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         38
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         39
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         78
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         293
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         345
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         346
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         370
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   MOD_RES         78
FT                   /note="3-oxoalanine (Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CARBOHYD        50
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        117
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         527
FT                   /note="H -> Y (in dbSNP:rs1052638)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:9192838"
FT                   /id="VAR_058846"
FT   CONFLICT        20..29
FT                   /note="CQAHRVHDDK -> WPGHTGCMTTR (in Ref. 1; CAA66462)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   590 AA;  65940 MW;  EA9B7289040AE79A CRC64;
     MRPRRPLVFM SLVCALLNTC QAHRVHDDKP NIVLIMVDDL GIGDLGCYGN DTMRTPHIDR
     LAREGVRLTQ HISAASLCSP SRSAFLTGRY PIRSGMVSSG NRRVIQNLAV PAGLPLNETT
     LAALLKKQGY STGLIGKWHQ GLNCDSRSDQ CHHPYNYGFD YYYGMPFTLV DSCWPDPSRN
     TELAFESQLW LCVQLVAIAI LTLTFGKLSG WVSVPWLLIF SMILFIFLLG YAWFSSHTSP
     LYWDCLLMRG HEITEQPMKA ERAGSIMVKE AISFLERHSK ETFLLFFSFL HVHTPLPTTD
     DFTGTSKHGL YGDNVEEMDS MVGKILDAID DFGLRNNTLV YFTSDHGGHL EARRGHAQLG
     GWNGIYKGGK GMGGWEGGIR VPGIVRWPGK VPAGRLIKEP TSLMDILPTV ASVSGGSLPQ
     DRVIDGRDLM PLLQGNVRHS EHEFLFHYCG SYLHAVRWIP KDDSGSVWKA HYVTPVFQPP
     ASGGCYVTSL CRCFGEQVTY HNPPLLFDLS RDPSESTPLT PATEPLHDFV IKKVANALKE
     HQETIVPVTY QLSELNQGRT WLKPCCGVFP FCLCDKEEEV SQPRGPNEKR
//