ID   ARSD_HUMAN              Reviewed;         593 AA.
AC   P51689; Q9UHJ8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   04-NOV-2008, sequence version 2.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Arylsulfatase D;
DE            Short=ASD;
DE            EC=3.1.6.-;
DE   Flags: Precursor;
GN   Name=ARSD;
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 3).
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 [MRNA] (ISOFORM 2), AND VARIANT CYS-224.
RC   TISSUE=Testis;
RX   PubMed=11177574; DOI=10.1089/104454900750058125;
RA   Urbitsch P., Salzer M.J., Hirschmann P., Vogt P.H.;
RT   "Arylsulfatase D gene in Xp22.3 encodes two protein isoforms.";
RL   DNA Cell Biol. 19:765-773(2000).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
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   [5]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-347.
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).
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   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P51689-1; Sequence=Displayed;
CC       Name=2; Synonyms=Beta;
CC         IsoId=P51689-2; Sequence=VSP_015798, VSP_015799;
CC       Name=3; Synonyms=Alpha;
CC         IsoId=P51689-3; Sequence=VSP_035667;
CC   -!- TISSUE SPECIFICITY: Expressed in the pancreas, kidney, liver, lung,
CC       placenta, brain and heart.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA58555.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; X83572; CAA58555.1; ALT_FRAME; mRNA.
DR   EMBL; AF160499; AAF22253.1; -; mRNA.
DR   EMBL; AC005295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC020229; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS35196.1; -. [P51689-1]
DR   PIR; I37186; I37186.
DR   RefSeq; NP_001660.2; NM_001669.3. [P51689-1]
DR   RefSeq; NP_033667.2; NM_009589.3.
DR   AlphaFoldDB; P51689; -.
DR   SMR; P51689; -.
DR   BioGRID; 106907; 3.
DR   STRING; 9606.ENSP00000370546; -.
DR   GlyConnect; 1017; 5 N-Linked glycans (2 sites).
DR   GlyCosmos; P51689; 3 sites, 4 glycans.
DR   GlyGen; P51689; 4 sites, 4 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; P51689; -.
DR   PhosphoSitePlus; P51689; -.
DR   SwissPalm; P51689; -.
DR   BioMuta; ARSD; -.
DR   DMDM; 212276422; -.
DR   EPD; P51689; -.
DR   jPOST; P51689; -.
DR   MassIVE; P51689; -.
DR   MaxQB; P51689; -.
DR   PaxDb; 9606-ENSP00000370546; -.
DR   PeptideAtlas; P51689; -.
DR   ProteomicsDB; 56374; -. [P51689-1]
DR   ProteomicsDB; 56375; -. [P51689-2]
DR   ProteomicsDB; 56376; -. [P51689-3]
DR   Antibodypedia; 441; 180 antibodies from 30 providers.
DR   DNASU; 414; -.
DR   Ensembl; ENST00000381154.6; ENSP00000370546.1; ENSG00000006756.16. [P51689-1]
DR   GeneID; 414; -.
DR   KEGG; hsa:414; -.
DR   MANE-Select; ENST00000381154.6; ENSP00000370546.1; NM_001669.4; NP_001660.2.
DR   UCSC; uc004cqy.4; human. [P51689-1]
DR   AGR; HGNC:717; -.
DR   CTD; 414; -.
DR   DisGeNET; 414; -.
DR   GeneCards; ARSD; -.
DR   HGNC; HGNC:717; ARSD.
DR   HPA; ENSG00000006756; Low tissue specificity.
DR   MIM; 300002; gene.
DR   neXtProt; NX_P51689; -.
DR   OpenTargets; ENSG00000006756; -.
DR   PharmGKB; PA25008; -.
DR   VEuPathDB; HostDB:ENSG00000006756; -.
DR   eggNOG; KOG3867; Eukaryota.
DR   GeneTree; ENSGT00940000161140; -.
DR   HOGENOM; CLU_006332_13_4_1; -.
DR   InParanoid; P51689; -.
DR   OMA; KLFNLRM; -.
DR   OrthoDB; 2913702at2759; -.
DR   PhylomeDB; P51689; -.
DR   TreeFam; TF314186; -.
DR   PathwayCommons; P51689; -.
DR   Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR   Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR   BioGRID-ORCS; 414; 9 hits in 767 CRISPR screens.
DR   ChiTaRS; ARSD; human.
DR   GenomeRNAi; 414; -.
DR   Pharos; P51689; Tbio.
DR   PRO; PR:P51689; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P51689; Protein.
DR   Bgee; ENSG00000006756; Expressed in renal medulla and 184 other cell types or tissues.
DR   ExpressionAtlas; P51689; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004065; F:arylsulfatase activity; IBA:GO_Central.
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:SF12; ARYLSULFATASE D; 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; P51689; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Glycoprotein; Hydrolase; Lysosome;
KW   Metal-binding; Reference proteome; Signal.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..593
FT                   /note="Arylsulfatase D"
FT                   /id="PRO_0000033424"
FT   ACT_SITE        89
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   ACT_SITE        150
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         49
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         50
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         89
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /note="via 3-oxoalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         148
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         304
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         356
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         357
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   BINDING         381
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   MOD_RES         89
FT                   /note="3-oxoalanine (Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P15289"
FT   CARBOHYD        61
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        128
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        347
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   VAR_SEQ         334..382
FT                   /note="GKVLNAIEDNGLKNSTFTYFTSDHGGHLEARDGHSQLGGWNGIYKGGKG ->
FT                   ASDFMSSSEVTESEAIKLMFRTMQRRCLPSMAFKKPWRGPVRLQILKRA (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11177574"
FT                   /id="VSP_015798"
FT   VAR_SEQ         383..593
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11177574"
FT                   /id="VSP_015799"
FT   VAR_SEQ         504..593
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:7720070"
FT                   /id="VSP_035667"
FT   VARIANT         224
FT                   /note="S -> C (in dbSNP:rs211653)"
FT                   /evidence="ECO:0000269|PubMed:11177574"
FT                   /id="VAR_052508"
FT   VARIANT         500
FT                   /note="V -> I (in dbSNP:rs2229557)"
FT                   /id="VAR_052509"
FT   VARIANT         564
FT                   /note="M -> T (in dbSNP:rs2228431)"
FT                   /id="VAR_052510"
SQ   SEQUENCE   593 AA;  64860 MW;  982B29D0FCEF9D34 CRC64;
     MRSAARRGRA APAARDSLPV LLFLCLLLKT CEPKTANAFK PNILLIMADD LGTGDLGCYG
     NNTLRTPNID QLAEEGVRLT QHLAAAPLCT PSRAAFLTGR HSFRSGMDAS NGYRALQWNA
     GSGGLPENET TFARILQQHG YATGLIGKWH QGVNCASRGD HCHHPLNHGF DYFYGMPFTL
     TNDCDPGRPP EVDAALRAQL WGYTQFLALG ILTLAAGQTC GFFSVSARAV TGMAGVGCLF
     FISWYSSFGF VRRWNCILMR NHDVTEQPMV LEKTASLMLK EAVSYIERHK HGPFLLFLSL
     LHVHIPLVTT SAFLGKSQHG LYGDNVEEMD WLIGKVLNAI EDNGLKNSTF TYFTSDHGGH
     LEARDGHSQL GGWNGIYKGG KGMGGWEGGI RVPGIFHWPG VLPAGRVIGE PTSLMDVFPT
     VVQLVGGEVP QDRVIDGHSL VPLLQGAEAR SAHEFLFHYC GQHLHAARWH QKDSGSVWKV
     HYTTPQFHPE GAGACYGRGV CPCSGEGVTH HRPPLLFDLS RDPSEARPLT PDSEPLYHAV
     IARVGAAVSE HRQTLSPVPQ QFSMSNILWK PWLQPCCGHF PFCSCHEDGD GTP
//