ARSD_HUMAN
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 03-AUG-2022, entry version 169.
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; 2.
DR STRING; 9606.ENSP00000370546; -.
DR GlyConnect; 1017; 5 N-Linked glycans (2 sites).
DR GlyGen; P51689; 4 sites, 4 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P51689; -.
DR PhosphoSitePlus; P51689; -.
DR BioMuta; ARSD; -.
DR DMDM; 212276422; -.
DR EPD; P51689; -.
DR jPOST; P51689; -.
DR MassIVE; P51689; -.
DR MaxQB; P51689; -.
DR PaxDb; P51689; -.
DR PeptideAtlas; P51689; -.
DR PRIDE; P51689; -.
DR ProteomicsDB; 56374; -. [P51689-1]
DR ProteomicsDB; 56375; -. [P51689-2]
DR ProteomicsDB; 56376; -. [P51689-3]
DR Antibodypedia; 441; 166 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 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; RNADHPF; -.
DR PhylomeDB; P51689; -.
DR TreeFam; TF314186; -.
DR PathwayCommons; P51689; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-1663150; The activation of arylsulfatases.
DR BioGRID-ORCS; 414; 9 hits in 691 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 182 other tissues.
DR ExpressionAtlas; P51689; baseline and differential.
DR Genevisible; P51689; HS.
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; 3.40.720.10; -; 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; 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
