ID SULF2_HUMAN Reviewed; 870 AA.
AC Q8IWU5; E1P5U6; Q5JYE1; Q6UX86; Q96SG2; Q9H1H0; Q9UJR3; Q9ULH3;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 27-MAR-2024, entry version 175.
DE RecName: Full=Extracellular sulfatase Sulf-2;
DE Short=hSulf-2;
DE AltName: Full=Arylsulfatase;
DE EC=3.1.6.1 {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513, ECO:0000269|PubMed:35294879};
DE AltName: Full=N-acetylglucosamine-6-sulfatase;
DE EC=3.1.6.14 {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513, ECO:0000269|PubMed:35294879};
DE Contains:
DE RecName: Full=Extracellular sulfatase Sulf-2 secreted form {ECO:0000303|PubMed:12368295, ECO:0000303|PubMed:30788513};
DE Flags: Precursor;
GN Name=SULF2; Synonyms=KIAA1247; ORFNames=UNQ559/PRO1120;
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), MUTAGENESIS OF 88-CYS-CYS-89,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PROTEOLYTIC
RP CLEAVAGE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Lung;
RX PubMed=12368295; DOI=10.1074/jbc.m205131200;
RA Morimoto-Tomita M., Uchimura K., Werb Z., Hemmerich S., Rosen S.D.;
RT "Cloning and characterization of two extracellular heparin-degrading
RT endosulfatases in mice and humans.";
RL J. Biol. Chem. 277:49175-49185(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-76.
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal skin;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 527-870 (ISOFORM 1).
RA Stavrides G.S., Huckle E.J., Deloukas P.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-198.
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).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, CLEAVAGE SITE, REGION
RP CATALYTIC DOMAIN, REGION HYDROPHILIC DOMAIN, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 180-LYS--LYS-182 AND 402-LYS--LYS-404.
RX PubMed=30788513; DOI=10.1007/s00018-019-03027-2;
RA Seffouh A., El Masri R., Makshakova O., Gout E., Hassoun Z.E.O.,
RA Andrieu J.P., Lortat-Jacob H., Vives R.R.;
RT "Expression and purification of recombinant extracellular sulfatase HSulf-2
RT allows deciphering of enzyme sub-domain coordinated role for the binding
RT and 6-O-desulfation of heparan sulfate.";
RL Cell. Mol. Life Sci. 76:1807-1819(2019).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP AND GLYCOSYLATION AT SER-583.
RX PubMed=35294879; DOI=10.1016/j.celrep.2022.110516;
RA El Masri R., Seffouh A., Roelants C., Seffouh I., Gout E., Perard J.,
RA Dalonneau F., Nishitsuji K., Noborn F., Nikpour M., Larson G., Cretinon Y.,
RA Friedel-Arboleas M., Uchimura K., Daniel R., Lortat-Jacob H., Filhol O.,
RA Vives R.R.;
RT "Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate
RT chain that modulates its enzyme activity.";
RL Cell Rep. 38:110516-110516(2022).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-531 AND ASN-573.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Exhibits arylsulfatase activity and highly specific
CC endoglucosamine-6-sulfatase activity (PubMed:12368295, PubMed:30788513,
CC PubMed:35294879). It can remove sulfate from the C-6 position of
CC glucosamine within specific subregions of intact heparin
CC (PubMed:12368295, PubMed:30788513, PubMed:35294879).
CC {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513,
CC ECO:0000269|PubMed:35294879}.
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:12368295, ECO:0000269|PubMed:30788513,
CC ECO:0000269|PubMed:35294879};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 6-sulfate groups of the N-acetyl-D-
CC glucosamine 6-sulfate units of heparan sulfate and keratan sulfate.;
CC EC=3.1.6.14; Evidence={ECO:0000269|PubMed:12368295,
CC ECO:0000269|PubMed:30788513, ECO:0000269|PubMed:35294879};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-8.0. for arylsulfatase activity.
CC {ECO:0000269|PubMed:12368295};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8VI60}. Golgi apparatus, Golgi stack
CC {ECO:0000250|UniProtKB:Q8VI60}. Cell surface
CC {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:35294879}.
CC -!- SUBCELLULAR LOCATION: [Extracellular sulfatase Sulf-2 secreted form]:
CC Secreted {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513,
CC ECO:0000269|PubMed:35294879}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IWU5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWU5-2; Sequence=VSP_013362;
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in the ovary, skeletal
CC muscle, stomach, brain, uterus, heart, kidney and placenta.
CC {ECO:0000269|PubMed:12368295}.
CC -!- PTM: Processing by furin produces a secreted form.
CC {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513,
CC ECO:0000269|PubMed:35294879}.
CC -!- PTM: Glycosylation at Ser-583 negatively regulates its N-
CC acetylglucosamine-6-sulfatase and arylsulfatase activities.
CC {ECO:0000269|PubMed:35294879}.
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 -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing acceptor splice
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20962.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA86561.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB61349.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY101176; AAM76861.1; -; mRNA.
DR EMBL; AB033073; BAA86561.2; ALT_INIT; mRNA.
DR EMBL; AY358461; AAQ88826.1; -; mRNA.
DR EMBL; CR749319; CAH18174.1; -; mRNA.
DR EMBL; AL354813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL034418; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75690.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75693.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75694.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75695.1; -; Genomic_DNA.
DR EMBL; BC020962; AAH20962.1; ALT_INIT; mRNA.
DR EMBL; BC110539; AAI10540.1; -; mRNA.
DR EMBL; AL133001; CAB61349.1; ALT_INIT; mRNA.
DR CCDS; CCDS13408.1; -. [Q8IWU5-1]
DR CCDS; CCDS13409.2; -. [Q8IWU5-2]
DR RefSeq; NP_001155313.1; NM_001161841.1. [Q8IWU5-1]
DR RefSeq; NP_061325.1; NM_018837.3. [Q8IWU5-1]
DR RefSeq; NP_940998.2; NM_198596.2. [Q8IWU5-2]
DR RefSeq; XP_005260515.1; XM_005260458.2.
DR RefSeq; XP_006723893.1; XM_006723830.1.
DR RefSeq; XP_016883444.1; XM_017027955.1.
DR AlphaFoldDB; Q8IWU5; -.
DR SMR; Q8IWU5; -.
DR BioGRID; 121010; 124.
DR IntAct; Q8IWU5; 21.
DR MINT; Q8IWU5; -.
DR STRING; 9606.ENSP00000353007; -.
DR GlyConnect; 1232; 6 N-Linked glycans (4 sites).
DR GlyCosmos; Q8IWU5; 12 sites, 6 glycans.
DR GlyGen; Q8IWU5; 13 sites, 14 N-linked glycans (5 sites).
DR iPTMnet; Q8IWU5; -.
DR PhosphoSitePlus; Q8IWU5; -.
DR BioMuta; SULF2; -.
DR DMDM; 33112446; -.
DR EPD; Q8IWU5; -.
DR jPOST; Q8IWU5; -.
DR MassIVE; Q8IWU5; -.
DR MaxQB; Q8IWU5; -.
DR PaxDb; 9606-ENSP00000353007; -.
DR PeptideAtlas; Q8IWU5; -.
DR ProteomicsDB; 70897; -. [Q8IWU5-1]
DR ProteomicsDB; 70898; -. [Q8IWU5-2]
DR Pumba; Q8IWU5; -.
DR TopDownProteomics; Q8IWU5-2; -. [Q8IWU5-2]
DR Antibodypedia; 1101; 356 antibodies from 33 providers.
DR DNASU; 55959; -.
DR Ensembl; ENST00000359930.8; ENSP00000353007.4; ENSG00000196562.16. [Q8IWU5-1]
DR Ensembl; ENST00000467815.5; ENSP00000418442.1; ENSG00000196562.16. [Q8IWU5-2]
DR Ensembl; ENST00000484875.5; ENSP00000418290.1; ENSG00000196562.16. [Q8IWU5-1]
DR Ensembl; ENST00000688720.1; ENSP00000508753.1; ENSG00000196562.16. [Q8IWU5-1]
DR GeneID; 55959; -.
DR KEGG; hsa:55959; -.
DR MANE-Select; ENST00000688720.1; ENSP00000508753.1; NM_001387048.1; NP_001373977.1.
DR UCSC; uc002xto.4; human. [Q8IWU5-1]
DR AGR; HGNC:20392; -.
DR CTD; 55959; -.
DR DisGeNET; 55959; -.
DR GeneCards; SULF2; -.
DR HGNC; HGNC:20392; SULF2.
DR HPA; ENSG00000196562; Low tissue specificity.
DR MIM; 610013; gene.
DR neXtProt; NX_Q8IWU5; -.
DR OpenTargets; ENSG00000196562; -.
DR PharmGKB; PA134902131; -.
DR VEuPathDB; HostDB:ENSG00000196562; -.
DR eggNOG; KOG3731; Eukaryota.
DR GeneTree; ENSGT00940000159151; -.
DR HOGENOM; CLU_006332_2_0_1; -.
DR InParanoid; Q8IWU5; -.
DR OMA; GEACACD; -.
DR OrthoDB; 1365192at2759; -.
DR PhylomeDB; Q8IWU5; -.
DR TreeFam; TF313545; -.
DR PathwayCommons; Q8IWU5; -.
DR SignaLink; Q8IWU5; -.
DR BioGRID-ORCS; 55959; 11 hits in 1157 CRISPR screens.
DR ChiTaRS; SULF2; human.
DR GeneWiki; SULF2; -.
DR GenomeRNAi; 55959; -.
DR Pharos; Q8IWU5; Tbio.
DR PRO; PR:Q8IWU5; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8IWU5; Protein.
DR Bgee; ENSG00000196562; Expressed in decidua and 185 other cell types or tissues.
DR ExpressionAtlas; Q8IWU5; baseline and differential.
DR Genevisible; Q8IWU5; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IMP:UniProtKB.
DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004065; F:arylsulfatase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005539; F:glycosaminoglycan binding; IBA:GO_Central.
DR GO; GO:0008449; F:N-acetylglucosamine-6-sulfatase activity; IDA:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0002063; P:chondrocyte development; ISS:UniProtKB.
DR GO; GO:0048706; P:embryonic skeletal system development; ISS:UniProtKB.
DR GO; GO:0014846; P:esophagus smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISS:UniProtKB.
DR GO; GO:0003094; P:glomerular filtration; ISS:UniProtKB.
DR GO; GO:0030201; P:heparan sulfate proteoglycan metabolic process; IDA:UniProtKB.
DR GO; GO:0060384; P:innervation; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:BHF-UCL.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:2000345; P:regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR CDD; cd16147; G6S; 1.
DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR014615; Extracellular_sulfatase.
DR InterPro; IPR024609; Extracellular_sulfatase_C.
DR InterPro; IPR024607; Sulfatase_CS.
DR InterPro; IPR000917; Sulfatase_N.
DR PANTHER; PTHR43108:SF4; EXTRACELLULAR SULFATASE SULF-2; 1.
DR PANTHER; PTHR43108; N-ACETYLGLUCOSAMINE-6-SULFATASE FAMILY MEMBER; 1.
DR Pfam; PF12548; DUF3740; 1.
DR Pfam; PF00884; Sulfatase; 1.
DR PIRSF; PIRSF036665; Sulf1; 1.
DR SUPFAM; SSF53649; Alkaline phosphatase-like; 2.
DR PROSITE; PS00523; SULFATASE_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Hydrolase; Metal-binding; Proteoglycan;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..870
FT /note="Extracellular sulfatase Sulf-2"
FT /id="PRO_0000033440"
FT CHAIN 539..870
FT /note="Extracellular sulfatase Sulf-2 secreted form"
FT /evidence="ECO:0000269|PubMed:30788513"
FT /id="PRO_0000457759"
FT REGION 1..415
FT /note="Catalytic domain; necessary for arylsulfatase
FT activity"
FT /evidence="ECO:0000269|PubMed:30788513"
FT REGION 416..715
FT /note="Hydrophilic domain; necessary for endoglucosamine-6-
FT sulfatase activity"
FT /evidence="ECO:0000269|PubMed:30788513"
FT REGION 560..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..580
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 88
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 52
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 53
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 88
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /note="via 3-oxoalanine"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 317
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 318
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT SITE 538..539
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000269|PubMed:30788513"
FT MOD_RES 88
FT /note="3-oxoalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 583
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000269|PubMed:35294879"
FT CARBOHYD 608
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 754
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 764
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 832..834
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013362"
FT VARIANT 76
FT /note="A -> T (in dbSNP:rs56218501)"
FT /evidence="ECO:0000269|PubMed:10574462"
FT /id="VAR_061885"
FT VARIANT 531
FT /note="Y -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036494"
FT VARIANT 573
FT /note="D -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036495"
FT VARIANT 674
FT /note="R -> H (in dbSNP:rs10048853)"
FT /id="VAR_052518"
FT MUTAGEN 88..89
FT /note="CC->AA: Loss of arylsulfatase activity."
FT /evidence="ECO:0000269|PubMed:12368295"
FT MUTAGEN 180..182
FT /note="KEK->AEA: No effect on N-acetylglucosamine-6-
FT sulfatase activity. Significant loss of N-
FT acetylglucosamine-6-sulfatase activity; when associated
FT with 402-A--A-404."
FT /evidence="ECO:0000269|PubMed:30788513"
FT MUTAGEN 402..404
FT /note="KKK->AAA: No effect on N-acetylglucosamine-6-
FT sulfatase activity. Significant loss of N-
FT acetylglucosamine-6-sulfatase activity; when associated
FT with 180-A--A-182."
FT /evidence="ECO:0000269|PubMed:30788513"
SQ SEQUENCE 870 AA; 100455 MW; 74B1069CE2774D73 CRC64;
MGPPSLVLCL LSATVFSLLG GSSAFLSHHR LKGRFQRDRR NIRPNIILVL TDDQDVELGS
MQVMNKTRRI MEQGGAHFIN AFVTTPMCCP SRSSILTGKY VHNHNTYTNN ENCSSPSWQA
QHESRTFAVY LNSTGYRTAF FGKYLNEYNG SYVPPGWKEW VGLLKNSRFY NYTLCRNGVK
EKHGSDYSKD YLTDLITNDS VSFFRTSKKM YPHRPVLMVI SHAAPHGPED SAPQYSRLFP
NASQHITPSY NYAPNPDKHW IMRYTGPMKP IHMEFTNMLQ RKRLQTLMSV DDSMETIYNM
LVETGELDNT YIVYTADHGY HIGQFGLVKG KSMPYEFDIR VPFYVRGPNV EAGCLNPHIV
LNIDLAPTIL DIAGLDIPAD MDGKSILKLL DTERPVNRFH LKKKMRVWRD SFLVERGKLL
HKRDNDKVDA QEENFLPKYQ RVKDLCQRAE YQTACEQLGQ KWQCVEDATG KLKLHKCKGP
MRLGGSRALS NLVPKYYGQG SEACTCDSGD YKLSLAGRRK KLFKKKYKAS YVRSRSIRSV
AIEVDGRVYH VGLGDAAQPR NLTKRHWPGA PEDQDDKDGG DFSGTGGLPD YSAANPIKVT
HRCYILENDT VQCDLDLYKS LQAWKDHKLH IDHEIETLQN KIKNLREVRG HLKKKRPEEC
DCHKISYHTQ HKGRLKHRGS SLHPFRKGLQ EKDKVWLLRE QKRKKKLRKL LKRLQNNDTC
SMPGLTCFTH DNQHWQTAPF WTLGPFCACT SANNNTYWCM RTINETHNFL FCEFATGFLE
YFDLNTDPYQ LMNAVNTLDR DVLNQLHVQL MELRSCKGYK QCNPRTRNMD LGLKDGGSYE
QYRQFQRRKW PEMKRPSSKS LGQLWEGWEG
//
