SULF1_HUMAN
ID SULF1_HUMAN Reviewed; 871 AA.
AC Q8IWU6; Q86YV8; Q8NCA2; Q9UPS5;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Extracellular sulfatase Sulf-1;
DE Short=hSulf-1;
DE EC=3.1.6.-;
DE Flags: Precursor;
GN Name=SULF1; Synonyms=KIAA1077;
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], CHARACTERIZATION, AND MUTAGENESIS OF
RP 87-CYS-CYS-88.
RC TISSUE=Prostate;
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 [MRNA], AND MUTAGENESIS OF 87-CYS-CYS-88.
RX PubMed=12686563; DOI=10.1074/jbc.m302203200;
RA Lai J., Chien J., Staub J., Avula R., Greene E.L., Matthews T.A.,
RA Smith D.I., Kaufmann S.H., Roberts L.R., Shridhar V.;
RT "Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in
RT cancer.";
RL J. Biol. Chem. 278:23107-23117(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-871.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 312-871.
RC TISSUE=Teratocarcinoma;
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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197.
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 -!- FUNCTION: Exhibits arylsulfatase activity and highly specific
CC endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-
CC 6 position of glucosamine within specific subregions of intact heparin.
CC Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits
CC signaling by heparin-dependent growth factors, diminishes
CC proliferation, and facilitates apoptosis in response to exogenous
CC stimulation.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-8.0.;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250}. Golgi
CC apparatus, Golgi stack {ECO:0000250}. Cell surface {ECO:0000250}.
CC Note=Also localized on the cell surface. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in testis, stomach,
CC skeletal muscle, lung, kidney, pancreas, small intestine and colon. It
CC is also detected in normal ovarian surface epithelial cells. Down-
CC regulation seen in ovarian carcinoma cell lines, ovarian cancers,
CC breast, pancreatic, renal and hepatocellular carcinoma cell lines.
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}.
CC -!- SIMILARITY: Belongs to the sulfatase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SULF1ID44378ch8q13.html";
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DR EMBL; AY101175; AAM76860.1; -; mRNA.
DR EMBL; AF545571; AAO33315.1; -; mRNA.
DR EMBL; AB029000; BAA83029.1; -; mRNA.
DR EMBL; AK074873; BAC11258.1; -; mRNA.
DR CCDS; CCDS6204.1; -.
DR RefSeq; NP_001121676.1; NM_001128204.1.
DR RefSeq; NP_001121677.1; NM_001128205.1.
DR RefSeq; NP_001121678.1; NM_001128206.1.
DR RefSeq; NP_055985.2; NM_015170.2.
DR AlphaFoldDB; Q8IWU6; -.
DR SMR; Q8IWU6; -.
DR BioGRID; 116820; 30.
DR IntAct; Q8IWU6; 5.
DR STRING; 9606.ENSP00000260128; -.
DR GlyConnect; 1231; 12 N-Linked glycans (6 sites).
DR GlyGen; Q8IWU6; 10 sites, 10 N-linked glycans (5 sites).
DR iPTMnet; Q8IWU6; -.
DR PhosphoSitePlus; Q8IWU6; -.
DR BioMuta; SULF1; -.
DR DMDM; 33112447; -.
DR jPOST; Q8IWU6; -.
DR MassIVE; Q8IWU6; -.
DR PaxDb; Q8IWU6; -.
DR PeptideAtlas; Q8IWU6; -.
DR PRIDE; Q8IWU6; -.
DR ProteomicsDB; 70899; -.
DR Antibodypedia; 25041; 125 antibodies from 24 providers.
DR DNASU; 23213; -.
DR Ensembl; ENST00000260128.8; ENSP00000260128.4; ENSG00000137573.14.
DR Ensembl; ENST00000402687.9; ENSP00000385704.4; ENSG00000137573.14.
DR Ensembl; ENST00000419716.7; ENSP00000390315.3; ENSG00000137573.14.
DR Ensembl; ENST00000458141.6; ENSP00000403040.2; ENSG00000137573.14.
DR GeneID; 23213; -.
DR KEGG; hsa:23213; -.
DR MANE-Select; ENST00000402687.9; ENSP00000385704.4; NM_001128205.2; NP_001121677.1.
DR UCSC; uc003xyd.3; human.
DR CTD; 23213; -.
DR DisGeNET; 23213; -.
DR GeneCards; SULF1; -.
DR HGNC; HGNC:20391; SULF1.
DR HPA; ENSG00000137573; Tissue enhanced (choroid).
DR MIM; 610012; gene.
DR neXtProt; NX_Q8IWU6; -.
DR OpenTargets; ENSG00000137573; -.
DR PharmGKB; PA134861022; -.
DR VEuPathDB; HostDB:ENSG00000137573; -.
DR eggNOG; KOG3731; Eukaryota.
DR GeneTree; ENSGT00940000157544; -.
DR HOGENOM; CLU_006332_2_0_1; -.
DR InParanoid; Q8IWU6; -.
DR OMA; TAPFWNX; -.
DR OrthoDB; 1273622at2759; -.
DR PhylomeDB; Q8IWU6; -.
DR TreeFam; TF313545; -.
DR PathwayCommons; Q8IWU6; -.
DR SignaLink; Q8IWU6; -.
DR BioGRID-ORCS; 23213; 9 hits in 1070 CRISPR screens.
DR ChiTaRS; SULF1; human.
DR GeneWiki; SULF1; -.
DR GenomeRNAi; 23213; -.
DR Pharos; Q8IWU6; Tbio.
DR PRO; PR:Q8IWU6; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8IWU6; protein.
DR Bgee; ENSG00000137573; Expressed in parietal pleura and 187 other tissues.
DR ExpressionAtlas; Q8IWU6; baseline and differential.
DR Genevisible; Q8IWU6; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060686; P:negative regulation of prostatic bud formation; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
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:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB.
DR Gene3D; 3.40.720.10; -; 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 Pfam; PF12548; DUF3740; 1.
DR Pfam; PF00884; Sulfatase; 1.
DR PIRSF; PIRSF036665; Sulf1; 1.
DR SUPFAM; SSF53649; SSF53649; 2.
DR PROSITE; PS00523; SULFATASE_1; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Calcium; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Hydrolase; Metal-binding; Reference proteome; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..871
FT /note="Extracellular sulfatase Sulf-1"
FT /id="PRO_0000033434"
FT REGION 508..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..607
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 87
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT BINDING 51
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 52
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /note="via 3-oxoalanine"
FT /evidence="ECO:0000250"
FT BINDING 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 87
FT /note="3-oxoalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:P15289"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 773
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 783
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 87..88
FT /note="CC->AA: Loss of arylsulfatase activity and loss of
FT ability to modulate apoptosis."
FT /evidence="ECO:0000269|PubMed:12368295,
FT ECO:0000269|PubMed:12686563"
FT CONFLICT 49
FT /note="L -> P (in Ref. 2; AAO33315)"
FT /evidence="ECO:0000305"
FT CONFLICT 728
FT /note="K -> R (in Ref. 4; BAC11258)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 871 AA; 101027 MW; 9A90ADB280304364 CRC64;
MKYSCCALVL AVLGTELLGS LCSTVRSPRF RGRIQQERKN IRPNIILVLT DDQDVELGSL
QVMNKTRKIM EHGGATFINA FVTTPMCCPS RSSMLTGKYV HNHNVYTNNE NCSSPSWQAM
HEPRTFAVYL NNTGYRTAFF GKYLNEYNGS YIPPGWREWL GLIKNSRFYN YTVCRNGIKE
KHGFDYAKDY FTDLITNESI NYFKMSKRMY PHRPVMMVIS HAAPHGPEDS APQFSKLYPN
ASQHITPSYN YAPNMDKHWI MQYTGPMLPI HMEFTNILQR KRLQTLMSVD DSVERLYNML
VETGELENTY IIYTADHGYH IGQFGLVKGK SMPYDFDIRV PFFIRGPSVE PGSIVPQIVL
NIDLAPTILD IAGLDTPPDV DGKSVLKLLD PEKPGNRFRT NKKAKIWRDT FLVERGKFLR
KKEESSKNIQ QSNHLPKYER VKELCQQARY QTACEQPGQK WQCIEDTSGK LRIHKCKGPS
DLLTVRQSTR NLYARGFHDK DKECSCRESG YRASRSQRKS QRQFLRNQGT PKYKPRFVHT
RQTRSLSVEF EGEIYDINLE EEEELQVLQP RNIAKRHDEG HKGPRDLQAS SGGNRGRMLA
DSSNAVGPPT TVRVTHKCFI LPNDSIHCER ELYQSARAWK DHKAYIDKEI EALQDKIKNL
REVRGHLKRR KPEECSCSKQ SYYNKEKGVK KQEKLKSHLH PFKEAAQEVD SKLQLFKENN
RRRKKERKEK RRQRKGEECS LPGLTCFTHD NNHWQTAPFW NLGSFCACTS SNNNTYWCLR
TVNETHNFLF CEFATGFLEY FDMNTDPYQL TNTVHTVERG ILNQLHVQLM ELRSCQGYKQ
CNPRPKNLDV GNKDGGSYDL HRGQLWDGWE G
