ID STS_HUMAN Reviewed; 583 AA. AC P08842; B2RA47; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 2. DT 01-MAY-2013, entry version 141. DE RecName: Full=Steryl-sulfatase; DE EC=3.1.6.2; DE AltName: Full=Arylsulfatase C; DE Short=ASC; DE AltName: Full=Steroid sulfatase; DE AltName: Full=Steryl-sulfate sulfohydrolase; DE Flags: Precursor; GN Name=STS; Synonyms=ARSC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT RP ASN-47 AND ASN-259, AND LACK OF GLYCOSYLATION AT ASN-333 AND ASN-459. RX PubMed=2668275; RA Stein C., Hille A., Seidel J., Rijnbout S., Waheed A., Schmidt B., RA Geuze H., von Figura K.; RT "Cloning and expression of human steroid-sulfatase. Membrane topology, RT glycosylation, and subcellular distribution in BHK-21 cells."; RL J. Biol. Chem. 264:13865-13872(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3032454; DOI=10.1016/0092-8674(87)90447-8; RA Yen P.H., Allen E., Marsh B., Mohandas T., Wang N., Taggart R.T., RA Shapiro L.J.; RT "Cloning and expression of steroid sulfatase cDNA and the frequent RT occurrence of deletions in STS deficiency: implications for X-Y RT interchange."; RL Cell 49:443-454(1987). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-174 AND 461-583. RX PubMed=3203382; DOI=10.1016/0092-8674(88)90257-7; RA Yen P.H., Marsh B., Allen E., Tsai S.P., Ellison J., Connolly L., RA Neiswanger K., Shapiro L.J.; RT "The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: RT evidence for an inversion of the Y chromosome during primate RT evolution."; RL Cell 55:1123-1135(1988). RN [6] RP PROTEIN SEQUENCE OF 22-45. RC TISSUE=Liver; RX PubMed=2765556; DOI=10.1016/0167-4838(89)90187-8; RA Kawano J., Kotani T., Ohtaki S., Minamino N., Matsuo H., Oinuma T., RA Aikawa E.; RT "Characterization of rat and human steroid sulfatases."; RL Biochim. Biophys. Acta 997:199-205(1989). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, RP COFACTOR, TRANSMEMBRANE TOPOLOGY, ACTIVE SITE, AND GLYCOSYLATION AT RP ASN-47 AND ASN-259. RX PubMed=12657638; DOI=10.1074/jbc.M211497200; RA Hernandez-Guzman F.G., Higashiyama T., Pangborn W., Osawa Y., RA Ghosh D.; RT "Structure of human estrone sulfatase suggests functional roles of RT membrane association."; RL J. Biol. Chem. 278:22989-22997(2003). RN [8] RP VARIANTS IXL LEU-341; ARG-372 AND TYR-446. RX PubMed=1539590; RA Basler E., Grompe M., Parenti G., Yates J., Ballabio A.; RT "Identification of point mutations in the steroid sulfatase gene of RT three patients with X-linked ichthyosis."; RL Am. J. Hum. Genet. 50:483-491(1992). RN [9] RP VARIANTS IXL LEU-341; ARG-372; SER-372; ARG-444 AND TYR-446. RX PubMed=9252398; DOI=10.1074/jbc.272.33.20756; RA Alperin E.S., Shapiro L.J.; RT "Characterization of point mutations in patients with X-linked RT ichthyosis. Effects on the structure and function of the steroid RT sulfatase protein."; RL J. Biol. Chem. 272:20756-20763(1997). RN [10] RP VARIANT IXL PRO-560. RX PubMed=10679952; RX DOI=10.1002/(SICI)1098-1004(200003)15:3<296::AID-HUMU17>3.0.CO;2-#; RA Sugawara T., Shimizu H., Hoshi N., Fujimoto Y., Nakajima A., RA Fujimoto S.; RT "PCR diagnosis of X-linked ichthyosis: identification of a novel RT mutation (E560P) of the steroid sulfatase gene."; RL Hum. Mutat. 15:296-296(2000). RN [11] RP VARIANT IXL ARG-380. RX PubMed=10844566; DOI=10.1046/j.1523-1747.2000.00004.x; RA Oyama N., Satoh M., Iwatsuki K., Kaneko F.; RT "Novel point mutations in the steroid sulfatase gene in patients with RT X-linked ichthyosis: transfection analysis using the mutated genes."; RL J. Invest. Dermatol. 114:1195-1199(2000). CC -!- FUNCTION: Conversion of sulfated steroid precursors to estrogens CC during pregnancy. CC -!- CATALYTIC ACTIVITY: 3-beta-hydroxyandrost-5-en-17-one 3-sulfate + CC H(2)O = 3-beta-hydroxyandrost-5-en-17-one + sulfate. CC -!- COFACTOR: Binds 1 calcium ion per subunit. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass CC membrane protein. CC -!- PTM: The conversion to 3-oxoalanine (also known as C- CC formylglycine, FGly), of a serine or cysteine residue in CC prokaryotes and of a cysteine residue in eukaryotes, is critical CC for catalytic activity (By similarity). CC -!- DISEASE: Ichthyosis, X-linked (IXL) [MIM:308100]: A keratinization CC disorder manifesting with mild erythroderma and generalized CC exfoliation of the skin within a few weeks after birth. Affected CC boys later develop large, polygonal, dark brown scales, especially CC on the neck, extremities, trunk, and buttocks. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the sulfatase family. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/STS"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Steroid sulfatase entry; CC URL="http://en.wikipedia.org/wiki/Steroid_sulfatase"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; J04964; AAA60597.1; -; mRNA. DR EMBL; M16505; AAA60596.1; -; mRNA. DR EMBL; AK314034; BAG36744.1; -; mRNA. DR EMBL; BC075030; AAH75030.1; -; mRNA. DR EMBL; M23945; AAA60598.1; -; Genomic_DNA. DR EMBL; M23556; AAA60599.1; -; Genomic_DNA. DR IPI; IPI00307433; -. DR PIR; A32641; KJHUAC. DR RefSeq; NP_000342.2; NM_000351.4. DR UniGene; Hs.522578; -. DR UniGene; Hs.700558; -. DR UniGene; Hs.700559; -. DR UniGene; Hs.740067; -. DR PDB; 1P49; X-ray; 2.60 A; A=22-583. DR PDBsum; 1P49; -. DR ProteinModelPortal; P08842; -. DR MINT; MINT-1177440; -. DR STRING; 9606.ENSP00000217961; -. DR PhosphoSite; P08842; -. DR DMDM; 135006; -. DR PaxDb; P08842; -. DR PRIDE; P08842; -. DR Ensembl; ENST00000217961; ENSP00000217961; ENSG00000101846. DR GeneID; 412; -. DR KEGG; hsa:412; -. DR UCSC; uc004cry.4; human. DR CTD; 412; -. DR GeneCards; GC0XP007147; -. DR HGNC; HGNC:11425; STS. DR HPA; HPA002904; -. DR MIM; 300747; gene. DR MIM; 308100; phenotype. DR neXtProt; NX_P08842; -. DR Orphanet; 461; Recessive X-linked ichthyosis. DR PharmGKB; PA36225; -. DR eggNOG; COG3119; -. DR HOGENOM; HOG000135352; -. DR HOVERGEN; HBG004283; -. DR InParanoid; P08842; -. DR KO; K01131; -. DR OMA; GLSCQCD; -. DR OrthoDB; EOG4V4379; -. DR PhylomeDB; P08842; -. DR Reactome; REACT_111217; Metabolism. DR Reactome; REACT_17015; Metabolism of proteins. DR BindingDB; P08842; -. DR ChEMBL; CHEMBL3559; -. DR DrugBank; DB00655; Estrone. DR EvolutionaryTrace; P08842; -. DR GenomeRNAi; 412; -. DR NextBio; 1743; -. DR Bgee; P08842; -. DR CleanEx; HS_STS; -. DR Genevestigator; P08842; -. DR GermOnline; ENSG00000101846; Homo sapiens. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005768; C:endosome; TAS:ProtInc. DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004773; F:steryl-sulfatase activity; TAS:Reactome. DR GO; GO:0008544; P:epidermis development; TAS:ProtInc. DR GO; GO:0007565; P:female pregnancy; IEA:UniProtKB-KW. DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006706; P:steroid catabolic process; TAS:ProtInc. DR Gene3D; 3.40.720.10; -; 2. DR InterPro; IPR017849; Alkaline_Pase-like_a/b/a. DR InterPro; IPR017850; Alkaline_phosphatase_core. DR InterPro; IPR000917; Sulfatase. DR InterPro; IPR024607; Sulfatase_CS. DR Pfam; PF00884; Sulfatase; 1. DR SUPFAM; SSF53649; Alkaline_phosphatase_core; 1. DR PROSITE; PS00523; SULFATASE_1; 1. DR PROSITE; PS00149; SULFATASE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Complete proteome; Direct protein sequencing; KW Disease mutation; Disulfide bond; Endoplasmic reticulum; Glycoprotein; KW Hydrolase; Ichthyosis; Lipid metabolism; Membrane; Metal-binding; KW Pregnancy; Reference proteome; Signal; Steroid metabolism; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 21 FT CHAIN 22 583 Steryl-sulfatase. FT /FTId=PRO_0000033414. FT TOPO_DOM 22 184 Lumenal. FT TRANSMEM 185 208 Helical. FT TOPO_DOM 209 212 Cytoplasmic. FT TRANSMEM 213 234 Helical. FT TOPO_DOM 235 583 Lumenal. FT ACT_SITE 136 136 FT METAL 35 35 Calcium. FT METAL 36 36 Calcium. FT METAL 75 75 Calcium; via 3-oxoalanine. FT METAL 342 342 Calcium. FT METAL 343 343 Calcium. FT SITE 333 333 Not glycosylated. FT SITE 459 459 Not glycosylated. FT MOD_RES 75 75 3-oxoalanine (Cys). FT CARBOHYD 47 47 N-linked (GlcNAc...). FT CARBOHYD 259 259 N-linked (GlcNAc...). FT DISULFID 141 148 FT DISULFID 170 242 FT DISULFID 446 489 FT DISULFID 481 487 FT DISULFID 562 570 FT DISULFID 563 572 FT VARIANT 341 341 S -> L (in IXL; loss of activity). FT /FTId=VAR_007240. FT VARIANT 372 372 W -> R (in IXL; loss of activity). FT /FTId=VAR_007241. FT VARIANT 372 372 W -> S (in IXL; loss of activity). FT /FTId=VAR_014020. FT VARIANT 380 380 G -> R (in IXL). FT /FTId=VAR_014021. FT VARIANT 444 444 H -> R (in IXL; loss of activity). FT /FTId=VAR_014022. FT VARIANT 446 446 C -> Y (in IXL; loss of activity). FT /FTId=VAR_007242. FT VARIANT 560 560 Q -> P (in IXL). FT /FTId=VAR_014023. FT CONFLICT 23 23 A -> E (in Ref. 2; AAA60596). FT STRAND 28 36 FT HELIX 43 45 FT STRAND 48 50 FT HELIX 53 56 FT TURN 57 61 FT STRAND 62 69 FT HELIX 77 84 FT HELIX 88 91 FT STRAND 96 98 FT HELIX 118 124 FT STRAND 128 134 FT STRAND 141 143 FT TURN 144 146 FT HELIX 151 153 FT STRAND 157 164 FT HELIX 168 170 FT HELIX 179 185 FT HELIX 187 205 FT HELIX 213 241 FT STRAND 244 246 FT STRAND 249 254 FT HELIX 260 273 FT TURN 274 277 FT STRAND 280 285 FT STRAND 290 292 FT TURN 297 299 FT STRAND 304 306 FT HELIX 307 328 FT HELIX 332 334 FT STRAND 335 343 FT STRAND 352 354 FT STRAND 370 372 FT HELIX 373 376 FT STRAND 380 383 FT TURN 385 387 FT HELIX 400 402 FT HELIX 403 411 FT STRAND 417 419 FT HELIX 427 430 FT STRAND 440 446 FT STRAND 449 455 FT STRAND 464 468 FT TURN 482 484 FT STRAND 489 491 FT STRAND 501 503 FT TURN 505 507 FT TURN 518 521 FT HELIX 523 537 FT HELIX 550 553 FT HELIX 557 559 FT STRAND 563 568 SQ SEQUENCE 583 AA; 65492 MW; 74746AFA9D21A0A6 CRC64; MPLRKMKIPF LLLFFLWEAE SHAASRPNII LVMADDLGIG DPGCYGNKTI RTPNIDRLAS GGVKLTQHLA ASPLCTPSRA AFMTGRYPVR SGMASWSRTG VFLFTASSGG LPTDEITFAK LLKDQGYSTA LIGKWHLGMS CHSKTDFCHH PLHHGFNYFY GISLTNLRDC KPGEGSVFTT GFKRLVFLPL QIVGVTLLTL AALNCLGLLH VPLGVFFSLL FLAALILTLF LGFLHYFRPL NCFMMRNYEI IQQPMSYDNL TQRLTVEAAQ FIQRNTETPF LLVLSYLHVH TALFSSKDFA GKSQHGVYGD AVEEMDWSVG QILNLLDELR LANDTLIYFT SDQGAHVEEV SSKGEIHGGS NGIYKGGKAN NWEGGIRVPG ILRWPRVIQA GQKIDEPTSN MDIFPTVAKL AGAPLPEDRI IDGRDLMPLL EGKSQRSDHE FLFHYCNAYL NAVRWHPQNS TSIWKAFFFT PNFNPVGSNG CFATHVCFCF GSYVTHHDPP LLFDISKDPR ERNPLTPASE PRFYEILKVM QEAADRHTQT LPEVPDQFSW NNFLWKPWLQ LCCPSTGLSC QCDREKQDKR LSR //