P08842 (STS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Steryl-sulfatase
EC=3.1.6.2

Alternative name(s):
Arylsulfatase C
Short name=ASC
Steroid sulfatase
Steryl-sulfate sulfohydrolase

Gene names

Name:	STS
Synonyms:	ARSC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	583 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Conversion of sulfated steroid precursors to estrogens during pregnancy.
Catalytic activity	3-beta-hydroxyandrost-5-en-17-one 3-sulfate + H2O = 3-beta-hydroxyandrost-5-en-17-one + sulfate.
Cofactor	Binds 1 calcium ion per subunit. Ref.7
Subunit structure	Homodimer.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Post-translational modification	The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity By similarity.
Involvement in disease	Ichthyosis, X-linked (IXL) [MIM:308100]: A keratinization disorder manifesting with mild erythroderma and generalized exfoliation of the skin within a few weeks after birth. Affected boys later develop large, polygonal, dark brown scales, especially on the neck, extremities, trunk, and buttocks. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the sulfatase family.

Ontologies

Keywords
Biological process	Lipid metabolism Pregnancy Steroid metabolism
Cellular component	Endoplasmic reticulum Membrane
Disease	Disease mutation Ichthyosis
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	epidermis development Traceable author statement Ref.9. Source: ProtInc female pregnancy Inferred from electronic annotation. Source: UniProtKB-KW glycosphingolipid metabolic process Traceable author statement. Source: Reactome post-translational protein modification Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome steroid catabolic process Traceable author statement PubMed 6957717. Source: ProtInc
Cellular_component	Golgi apparatus Traceable author statement Ref.1. Source: ProtInc endoplasmic reticulum lumen Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome endosome Traceable author statement Ref.1. Source: ProtInc integral component of membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosome Traceable author statement Ref.1. Source: ProtInc plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW steryl-sulfatase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.6

Chain

22 – 583

562

Steryl-sulfatase

PRO_0000033414

Regions

Topological domain

22 – 184

163

Lumenal Ref.7

Transmembrane

185 – 208

24

Helical

Topological domain

209 – 212

4

Cytoplasmic Ref.7

Transmembrane

213 – 234

22

Helical

Topological domain

235 – 583

349

Lumenal Ref.7

Sites

Active site

136

1

Ref.7

Metal binding

35

1

Calcium

Metal binding

36

1

Calcium

Metal binding

75

1

Calcium; via 3-oxoalanine

Metal binding

342

1

Calcium

Metal binding

343

1

Calcium

Site

333

1

Not glycosylated

Site

459

1

Not glycosylated

Amino acid modifications

Modified residue

75

1

3-oxoalanine (Cys)

Glycosylation

47

1

N-linked (GlcNAc...) Ref.1 Ref.7

Glycosylation

259

1

N-linked (GlcNAc...) Ref.1 Ref.7

Disulfide bond

141 ↔ 148

Disulfide bond

170 ↔ 242

Disulfide bond

446 ↔ 489

Disulfide bond

481 ↔ 487

Disulfide bond

562 ↔ 570

Disulfide bond

563 ↔ 572

Natural variations

Natural variant

341

1

S → L in IXL; loss of activity. Ref.8 Ref.9

VAR_007240

Natural variant

372

1

W → R in IXL; loss of activity. Ref.8 Ref.9

VAR_007241

Natural variant

372

1

W → S in IXL; loss of activity. Ref.9

VAR_014020

Natural variant

380

1

G → R in IXL. Ref.11

VAR_014021

Natural variant

444

1

H → R in IXL; loss of activity. Ref.9

VAR_014022

Natural variant

446

1

C → Y in IXL; loss of activity. Ref.8 Ref.9

VAR_007242

Natural variant

560

1

Q → P in IXL. Ref.10

VAR_014023

Experimental info

Sequence conflict

23

1

A → E in AAA60596. Ref.2

Secondary structure

1

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583

Helix Strand Turn

Details...

Beta strand

28 – 36

9

Helix

43 – 45

3

Beta strand

48 – 50

3

Helix

53 – 56

4

Turn

57 – 61

5

Beta strand

62 – 69

8

Helix

77 – 84

8

Helix

88 – 91

4

Beta strand

96 – 98

3

Helix

118 – 124

7

Beta strand

128 – 134

7

Beta strand

141 – 143

3

Turn

144 – 146

3

Helix

151 – 153

3

Beta strand

157 – 164

8

Helix

168 – 170

3

Helix

179 – 185

7

Helix

187 – 205

19

Helix

213 – 241

29

Beta strand

244 – 246

3

Beta strand

249 – 254

6

Helix

260 – 273

14

Turn

274 – 277

4

Beta strand

280 – 285

6

Beta strand

290 – 292

3

Turn

297 – 299

3

Beta strand

304 – 306

3

Helix

307 – 328

22

Helix

332 – 334

3

Beta strand

335 – 343

9

Beta strand

352 – 354

3

Beta strand

370 – 372

3

Helix

373 – 376

4

Beta strand

380 – 383

4

Turn

385 – 387

3

Helix

400 – 402

3

Helix

403 – 411

9

Beta strand

417 – 419

3

Helix

427 – 430

4

Beta strand

440 – 446

7

Beta strand

449 – 455

7

Beta strand

464 – 468

5

Turn

482 – 484

3

Beta strand

489 – 491

3

Beta strand

501 – 503

3

Turn

505 – 507

3

Turn

518 – 521

4

Helix

523 – 537

15

Helix

550 – 553

4

Helix

557 – 559

3

Beta strand

563 – 568

6

Sequences

	Sequence		Length	Mass (Da)
	P08842 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: 74746AFA9D21A0A6	FASTA	583	65,492
	10 20 30 40 50 60 MPLRKMKIPF LLLFFLWEAE SHAASRPNII LVMADDLGIG DPGCYGNKTI RTPNIDRLAS 70 80 90 100 110 120 GGVKLTQHLA ASPLCTPSRA AFMTGRYPVR SGMASWSRTG VFLFTASSGG LPTDEITFAK 130 140 150 160 170 180 LLKDQGYSTA LIGKWHLGMS CHSKTDFCHH PLHHGFNYFY GISLTNLRDC KPGEGSVFTT 190 200 210 220 230 240 GFKRLVFLPL QIVGVTLLTL AALNCLGLLH VPLGVFFSLL FLAALILTLF LGFLHYFRPL 250 260 270 280 290 300 NCFMMRNYEI IQQPMSYDNL TQRLTVEAAQ FIQRNTETPF LLVLSYLHVH TALFSSKDFA 310 320 330 340 350 360 GKSQHGVYGD AVEEMDWSVG QILNLLDELR LANDTLIYFT SDQGAHVEEV SSKGEIHGGS 370 380 390 400 410 420 NGIYKGGKAN NWEGGIRVPG ILRWPRVIQA GQKIDEPTSN MDIFPTVAKL AGAPLPEDRI 430 440 450 460 470 480 IDGRDLMPLL EGKSQRSDHE FLFHYCNAYL NAVRWHPQNS TSIWKAFFFT PNFNPVGSNG 490 500 510 520 530 540 CFATHVCFCF GSYVTHHDPP LLFDISKDPR ERNPLTPASE PRFYEILKVM QEAADRHTQT 550 560 570 580 LPEVPDQFSW NNFLWKPWLQ LCCPSTGLSC QCDREKQDKR LSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human steroid-sulfatase. Membrane topology, glycosylation, and subcellular distribution in BHK-21 cells." Stein C., Hille A., Seidel J., Rijnbout S., Waheed A., Schmidt B., Geuze H., von Figura K. J. Biol. Chem. 264:13865-13872(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-47 AND ASN-259, LACK OF GLYCOSYLATION AT ASN-333 AND ASN-459.
[2]	"Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange." Yen P.H., Allen E., Marsh B., Mohandas T., Wang N., Taggart R.T., Shapiro L.J. Cell 49:443-454(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution." Yen P.H., Marsh B., Allen E., Tsai S.P., Ellison J., Connolly L., Neiswanger K., Shapiro L.J. Cell 55:1123-1135(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-174 AND 461-583.
[6]	"Characterization of rat and human steroid sulfatases." Kawano J., Kotani T., Ohtaki S., Minamino N., Matsuo H., Oinuma T., Aikawa E. Biochim. Biophys. Acta 997:199-205(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-45. Tissue: Liver.
[7]	"Structure of human estrone sulfatase suggests functional roles of membrane association." Hernandez-Guzman F.G., Higashiyama T., Pangborn W., Osawa Y., Ghosh D. J. Biol. Chem. 278:22989-22997(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, COFACTOR, TRANSMEMBRANE TOPOLOGY, ACTIVE SITE, GLYCOSYLATION AT ASN-47 AND ASN-259.
[8]	"Identification of point mutations in the steroid sulfatase gene of three patients with X-linked ichthyosis." Basler E., Grompe M., Parenti G., Yates J., Ballabio A. Am. J. Hum. Genet. 50:483-491(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS IXL LEU-341; ARG-372 AND TYR-446.
[9]	"Characterization of point mutations in patients with X-linked ichthyosis. Effects on the structure and function of the steroid sulfatase protein." Alperin E.S., Shapiro L.J. J. Biol. Chem. 272:20756-20763(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS IXL LEU-341; ARG-372; SER-372; ARG-444 AND TYR-446.
[10]	"PCR diagnosis of X-linked ichthyosis: identification of a novel mutation (E560P) of the steroid sulfatase gene." Sugawara T., Shimizu H., Hoshi N., Fujimoto Y., Nakajima A., Fujimoto S. Hum. Mutat. 15:296-296(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT IXL PRO-560.
[11]	"Novel point mutations in the steroid sulfatase gene in patients with X-linked ichthyosis: transfection analysis using the mutated genes." Oyama N., Satoh M., Iwatsuki K., Kaneko F. J. Invest. Dermatol. 114:1195-1199(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT IXL ARG-380.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Steroid sulfatase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J04964 mRNA. Translation: AAA60597.1.
M16505 mRNA. Translation: AAA60596.1.
AK314034 mRNA. Translation: BAG36744.1.
BC075030 mRNA. Translation: AAH75030.1.
M23945 Genomic DNA. Translation: AAA60598.1.
M23556 Genomic DNA. Translation: AAA60599.1.

PIR

KJHUAC. A32641.

RefSeq

NP_000342.2. NM_000351.4.

UniGene

Hs.522578.
Hs.700558.
Hs.700559.
Hs.740067.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P49	X-ray	2.60	A	22-583	[»]

ProteinModelPortal

P08842.

SMR

P08842. Positions 23-575.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

IntAct

P08842. 1 interaction.

MINT

MINT-1177440.

STRING

9606.ENSP00000217961.

Chemistry

BindingDB

P08842.

ChEMBL

CHEMBL3559.

DrugBank

DB00655. Estrone.

PTM databases

PhosphoSite

P08842.

Polymorphism databases

DMDM

135006.

Proteomic databases

PaxDb

P08842.

PRIDE

P08842.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000217961; ENSP00000217961; ENSG00000101846.

GeneID

412.

KEGG

hsa:412.

UCSC

uc004cry.4. human.

Organism-specific databases

CTD

412.

GeneCards

GC0XP007147.

HGNC

HGNC:11425. STS.

HPA

HPA002904.

MIM

300747. gene.
308100. phenotype.

neXtProt

NX_P08842.

Orphanet

461. Recessive X-linked ichthyosis.
281090. Syndromic X-linked ichthyosis.

PharmGKB

PA36225.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3119.

HOGENOM

HOG000135352.

HOVERGEN

HBG004283.

InParanoid

P08842.

KO

K01131.

OMA

GLSCQCD.

OrthoDB

EOG7QZG9J.

PhylomeDB

P08842.

TreeFam

TF314186.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.

Gene expression databases

Bgee

P08842.

CleanEx

HS_STS.

Genevestigator

P08842.

Family and domain databases

Gene3D

3.40.720.10. 2 hits.

InterPro

IPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR000917. Sulfatase.
IPR024607. Sulfatase_CS.
[Graphical view]

Pfam

PF00884. Sulfatase. 1 hit.
[Graphical view]

SUPFAM

SSF53649. SSF53649. 1 hit.

PROSITE

PS00523. SULFATASE_1. 1 hit.
PS00149. SULFATASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P08842.

GeneWiki

Steroid_sulfatase.

GenomeRNAi

412.

NextBio

1743.

PRO

P08842.

SOURCE

Search...

Entry information

Entry name

STS_HUMAN

Accession

Primary (citable) accession number: P08842
Secondary accession number(s): B2RA47

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	April 1, 1990
Last modified:	February 19, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.