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SULF1 (sulfatase 1)

Written2012-03Jérôme Moreaux
INSERM U1040, institut de recherche en biotherapie, CHRU Saint Eloi, 80 Av Augustain Fliche, 34295 Montpellier CEDEX 5, France

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)KIAA1077
SULF-1
Other aliasHSULF-1
HGNC (Hugo) SULF1
LocusID (NCBI) 23213
Atlas_Id 44378
Location 8q13.2  [Link to chromosome band 8q13]
Location_base_pair Starts at 69466624 and ends at 69660912 bp from pter ( according to hg19-Feb_2009)  [Mapping SULF1.png]
Fusion genes
(updated 2016)
FEN1 (11q12.2) / SULF1 (8q13.2)SULF1 (8q13.2) / PLSCR1 (3q24)

DNA/RNA

Note The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 is an endosulfatase able to cleave specific 6-O sulfate groups within the heparan chains. This action can modulate signaling processes, modulating the effects of heparan sulfate by altering binding sites for signaling molecules.
 
  Adapted from Genecards.
Description Size: 5551 bp.
Transcription 4 isoforms:
- Homo sapiens sulfatase 1 (SULF1), transcript variant 1, mRNA, 5716 bp
Accession: NM_001128205.1 GI: 189571640
- Homo sapiens sulfatase 1 (SULF1), transcript variant 2, mRNA, 5554 bp
Accession: NM_001128206.1 GI: 189571642
- Homo sapiens sulfatase 1 (SULF1), transcript variant 3, mRNA, 5710 bp
Accession: NM_015170.2 GI: 189571635
- Homo sapiens sulfatase 1 (SULF1), transcript variant 4, mRNA, 5548 bp
Accession: NM_001128204.1 GI: 189571637

Protein

Note Sulfs are sulfatases that edit the sulfation status of heparan sulfate proteoglycans on the outside of cells and regulate a number of critical signaling pathways. The Sulfs are dysregulated in many cancers. The Sulfs are synthesized as pre-proproteins. The signal sequence is removed and the pro-protein is cleaved by a furin-type proteinase. Sulfs mature proteins are secreted as well as retained on the cell surface.
Description 871 amino acids; 101027 Da.
Expression Expressed at highest levels in testis, stomach, skeletal muscle, lung, kidney, pancreas, small intestine and colon. It is also detected in normal ovarian surface epithelial cells.
Localisation Sulfs mature proteins are secreted as well as retained on the cell surface.
Function The Sulfs are endoglucosamine-6-sulfatases. They liberate 6-O-S mainly from trisulfated disaccharide units within the S-domains of heparin/HS chains. The Sulfs have been shown to modulate the interaction of a number of protein ligands with heparin or heparan sulfate.
Homology SULF1 shares about 64% identity with SULF2.

Implicated in

Note
  
Entity Ovarian cancer
Oncogenesis Sulf1 expression was found to be absent or significantly downregulated in ovarian cancer resulting in highly sulfated heparin sulfate proteoglycans. It has been observed that this down-regulation results in increased sulfation of heparin sulfate chains and could produce the stabilization of ternary receptor complexes, leading to an increased in GF signaling, as described for heparin-binding epidermal growth factor-like growth factor (HB-EGF), fibroblast growth factor 2 (FGF2) or amphiregulin in ovarian cancer. This modulation of GF effects can affect major events including proliferation of tumor cells. Epigenetic silencing by methylation is associated with ovarian cancer cells and primary ovarian cancer tissues lacking Sulf1 expression. Cisplatin-induced apoptosis of the ovarian cancer cell line, OV207, requires Sulf1 activity.
  
  
Entity Breast cancer
Oncogenesis Sulf1 expression was first described to be significantly downregulated in breast cancer. Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in breast cancer compared to normal counterpart. It has been observed that this down-regulation results in increased sulfation of heparin sulfate chains and could produce the stabilization of ternary receptor complexes, leading to an increased in growth factors signaling, as described for heparin-binding epidermal growth factor-like growth factor (HB-EGF), fibroblast growth factor 2 (FGF2) or amphiregulin in breast cancer. This modulation of GF effects can affect major events including proliferation of tumor cells. A marked reduction of the growth of myeloma or breast cancer cell lines was observed in severe combined immunodeficient mice when injected cell lines were transfected with SULF1 cDNA. It was found an aberrant hypermethylation of the Sulf1 promoter in breast cancer cell lines and patient samples, leading to a reduction of Sulf1 expression.
  
  
Entity Hepatocellular carcinoma
Oncogenesis Sulf1 expression was also found to be significantly downregulated in hepatocellular carcinoma. It has also been observed that this down-regulation results in increased sulfation of heparin sulfate chains and could produce the stabilization of ternary receptor complexes, leading to an increased in growth factors signaling. Forced expression of SULF1 also significantly delayed the growth of hepatocellular carcinoma cell lines xenografts in nude mice. Sulf1 enhances acetylation of histone H4 by inhibiting HDAC, which subsequently decreased hepatocellular carcinoma cell tumorogenesis in mouse model.
  
  
Entity Pancreatic cancer
Oncogenesis Hsulf-1-mediated desulphation of HSPGs reduces the growth ability of pancreatic cancer cells, but increases the basal invasiveness of these cells and chemoresistance, suggesting an important role of this enzyme in pancreatic cancer progression. Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in pancreatic adenocarinoma compared to normal counterpart.
  
  
Entity Head and neck squamous cell carcinoma
Oncogenesis Sulf1 expression was also found to be significantly downregulated in head and neck squamous cell carcinoma cell lines. It has also been observed that this down-regulation results in increased sulfation of heparin sulfate chains and could produce the stabilization of ternary receptor complexes, leading to an increased in growth factors signaling in head and neck squamous cell carcinoma cell lines. Hepatocyte growth factor (HGF)-mediated motility and invasion were attenuated in neck squamous cell carcinoma cell lines displaying an overexpression of this sulfatase. However, recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in head and neck squamous cell carcinoma compared to normal counterpart.
  
  
Entity Leukemia
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in leukemia compared to normal counterpart.
  
  
Entity Gastric cancer
Oncogenesis Promoter hypermethylation is correlated with the HSulf-1 silencing in gastric cancer. The restoration of the expression of HSulf-1 inhibited cell proliferation, motility, and invasion of the MKN28 cell line in vitro, as well as in a xenograft mouse model. No noticeable changes in proliferation and motility were observed following restoration of HSulf-1 in another gastric cancer cell line AGS. HSulf-1 function as a negative regulator of proliferation and invasion in MKN28 gastric cancer cell line by suppressing Wnt/β-catenin signaling. However, as for others cancers, recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in leukemia compared to normal counterpart.
  
  
Entity Colon cancer
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in colon cancer compared to normal counterpart.
  
  
Entity Adrenal cancer
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in adrenal cancer compared to normal counterpart.
  
  
Entity Esophageal cancer
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in esophageal cancer compared to normal counterpart.
  
  
Entity Lung cancer
Prognosis In a cohort of 127 patients with lung adenocarcinoma, it was described that high expression of Sulf1 is associated with a bad prognosis compared to patients with low Sulf1 expression.
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in esophageal cancer compared to normal counterpart.
  
  
Entity Mesothelioma
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in mesothelioma compared to normal counterpart. Furthermore, a review of transcriptome studies identified Sulf1 as a mesothelioma gene that could represent a new biomarker or therapeutic target in mesothelioma.
  
  
Entity Renal carcinoma
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in renal carcinoma compared to normal counterpart.
  
  
Entity Sarcoma
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in sarcoma compared to normal counterpart.
  
  
Entity Melanoma
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in cutaneous melanoma compared to normal skin.
  
  
Entity Testicular cancer
Oncogenesis Recent analysis using microarray data demonstrated a significant upregulation of Sulf1 in testicular cancer compared to normal counterpart.
  

Bibliography

Hsulf-1 regulates growth and invasion of pancreatic cancer cells.
Abiatari I, Kleeff J, Li J, Felix K, Buchler MW, Friess H.
J Clin Pathol. 2006 Oct;59(10):1052-8. Epub 2006 Apr 7.
PMID 16603650
 
SULFs in human neoplasia: implication as progression and prognosis factors.
Bret C, Moreaux J, Schved JF, Hose D, Klein B.
J Transl Med. 2011 May 21;9:72. doi: 10.1186/1479-5876-9-72.
PMID 21599997
 
Promoter hypermethylation correlates with the Hsulf-1 silencing in human breast and gastric cancer.
Chen Z, Fan JQ, Li J, Li QS, Yan Z, Jia XK, Liu WD, Wei LJ, Zhang FZ, Gao H, Xu JP, Dong XM, Dai J, Zhou HM.
Int J Cancer. 2009 Feb 1;124(3):739-44.
PMID 19006069
 
Fibroblast growth factor-2 binds to small heparin-derived oligosaccharides and stimulates a sustained phosphorylation of p42/44 mitogen-activated protein kinase and proliferation of rat mammary fibroblasts.
Delehedde M, Lyon M, Gallagher JT, Rudland PS, Fernig DG.
Biochem J. 2002 Aug 15;366(Pt 1):235-44.
PMID 12000311
 
Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma.
Dong G, Chen Z, Li ZY, Yeh NT, Bancroft CC, Van Waes C.
Cancer Res. 2001 Aug 1;61(15):5911-8.
PMID 11479233
 
Detection of MET oncogene/hepatocyte growth factor receptor in lymph node metastases from head and neck squamous cell carcinomas.
Galeazzi E, Olivero M, Gervasio FC, De Stefani A, Valente G, Comoglio PM, Di Renzo MF, Cortesina G.
Eur Arch Otorhinolaryngol. 1997;254 Suppl 1:S138-43.
PMID 9065649
 
Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer.
Lai J, Chien J, Staub J, Avula R, Greene EL, Matthews TA, Smith DI, Kaufmann SH, Roberts LR, Shridhar V.
J Biol Chem. 2003 Jun 20;278(25):23107-17. Epub 2003 Apr 9.
PMID 12686563
 
HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma.
Lai JP, Chien J, Strome SE, Staub J, Montoya DP, Greene EL, Smith DI, Roberts LR, Shridhar V.
Oncogene. 2004 Feb 19;23(7):1439-47.
PMID 14973553
 
SULF1 inhibits tumor growth and potentiates the effects of histone deacetylase inhibitors in hepatocellular carcinoma.
Lai JP, Yu C, Moser CD, Aderca I, Han T, Garvey TD, Murphy LM, Garrity-Park MM, Shridhar V, Adjei AA, Roberts LR.
Gastroenterology. 2006 Jun;130(7):2130-44.
PMID 16762634
 
Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer.
Li J, Kleeff J, Abiatari I, Kayed H, Giese NA, Felix K, Giese T, Buchler MW, Friess H.
Mol Cancer. 2005 Apr 7;4(1):14.
PMID 15817123
 
Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis.
Lundin L, Larsson H, Kreuger J, Kanda S, Lindahl U, Salmivirta M, Claesson-Welsh L.
J Biol Chem. 2000 Aug 11;275(32):24653-60.
PMID 10816596
 
A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma.
Melaiu O, Cristaudo A, Melissari E, Di Russo M, Bonotti A, Bruno R, Foddis R, Gemignani F, Pellegrini S, Landi S.
Mutat Res. 2011 Dec 15. [Epub ahead of print]
PMID 22198210
 
Loss of HSulf-1 expression enhances autocrine signaling mediated by amphiregulin in breast cancer.
Narita K, Chien J, Mullany SA, Staub J, Qian X, Lingle WL, Shridhar V.
J Biol Chem. 2007 May 11;282(19):14413-20. Epub 2007 Mar 15.
PMID 17363371
 
HSulf-1 inhibits angiogenesis and tumorigenesis in vivo.
Narita K, Staub J, Chien J, Meyer K, Bauer M, Friedl A, Ramakrishnan S, Shridhar V.
Cancer Res. 2006 Jun 15;66(12):6025-32.
PMID 16778174
 
Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate.
Rosen SD, Lemjabbar-Alaoui H.
Expert Opin Ther Targets. 2010 Sep;14(9):935-49. (REVIEW)
PMID 20629619
 
Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance.
Staub J, Chien J, Pan Y, Qian X, Narita K, Aletti G, Scheerer M, Roberts LR, Molina J, Shridhar V.
Oncogene. 2007 Jul 26;26(34):4969-78. Epub 2007 Feb 19.
PMID 17310998
 

Citation

This paper should be referenced as such :
Moreaux, J
SULF1 (sulfatase 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):555-558.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SULF1ID44378ch8q13.html


External links

Nomenclature
HGNC (Hugo)SULF1   20391
Cards
AtlasSULF1ID44378ch8q13
Entrez_Gene (NCBI)SULF1  23213  sulfatase 1
AliasesSULF-1
GeneCards (Weizmann)SULF1
Ensembl hg19 (Hinxton)ENSG00000137573 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000137573 [Gene_View]  chr8:69466624-69660912 [Contig_View]  SULF1 [Vega]
ICGC DataPortalENSG00000137573
TCGA cBioPortalSULF1
AceView (NCBI)SULF1
Genatlas (Paris)SULF1
WikiGenes23213
SOURCE (Princeton)SULF1
Genetics Home Reference (NIH)SULF1
Genomic and cartography
GoldenPath hg38 (UCSC)SULF1  -     chr8:69466624-69660912 +  8q13.2-q13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SULF1  -     8q13.2-q13.3   [Description]    (hg19-Feb_2009)
EnsemblSULF1 - 8q13.2-q13.3 [CytoView hg19]  SULF1 - 8q13.2-q13.3 [CytoView hg38]
Mapping of homologs : NCBISULF1 [Mapview hg19]  SULF1 [Mapview hg38]
OMIM610012   
Gene and transcription
Genbank (Entrez)AB029000 AF545571 AK055467 AK055607 AK074873
RefSeq transcript (Entrez)NM_001128204 NM_001128205 NM_001128206 NM_015170
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SULF1
Cluster EST : UnigeneHs.409602 [ NCBI ]
CGAP (NCI)Hs.409602
Alternative Splicing GalleryENSG00000137573
Gene ExpressionSULF1 [ NCBI-GEO ]   SULF1 [ EBI - ARRAY_EXPRESS ]   SULF1 [ SEEK ]   SULF1 [ MEM ]
Gene Expression Viewer (FireBrowse)SULF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23213
GTEX Portal (Tissue expression)SULF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IWU6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IWU6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IWU6
Splice isoforms : SwissVarQ8IWU6
Catalytic activity : Enzyme3.1.6.- [ Enzyme-Expasy ]   3.1.6.-3.1.6.- [ IntEnz-EBI ]   3.1.6.- [ BRENDA ]   3.1.6.- [ KEGG ]   
PhosPhoSitePlusQ8IWU6
Domaine pattern : Prosite (Expaxy)SULFATASE_1 (PS00523)   
Domains : Interpro (EBI)Alkaline_Pase-like_a/b/a    Alkaline_phosphatase_core    Extracellular_sulfatase    Extracellular_sulfatase_C    Sulfatase_CS    Sulfatase_N   
Domain families : Pfam (Sanger)DUF3740 (PF12548)    Sulfatase (PF00884)   
Domain families : Pfam (NCBI)pfam12548    pfam00884   
Conserved Domain (NCBI)SULF1
DMDM Disease mutations23213
Blocks (Seattle)SULF1
SuperfamilyQ8IWU6
Human Protein AtlasENSG00000137573
Peptide AtlasQ8IWU6
HPRD15450
IPIIPI00293203   IPI00480012   IPI00985136   IPI00981167   IPI00981828   IPI00982475   IPI00980828   IPI00978157   
Protein Interaction databases
DIP (DOE-UCLA)Q8IWU6
IntAct (EBI)Q8IWU6
FunCoupENSG00000137573
BioGRIDSULF1
STRING (EMBL)SULF1
ZODIACSULF1
Ontologies - Pathways
QuickGOQ8IWU6
Ontology : AmiGOkidney development  negative regulation of endothelial cell proliferation  chondrocyte development  glomerular filtration  arylsulfatase activity  arylsulfatase activity  calcium ion binding  extracellular space  extracellular space  endoplasmic reticulum  Golgi apparatus  Golgi stack  plasma membrane  apoptotic process  N-acetylglucosamine-6-sulfatase activity  N-acetylglucosamine-6-sulfatase activity  cell surface  positive regulation of vascular endothelial growth factor production  esophagus smooth muscle contraction  negative regulation of angiogenesis  positive regulation of Wnt signaling pathway  heparan sulfate proteoglycan metabolic process  heparan sulfate proteoglycan metabolic process  negative regulation of cell migration  positive regulation of BMP signaling pathway  glomerular basement membrane development  glial cell-derived neurotrophic factor receptor signaling pathway  regulation of fibroblast growth factor receptor signaling pathway  negative regulation of fibroblast growth factor receptor signaling pathway  negative regulation of fibroblast growth factor receptor signaling pathway  membrane raft  vascular endothelial growth factor receptor signaling pathway  embryonic skeletal system development  cartilage development  bone development  innervation  negative regulation of prostatic bud formation  
Ontology : EGO-EBIkidney development  negative regulation of endothelial cell proliferation  chondrocyte development  glomerular filtration  arylsulfatase activity  arylsulfatase activity  calcium ion binding  extracellular space  extracellular space  endoplasmic reticulum  Golgi apparatus  Golgi stack  plasma membrane  apoptotic process  N-acetylglucosamine-6-sulfatase activity  N-acetylglucosamine-6-sulfatase activity  cell surface  positive regulation of vascular endothelial growth factor production  esophagus smooth muscle contraction  negative regulation of angiogenesis  positive regulation of Wnt signaling pathway  heparan sulfate proteoglycan metabolic process  heparan sulfate proteoglycan metabolic process  negative regulation of cell migration  positive regulation of BMP signaling pathway  glomerular basement membrane development  glial cell-derived neurotrophic factor receptor signaling pathway  regulation of fibroblast growth factor receptor signaling pathway  negative regulation of fibroblast growth factor receptor signaling pathway  negative regulation of fibroblast growth factor receptor signaling pathway  membrane raft  vascular endothelial growth factor receptor signaling pathway  embryonic skeletal system development  cartilage development  bone development  innervation  negative regulation of prostatic bud formation  
NDEx NetworkSULF1
Atlas of Cancer Signalling NetworkSULF1
Wikipedia pathwaysSULF1
Orthology - Evolution
OrthoDB23213
GeneTree (enSembl)ENSG00000137573
Phylogenetic Trees/Animal Genes : TreeFamSULF1
HOVERGENQ8IWU6
HOGENOMQ8IWU6
Homologs : HomoloGeneSULF1
Homology/Alignments : Family Browser (UCSC)SULF1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSULF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SULF1
dbVarSULF1
ClinVarSULF1
1000_GenomesSULF1 
Exome Variant ServerSULF1
ExAC (Exome Aggregation Consortium)SULF1 (select the gene name)
Genetic variants : HAPMAP23213
Genomic Variants (DGV)SULF1 [DGVbeta]
DECIPHERSULF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSULF1 
Mutations
ICGC Data PortalSULF1 
TCGA Data PortalSULF1 
Broad Tumor PortalSULF1
OASIS PortalSULF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSULF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSULF1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SULF1
DgiDB (Drug Gene Interaction Database)SULF1
DoCM (Curated mutations)SULF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SULF1 (select a term)
intoGenSULF1
NCG5 (London)SULF1
Cancer3DSULF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610012   
Orphanet
MedgenSULF1
Genetic Testing Registry SULF1
NextProtQ8IWU6 [Medical]
TSGene23213
GENETestsSULF1
Target ValidationSULF1
Huge Navigator SULF1 [HugePedia]
snp3D : Map Gene to Disease23213
BioCentury BCIQSULF1
ClinGenSULF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23213
Chemical/Pharm GKB GenePA134861022
Clinical trialSULF1
Miscellaneous
canSAR (ICR)SULF1 (select the gene name)
Probes
Litterature
PubMed98 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSULF1
EVEXSULF1
GoPubMedSULF1
iHOPSULF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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