Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., ... See more...

Aliases for SULF2 Gene

Aliases for SULF2 Gene

  • Sulfatase 2 2 3 5
  • Extracellular Sulfatase Sulf-2 3 4
  • EC 3.1.6.14 52
  • EC 3.1.6.- 4
  • KIAA1247 4
  • EC 3.1.6 52
  • HSULF-2 3
  • HSulf-2 4

External Ids for SULF2 Gene

Previous GeneCards Identifiers for SULF2 Gene

  • GC20M045974
  • GC20M046924
  • GC20M046971
  • GC20M045719
  • GC20M046285
  • GC20M043027

Summaries for SULF2 Gene

Entrez Gene Summary for SULF2 Gene

  • Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., 2005 [PubMed 16192265]).[supplied by OMIM, Mar 2008]

GeneCards Summary for SULF2 Gene

SULF2 (Sulfatase 2) is a Protein Coding gene. Diseases associated with SULF2 include Achondrogenesis, Type Ib and Atelosteogenesis. Gene Ontology (GO) annotations related to this gene include calcium ion binding and arylsulfatase activity. An important paralog of this gene is SULF1.

UniProtKB/Swiss-Prot Summary for SULF2 Gene

  • Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin.

Gene Wiki entry for SULF2 Gene

Additional gene information for SULF2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SULF2 Gene

Genomics for SULF2 Gene

GeneHancer (GH) Regulatory Elements for SULF2 Gene

Promoters and enhancers for SULF2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20J047783 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +1.5 1516 4.2 CTCF ZBTB26 REST KLF4 ZBTB25 TGIF2 RAD21 SKI TRIM22 TEAD1 SULF2 lnc-NCOA3-23 RF00017-3611 lnc-NCOA3-4
GH20J047787 Promoter/Enhancer 0.5 Ensembl dbSUPER 500.7 -0.9 -872 0.2 SULF2 lnc-NCOA3-23 lnc-SULF2-6 lnc-NCOA3-4
GH20J047857 Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas dbSUPER 15.8 -71.4 -71381 2.4 ZNF217 RFX1 CHD1 ATF2 NFYB CTBP1 OSR2 HCFC1 SIN3A ESRRA SRMP1 SULF2 LOC105372636 lnc-NCOA3-4
GH20J047808 Enhancer 1.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 14.6 -23.3 -23301 2.5 KLF4 CTBP1 HES1 ZNF592 GABPA FOS MLLT1 ELF1 ZNF512B RCOR1 SULF2 lnc-SULF2-8 lnc-SULF2-6 lnc-NCOA3-4
GH20J048002 Enhancer 1.3 FANTOM5 Ensembl ENCODE 15.9 -218.1 -218072 6.6 ZNF217 SP1 RFX1 KLF4 CUX1 CHD1 TRIM22 GATAD2B CTBP1 BCL11A SULF2 ENSG00000228503 lnc-NCOA3-31 lnc-NCOA3-30 ENSG00000286179
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SULF2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SULF2

Top Transcription factor binding sites by QIAGEN in the SULF2 gene promoter:
  • AML1a
  • c-Myc
  • FOXI1
  • HFH-3
  • Max1
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2
  • Nkx6-1
  • Pax-4a

Genomic Locations for SULF2 Gene

Genomic Locations for SULF2 Gene
chr20:47,656,348-47,786,629
(GRCh38/hg38)
Size:
130,282 bases
Orientation:
Minus strand
chr20:46,285,092-46,415,360
(GRCh37/hg19)
Size:
130,269 bases
Orientation:
Minus strand

Genomic View for SULF2 Gene

Genes around SULF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SULF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SULF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SULF2 Gene

Proteins for SULF2 Gene

  • Protein details for SULF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IWU5-SULF2_HUMAN
    Recommended name:
    Extracellular sulfatase Sulf-2
    Protein Accession:
    Q8IWU5
    Secondary Accessions:
    • E1P5U6
    • Q5JYE1
    • Q6UX86
    • Q96SG2
    • Q9H1H0
    • Q9UJR3
    • Q9ULH3

    Protein attributes for SULF2 Gene

    Size:
    870 amino acids
    Molecular mass:
    100455 Da
    Cofactor:
    Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • [Isoform 2]: May be due to a competing acceptor splice site.
    SequenceCaution:
    • Sequence=AAH20962.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA86561.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAB61349.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for SULF2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SULF2 Gene

Selected DME Specific Peptides for SULF2 Gene

Q8IWU5:
  • GYKQCNPR
  • LTGKYVHNHN
  • PIHMEFTN
  • TGYRTAFFGKYLNEYNGSY
  • NNNTYWC
  • GKYLNEY
  • NIRPNIILVLTDDQDVELGS
  • RTFAVYLN
  • NETHNFL
  • YTNNENCSSPSWQA
  • FDIRVPF
  • YTADHGYHIGQFGLVKGKSMPY
  • KNSRFYNYT
  • IVLNIDLAPTILDIAGLD
  • YQTACEQ
  • TTPMCCP
  • PNASQHITPSYNYAPN
  • PGLTCFTHDN
  • APHGPED

Post-translational modifications for SULF2 Gene

  • 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.
  • Glycosylation at Asn65, Asn112, Asn132, Asn149, Asn171, Asn198, Asn241, Asn561, Asn608, Asn717, Asn754, and Asn764
  • Ubiquitination at Lys694, Lys834, and Lys859
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • SULF2_HUMAN (1232)

Domains & Families for SULF2 Gene

Gene Families for SULF2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for SULF2 Gene

Suggested Antigen Peptide Sequences for SULF2 Gene

GenScript: Design optimal peptide antigens:
  • SULF2 protein (Q5BKT1_HUMAN)
  • SULF2 protein (Q6DKK3_HUMAN)
  • Extracellular sulfatase Sulf-2 (SULF2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IWU5

UniProtKB/Swiss-Prot:

SULF2_HUMAN :
  • Belongs to the sulfatase family.
Family:
  • Belongs to the sulfatase family.
genes like me logo Genes that share domains with SULF2: view

Function for SULF2 Gene

Molecular function for SULF2 Gene

UniProtKB/Swiss-Prot Function:
Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 7.0-8.0.;

Enzyme Numbers (IUBMB) for SULF2 Gene

Phenotypes From GWAS Catalog for SULF2 Gene

Gene Ontology (GO) - Molecular Function for SULF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004065 arylsulfatase activity IMP 19520866
GO:0005509 calcium ion binding IEA --
GO:0005539 glycosaminoglycan binding IBA 21873635
GO:0008449 N-acetylglucosamine-6-sulfatase activity IBA,IMP 19520866
genes like me logo Genes that share ontologies with SULF2: view
genes like me logo Genes that share phenotypes with SULF2: view

Animal Models for SULF2 Gene

MGI Knock Outs for SULF2:

Animal Model Products

  • Taconic Biosciences Mouse Models for SULF2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SULF2

Clone Products

  • Addgene plasmids for SULF2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SULF2 Gene

Localization for SULF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SULF2 Gene

Endoplasmic reticulum. Golgi apparatus, Golgi stack. Cell surface. Note=Also localized on the cell surface. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SULF2 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
plasma membrane 4
golgi apparatus 4
lysosome 3
cytoskeleton 2
mitochondrion 2
nucleus 2
cytosol 2
peroxisome 1
endosome 1

Gene Ontology (GO) - Cellular Components for SULF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space NAS 12368295
GO:0005783 endoplasmic reticulum IDA,IBA 18687675
GO:0005794 Golgi apparatus IEA --
GO:0005795 Golgi stack IEA --
GO:0005886 plasma membrane IBA,ISS --
genes like me logo Genes that share ontologies with SULF2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SULF2 Gene

Pathways & Interactions for SULF2 Gene

PathCards logo

SuperPathways for SULF2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SULF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001822 kidney development ISS --
GO:0002063 chondrocyte development ISS --
GO:0003094 glomerular filtration ISS --
GO:0009611 response to wounding IEA --
GO:0010575 positive regulation of vascular endothelial growth factor production ISS --
genes like me logo Genes that share ontologies with SULF2: view

No data available for Pathways by source and SIGNOR curated interactions for SULF2 Gene

Drugs & Compounds for SULF2 Gene

(3) Drugs for SULF2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884

(1) Additional Compounds for SULF2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SULF2: view

Transcripts for SULF2 Gene

mRNA/cDNA for SULF2 Gene

3 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SULF2

Clone Products

  • Addgene plasmids for SULF2

Alternative Splicing Database (ASD) splice patterns (SP) for SULF2 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^
SP1:
SP2:
SP3:
SP4:
SP5: - -
SP6: -
SP7: - - -
SP8:
SP9:
SP10: -

ExUns: 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22a · 22b
SP1:
SP2: -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:

Relevant External Links for SULF2 Gene

GeneLoc Exon Structure for
SULF2

Expression for SULF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SULF2 Gene

Protein differential expression in normal tissues from HIPED for SULF2 Gene

This gene is overexpressed in Urine (60.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SULF2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SULF2

SOURCE GeneReport for Unigene cluster for SULF2 Gene:

Hs.162016

mRNA Expression by UniProt/SwissProt for SULF2 Gene:

Q8IWU5-SULF2_HUMAN
Tissue specificity: Expressed at highest levels in the ovary, skeletal muscle, stomach, brain, uterus, heart, kidney and placenta.

Evidence on tissue expression from TISSUES for SULF2 Gene

  • Nervous system(4.6)
  • Intestine(4.4)
  • Liver(4.4)
  • Lung(4.3)
  • Skin(4.2)
genes like me logo Genes that share expression patterns with SULF2: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SULF2 Gene

Orthologs for SULF2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SULF2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SULF2 30
  • 97.31 (n)
dog
(Canis familiaris)
Mammalia SULF2 31 30
  • 91.56 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SULF2 31 30
  • 91.45 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SULF2 31
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sulf2 30
  • 88.26 (n)
mouse
(Mus musculus)
Mammalia Sulf2 17 31 30
  • 87.99 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SULF2 31
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves SULF2 31 30
  • 76.75 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SULF2 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sulf2 30
  • 75.76 (n)
Str.5319 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.15452 30
zebrafish
(Danio rerio)
Actinopterygii sulf2b 31 30
  • 73.32 (n)
OneToMany
sulf2a 31
  • 68 (a)
OneToMany
zgc55612 30
fruit fly
(Drosophila melanogaster)
Insecta Sulf1 31
  • 34 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sul-1 31
  • 44 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 42 (a)
OneToMany
Species where no ortholog for SULF2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SULF2 Gene

ENSEMBL:
Gene Tree for SULF2 (if available)
TreeFam:
Gene Tree for SULF2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SULF2: view image

Paralogs for SULF2 Gene

(4) SIMAP similar genes for SULF2 Gene using alignment to 6 proteins:

  • SULF2_HUMAN
  • B1AMP9_HUMAN
  • G3XAE6_HUMAN
  • H0Y872_HUMAN
  • Q5BKT1_HUMAN
  • Q6DKK3_HUMAN
genes like me logo Genes that share paralogs with SULF2: view

Variants for SULF2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SULF2 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
VAR_036494 A breast cancer sample p.Tyr531His
VAR_036495 A breast cancer sample p.Asp573Asn
rs10048853 - p.Arg674His
rs56218501 - p.Ala76Thr

Additional dbSNP identifiers (rs#s) for SULF2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SULF2 Gene

Variant ID Type Subtype PubMed ID
dgv4322n100 CNV loss 25217958
esv2650626 CNV insertion 19546169
esv2678560 CNV deletion 23128226
esv2758799 CNV gain 17122850
esv3645974 CNV loss 21293372
esv3645976 CNV gain 21293372
nsv1066907 CNV gain 25217958
nsv1073065 CNV deletion 25765185
nsv1076839 CNV insertion 25765185
nsv1133507 CNV deletion 24896259
nsv1143986 CNV deletion 24896259
nsv3396 CNV insertion 18451855
nsv3397 CNV deletion 18451855
nsv469534 CNV loss 16826518
nsv513547 CNV insertion 21212237
nsv524279 CNV loss 19592680
nsv586156 CNV gain 21841781
nsv833995 CNV loss 17160897

Variation tolerance for SULF2 Gene

Residual Variation Intolerance Score: 11.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.66; 72.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SULF2 Gene

Human Gene Mutation Database (HGMD)
SULF2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SULF2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SULF2 Gene

Disorders for SULF2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for SULF2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
achondrogenesis, type ib
  • acg1b
atelosteogenesis
  • atelosteogenesis, type 1
breast adenocarcinoma
  • adenocarcinoma of breast
breast cancer
  • breast cancer, familial
- elite association - COSMIC cancer census association via MalaCards
Search SULF2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SULF2

genes like me logo Genes that share disorders with SULF2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SULF2 Gene

Publications for SULF2 Gene

  1. Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. (PMID: 12368295) Morimoto-Tomita M … Rosen SD (The Journal of biological chemistry 2002) 2 3 4 54
  2. Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. (PMID: 18937294) Lasky-Su J … Faraone SV (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2008) 3 41 54
  3. HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1. (PMID: 16417632) Uchimura K … Rosen SD (BMC biochemistry 2006) 3 23 54
  4. HSulf-1 and HSulf-2 are potent inhibitors of myeloma tumor growth in vivo. (PMID: 16192265) Dai Y … Sanderson RD (The Journal of biological chemistry 2005) 3 23 54
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54

Products for SULF2 Gene

Sources for SULF2 Gene