UniProtKB - P15586 (GNS_HUMAN)
Protein
N-acetylglucosamine-6-sulfatase
Gene
GNS
Organism
Homo sapiens (Human)
Status
Functioni
Catalytic activityi
- Hydrolysis of the 6-sulfate groups of the N-acetyl-D-glucosamine 6-sulfate units of heparan sulfate and keratan sulfate. EC:3.1.6.14
Cofactori
Ca2+By similarityNote: Binds 1 Ca2+ ion per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 55 | CalciumBy similarity | 1 | |
Metal bindingi | 56 | CalciumBy similarity | 1 | |
Active sitei | 91 | NucleophileBy similarity | 1 | |
Metal bindingi | 91 | Calcium; via 3-oxoalanineBy similarity | 1 | |
Metal bindingi | 326 | CalciumBy similarity | 1 | |
Metal bindingi | 327 | CalciumBy similarity | 1 |
GO - Molecular functioni
- glycosaminoglycan binding Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- N-acetylglucosamine-6-sulfatase activity Source: GO_Central
- sulfuric ester hydrolase activity Source: MGI
GO - Biological processi
- glycosaminoglycan catabolic process Source: ProtInc
- keratan sulfate catabolic process Source: GO_Central
- neutrophil degranulation Source: Reactome
Keywordsi
Molecular function | Hydrolase |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06046-MONOMER |
BRENDAi | 3.1.6.14 2681 |
Reactomei | R-HSA-2022857 Keratan sulfate degradation R-HSA-2206305 MPS IIID - Sanfilippo syndrome D R-HSA-432720 Lysosome Vesicle Biogenesis R-HSA-6798695 Neutrophil degranulation |
SABIO-RKi | P15586 |
Names & Taxonomyi
Protein namesi | Recommended name: N-acetylglucosamine-6-sulfatase (EC:3.1.6.14)Alternative name(s): Glucosamine-6-sulfatase Short name: G6S |
Gene namesi | Name:GNS |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000135677.10 |
HGNCi | HGNC:4422 GNS |
MIMi | 607664 gene |
neXtProti | NX_P15586 |
Subcellular locationi
Lysosome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
Lysosome
- azurophil granule lumen Source: Reactome
- lysosomal lumen Source: Reactome
- lysosome Source: GO_Central
Other locations
- ficolin-1-rich granule lumen Source: Reactome
Keywords - Cellular componenti
LysosomePathology & Biotechi
Involvement in diseasei
Mucopolysaccharidosis 3D (MPS3D)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life.
See also OMIM:252940Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064070 | 94 | S → I in MPS3D. 1 Publication | 1 | |
Natural variantiVAR_064071 | 304 – 306 | Missing in MPS3D. 1 Publication | 3 | |
Natural variantiVAR_064072 | 340 | K → R in MPS3D. 1 Publication | 1 | |
Natural variantiVAR_064073 | 418 | G → E in MPS3D. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, MucopolysaccharidosisOrganism-specific databases
DisGeNETi | 2799 |
MalaCardsi | GNS |
MIMi | 252940 phenotype |
OpenTargetsi | ENSG00000135677 |
Orphaneti | 79272 Sanfilippo syndrome type D |
PharmGKBi | PA28802 |
Polymorphism and mutation databases
BioMutai | GNS |
DMDMi | 232126 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 36 | Add BLAST | 36 | |
ChainiPRO_0000033413 | 37 – 552 | N-acetylglucosamine-6-sulfataseAdd BLAST | 516 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 91 | 3-oxoalanine (Cys)By similarity | 1 | |
Glycosylationi | 111 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 117 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 183 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 198 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 210 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 279 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 317 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 362 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 387 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 405 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 422 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 449 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 480 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 541 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
The form A (78 kDa) is processed by internal peptidase cleavage to a 32 kDa N-terminal species (form B) and a 48 kDa C-terminal species.
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
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | P15586 |
jPOSTi | P15586 |
MaxQBi | P15586 |
PaxDbi | P15586 |
PeptideAtlasi | P15586 |
PRIDEi | P15586 |
ProteomicsDBi | 53189 |
PTM databases
GlyConnecti | 796 |
iPTMneti | P15586 |
PhosphoSitePlusi | P15586 |
UniCarbKBi | P15586 |
Expressioni
Gene expression databases
Bgeei | ENSG00000135677 Expressed in 239 organ(s), highest expression level in metanephros |
ExpressionAtlasi | P15586 baseline and differential |
Genevisiblei | P15586 HS |
Organism-specific databases
HPAi | CAB026011 HPA013695 HPA048508 |
Interactioni
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
NCK1 | P16333 | 2 | EBI-1752200,EBI-389883 |
Protein-protein interaction databases
BioGridi | 109061, 34 interactors |
IntActi | P15586, 14 interactors |
MINTi | P15586 |
STRINGi | 9606.ENSP00000258145 |
Family & Domainsi
Sequence similaritiesi
Belongs to the sulfatase family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3731 Eukaryota COG3119 LUCA |
GeneTreei | ENSGT00940000158420 |
HOGENOMi | HOG000169239 |
HOVERGENi | HBG005840 |
InParanoidi | P15586 |
KOi | K01137 |
OrthoDBi | 1454612at2759 |
PhylomeDBi | P15586 |
TreeFami | TF313545 |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017849 Alkaline_Pase-like_a/b/a IPR017850 Alkaline_phosphatase_core_sf IPR012251 GlcNAc_6-SO4ase IPR015981 GlcNAc_6-SO4ase_met IPR024607 Sulfatase_CS IPR000917 Sulfatase_N |
PANTHERi | PTHR43108:SF5 PTHR43108:SF5, 1 hit |
Pfami | View protein in Pfam PF00884 Sulfatase, 1 hit |
PIRSFi | PIRSF036666 G6S, 1 hit |
SUPFAMi | SSF53649 SSF53649, 1 hit |
PROSITEi | View protein in PROSITE PS00523 SULFATASE_1, 1 hit PS00149 SULFATASE_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P15586-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MRLLPLAPGR LRRGSPRHLP SCSPALLLLV LGGCLGVFGV AAGTRRPNVV
60 70 80 90 100
LLLTDDQDEV LGGMTPLKKT KALIGEMGMT FSSAYVPSAL CCPSRASILT
110 120 130 140 150
GKYPHNHHVV NNTLEGNCSS KSWQKIQEPN TFPAILRSMC GYQTFFAGKY
160 170 180 190 200
LNEYGAPDAG GLEHVPLGWS YWYALEKNSK YYNYTLSING KARKHGENYS
210 220 230 240 250
VDYLTDVLAN VSLDFLDYKS NFEPFFMMIA TPAPHSPWTA APQYQKAFQN
260 270 280 290 300
VFAPRNKNFN IHGTNKHWLI RQAKTPMTNS SIQFLDNAFR KRWQTLLSVD
310 320 330 340 350
DLVEKLVKRL EFTGELNNTY IFYTSDNGYH TGQFSLPIDK RQLYEFDIKV
360 370 380 390 400
PLLVRGPGIK PNQTSKMLVA NIDLGPTILD IAGYDLNKTQ MDGMSLLPIL
410 420 430 440 450
RGASNLTWRS DVLVEYQGEG RNVTDPTCPS LSPGVSQCFP DCVCEDAYNN
460 470 480 490 500
TYACVRTMSA LWNLQYCEFD DQEVFVEVYN LTADPDQITN IAKTIDPELL
510 520 530 540 550
GKMNYRLMML QSCSGPTCRT PGVFDPGYRF DPRLMFSNRG SVRTRRFSKH
LL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7C3P4 | H7C3P4_HUMAN | N-acetylglucosamine-6-sulfatase | GNS hCG_1640559 | 496 | Annotation score: | ||
F6S8M0 | F6S8M0_HUMAN | N-acetylglucosamine-6-sulfatase | GNS | 584 | Annotation score: | ||
F5H4C6 | F5H4C6_HUMAN | N-acetylglucosamine-6-sulfatase | GNS | 247 | Annotation score: | ||
H0YFA9 | H0YFA9_HUMAN | N-acetylglucosamine-6-sulfatase | GNS | 303 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 252 | F → C in BAD97204 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064070 | 94 | S → I in MPS3D. 1 Publication | 1 | |
Natural variantiVAR_064071 | 304 – 306 | Missing in MPS3D. 1 Publication | 3 | |
Natural variantiVAR_064072 | 340 | K → R in MPS3D. 1 Publication | 1 | |
Natural variantiVAR_064073 | 418 | G → E in MPS3D. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056486 | 65 – 84 | Missing in isoform 2. 1 PublicationAdd BLAST | 20 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z12173 mRNA Translation: CAA78164.1 AK302443 mRNA Translation: BAG63740.1 AK223484 mRNA Translation: BAD97204.1 AC025262 Genomic DNA No translation available. BC012482 mRNA Translation: AAH12482.1 |
CCDSi | CCDS8970.1 [P15586-1] |
PIRi | S27164 KJHUGU |
RefSeqi | NP_002067.1, NM_002076.3 [P15586-1] |
UniGenei | Hs.334534 |
Genome annotation databases
Ensembli | ENST00000258145; ENSP00000258145; ENSG00000135677 [P15586-1] ENST00000542058; ENSP00000444819; ENSG00000135677 [P15586-2] |
GeneIDi | 2799 |
KEGGi | hsa:2799 |
UCSCi | uc001ssg.5 human [P15586-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z12173 mRNA Translation: CAA78164.1 AK302443 mRNA Translation: BAG63740.1 AK223484 mRNA Translation: BAD97204.1 AC025262 Genomic DNA No translation available. BC012482 mRNA Translation: AAH12482.1 |
CCDSi | CCDS8970.1 [P15586-1] |
PIRi | S27164 KJHUGU |
RefSeqi | NP_002067.1, NM_002076.3 [P15586-1] |
UniGenei | Hs.334534 |
3D structure databases
ProteinModelPortali | P15586 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 109061, 34 interactors |
IntActi | P15586, 14 interactors |
MINTi | P15586 |
STRINGi | 9606.ENSP00000258145 |
PTM databases
GlyConnecti | 796 |
iPTMneti | P15586 |
PhosphoSitePlusi | P15586 |
UniCarbKBi | P15586 |
Polymorphism and mutation databases
BioMutai | GNS |
DMDMi | 232126 |
Proteomic databases
EPDi | P15586 |
jPOSTi | P15586 |
MaxQBi | P15586 |
PaxDbi | P15586 |
PeptideAtlasi | P15586 |
PRIDEi | P15586 |
ProteomicsDBi | 53189 |
Protocols and materials databases
DNASUi | 2799 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000258145; ENSP00000258145; ENSG00000135677 [P15586-1] ENST00000542058; ENSP00000444819; ENSG00000135677 [P15586-2] |
GeneIDi | 2799 |
KEGGi | hsa:2799 |
UCSCi | uc001ssg.5 human [P15586-1] |
Organism-specific databases
CTDi | 2799 |
DisGeNETi | 2799 |
EuPathDBi | HostDB:ENSG00000135677.10 |
GeneCardsi | GNS |
H-InvDBi | HIX0010785 |
HGNCi | HGNC:4422 GNS |
HPAi | CAB026011 HPA013695 HPA048508 |
MalaCardsi | GNS |
MIMi | 252940 phenotype 607664 gene |
neXtProti | NX_P15586 |
OpenTargetsi | ENSG00000135677 |
Orphaneti | 79272 Sanfilippo syndrome type D |
PharmGKBi | PA28802 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3731 Eukaryota COG3119 LUCA |
GeneTreei | ENSGT00940000158420 |
HOGENOMi | HOG000169239 |
HOVERGENi | HBG005840 |
InParanoidi | P15586 |
KOi | K01137 |
OrthoDBi | 1454612at2759 |
PhylomeDBi | P15586 |
TreeFami | TF313545 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06046-MONOMER |
BRENDAi | 3.1.6.14 2681 |
Reactomei | R-HSA-2022857 Keratan sulfate degradation R-HSA-2206305 MPS IIID - Sanfilippo syndrome D R-HSA-432720 Lysosome Vesicle Biogenesis R-HSA-6798695 Neutrophil degranulation |
SABIO-RKi | P15586 |
Miscellaneous databases
ChiTaRSi | GNS human |
GenomeRNAii | 2799 |
PROi | PR:P15586 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000135677 Expressed in 239 organ(s), highest expression level in metanephros |
ExpressionAtlasi | P15586 baseline and differential |
Genevisiblei | P15586 HS |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017849 Alkaline_Pase-like_a/b/a IPR017850 Alkaline_phosphatase_core_sf IPR012251 GlcNAc_6-SO4ase IPR015981 GlcNAc_6-SO4ase_met IPR024607 Sulfatase_CS IPR000917 Sulfatase_N |
PANTHERi | PTHR43108:SF5 PTHR43108:SF5, 1 hit |
Pfami | View protein in Pfam PF00884 Sulfatase, 1 hit |
PIRSFi | PIRSF036666 G6S, 1 hit |
SUPFAMi | SSF53649 SSF53649, 1 hit |
PROSITEi | View protein in PROSITE PS00523 SULFATASE_1, 1 hit PS00149 SULFATASE_2, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | GNS_HUMAN | |
Accessioni | P15586Primary (citable) accession number: P15586 Secondary accession number(s): B4DYH8, Q53F05 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
Last sequence update: | April 1, 1993 | |
Last modified: | February 13, 2019 | |
This is version 178 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations