P15586 (GNS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-acetylglucosamine-6-sulfatase
EC=3.1.6.14

Alternative name(s):
Glucosamine-6-sulfatase
Short name=G6S

Gene names

Name:

GNS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	552 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)

Catalytic activity	Hydrolysis of the 6-sulfate groups of the N-acetyl-D-glucosamine 6-sulfate units of heparan sulfate and keratan sulfate.
Cofactor	Binds 1 calcium ion per subunit By similarity.
Subcellular location	Lysosome.
Post-translational modification	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.
Involvement in disease	Defects in GNS are the cause of mucopolysaccharidosis type 3D (MPS3D) [MIM:252940]; also known as Sanfilippo D syndrome. MPS3D is a 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. Ref.8 Ref.10
Sequence similarities	Belongs to the sulfatase family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mucopolysaccharidosis
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	N-acetylglucosamine-6-sulfatase activity Traceable author statement. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1752200,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 36	36
	Chain	37 – 552	516	N-acetylglucosamine-6-sulfatase		PRO_0000033413
Sites
	Metal binding	55	1	Calcium By similarity
	Metal binding	56	1	Calcium By similarity
	Metal binding	91	1	Calcium; via 3-oxoalanine By similarity
	Metal binding	326	1	Calcium By similarity
	Metal binding	327	1	Calcium By similarity
Amino acid modifications
	Modified residue	91	1	3-oxoalanine (Cys) By similarity
	Glycosylation	111	1	N-linked (GlcNAc...) Potential
	Glycosylation	117	1	N-linked (GlcNAc...) Potential
	Glycosylation	183	1	N-linked (GlcNAc...) Ref.6 Ref.7
	Glycosylation	198	1	N-linked (GlcNAc...) Potential
	Glycosylation	210	1	N-linked (GlcNAc...) Potential
	Glycosylation	279	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	317	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	362	1	N-linked (GlcNAc...) Potential
	Glycosylation	387	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	405	1	N-linked (GlcNAc...) Potential
	Glycosylation	422	1	N-linked (GlcNAc...) Ref.1 Ref.7
	Glycosylation	449	1	N-linked (GlcNAc...) Potential
	Glycosylation	480	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	94	1	S → I in MPS3D. Ref.10		VAR_064070
	Natural variant	304 – 306	3	Missing in MPS3D.		VAR_064071
	Natural variant	340	1	K → R in MPS3D. Ref.10		VAR_064072
	Natural variant	418	1	G → E in MPS3D. Ref.10		VAR_064073
	Natural variant	550	1	H → Q. Corresponds to variant rs2230292 [ dbSNP | Ensembl ].		VAR_064074
Experimental info
	Sequence conflict	252	1	F → C in BAD97204. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P15586 [UniParc]. Last modified April 1, 1993. Version 3. Checksum: 85094043F6E64468	FASTA	552	62,082
	10 20 30 40 50 60 MRLLPLAPGR LRRGSPRHLP SCSPALLLLV LGGCLGVFGV AAGTRRPNVV LLLTDDQDEV 70 80 90 100 110 120 LGGMTPLKKT KALIGEMGMT FSSAYVPSAL CCPSRASILT GKYPHNHHVV NNTLEGNCSS 130 140 150 160 170 180 KSWQKIQEPN TFPAILRSMC GYQTFFAGKY LNEYGAPDAG GLEHVPLGWS YWYALEKNSK 190 200 210 220 230 240 YYNYTLSING KARKHGENYS VDYLTDVLAN VSLDFLDYKS NFEPFFMMIA TPAPHSPWTA 250 260 270 280 290 300 APQYQKAFQN VFAPRNKNFN IHGTNKHWLI RQAKTPMTNS SIQFLDNAFR KRWQTLLSVD 310 320 330 340 350 360 DLVEKLVKRL EFTGELNNTY IFYTSDNGYH TGQFSLPIDK RQLYEFDIKV PLLVRGPGIK 370 380 390 400 410 420 PNQTSKMLVA NIDLGPTILD IAGYDLNKTQ MDGMSLLPIL RGASNLTWRS DVLVEYQGEG 430 440 450 460 470 480 RNVTDPTCPS LSPGVSQCFP DCVCEDAYNN TYACVRTMSA LWNLQYCEFD DQEVFVEVYN 490 500 510 520 530 540 LTADPDQITN IAKTIDPELL GKMNYRLMML QSCSGPTCRT PGVFDPGYRF DPRLMFSNRG 550 SVRTRRFSKH LL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cDNA clone for human glucosamine-6-sulphatase reveals differences between arylsulphatases and non-arylsulphatases." Robertson D.A., Freeman C., Morris C.P., Hopwood J.J. Biochem. J. 288:539-544(1992) [PubMed: 1463457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-422. Tissue: Endothelial cell.
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[5]	"Human glucosamine-6-sulfatase cDNA reveals homology with steroid sulfatase." Robertson D.A., Freeman C., Nelson P.V., Morris C.P., Hopwood J.J. Biochem. Biophys. Res. Commun. 157:218-224(1988) [PubMed: 3196333] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 178-552, PARTIAL PROTEIN SEQUENCE.
[6]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-183 AND ASN-279.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-183; ASN-317; ASN-387 AND ASN-422, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase." Mok A., Cao H., Hegele R.A. Genomics 81:1-5(2003) [PubMed: 12573255] [Abstract] Cited for: INVOLVEMENT IN MPS3D.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations." Valstar M.J., Bertoli-Avella A.M., Wessels M.W., Ruijter G.J.G., de Graaf B., Olmer R., Elfferich P., Neijs S., Kariminejad R., Suheyl Ezgue F., Tokatli A., Czartoryska B., Bosschaart A.N., van den Bos-Terpstra F., Puissant H., Buerger F., Omran H., Eckert D. , Filocamo M., Simeonov E., Willems P.J., Wevers R.A., Niermeijer M.F., Halley D.J.J., Poorthuis B.J.H.M., van Diggelen O.P. Hum. Mutat. 31:E1348-E1360(2010) [PubMed: 20232353] [Abstract] Cited for: VARIANTS MPS3D ILE-94; 304-GLU--LEU-306 DEL; ARG-340 AND GLU-418.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z12173 mRNA. Translation: CAA78164.1. AK223484 mRNA. Translation: BAD97204.1. AC025262 Genomic DNA. No translation available. BC012482 mRNA. Translation: AAH12482.1.
IPI	IPI00012102.
PIR	KJHUGU. S27164.
RefSeq	NP_002067.1. NM_002076.3.
UniGene	Hs.334534.
3D structure databases
ProteinModelPortal	P15586.
SMR	P15586. Positions 289-397.
ModBase	Search...
Protein-protein interaction databases
IntAct	P15586. 7 interactions.
STRING	P15586.
Polymorphism databases
DMDM	232126.
Proteomic databases
PeptideAtlas	P15586.
PRIDE	P15586.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258145; ENSP00000258145; ENSG00000135677.
GeneID	2799.
KEGG	hsa:2799.
UCSC	uc001ssg.2. human.
Organism-specific databases
CTD	2799.
GeneCards	GC12M065107.
H-InvDB	HIX0010785.
HGNC	HGNC:4422. GNS.
HPA	CAB026011. HPA013695.
MIM	252940. phenotype. 607664. gene.
neXtProt	NX_P15586.
Orphanet	79272. Sanfilippo syndrome type D.
PharmGKB	PA28802.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17579.
HOVERGEN	HBG005840.
InParanoid	P15586.
OrthoDB	EOG4NGGMF.
PhylomeDB	P15586.
Enzyme and pathway databases
BioCyc	MetaCyc:HS06046-MONOMER.
BRENDA	3.1.6.14. 2681.
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	P15586.
Bgee	P15586.
CleanEx	HS_GNS.
Genevestigator	P15586.
GermOnline	ENSG00000135677. Homo sapiens.
Family and domain databases
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR017850. Alkaline_phosphatase_core. IPR012251. GlcNAc_6-SO4ase. IPR015981. GlcNAc_6-SO4ase_euk. IPR000917. Sulfatase. IPR024607. Sulfatase_CS. [Graphical view]
Gene3D	G3DSA:3.40.720.10. Alk_phosphtse. 3 hits.
KO	K01137.
PANTHER	PTHR10342:SF5. G6S. 1 hit.
Pfam	PF00884. Sulfatase. 1 hit. [Graphical view]
PIRSF	PIRSF036666. G6S. 1 hit.
SUPFAM	SSF53649. Alkaline_phosphatase_core. 1 hit.
PROSITE	PS00523. SULFATASE_1. 1 hit. PS00149. SULFATASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	11033.
SOURCE	Search...

Entry information

Entry name

GNS_HUMAN

Accession

Primary (citable) accession number: P15586
Secondary accession number(s): Q53F05

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1993
Last modified:	January 25, 2012
This is version 112 of the entry and version 3 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.