Q9Y4C5 (CHST2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbohydrate sulfotransferase 2
EC=2.8.2.-

Alternative name(s):
Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 2
Short name=GST-2
N-acetylglucosamine 6-O-sulfotransferase 1
Short name=GlcNAc6ST-1
Short name=Gn6ST-1

Gene names

Name:	CHST2
Synonyms:	GN6ST

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues within keratan-like structures on N-linked glycans and within mucin-associated glycans that can ultimately serve as SELL ligands. SELL ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. Participates in biosynthesis of the SELL ligand sialyl 6-sulfo Lewis X and in lymphocyte homing to Peyer patches. Has no activity toward O-linked sugars. Its substrate specificity may be influenced by its subcellular location. Sulfates GlcNAc residues at terminal, non-reducing ends of oligosaccharide chains. Ref.4
Subunit structure	Homodimer; disulfide-linked. Homodimerization is not essential for enzyme activity. Ref.12
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Single-pass type II membrane protein Probable Ref.10.
Tissue specificity	Widely expressed. Highly expressed in bone marrow, peripheral blood leukocytes, spleen, brain, spinal cord, ovary and placenta. Expressed by high endothelial cells (HEVs) and leukocytes. Ref.1 Ref.3 Ref.7
Induction	Up-regulated upon cytokine activation. Ref.7
Sequence similarities	Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Caution	It is uncertain whether Met-1 or Met-48 is the initiator.
Biophysicochemical properties	Kinetic parameters: KM=3.9 µM for PAPS Ref.8 KM=1.4 mM for BetaBnO-GlcNAc
Sequence caution	The sequence BAA34265.2 differs from that shown. Reason: Erroneous initiation. The sequence BAB16886.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB16887.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Inflammatory response
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative initiation
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	N-acetylglucosamine metabolic process Inferred from direct assay Ref.1. Source: UniProtKB carbohydrate metabolic process Traceable author statement. Source: Reactome inflammatory response Traceable author statement Ref.3. Source: ProtInc keratan sulfate biosynthetic process Traceable author statement. Source: Reactome multicellular organismal development Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intrinsic to Golgi membrane Non-traceable author statement Ref.10. Source: UniProtKB trans-Golgi network Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	N-acetylglucosamine 6-O-sulfotransferase activity Inferred from direct assay Ref.4Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: Q9Y4C5-1)

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.

Note: No experimental confirmation available.

Isoform 2 (identifier: Q9Y4C5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 530	530	Carbohydrate sulfotransferase 2		PRO_0000085186
Regions
	Topological domain	1 – 54	54	Cytoplasmic Potential
	Transmembrane	55 – 75	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	76 – 530	455	Lumenal Potential
	Nucleotide binding	173 – 179	7	PAPS Probable
	Nucleotide binding	332 – 340	9	PAPS Probable
Amino acid modifications
	Glycosylation	152	1	N-linked (GlcNAc...) Potential
	Glycosylation	243	1	N-linked (GlcNAc...) Potential
	Glycosylation	457	1	N-linked (GlcNAc...) Potential
	Glycosylation	475	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 47	47	Missing in isoform 2.		VSP_018887
Experimental info
	Mutagenesis	59	1	C → S: Does not affect homodimerization. Abolishes homodimerization but not enzyme activity; when associated with S-39. Ref.12
	Mutagenesis	86	1	C → S: Induces migration in both homodimeric and monomeric forms. Abolishes homodimerization but not enzyme activity; when associated with S-12. Ref.12
	Mutagenesis	174	1	R → A: Induces a strong decrease in enzyme activity. Ref.8
	Mutagenesis	296	1	R → A: Induces a strong decrease in enzyme activity. Ref.8
	Mutagenesis	304	1	K → A: Loss of function. Ref.8
	Mutagenesis	332	1	R → A: Loss of function. Ref.8
	Mutagenesis	341	1	R → A: Induces a strong decrease in enzyme activity. Ref.8
	Mutagenesis	518	1	K → A: Has weak or no effect. Ref.11
	Mutagenesis	519	1	D → A: Has weak or no effect. Ref.11
	Mutagenesis	520	1	L → A: Has weak or no effect. Ref.11
	Mutagenesis	521	1	S → A: No effect. Ref.11
	Mutagenesis	522	1	K → A: No effect. Ref.11
	Mutagenesis	523	1	T → A: Has weak or no effect. Ref.11
	Mutagenesis	524	1	L → A or T: Induces a strong decrease in enzyme activity. Ref.11
	Mutagenesis	525	1	L → A: Induces a strong decrease in enzyme activity. Ref.11
	Mutagenesis	525	1	L → T: Has weak or no effect. Ref.11
	Mutagenesis	526	1	R → A: Has weak or no effect. Ref.11
	Mutagenesis	527	1	K → A: No effect. Ref.11
	Mutagenesis	528	1	P → A: Has weak or no effect. Ref.11
	Mutagenesis	529	1	R → A: No effect. Ref.11
	Mutagenesis	530	1	L → A or T: Induces a strong decrease in enzyme activity. Ref.11
	Sequence conflict	8	1	A → V in BAB16887. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 2. Checksum: A82CA227B9D5651B	FASTA	530	57,857
	10 20 30 40 50 60 MSRSPQRALP PGALPRLLQA APAAAPRALL PQWPRRPGRR WPASPLGMKV FRRKALVLCA 70 80 90 100 110 120 GYALLLVLTM LNLLDYKWHK EPLQQCNPDG PLGAAAGAAG GSWGRPGPPP AGPPRAHARL 130 140 150 160 170 180 DLRTPYRPPA AAVGAAPAAA AGMAGVAAPP GNGTRGTGGV GDKRQLVYVF TTWRSGSSFF 190 200 210 220 230 240 GELFNQNPEV FFLYEPVWHV WQKLYPGDAV SLQGAARDML SALYRCDLSV FQLYSPAGSG 250 260 270 280 290 300 GRNLTTLGIF GAATNKVVCS SPLCPAYRKE VVGLVDDRVC KKCPPQRLAR FEEECRKYRT 310 320 330 340 350 360 LVIKGVRVFD VAVLAPLLRD PALDLKVIHL VRDPRAVASS RIRSRHGLIR ESLQVVRSRD 370 380 390 400 410 420 PRAHRMPFLE AAGHKLGAKK EGVGGPADYH ALGAMEVICN SMAKTLQTAL QPPDWLQGHY 430 440 450 460 470 480 LVVRYEDLVG DPVKTLRRVY DFVGLLVSPE MEQFALNMTS GSGSSSKPFV VSARNATQAA 490 500 510 520 530 NAWRTALTFQ QIKQVEEFCY QPMAVLGYER VNSPEEVKDL SKTLLRKPRL
	Isoform 2 [UniParc]. Checksum: E27797D44931BA18	FASTA	483	52,787
	10 20 30 40 50 60 MKVFRRKALV LCAGYALLLV LTMLNLLDYK WHKEPLQQCN PDGPLGAAAG AAGGSWGRPG 70 80 90 100 110 120 PPPAGPPRAH ARLDLRTPYR PPAAAVGAAP AAAAGMAGVA APPGNGTRGT GGVGDKRQLV 130 140 150 160 170 180 YVFTTWRSGS SFFGELFNQN PEVFFLYEPV WHVWQKLYPG DAVSLQGAAR DMLSALYRCD 190 200 210 220 230 240 LSVFQLYSPA GSGGRNLTTL GIFGAATNKV VCSSPLCPAY RKEVVGLVDD RVCKKCPPQR 250 260 270 280 290 300 LARFEEECRK YRTLVIKGVR VFDVAVLAPL LRDPALDLKV IHLVRDPRAV ASSRIRSRHG 310 320 330 340 350 360 LIRESLQVVR SRDPRAHRMP FLEAAGHKLG AKKEGVGGPA DYHALGAMEV ICNSMAKTLQ 370 380 390 400 410 420 TALQPPDWLQ GHYLVVRYED LVGDPVKTLR RVYDFVGLLV SPEMEQFALN MTSGSGSSSK 430 440 450 460 470 480 PFVVSARNAT QAANAWRTAL TFQQIKQVEE FCYQPMAVLG YERVNSPEEV KDLSKTLLRK PRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human N-acetylglucosamine-6-O-sulfotransferase involved in the biosynthesis of 6-sulfo sialyl Lewis X: molecular cloning, chromosomal mapping, and expression in various organs and tumor cells." Uchimura K., Muramatsu H., Kaname T., Ogawa H., Yamakawa T., Fan Q.-W., Mitsuoka C., Kannagi R., Habuchi O., Yokoyama I., Yamamura K., Ozaki T., Nakagawara A., Kadomatsu K., Muramatsu T. J. Biochem. 124:670-678(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, ALTERNATIVE INITIATION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	Uchimura K., Muramatsu H., Muramatsu T. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial cells: cDNA cloning, expression, and chromosomal localization." Li X., Tedder T.F. Genomics 55:345-347(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Umbilical vein endothelial cell.
[4]	"Functional expression and genomic structure of human N-acetylglucosamine-6-O-sulfotransferase that transfers sulfate to b-N-acetylglucosamine at the nonreducing end of an N-acetyllactosamine sequence." Sakaguchi H., Kitagawa H., Sugahara K. Biochim. Biophys. Acta 1523:269-276(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION. Tissue: Placenta.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Brain.
[7]	"CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling via L-selectin." Li X., Tu L., Murphy P.G., Kadono T., Steeber D.A., Tedder T.F. J. Leukoc. Biol. 69:565-574(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[8]	"Characterization and mutagenesis of Gal/GlcNAc-6-O-sulfotransferases." Grunwell J.R., Rath V.L., Rasmussen J., Cabrilo Z., Bertozzi C.R. Biochemistry 41:15590-15600(2002) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-174; ARG-296; LYS-304; ARG-332 AND ARG-341.
[9]	"Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression." Uchimura K., El-Fasakhany F.M., Hori M., Hemmerich S., Blink S.E., Kansas G.S., Kanamori A., Kumamoto K., Kannagi R., Muramatsu T. J. Biol. Chem. 277:3979-3984(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE SPECIFICITY.
[10]	"Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis." de Graffenried C.L., Bertozzi C.R. J. Biol. Chem. 278:40282-40295(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Role of the carboxyl-terminal region in the activity of N-acetylglucosamine 6-o-sulfotransferase-1." Chen L., Ichihara-Tanaka K., Muramatsu T. J. Biochem. 136:659-664(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-518; ASP-519; LEU-520; SER-521; LYS-522; THR-523; LEU-524; LEU-525; ARG-526; LYS-527; PRO-528; ARG-529 AND LEU-530.
[12]	"The stem region of the sulfotransferase GlcNAc6ST-1 is a determinant of substrate specificity." de Graffenried C.L., Bertozzi C.R. J. Biol. Chem. 279:40035-40043(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF CYS-59 AND CYS-86.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB014679 mRNA. Translation: BAA34265.2. Different initiation. AB014680 mRNA. Translation: BAA34266.2. AF083066 mRNA. Translation: AAD20981.1. AB021124 mRNA. Translation: BAB16886.1. Different initiation. AB021125 Genomic DNA. Translation: BAB16887.1. Different initiation. CH471052 Genomic DNA. Translation: EAW78952.1. CH471052 Genomic DNA. Translation: EAW78953.1. BC105010 mRNA. Translation: AAI05011.1. BC105012 mRNA. Translation: AAI05013.1.
IPI	IPI00098769. IPI00759564.
RefSeq	NP_004258.2. NM_004267.4.
UniGene	Hs.529249. Hs.741449.
3D structure databases
ProteinModelPortal	Q9Y4C5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000307911.
PTM databases
PhosphoSite	Q9Y4C5.
Polymorphism databases
DMDM	61212252.
Proteomic databases
PaxDb	Q9Y4C5.
PRIDE	Q9Y4C5.
Protocols and materials databases
DNASU	9435.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309575; ENSP00000307911; ENSG00000175040.
GeneID	9435.
KEGG	hsa:9435.
UCSC	uc003evm.3. human.
Organism-specific databases
CTD	9435.
GeneCards	GC03P142838.
HGNC	HGNC:1970. CHST2.
HPA	HPA013313.
MIM	603798. gene.
neXtProt	NX_Q9Y4C5.
PharmGKB	PA26502.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG67451.
HOGENOM	HOG000261614.
HOVERGEN	HBG050949.
InParanoid	Q9Y4C5.
KO	K04745.
OMA	RAHTRLD.
OrthoDB	EOG4GF3FW.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
SABIO-RK	Q9Y4C5.
Gene expression databases
Bgee	Q9Y4C5.
CleanEx	HS_CHST2.
Genevestigator	Q9Y4C5.
GermOnline	ENSG00000175040. Homo sapiens.
Family and domain databases
InterPro	IPR016469. Carbohydrate_sulfotransferase. IPR000863. Sulfotransferase_dom. [Graphical view]
Pfam	PF00685. Sulfotransfer_1. 1 hit. [Graphical view]
PIRSF	PIRSF005883. Carbohydrate_sulfotransferase. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	CHST2. human.
GenomeRNAi	9435.
NextBio	35332.
SOURCE	Search...

Entry information

Entry name

CHST2_HUMAN

Accession

Primary (citable) accession number: Q9Y4C5
Secondary accession number(s): D3DNG5 , Q2M370, Q9GZN5, Q9UED5, Q9Y6F2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 96 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.