Q8NCG5 (CHST4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbohydrate sulfotransferase 4
EC=2.8.2.-

Alternative name(s):
Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 3
Short name=GST-3
High endothelial cells N-acetylglucosamine 6-O-sulfotransferase
Short name=HEC-GlcNAc6ST
L-selectin ligand sulfotransferase
Short name=LSST
N-acetylglucosamine 6-O-sulfotransferase 2
Short name=GlcNAc6ST-2
Short name=Gn6st-2

Gene names

Name:

CHST4

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	386 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 mucin-associated glycans that 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 on receptors SPN/CD43, GLYCAM1 and MADCAM1. Also involved in biosynthesis of SELL ligand recognized by MECA-79 antibody. Plays a central role in lymphocyte trafficking during chronic inflammation. Has a catalytic preference for core 2-branched mucin-type O-glycans. Can use GlcNAcbeta1-6[Galbeta1-3]GalNAc-pNP (core 2), GlcNAcbeta1-6ManOMe and GlcNAcbeta1-2Man oligosaccharide structures as acceptors. Has also activity toward core 3 of GlcNAcbeta1-3GalNAc-pNP. Its substrate specificity may be influenced by its subcellular location. Ref.1
Subunit structure	Monomer. Ref.10
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein Ref.9.
Tissue specificity	Specifically expressed in HEV. Weakly expressed in spleen. Not expressed in other tissues. Expressed in colonic mucinous adenocarcinoma. Ref.1 Ref.6 Ref.7
Induction	Upon cytokine activation, it is expressed at low level. Ref.6
Miscellaneous	May serve as a antiinflammatory target.
Sequence similarities	Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Sequence caution	The sequence AAH35282.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Inflammatory response
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	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 Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Traceable author statement Ref.1. Source: ProtInc cell-cell signaling Traceable author statement Ref.1. Source: ProtInc cellular component movement Traceable author statement Ref.1. Source: ProtInc immune response Traceable author statement Ref.1. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW leukocyte tethering or rolling Inferred from electronic annotation. Source: Compara protein sulfation 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.9. Source: UniProtKB trans-Golgi network Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	N-acetylglucosamine 6-O-sulfotransferase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 386	386	Carbohydrate sulfotransferase 4		PRO_0000085193
Regions
	Topological domain	1 – 7	7	Cytoplasmic Potential
	Transmembrane	8 – 28	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	29 – 386	358	Lumenal Potential
	Nucleotide binding	51 – 57	7	PAPS By similarity
	Nucleotide binding	205 – 213	9	PAPS By similarity
Amino acid modifications
	Glycosylation	30	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Glycosylation	329	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	361	1	H → Q. Corresponds to variant rs3813744 [ dbSNP | Ensembl ].		VAR_052528
Experimental info
	Sequence conflict	225	1	S → N in BAC11177. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q8NCG5 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 0C3BB4022417143A	FASTA	386	45,134
	10 20 30 40 50 60 MLLPKKMKLL LFLVSQMAIL ALFFHMYSHN ISSLSMKAQP ERMHVLVLSS WRSGSSFVGQ 70 80 90 100 110 120 LFGQHPDVFY LMEPAWHVWM TFKQSTAWML HMAVRDLIRA VFLCDMSVFD AYMEPGPRRQ 130 140 150 160 170 180 SSLFQWENSR ALCSAPACDI IPQDEIIPRA HCRLLCSQQP FEVVEKACRS YSHVVLKEVR 190 200 210 220 230 240 FFNLQSLYPL LKDPSLNLHI VHLVRDPRAV FRSRERTKGD LMIDSRIVMG QHEQKLKKED 250 260 270 280 290 300 QPYYVMQVIC QSQLEIYKTI QSLPKALQER YLLVRYEDLA RAPVAQTSRM YEFVGLEFLP 310 320 330 340 350 360 HLQTWVHNIT RGKGMGDHAF HTNARDALNV SQAWRWSLPY EKVSRLQKAC GDAMNLLGYR 370 380 HVRSEQEQRN LLLDLLSTWT VPEQIH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin." Bistrup A., Bhakta S., Lee J.K., Belov Y.Y., Gunn M.D., Zuo F.-R., Huang C.-C., Kannagi R., Rosen S.D., Hemmerich S. J. Cell Biol. 145:899-910(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Tonsil.
[2]	"Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase." Yeh J.-C., Hiraoka N., Petryniak B., Nakayama J., Ellies L.G., Rabuka D., Hindsgaul O., Marth J.D., Lowe J.B., Fakuda M. Cell 105:957-969(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Chromosomal localization and genomic organization for the galactose/ N-acetylgalactosamine/N-acetylglucosamine 6-O-sulfotransferase gene family." Hemmerich S., Lee J.K., Bhakta S., Bistrup A., Ruddle N.R., Rosen S.D. Glycobiology 11:75-87(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Tonsil.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Teratocarcinoma.
[5]	"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.
[6]	"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.
[7]	"Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma." Seko A., Nagata K., Yonezawa S., Yamashita K. Glycobiology 12:379-388(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"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.
[9]	"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.
[10]	"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.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF131235 mRNA. Translation: AAD33015.1. AF149783 mRNA. Translation: AAK48417.1. AF280088 mRNA. Translation: AAG48246.1. AK074746 mRNA. Translation: BAC11177.1. BC035282 mRNA. Translation: AAH35282.1. Different initiation.
IPI	IPI00301494.
RefSeq	NP_001159867.1. NM_001166395.1. NP_005760.1. NM_005769.2.
UniGene	Hs.251383.
3D structure databases
ProteinModelPortal	Q8NCG5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NCG5. 1 interaction.
STRING	9606.ENSP00000341206.
PTM databases
PhosphoSite	Q8NCG5.
Polymorphism databases
DMDM	61211834.
Proteomic databases
PaxDb	Q8NCG5.
PRIDE	Q8NCG5.
Protocols and materials databases
DNASU	10164.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338482; ENSP00000341206; ENSG00000140835. ENST00000539698; ENSP00000441204; ENSG00000140835. ENST00000572450; ENSP00000461839; ENSG00000140835.
GeneID	10164.
KEGG	hsa:10164.
UCSC	uc002fan.3. human.
Organism-specific databases
CTD	10164.
GeneCards	GC16P071560.
HGNC	HGNC:1972. CHST4.
HPA	HPA021955.
neXtProt	NX_Q8NCG5.
PharmGKB	PA26504.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG80862.
HOGENOM	HOG000261614.
HOVERGEN	HBG050949.
InParanoid	Q8NCG5.
KO	K04746.
OMA	VEKACRS.
OrthoDB	EOG4RXZ09.
Enzyme and pathway databases
SABIO-RK	Q8NCG5.
Gene expression databases
Bgee	Q8NCG5.
CleanEx	HS_CHST4.
Genevestigator	Q8NCG5.
GermOnline	ENSG00000140835. 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
ChEMBL	CHEMBL2239.
GenomeRNAi	10164.
NextBio	38482.

Entry information

Entry name

CHST4_HUMAN

Accession

Primary (citable) accession number: Q8NCG5
Secondary accession number(s): Q8IV46, Q9Y5R3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	April 3, 2013
This is version 86 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.