Reviewed, UniProtKB/Swiss-Prot Q9UBQ6 (EXTL2_HUMAN)

Names and origin

Protein names

Recommended name:
    Exostosin-like 2
    EC=2.4.1.223
Alternative name(s):
    Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
    Alpha-1,4-N-acetylhexosaminyltransferase EXTL2
    Alpha-GalNAcT EXTL2
    EXT-related protein 2
Cleaved into the following chain:
    1- Recommended name:
            Processed exostosin-like 2

Gene names

Name:	EXTL2
Synonyms:	EXTR2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	330 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)

Function	Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains. Ref.4
Catalytic activity	UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl-proteoglycan = UDP + alpha-N-acetyl-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl-proteoglycan.
Pathway	Glycan metabolism; heparan sulfate biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein By similarity. Processed exostosin-like 2: Secreted. Note: A soluble form is found in the serum. Ref.3
Tissue specificity	Ubiquitous.
Post-translational modification	The soluble form derives from the membrane form by proteolytic processing.
Sequence similarities	Belongs to the glycosyltransferase 47 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Secreted
Domain	Signal-anchor Transmembrane
Ligand	Manganese Metal-binding
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	N-acetylglucosamine metabolic process Ref.4 Inferred from direct assay. Source: UniProtKB UDP-N-acetylgalactosamine metabolic process Ref.4 Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro
Molecular function	alpha-1,4-N-acetylgalactosaminyltransferase activity Ref.4 Inferred from direct assay. Source: UniProtKB glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Ref.4 Inferred from direct assay. Source: UniProtKB manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	Exostosin-like 2		PRO_0000149655
	Chain	? – 330		Processed exostosin-like 2		PRO_0000296227
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Signal-anchor for type II membrane protein Potential
	Topological domain	44 – 330	287	Lumenal Potential
Sites
	Metal binding	152	1	Manganese; catalytic By similarity
	Site	53 – 54	2	Cleavage
Amino acid modifications
	Glycosylation	74	1	N-linked (GlcNAc...)
	Disulfide bond	243 ↔ 296		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9UBQ6-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6976BE7EC6F588C8	FASTA	330	37,466
	10 20 30 40 50 60 MRCCHICKLP GRVMGIRVLR LSLVVILVLL LVAGALTALL PSVKEDKMLM LRREIKSQGK 70 80 90 100 110 120 STMDSFTLIM QTYNRTDLLL KLLNHYQAVP NLHKVIVVWN NIGEKAPDEL WNSLGPHPIP 130 140 150 160 170 180 VIFKQQTANR MRNRLQVFPE LETNAVLMVD DDTLISTPDL VFAFSVWQQF PDQIVGFVPR 190 200 210 220 230 240 KHVSTSSGIY SYGSFEMQAP GSGNGDQYSM VLIGASFFNS KYLELFQRQP AAVHALIDDT 250 260 270 280 290 300 QNCDDIAMNF IIAKHIGKTS GIFVKPVNMD NLEKETNSGY SGMWHRAEHA LQRSYCINKL 310 320 330 VNIYDSMPLR YSNIMISQFG FPYANYKRKI

References

[1]	"Identification and characterization of a novel member of the EXT gene family, EXTL2." Wuyts W., Van Hul W., Hendrickx J., Speleman F., Wauters J., De Boulle K., Van Roy N., Van Agtmael T., Bossuyt P., Willems P.J. Eur. J. Hum. Genet. 5:382-389(1997) [PubMed: 9450183] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure, chromosomal location, and expression profile of EXTR1 and EXTR2, new members of the multiple exostoses gene family." Saito T., Seki N., Yamauchi M., Tsuji S., Hayashi A., Kozuma S., Hori T.-A. Biochem. Biophys. Res. Commun. 243:61-66(1998) [PubMed: 9473480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate." McCormick C., Duncan G., Goutsos K.T., Tufaro F. Proc. Natl. Acad. Sci. U.S.A. 97:668-673(2000) [PubMed: 10639137] [Abstract] Cited for: SUBCELLULAR LOCATION.
[4]	"The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate." Kitagawa H., Shimakawa H., Sugahara K. J. Biol. Chem. 274:13933-13937(1999) [PubMed: 10318803] [Abstract] Cited for: FUNCTION, PROTEIN SEQUENCE OF 54-83.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Exostosin-like 2

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF000416 mRNA. Translation: AAC02898.1. AB009284 mRNA. Translation: BAA24081.1.
IPI	IPI00002732.
PIR	JC5935.
RefSeq	NP_001028197.1. NP_001430.1.
UniGene	Hs.357637
3D structure databases
HSSP	HSSP built from PDB template 1ON8 based on UniProtKB Q9ES89.
SMR	Q9UBQ6. Positions 63-327.
ModBase	Search...
Protein family/group databases
CAZy	GT64. Glycosyltransferase Family 64.
Proteomic databases
PRIDE	Q9UBQ6.
Genome annotation databases
Ensembl	ENSG00000162694. Homo sapiens. [Contig view]
GeneID	2135.
KEGG	hsa:2135.
UCSC	uc001dtk.1. human.
Organism-specific databases
GeneCards	GC01M101049.
H-InvDB	HIX0000818.
HGNC	HGNC:3516. EXTL2.
MIM	602411. gene.
PharmGKB	PA27928.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UBQ6.
HOVERGEN	Q9UBQ6.
OMA	Q9UBQ6. HICKLPG.
Enzyme and pathway databases
BRENDA	2.4.1.223. 247.
Gene expression databases
ArrayExpress	Q9UBQ6.
Bgee	Q9UBQ6.
CleanEx	HS_EXTL2.
GermOnline	ENSG00000162694. Homo sapiens.
Family and domain databases
InterPro	IPR015338. HexNAc_Trfase_a. [Graphical view]
Pfam	PF09258. Glyco_transf_64. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	8627.
SOURCE	Search...

Entry information

Entry name

EXTL2_HUMAN

Accession

Primary (citable) accession number: Q9UBQ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	July 7, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)