Q9UBQ6 (EXTL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exostosin-like 2
EC=2.4.1.223

Alternative name(s):
Alpha-1,4-N-acetylhexosaminyltransferase EXTL2
Alpha-GalNAcT EXTL2
EXT-related protein 2
Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase

Cleaved into the following chain:

1. Processed exostosin-like 2

Gene names

Name:	EXTL2
Synonyms:	EXTR2

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	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 Ref.3. 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 Transmembrane helix
Ligand	Manganese Metal-binding
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	N-acetylglucosamine metabolic process Inferred from direct assay Ref.4. Source: UniProtKB UDP-N-acetylgalactosamine metabolic process Inferred from direct assay Ref.4. Source: UniProtKB heparan sulfate proteoglycan biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.3. Source: BHF-UCL extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell 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 Inferred from direct assay Ref.4. Source: UniProtKB glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Inferred from direct assay Ref.4. Source: UniProtKB metal 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	Helical; 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 [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

	« Hide 'large scale' referencesShow 'large scale' 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, PROTEIN SEQUENCE OF 54-83.
[5]	"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: Amygdala.
[6]	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].
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Exostosin-like 2

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF000416 mRNA. Translation: AAC02898.1. AB009284 mRNA. Translation: BAA24081.1. AK312895 mRNA. Translation: BAG35742.1. CH471097 Genomic DNA. Translation: EAW72946.1. CH471097 Genomic DNA. Translation: EAW72948.1.
IPI	IPI00002732.
PIR	JC5935.
RefSeq	NP_001028197.1. NM_001033025.2. NP_001430.1. NM_001439.3.
UniGene	Hs.357637.
3D structure databases
ProteinModelPortal	Q9UBQ6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000359131.
Protein family/group databases
CAZy	GT64. Glycosyltransferase Family 64.
PTM databases
PhosphoSite	Q9UBQ6.
Polymorphism databases
DMDM	9296986.
Proteomic databases
PaxDb	Q9UBQ6.
PRIDE	Q9UBQ6.
Protocols and materials databases
DNASU	2135.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370113; ENSP00000359131; ENSG00000162694. ENST00000370114; ENSP00000359132; ENSG00000162694.
GeneID	2135.
KEGG	hsa:2135.
UCSC	uc001dtk.1. human.
Organism-specific databases
CTD	2135.
GeneCards	GC01M101337.
HGNC	HGNC:3516. EXTL2.
HPA	CAB020716.
MIM	602411. gene.
neXtProt	NX_Q9UBQ6.
PharmGKB	PA27928.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG276916.
HOGENOM	HOG000054215.
HOVERGEN	HBG051525.
InParanoid	Q9UBQ6.
KO	K02369.
OMA	NHYQAVP.
OrthoDB	EOG4RNB91.
PhylomeDB	Q9UBQ6.
Enzyme and pathway databases
BioCyc	MetaCyc:HS08719-MONOMER.
UniPathway	UPA00756.
Gene expression databases
ArrayExpress	Q9UBQ6.
Bgee	Q9UBQ6.
CleanEx	HS_EXTL2.
Genevestigator	Q9UBQ6.
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
ChiTaRS	EXTL2. human.
GenomeRNAi	2135.
NextBio	8627.
SOURCE	Search...

Entry information

Entry name

EXTL2_HUMAN

Accession

Primary (citable) accession number: Q9UBQ6
Secondary accession number(s): B2R795, D3DT60

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 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.