EXTL2_HUMAN
ID EXTL2_HUMAN Reviewed; 330 AA.
AC Q9UBQ6; B2R795; D3DT60;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Exostosin-like 2;
DE EC=2.4.1.223 {ECO:0000250|UniProtKB:Q9ES89};
DE AltName: Full=Alpha-1,4-N-acetylhexosaminyltransferase EXTL2;
DE AltName: Full=Alpha-GalNAcT EXTL2;
DE AltName: Full=EXT-related protein 2;
DE AltName: Full=Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase;
DE Contains:
DE RecName: Full=Processed exostosin-like 2;
GN Name=EXTL2; Synonyms=EXTR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9450183;
RA Wuyts W., Van Hul W., Hendrickx J., Speleman F., Wauters J., De Boulle K.,
RA Van Roy N., Van Agtmael T., Bossuyt P., Willems P.J.;
RT "Identification and characterization of a novel member of the EXT gene
RT family, EXTL2.";
RL Eur. J. Hum. Genet. 5:382-389(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9473480; DOI=10.1006/bbrc.1997.8062;
RA Saito T., Seki N., Yamauchi M., Tsuji S., Hayashi A., Kozuma S.,
RA Hori T.-A.;
RT "Structure, chromosomal location, and expression profile of EXTR1 and
RT EXTR2, new members of the multiple exostoses gene family.";
RL Biochem. Biophys. Res. Commun. 243:61-66(1998).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=10639137; DOI=10.1073/pnas.97.2.668;
RA McCormick C., Duncan G., Goutsos K.T., Tufaro F.;
RT "The putative tumor suppressors EXT1 and EXT2 form a stable complex that
RT accumulates in the Golgi apparatus and catalyzes the synthesis of heparan
RT sulfate.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:668-673(2000).
RN [4]
RP FUNCTION, PROTEIN SEQUENCE OF 54-83, AND CATALYTIC ACTIVITY.
RX PubMed=10318803; DOI=10.1074/jbc.274.20.13933;
RA Kitagawa H., Shimakawa H., Sugahara K.;
RT "The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-
RT acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-
RT acetylglucosamine to the common glycosaminoglycan-protein linkage region.
RT The key enzyme for the chain initiation of heparan sulfate.";
RL J. Biol. Chem. 274:13933-13937(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-
CC sulfate and responsible for the alternating addition of beta-1-4-linked
CC glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine
CC (GlcNAc) units to nascent heparan sulfate chains.
CC {ECO:0000269|PubMed:10318803}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-
CC O-(alpha-D-GlcNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-
CC Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:16221, Rhea:RHEA-COMP:12573, Rhea:RHEA-COMP:12574,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132093, ChEBI:CHEBI:132104; EC=2.4.1.223;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9ES89};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC -!- INTERACTION:
CC Q9UBQ6; P14136: GFAP; NbExp=3; IntAct=EBI-21506125, EBI-744302;
CC Q9UBQ6; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-21506125, EBI-1055254;
CC Q9UBQ6; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-21506125, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type II membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Processed exostosin-like 2]: Secreted. Note=A
CC soluble form is found in the serum.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: The soluble form derives from the membrane form by proteolytic
CC processing.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Exostosin-like 2;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_530";
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DR EMBL; AF000416; AAC02898.1; -; mRNA.
DR EMBL; AB009284; BAA24081.1; -; mRNA.
DR EMBL; AK312895; BAG35742.1; -; mRNA.
DR EMBL; CH471097; EAW72946.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72948.1; -; Genomic_DNA.
DR CCDS; CCDS775.1; -.
DR PIR; JC5935; JC5935.
DR RefSeq; NP_001028197.1; NM_001033025.2.
DR RefSeq; NP_001430.1; NM_001439.3.
DR RefSeq; XP_005270678.1; XM_005270621.1.
DR AlphaFoldDB; Q9UBQ6; -.
DR SMR; Q9UBQ6; -.
DR BioGRID; 108436; 49.
DR IntAct; Q9UBQ6; 20.
DR STRING; 9606.ENSP00000359132; -.
DR DrugBank; DB03435; Uridine-5'-Diphosphate.
DR DrugBank; DB02196; Uridine-Diphosphate-N-Acetylgalactosamine.
DR DrugBank; DB03397; Uridine-Diphosphate-N-Acetylglucosamine.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q9UBQ6; 1 site.
DR iPTMnet; Q9UBQ6; -.
DR PhosphoSitePlus; Q9UBQ6; -.
DR SwissPalm; Q9UBQ6; -.
DR BioMuta; EXTL2; -.
DR DMDM; 9296986; -.
DR EPD; Q9UBQ6; -.
DR jPOST; Q9UBQ6; -.
DR MassIVE; Q9UBQ6; -.
DR MaxQB; Q9UBQ6; -.
DR PaxDb; Q9UBQ6; -.
DR PeptideAtlas; Q9UBQ6; -.
DR PRIDE; Q9UBQ6; -.
DR ProteomicsDB; 84033; -.
DR Antibodypedia; 33697; 147 antibodies from 24 providers.
DR DNASU; 2135; -.
DR Ensembl; ENST00000370113.7; ENSP00000359131.3; ENSG00000162694.14.
DR Ensembl; ENST00000370114.8; ENSP00000359132.3; ENSG00000162694.14.
DR GeneID; 2135; -.
DR KEGG; hsa:2135; -.
DR MANE-Select; ENST00000370114.8; ENSP00000359132.3; NM_001033025.3; NP_001028197.1.
DR UCSC; uc001dtk.3; human.
DR CTD; 2135; -.
DR DisGeNET; 2135; -.
DR GeneCards; EXTL2; -.
DR HGNC; HGNC:3516; EXTL2.
DR HPA; ENSG00000162694; Low tissue specificity.
DR MIM; 602411; gene.
DR neXtProt; NX_Q9UBQ6; -.
DR OpenTargets; ENSG00000162694; -.
DR PharmGKB; PA27928; -.
DR VEuPathDB; HostDB:ENSG00000162694; -.
DR eggNOG; KOG1022; Eukaryota.
DR GeneTree; ENSGT00940000158820; -.
DR HOGENOM; CLU_013906_0_0_1; -.
DR InParanoid; Q9UBQ6; -.
DR OMA; IKDDKMP; -.
DR OrthoDB; 750735at2759; -.
DR PhylomeDB; Q9UBQ6; -.
DR TreeFam; TF314231; -.
DR BioCyc; MetaCyc:HS08719-MON; -.
DR BRENDA; 2.4.1.223; 2681.
DR PathwayCommons; Q9UBQ6; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR SignaLink; Q9UBQ6; -.
DR UniPathway; UPA00756; -.
DR BioGRID-ORCS; 2135; 35 hits in 1078 CRISPR screens.
DR ChiTaRS; EXTL2; human.
DR GeneWiki; EXTL2; -.
DR GenomeRNAi; 2135; -.
DR Pharos; Q9UBQ6; Tbio.
DR PRO; PR:Q9UBQ6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UBQ6; protein.
DR Bgee; ENSG00000162694; Expressed in adrenal tissue and 195 other tissues.
DR ExpressionAtlas; Q9UBQ6; baseline and differential.
DR Genevisible; Q9UBQ6; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0035248; F:alpha-1,4-N-acetylgalactosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0001888; F:glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0047237; F:glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase activity; IEA:Ensembl.
DR GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; IEA:InterPro.
DR GO; GO:0019276; P:UDP-N-acetylgalactosamine metabolic process; IDA:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR004263; Exostosin.
DR InterPro; IPR015338; GT64.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR PANTHER; PTHR11062; PTHR11062; 1.
DR Pfam; PF09258; Glyco_transf_64; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Manganese; Membrane; Metal-binding;
KW Reference proteome; Secreted; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..330
FT /note="Exostosin-like 2"
FT /id="PRO_0000149655"
FT CHAIN ?..330
FT /note="Processed exostosin-like 2"
FT /id="PRO_0000296227"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..330
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 245
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 129..134
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 150..152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 152
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 241..245
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT BINDING 280..293
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
FT SITE 53..54
FT /note="Cleavage"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 243..296
FT /evidence="ECO:0000250|UniProtKB:Q9ES89"
SQ SEQUENCE 330 AA; 37466 MW; 6976BE7EC6F588C8 CRC64;
MRCCHICKLP GRVMGIRVLR LSLVVILVLL LVAGALTALL PSVKEDKMLM LRREIKSQGK
STMDSFTLIM QTYNRTDLLL KLLNHYQAVP NLHKVIVVWN NIGEKAPDEL WNSLGPHPIP
VIFKQQTANR MRNRLQVFPE LETNAVLMVD DDTLISTPDL VFAFSVWQQF PDQIVGFVPR
KHVSTSSGIY SYGSFEMQAP GSGNGDQYSM VLIGASFFNS KYLELFQRQP AAVHALIDDT
QNCDDIAMNF IIAKHIGKTS GIFVKPVNMD NLEKETNSGY SGMWHRAEHA LQRSYCINKL
VNIYDSMPLR YSNIMISQFG FPYANYKRKI
