EXTL2_MOUSE
ID EXTL2_MOUSE Reviewed; 330 AA.
AC Q9ES89; Q505Q8; Q9CX90;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Exostosin-like 2;
DE EC=2.4.1.223 {ECO:0000269|PubMed:12562774};
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;
GN Name=Extl2; Synonyms=Extr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10965119; DOI=10.1159/000015609;
RA Wuyts W., Van Hul W.;
RT "Characterization and genomic localization of the mouse Extl2 gene.";
RL Cytogenet. Cell Genet. 89:185-188(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 38-330 IN COMPLEX WITH SUBSTRATE,
RP METAL-BINDING, DISULFIDE BOND, MUTAGENESIS OF ASN-243; ASP-246 AND ARG-293,
RP CATALYTIC ACTIVITY, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP COFACTOR.
RX PubMed=12562774; DOI=10.1074/jbc.m210532200;
RA Pedersen L.C., Dong J., Taniguchi F., Kitagawa H., Krahn J.M.,
RA Pedersen L.G., Sugahara K., Negishi M.;
RT "Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2),
RT a member of the exostosin gene family involved in heparan sulfate
RT biosynthesis.";
RL J. Biol. Chem. 278:14420-14428(2003).
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. {ECO:0000250}.
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:0000269|PubMed:12562774};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:12562774};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=320 uM for UDP-GalNAc {ECO:0000269|PubMed:12562774};
CC KM=560 uM for UDP-GlcNAc {ECO:0000269|PubMed:12562774};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type II membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC {ECO:0000305}.
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DR EMBL; AF200973; AAG17542.1; -; mRNA.
DR EMBL; AK019370; BAB31683.2; -; mRNA.
DR EMBL; BC031438; AAH31438.1; -; mRNA.
DR EMBL; BC094444; AAH94444.1; -; mRNA.
DR CCDS; CCDS17784.1; -.
DR RefSeq; NP_001156986.1; NM_001163514.1.
DR RefSeq; NP_067363.3; NM_021388.4.
DR PDB; 1OMX; X-ray; 2.40 A; A/B=38-330.
DR PDB; 1OMZ; X-ray; 2.10 A; A/B=38-330.
DR PDB; 1ON6; X-ray; 2.30 A; A/B=38-330.
DR PDB; 1ON8; X-ray; 2.70 A; A/B=38-330.
DR PDBsum; 1OMX; -.
DR PDBsum; 1OMZ; -.
DR PDBsum; 1ON6; -.
DR PDBsum; 1ON8; -.
DR AlphaFoldDB; Q9ES89; -.
DR SMR; Q9ES89; -.
DR STRING; 10090.ENSMUSP00000029575; -.
DR CAZy; GT64; Glycosyltransferase Family 64.
DR GlyGen; Q9ES89; 1 site.
DR PhosphoSitePlus; Q9ES89; -.
DR MaxQB; Q9ES89; -.
DR PaxDb; Q9ES89; -.
DR PRIDE; Q9ES89; -.
DR ProteomicsDB; 275560; -.
DR Antibodypedia; 33697; 147 antibodies from 24 providers.
DR DNASU; 58193; -.
DR Ensembl; ENSMUST00000029575; ENSMUSP00000029575; ENSMUSG00000027963.
DR Ensembl; ENSMUST00000106502; ENSMUSP00000102111; ENSMUSG00000027963.
DR GeneID; 58193; -.
DR KEGG; mmu:58193; -.
DR UCSC; uc008rbu.2; mouse.
DR CTD; 2135; -.
DR MGI; MGI:1889574; Extl2.
DR VEuPathDB; HostDB:ENSMUSG00000027963; -.
DR eggNOG; KOG1022; Eukaryota.
DR GeneTree; ENSGT00940000158820; -.
DR InParanoid; Q9ES89; -.
DR OMA; IKDDKMP; -.
DR OrthoDB; 750735at2759; -.
DR PhylomeDB; Q9ES89; -.
DR TreeFam; TF314231; -.
DR BRENDA; 2.4.1.223; 3474.
DR BioGRID-ORCS; 58193; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Extl2; mouse.
DR EvolutionaryTrace; Q9ES89; -.
DR PRO; PR:Q9ES89; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9ES89; protein.
DR Bgee; ENSMUSG00000027963; Expressed in facial nucleus and 240 other tissues.
DR ExpressionAtlas; Q9ES89; baseline and differential.
DR Genevisible; Q9ES89; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0035248; F:alpha-1,4-N-acetylgalactosaminyltransferase activity; IMP:CAFA.
DR GO; GO:0001888; F:glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; ISO:MGI.
DR GO; GO:0047237; F:glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase activity; IMP:CAFA.
DR GO; GO:0005539; F:glycosaminoglycan binding; IMP:CAFA.
DR GO; GO:0030145; F:manganese ion binding; IMP:CAFA.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; IMP:CAFA.
DR GO; GO:0006486; P:protein glycosylation; IEA:InterPro.
DR GO; GO:0019276; P:UDP-N-acetylgalactosamine metabolic process; IMP:CAFA.
DR DisProt; DP00397; -.
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 3D-structure; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..330
FT /note="Exostosin-like 2"
FT /id="PRO_0000149656"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..330
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 246
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 130..135
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 151..153
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 153
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 242..246
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT BINDING 280..293
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12562774"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 244..296
FT /evidence="ECO:0000269|PubMed:12562774"
FT MUTAGEN 243
FT /note="N->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:12562774"
FT MUTAGEN 246
FT /note="D->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:12562774"
FT MUTAGEN 293
FT /note="R->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:12562774"
FT CONFLICT 191
FT /note="Y -> D (in Ref. 2; BAB31683)"
FT /evidence="ECO:0000305"
FT STRAND 67..75
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 77..87
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 132..136
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 158..168
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:1OMZ"
FT HELIX 245..257
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:1ON8"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:1ON8"
FT HELIX 288..304
FT /evidence="ECO:0007829|PDB:1OMZ"
FT STRAND 314..318
FT /evidence="ECO:0007829|PDB:1OMZ"
FT TURN 323..326
FT /evidence="ECO:0007829|PDB:1OMZ"
SQ SEQUENCE 330 AA; 37391 MW; 51F88BE5D3E5EADF CRC64;
MMRGCHICKL PGRVMGIRVL RFSLVVILVL LLVAGALTNL LPNIKEDKML TLRREIKSPS
KSALDSFTLI MQTYNRTDLL LRLLNHYQAV PSLHKVIVVW NNVGEKGPEE LWNSLGPHPI
PVIFKPQTAN KMRNRLQVFP EVETNAVLMV DDDTLISAQD LVFAFSIWQQ FPDQIIGFVP
RKHVSTSSGI YSYGGFELQT PGPGNGDQYS MVLIGASFFN SKYLELFQKQ PAAVHALIDE
TQNCDDIAMN FLVTRHTGKP SGIFVKPINM VNLEKETNGY SGMWHRAEHF LQRSYCINKL
VNIYDGMPLK YSNIMISQFG FPYANHKSKM
