ID   A2VE26_BOVIN            Unreviewed;       919 AA.
AC   A2VE26; F1MYW6;
DT   20-MAR-2007, integrated into UniProtKB/TrEMBL.
DT   20-MAR-2007, sequence version 1.
DT   02-SEP-2026, entry version 121.
DE   RecName: Full=Exostosin-like 3 {ECO:0000256|ARBA:ARBA00074807};
DE            EC=2.4.1.223 {ECO:0000256|ARBA:ARBA00066812};
DE   AltName: Full=Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase {ECO:0000256|ARBA:ARBA00083226};
DE   AltName: Full=Multiple exostosis-like protein 3 {ECO:0000256|ARBA:ARBA00079618};
GN   Name=EXTL3 {ECO:0000313|EMBL:AAI33541.1};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913 {ECO:0000313|EMBL:AAI33541.1};
RN   [1] {ECO:0000313|EMBL:AAI33541.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=L1 Hereford {ECO:0000313|EMBL:AAI33541.1};
RC   TISSUE=Fetal skin {ECO:0000313|EMBL:AAI33541.1};
RA   Moore S., Alexander L., Brownstein M., Guan L., Lobo S., Meng Y.,
RA   Tanaguchi M., Wang Z., Yu J., Prange C., Schreiber K., Shenmen C.,
RA   Wagner L., Bala M., Barbazuk S., Barber S., Babakaiff R., Beland J.,
RA   Chun E., Del Rio L., Gibson S., Hanson R., Kirkpatrick R., Liu J.,
RA   Matsuo C., Mayo M., Santos R.R., Stott J., Tsai M., Wong D., Siddiqui A.,
RA   Holt R., Jones S.J., Marra M.A.;
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Glycosyltransferase which regulates the biosynthesis of
CC       heparan sulfate (HS). Initiates HS synthesis by transferring the first
CC       N-acetyl-alpha-D-glucosamine (alpha-GlcNAc) residue (GlcNAcT-I
CC       activity) to the tetrasaccharide linker (GlcA-Gal-Gal-Xyl-)Ser core
CC       linker. May also transfer alpha-GlcNAc residues during HS elongation
CC       (GlcNAcT-II activity). Lacks glucuronyl transferase II (GlcAT-II)
CC       activity. Important for both skeletal development and hematopoiesis,
CC       through the formation of HS proteoglycans (HSPGs). Through the
CC       synthesis of HS, regulates postnatal pancreatic islet maturation and
CC       insulin secretion. {ECO:0000256|ARBA:ARBA00058474}.
CC   -!- FUNCTION: Receptor for REG3A, REG3B and REG3G, induces the activation
CC       of downstream signaling pathways such as PI3K-AKT or RAS-RAF-MEK-ERK
CC       signaling pathway. Required for the function of REG3A in regulating
CC       keratinocyte proliferation and differentiation. Required for the
CC       inhibition of skin inflammation mediated by REG3A through the
CC       activation of PI3K-AKT-STAT3 pathway. Required for the function of
CC       REG3A and REG3G in glucose tolerance in pancreas. Expressed in
CC       microglia, is activated by nociceptor-derived REG3G in response to
CC       endotoxins, leading to the inhibition of kynurenine pathway to prevent
CC       endotoxic death. {ECO:0000256|ARBA:ARBA00058348}.
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] + UDP + H(+);
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:0000256|ARBA:ARBA00050948};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000256|ARBA:ARBA00001936};
CC   -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC       {ECO:0000256|ARBA:ARBA00005093}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with REG3A.
CC       {ECO:0000256|ARBA:ARBA00061763}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000256|ARBA:ARBA00004648}; Single-pass type II membrane protein
CC       {ECO:0000256|ARBA:ARBA00004648}. Golgi apparatus
CC       {ECO:0000256|ARBA:ARBA00004555}.
CC   -!- SIMILARITY: Belongs to the glycosyltransferase 47 family.
CC       {ECO:0000256|ARBA:ARBA00010271}.
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DR   EMBL; BC133540; AAI33541.1; -; mRNA.
DR   RefSeq; NP_001075942.1; NM_001082473.1.
DR   RefSeq; XP_005209925.1; XM_005209868.5.
DR   RefSeq; XP_005209926.1; XM_005209869.5.
DR   RefSeq; XP_010806029.1; XM_010807727.4.
DR   RefSeq; XP_059745272.1; XM_059889289.1.
DR   AlphaFoldDB; A2VE26; -.
DR   SMR; A2VE26; -.
DR   STRING; 9913.ENSBTAP00000011645; -.
DR   PaxDb; 9913-ENSBTAP00000011645; -.
DR   GeneID; 783970; -.
DR   KEGG; bta:783970; -.
DR   CTD; 2137; -.
DR   VEuPathDB; HostDB:ENSBTAG00000008844; -.
DR   eggNOG; KOG2264; Eukaryota.
DR   GeneTree; ENSGT00940000156692; -.
DR   HOGENOM; CLU_013906_3_0_1; -.
DR   OMA; KFMGSHT; -.
DR   OrthoDB; 5954868at2759; -.
DR   Reactome; R-BTA-2022928; HS-GAG biosynthesis.
DR   Bgee; ENSBTAG00000008844; Expressed in cardiac ventricle and 109 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR   GO; GO:0001888; F:glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR   GO; GO:0016500; F:protein-hormone receptor activity; IEA:Ensembl.
DR   GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IEA:Ensembl.
DR   GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IEA:Ensembl.
DR   GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IEA:Ensembl.
DR   GO; GO:0010838; P:positive regulation of keratinocyte proliferation; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR   FunFam; 3.90.550.10:FF:000033; Exostosin-like glycosyltransferase 3; 1.
DR   Gene3D; 3.90.550.10; Spore Coat Polysaccharide Biosynthesis Protein SpsA, Chain A; 1.
DR   InterPro; IPR004263; Exostosin.
DR   InterPro; IPR040911; Exostosin_GT47.
DR   InterPro; IPR015338; GT64_dom.
DR   InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR   PANTHER; PTHR48261; ACETYLGLUCOSAMINYLTRANSFERASE; 1.
DR   PANTHER; PTHR48261:SF4; EXOSTOSIN LIKE GLYCOSYLTRANSFERASE 3; 1.
DR   Pfam; PF03016; Exostosin_GT47; 1.
DR   Pfam; PF09258; Glyco_transf_64; 1.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
PE   2: Evidence at transcript level;
KW   Coiled coil {ECO:0000256|SAM:Coils};
KW   Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW   Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW   Glycosyltransferase {ECO:0000256|ARBA:ARBA00022676};
KW   Golgi apparatus {ECO:0000256|ARBA:ARBA00023034};
KW   Manganese {ECO:0000256|ARBA:ARBA00023211};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Signal-anchor {ECO:0000256|ARBA:ARBA00022968};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW   ECO:0000256|SAM:Phobius}.
FT   TRANSMEM        29..51
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   DOMAIN          192..500
FT                   /note="Exostosin GT47"
FT                   /evidence="ECO:0000259|Pfam:PF03016"
FT   DOMAIN          663..904
FT                   /note="Glycosyl transferase 64"
FT                   /evidence="ECO:0000259|Pfam:PF09258"
FT   COILED          86..148
FT                   /evidence="ECO:0000256|SAM:Coils"
SQ   SEQUENCE   919 AA;  104307 MW;  8A999A5395B22EC7 CRC64;
     MTGYTMLRNG GAGNGGQTCM LRWSNRIRLT WLSFTLFIIL VFFPLIAHYY LTTLDEADEA
     GKRIFGPRAG SELCEVKHVL DLCRIRESVS EELLQLEAKR QELNSEIAKL NLKIEACKKS
     IENAKQDLLQ LKNVISQTEH SYKELMAQNQ PKLSLPIRLL PEKDDAGLPP PKAQRGCRLH
     NCFDYSRCPL TSGFPVYVYD SDQFAFGSYL DPLVKQAFQA TARANVYVTD NADIACLYVI
     LVGEMQEPAV LRPADLEKQL LSLPHWRTDG HNHVIISLSR KSDTQNLLYN VSTGRAMVAQ
     STFYAAQYRP GFDLVVSPLV HAMSEPNFME IPPQVPVKRK YLFTFQGEKI ESLRSSLQEA
     RSFEEEMEGD PPADYDDRII ATLKAVQDSK LDQVLVEFTC KSQPRASLPT EWALCGERED
     RLELLKLSTF ALIITPGDPR LLVSSGCATR LFEALEVGAV PVVLGEHVQL PYQDVLQWSE
     AALVVPKPRV TEVHFLLRSL SDSDLLAMRR QGRFLWETYF STTDSIFSTV LAVIRTRIQI
     PAAPIREEAA AEIPHRSGKA AGTDPNMADT GDLDLGPVET EPPYASPKYL RNFTLTVTDL
     YRSWNSAPGP FHLFPHTPFD PVLPSEAKFL GSGTGFRPIG GGAGGSGKEF QAALGGNVPR
     EQFTVVMLTY EREEVLMNSL ERLNGLPYLN KVVVVWNSPK LPSEDLVWPD IGVPIMVVRT
     EKNSLNNRFL PWNEIETEAI LSIDDDAHLR HDEIMFGFRV WREARDRIVG FPGRYHAWDI
     PHQSWLYNSN YSCELSMVLT GAAFFHKYYA YLYSYVMPQA IRDMVDEYIN CEDIAMNFLV
     SHITRKPPIK VTSRWTFRCP GCPQALSHDD SHFHERHKCI NFFVKVYGYM PLLYTQFRVD
     SVLFKTRLPH DKTKCFKFI
//