FuncClass

GlycoEnzDB
Comprehensive glycoEnzyme database and dynamic pathway generation

Description: The GlycoEnzDB is a manually curated glycoEnzyme database, primarily focused on humans. It covers 390 enzymes across 28 pathway maps. Facilities are also available to create custom glycosylation reaction pathways using experimental data in SBML format and for pathway simulation
Contacts: Sriram Neelamegham (neel@buffalo.edu), Yusen Zhou (yusenzho@buffalo.edu) or Ted Groth (tgroth@buffalo.edu).

GlycoEnzDB
Create glycosylation pathway
Custom database generation
Instructions/Reference
 

Pathway Map

EXTL2



General Information
Gene Symbol:   
EXTL2
Protein name:   
Exostosin-like 2
Enzyme Class:   
Glycosyltransferase
CAZy Family:   
E.C. No:   
Organs:   
Reaction (SNFG):   
+
+ UDP
+
+ UDP
Reaction (IUBMB):   
No specified reaction.

About

• The initiation of heparan sulfate biosynthesis is catalyzed by an αGlcNAc transferase activity that is termed ?GlcNAcT-I?. Addition of GlcA (HS-GlcAT-II) and GlcNAc (GlcNAcT-II) then ensues to form an HS backbone.
• These activities are mediated by several enzymes of the EXT (EXT-1/2) and EXT-like (EXTL-1/2/3) gene family. EXTL-1, -2 and -3 all have only HexNAc transferase activity, and they were discovered after EXT1/2. EXT1/2 have dual enzyme activity.
• EXTL3 has both GlcNAcT-I activity and GlcNAcT-II activity. Thus, it participate in both chain initiation and extension. EXTL3 knockout is embryonic lethal, it is most likely responsible for adding the first GlcNAc to the tetrasaccharide linker to initiate HS chain extension by EXT1/EXT2. Homozygous mutation of EXTL3 has recently been found to cause severe developmental delay.
• EXTL2 (α1,4-N-Acetylhexosaminyltransferase) catalyzes the transfer of a α(1-4)GlcNAc or alternatively α(1-4)GalNAc residue from UDP-GalNAc/GlcNAc to the core oligosaccharide representing the GAG-protein linker (i.e. GlcNAcT-I activity). EXTL2 is widely distributed in various mammalian tissues and cells as well as in serum. α-GalNAc activity of EXTL2 may suppress HS biosynthesis, as this can no longer be extended by EXT1/EXT2. EXTL2 knockout mice is largely normal but shown various defects when challenged with disease models.
• EXTL1 only has GlcNAcT-II activity.
• EXT1 and EXT2 form a heterodimeric complex of Type II-proteins in cis-Golgi. EXT1-EXT2 interaction and core proteins are critical and required for the heparan chain polymerization reactions.
• EXT1 (Exostosin) and EXT2 both have GlcAT and GlcNAcT activities (i.e. they are bifunctional) and are together responsible for HS chain polymerization. Knocking out either EXT1 or EXT2 is embryonic lethal.
• Even heterozygous mutations in EXT1 or EXT2 led to reduction in HS biosynthesis and can cause a bone disease called Exostosis.


Related Pathway
KEGG ORTHOLOGY:   
KEGG Pathway:   
Reactome:   

Related Database
Organism:   
Homo sapiens
Uniprot:   
NCBI GeneID:   
GlyMap GeneID:   
DNA aRefSeq:   
Protein RefSeq:   
BRENDA:   
OMIM number:   
GeneCards database:   

Enzyme Specificity
Glycan Type:  
     GAG
Compartment:  
     ER
Substrate:  
     GlcA(b1-3) or GlcA(b1-3)Gal(b1-3)Gal(b1-4)Xyl(b1-?)Ser
Product:  
     GalNAc(a1-4)GlcA(b1-3) or GlcNAc(a1-4)GlcA(b1-3)Gal(b1-3)Gal(b1-4)Xyl(b1-?)Ser

Simulation Parameters
Mechaelis-Menten parameters (suggested)
VM:       (pmol/cell • hr)       KM:       (pM)
Relative conc of enzymes in compartment.(sum will be normalized to 1)
ER Cis- Medial- Trans- TGN











Expression Data in Tissue {ref. 5} Source from NCBI gene database
adrenal appendix bone marrow brain colon duodenum endometrium esophagus fat gall bladder heart kidney liver lung lymph node ovary pancreas placenta prostate salivary gland skin small intestine spleen stomach testis thyroid urinary bladder 12 10 8 6 4 2 0 RPKM
Expression Data in Cells {ref. 13} Source from Cancer Cell Line Encyclopedia database
Kidney Lung Breast Prostate Large intestine Ovary HL60 haematopoietic and lymphoid tissue Skin Central nervous system 786O A498 ACHN CAKI1 UO31 A549 EKVX HOP62 HOP92 NCIH226 NCIH23 NCIH322 NCIH460 NCIH522 SHP77 BT549 HS578T MCF7 MDAMB231 MDAMB468 T47D DU145 PC3 HCT116 HCT15 HT29 KM12 SW620 OVCAR4 OVCAR8 IGROV1 SKOV3 HL60 K562 RPMI8226 LOXIMVI MALME3M RPMI7951 SKMEL28 SKMEL5 UACC257 UACC62 SF268 SF295 SF539 SNB75 50 40 30 20 10 0 Transcripts per million (TPM)
Transcription factor {ref. 10}
No high degree of confidence data

miRNA-GlycoEnzyme Interactome {ref. 9}
miRNA Name Pos. Context Score Frac. Wt. Context Frac. Conserved Quality
hsa-miR-4686 1524-1531 -0.488 99.0 -0.479 99.0 noncon
hsa-miR-4703-3p 1017-1024 -0.487 99.0 -0.487 99.0 noncon
hsa-miR-4308 218-225 -0.437 99.0 -0.437 99.0 noncon
hsa-miR-3151-3p 330-337 -0.436 98.0 -0.436 98.0 noncon
hsa-miR-516b-5p 98-105 -0.426 98.0 -0.426 99.0 noncon
hsa-miR-550b-3p 856-863 -0.412 99.0 -0.412 99.0 noncon
hsa-miR-30b-5p 252-259 -0.397 98.0 -0.397 98.0 con
hsa-miR-30c-5p 252-259 -0.397 98.0 -0.397 98.0 con
hsa-miR-1915-5p 1175-1182 -0.39 96.0 -0.39 97.0 noncon
hsa-miR-30e-5p 252-259 -0.389 98.0 -0.389 98.0 con
hsa-miR-30d-5p 252-259 -0.389 98.0 -0.389 98.0 con
hsa-miR-30a-5p 252-259 -0.389 98.0 -0.389 98.0 con
hsa-miR-134-5p 461-468 -0.387 98.0 -0.387 98.0 noncon
hsa-miR-3118 461-468 -0.387 98.0 -0.387 98.0 noncon
hsa-miR-3916 1517-1524 -0.385 99.0 -0.378 99.0 noncon
hsa-miR-5690 619-626 -0.382 99.0 -0.382 99.0 noncon
hsa-miR-4771 1075-1082 -0.378 97.0 -0.378 98.0 noncon
hsa-miR-877-3p 472-479 -0.374 97.0 -0.374 98.0 noncon
hsa-miR-6780a-3p 1058-1065 -0.37 98.0 -0.37 98.0 noncon
hsa-miR-433-3p 81-88 -0.37 98.0 -0.37 99.0 con
hsa-miR-3125 1517-1524 -0.367 99.0 -0.36 99.0 noncon
hsa-miR-942-3p 438-445 -0.365 98.0 -0.365 99.0 noncon
hsa-miR-8066 152-159 -0.352 99.0 -0.352 99.0 noncon
hsa-miR-6832-5p 107-114 -0.343 97.0 -0.343 97.0 noncon
hsa-miR-6844 1430-1437 -0.343 98.0 -0.337 98.0 noncon
hsa-miR-765 1219-1225 -0.341 96.0 -0.341 97.0 noncon
hsa-miR-6857-3p 459-466 -0.336 97.0 -0.336 98.0 noncon
hsa-miR-4520-2-3p 1481-1487 -0.332 94.0 -0.326 96.0 noncon
hsa-miR-4727-5p 866-873 -0.331 97.0 -0.331 98.0 noncon
hsa-miR-4279 1031-1038 -0.33 98.0 -0.33 98.0 noncon
hsa-miR-7852-3p 1019-1026 -0.327 97.0 -0.327 98.0 noncon
hsa-miR-580-3p 1276-1283 -0.325 99.0 -0.325 99.0 noncon
hsa-miR-4460 1167-1174 -0.312 93.0 -0.312 95.0 noncon
hsa-miR-432-3p 1549-1555 -0.309 96.0 -0.171 88.0 noncon
hsa-miR-124-3p.2 299-306 -0.308 91.0 -0.308 94.0 con
hsa-miR-3935 92-98 -0.306 96.0 -0.306 97.0 noncon
hsa-miR-6850-5p 1355-1361 -0.303 90.0 -0.303 92.0 noncon
hsa-miR-4717-3p 1553-1559 -0.303 98.0 0.0 0.0 noncon
hsa-miR-6873-5p 1228-1234 -0.301 97.0 -0.301 98.0 noncon
hsa-miR-6859-5p 1517-1524 -0.299 99.0 -0.294 99.0 noncon
hsa-miR-6759-3p 371-378 -0.297 95.0 -0.297 97.0 noncon
hsa-miR-3664-3p 260-267 -0.296 98.0 -0.296 98.0 noncon
hsa-miR-5190 762-769 -0.295 98.0 -0.295 98.0 noncon
hsa-miR-520g-5p 1519-1525 -0.294 95.0 -0.289 97.0 noncon
hsa-miR-5581-3p 668-674 -0.292 96.0 -0.292 97.0 noncon
hsa-miR-5087 18-24 -0.288 97.0 -0.288 98.0 noncon
hsa-miR-4501 463-470 -0.285 97.0 -0.285 98.0 noncon
hsa-miR-1257 965-972 -0.284 96.0 -0.284 97.0 noncon
hsa-miR-5006-5p 290-296 -0.284 95.0 -0.284 96.0 noncon
hsa-miR-6719-3p 1464-1470 -0.282 97.0 -0.277 98.0 noncon
hsa-miR-5703 50-57 -0.28 96.0 -0.28 97.0 noncon
hsa-miR-6891-5p 1239-1245 -0.279 96.0 -0.279 97.0 noncon
hsa-miR-4740-5p 540-547 -0.278 94.0 -0.278 96.0 noncon
hsa-miR-1825 912-918 -0.271 96.0 -0.271 97.0 noncon
hsa-miR-3150b-3p 1245-1251 -0.268 96.0 -0.268 96.0 noncon
hsa-miR-4784 1245-1251 -0.268 96.0 -0.268 96.0 noncon
hsa-miR-4464 19-25 -0.265 97.0 -0.265 98.0 noncon
hsa-miR-4434 50-57 -0.264 96.0 -0.264 97.0 noncon
hsa-miR-297 1022-1029 -0.264 95.0 -0.264 96.0 noncon
hsa-miR-4793-3p 126-132 -0.264 97.0 -0.264 98.0 noncon
hsa-miR-6801-5p 771-777 -0.262 95.0 -0.262 96.0 noncon
hsa-miR-1251-3p 1288-1294 -0.258 95.0 -0.258 97.0 noncon
hsa-miR-506-3p 299-306 -0.256 91.0 -0.256 94.0 con
hsa-miR-6891-5p 1221-1227 -0.255 95.0 -0.255 96.0 noncon
hsa-miR-3606-5p 365-372 -0.255 93.0 -0.255 96.0 noncon
hsa-miR-1262 1137-1143 -0.252 94.0 -0.252 96.0 noncon
hsa-miR-6738-3p 867-873 -0.251 94.0 -0.251 96.0 noncon