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

EXTL1



General Information
Gene Symbol:   
EXTL1
Protein name:   
Exostosin-like 1
Enzyme Class:   
Glycosyltransferase
CAZy Family:   
E.C. No:   
Organs:   
Reaction (SNFG):   
+
+ 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(b1-4)
Product:  
     GlcNAc(a1-4)GlcA(b1-4)
Constraints:  
     !IdoA(a1-4)&!GlcN(a1-4 NS-2)

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 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-1292-3p 968-975 -0.568 98.0 -0.368 94.0 noncon
hsa-miR-185-3p 904-911 -0.561 99.0 -0.363 95.0 noncon
hsa-miR-663a 570-577 -0.507 97.0 -0.331 91.0 noncon
hsa-miR-1908-5p 570-577 -0.486 97.0 -0.318 90.0 noncon
hsa-miR-3656 814-821 -0.465 97.0 -0.305 92.0 noncon
hsa-miR-1237-5p 318-325 -0.458 98.0 -0.458 98.0 noncon
hsa-miR-4488 318-325 -0.455 98.0 -0.455 98.0 noncon
hsa-miR-6787-5p 570-577 -0.449 96.0 -0.295 87.0 noncon
hsa-miR-4697-5p 318-325 -0.439 98.0 -0.439 98.0 noncon
hsa-miR-3196 562-569 -0.417 90.0 -0.275 76.0 noncon
hsa-miR-1229-3p 1000-1007 -0.415 98.0 -0.274 96.0 noncon
hsa-miR-3180 562-569 -0.404 90.0 -0.267 75.0 noncon
hsa-miR-3180-3p 562-569 -0.404 90.0 -0.267 75.0 noncon
hsa-miR-346 488-495 -0.403 96.0 -0.266 93.0 noncon
hsa-miR-6836-5p 762-769 -0.397 97.0 -0.262 94.0 noncon
hsa-miR-6726-5p 40-47 -0.394 97.0 -0.394 97.0 noncon
hsa-miR-6852-5p 389-396 -0.383 98.0 -0.383 99.0 noncon
hsa-miR-6805-5p 1093-1099 -0.379 95.0 -0.251 88.0 noncon
hsa-miR-6132 762-769 -0.378 97.0 -0.25 93.0 noncon
hsa-miR-6846-5p 319-325 -0.355 93.0 -0.355 94.0 noncon
hsa-miR-5591-5p 40-47 -0.349 96.0 -0.349 97.0 noncon
hsa-miR-4300 40-47 -0.341 96.0 -0.341 97.0 noncon
hsa-miR-1247-3p 598-605 -0.336 96.0 -0.224 88.0 noncon
hsa-miR-4749-5p 727-734 -0.332 91.0 -0.221 82.0 noncon
hsa-miR-3675-5p 906-912 -0.331 96.0 -0.221 92.0 noncon
hsa-miR-6848-5p 319-325 -0.331 91.0 -0.331 93.0 noncon
hsa-miR-1288-3p 352-359 -0.318 95.0 -0.318 96.0 noncon
hsa-miR-6511b-5p 920-926 -0.303 96.0 -0.203 93.0 noncon
hsa-miR-3186-5p 621-627 -0.295 94.0 -0.197 92.0 noncon
hsa-miR-363-5p 244-251 -0.293 95.0 -0.293 96.0 noncon
hsa-miR-920 40-47 -0.289 96.0 -0.289 97.0 noncon
hsa-miR-6745 244-251 -0.28 95.0 -0.28 96.0 noncon
hsa-miR-4267 1053-1060 -0.266 96.0 -0.178 93.0 noncon
hsa-miR-6829-5p 33-40 -0.265 93.0 -0.265 95.0 noncon
hsa-miR-4731-5p 19-26 -0.264 95.0 -0.264 96.0 noncon
hsa-miR-6817-5p 486-493 -0.256 96.0 -0.256 97.0 noncon
hsa-miR-4769-3p 486-493 -0.256 96.0 -0.256 98.0 noncon