EnzFunc

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

EXT1



General Information
Gene Symbol:   
EXT1
Protein name:   
Exostosin-1
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, Cis, Medial, Trans, TGN
Substrate:  
     GlcNAc(a1-4) or GlcA(b1-4)
Product:  
     GlcA(b1-4)GlcNAc(a1-4) or 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 30 20 10 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 400 300 200 100 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-6887-3p 19-26 -0.621 99.0 -0.621 99.0 noncon
hsa-miR-6859-3p 40-47 -0.604 99.0 -0.604 99.0 noncon
hsa-miR-6828-3p 122-129 -0.557 99.0 -0.557 99.0 noncon
hsa-miR-4715-5p 99-106 -0.537 99.0 -0.537 99.0 noncon
hsa-miR-7854-3p 199-206 -0.506 99.0 -0.506 99.0 noncon
hsa-miR-767-3p 121-128 -0.503 99.0 -0.503 99.0 noncon
hsa-miR-760 85-92 -0.481 98.0 -0.481 98.0 noncon
hsa-miR-548g-3p 238-245 -0.478 99.0 -0.478 99.0 noncon
hsa-miR-6081 188-195 -0.469 98.0 -0.469 99.0 noncon
hsa-miR-633 315-322 -0.467 99.0 -0.428 99.0 noncon
hsa-miR-149-5p 87-94 -0.464 99.0 -0.464 99.0 con
hsa-miR-29b-1-5p 323-330 -0.457 99.0 -0.419 99.0 noncon
hsa-miR-6826-3p 20-27 -0.442 98.0 -0.442 98.0 noncon
hsa-miR-4298 217-224 -0.439 98.0 -0.439 99.0 noncon
hsa-miR-8075 79-86 -0.418 98.0 -0.418 98.0 noncon
hsa-miR-1302 217-224 -0.41 98.0 -0.41 99.0 noncon
hsa-miR-4793-3p 65-72 -0.406 99.0 -0.406 99.0 noncon
hsa-miR-135a-5p 5062-5069 -0.397 98.0 -0.002 32.0 con
hsa-miR-135b-5p 5062-5069 -0.397 98.0 -0.002 32.0 con
hsa-miR-646 374-381 -0.394 99.0 -0.002 32.0 noncon
hsa-miR-96-5p 97-103 -0.388 97.0 -0.388 98.0 con
hsa-miR-93-3p 81-88 -0.372 99.0 -0.372 99.0 noncon
hsa-miR-153-3p 283-289 -0.366 98.0 -0.336 98.0 con
hsa-miR-1295b-3p 3314-3321 -0.365 96.0 -0.002 25.0 noncon
hsa-miR-1271-5p 97-103 -0.363 97.0 -0.363 98.0 con
hsa-miR-4749-3p 4811-4818 -0.362 96.0 -0.002 32.0 noncon
hsa-miR-514a-5p 326-332 -0.348 99.0 -0.318 98.0 noncon
hsa-miR-6764-3p 325-331 -0.347 98.0 -0.317 98.0 noncon
hsa-miR-146b-3p 3352-3359 -0.336 98.0 -0.002 30.0 noncon
hsa-miR-6824-3p 325-331 -0.336 98.0 -0.307 98.0 noncon
hsa-miR-5088-3p 31-38 -0.325 97.0 -0.325 98.0 noncon
hsa-miR-548q 180-187 -0.32 98.0 -0.32 98.0 noncon
hsa-miR-3683 588-594 -0.309 93.0 -0.002 21.0 noncon
hsa-miR-3663-3p 3115-3122 -0.293 92.0 -0.002 27.0 noncon
hsa-miR-4721 5020-5027 -0.291 93.0 -0.002 18.0 noncon
hsa-miR-324-3p 4813-4820 -0.29 96.0 -0.002 40.0 noncon
hsa-miR-3194-3p 84-90 -0.289 96.0 -0.289 97.0 noncon
hsa-miR-6841-5p 4244-4251 -0.288 93.0 -0.002 22.0 noncon
hsa-miR-183-5p.2 97-103 -0.287 94.0 -0.287 95.0 con
hsa-miR-371b-3p 3355-3361 -0.28 93.0 -0.002 28.0 noncon
hsa-miR-1294 201-207 -0.279 95.0 -0.279 96.0 noncon
hsa-miR-3944-5p 2028-2034 -0.279 95.0 -0.002 43.0 noncon
hsa-miR-1913 4813-4820 -0.272 95.0 -0.002 41.0 noncon
hsa-miR-549a 4430-4437 -0.266 93.0 -0.002 22.0 noncon
hsa-miR-2115-5p 24-30 -0.265 93.0 -0.265 95.0 noncon
hsa-miR-6769a-5p 768-775 -0.265 95.0 -0.002 23.0 noncon
hsa-miR-1266-3p 2363-2370 -0.264 95.0 -0.002 41.0 noncon
hsa-miR-3126-3p 89-95 -0.264 95.0 -0.264 96.0 noncon
hsa-miR-195-5p 375-381 -0.263 93.0 -0.002 26.0 noncon
hsa-miR-6795-3p 20-26 -0.262 97.0 -0.262 97.0 noncon
hsa-miR-4680-5p 328-334 -0.258 95.0 -0.236 96.0 noncon
hsa-miR-4715-3p 4852-4859 -0.258 97.0 -0.002 46.0 noncon
hsa-miR-3692-5p 82-88 -0.255 96.0 -0.255 97.0 noncon
hsa-miR-3681-5p 72-78 -0.252 96.0 -0.252 97.0 noncon
hsa-miR-4506 475-482 -0.252 95.0 -0.002 24.0 noncon
hsa-miR-190b 2895-2902 -0.252 92.0 -0.002 24.0 noncon
hsa-miR-16-5p 375-381 -0.251 92.0 -0.002 26.0 noncon