Heparan sulfate and chondroitin sulfate chains are built in the endoplasmic reticulum and Golgi on serine residues of core proteins such as the glypicans Dally and Dally-like, Syndecan and Perlecan. Both start on a shared tetrasaccharide linker (xylose-galactose-galactose-glucuronic acid) made by Oxt, beta4GalT7, beta3GalTII and GlcAT-I. Addition of N-acetylglucosamine by Brother of tout-velu (Botv) commits the chain to heparan sulfate; the Tout-velu (Ttv) and Sister of tout-velu (Sotv) exostosin complex then polymerizes alternating glucuronic acid and N-acetylglucosamine. The chain is modified by the N-deacetylase/N-sulfotransferase Sulfateless (Sfl), the C5-epimerase Hsepi and the 2-O-, 6-O- and 3-O-sulfotransferases (Hs2st, Hs6st, Hs3st-A, Hs3st-B). Addition of N-acetylgalactosamine by Csgalnact instead starts chondroitin chains, which are polymerized by Chsy and Chpf and sulfated by C4st. Heparan sulfate made by this pathway is required for Wingless, Hedgehog, Dpp and FGF signaling in Drosophila.
Boundary. The module joins three FlyBase groups: heparan sulfate proteoglycan biosynthesis (GAHSB), chondroitin sulfate proteoglycan biosynthesis (GACSB) and the EXT1-EXT2 complex. Core proteins, the PAPS synthesis and transport machinery (Papss, Papst1, Papst2), UDP-sugar transporters and the extracellular 6-O-endosulfatase Sulf1 are not parts. Molecular functions are assigned where the fly enzyme or its well-studied ortholog has an established activity; beta3GalTII, Csgalnact, Chsy, Chpf and C4st and the Ttv-Sotv complex are left without a function term (the copolymerase has two activities that no single GO term captures). FlyBase groups realized by this module: EXT1-EXT2 (FBgg0001998), GACSB (FBgg0002060), GAHSB (FBgg0002062). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_glycosaminoglycan_biosynthesis.yaml. Member genes with a gene review in this repository: ttv.
All recommended fields populated.
✗ none found
No MODULE:dmel_glycosaminoglycan_biosynthesis deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
0 gene-function check(s) reflected in core functions · 0 conflict(s) · 10 evidence or coverage gap(s) (10 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| xylosylation_oxt | Oxt UniProtKB:Q7KVA1 Gene |
protein xylosyltransferase activity GO:0030158 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| first_galactosylation_beta4galt7 | beta4GalT7 UniProtKB:Q9VBZ9 Gene |
xylosylprotein 4-beta-galactosyltransferase activity GO:0046525 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| linker_glucuronylation_glcat_i | GlcAT-I UniProtKB:O97422 Gene |
galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity GO:0015018 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_initiation_botv | botv UniProtKB:Q9XZ08 Gene |
glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity GO:0001888 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_n_sulfation_sfl | sfl UniProtKB:Q9V3L1 Gene |
heparan sulfate N-sulfotransferase activity GO:0015016 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_epimerization_hsepi | Hsepi UniProtKB:A1Z6M8 Gene |
heparosan-N-sulfate-glucuronate 5-epimerase activity GO:0047464 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_2_o_sulfation_hs2st | Hs2st UniProtKB:P25722 Gene |
heparan sulfate 2-sulfotransferase activity GO:0004394 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_6_o_sulfation_hs6st | Hs6st UniProtKB:Q9VDR6 Gene |
heparan sulfate 6-sulfotransferase activity GO:0017095 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_3_o_sulfation_hs3st_a | Hs3st-A UniProtKB:A1ZBD3 Gene |
[heparan sulfate]-glucosamine 3-sulfotransferase activity GO:0008467 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| hs_3_o_sulfation_hs3st_b | Hs3st-B UniProtKB:Q9VWJ7 Gene |
[heparan sulfate]-glucosamine 3-sulfotransferase activity GO:0008467 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
1 complete review(s) · 1 with deep research · 16 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Hsepi A1Z6M8 | ✗ | — | — |
| beta3GalTII A1Z7G9 | ✗ | — | — |
| Csgalnact A1Z863 | ✗ | — | — |
| Hs3st-A A1ZBD3 | ✗ | — | — |
| GlcAT-I O97422 | ✗ | — | — |
| Hs2st P25722 | ✗ | — | — |
| Chsy Q7KUZ9 | ✗ | — | — |
| Oxt Q7KVA1 | ✗ | — | — |
| sfl Q9V3L1 | ✗ | — | — |
| beta4GalT7 Q9VBZ9 | ✗ | — | — |
| Hs6st Q9VDR6 | ✗ | — | — |
| C4st Q9VJG5 | ✗ | — | — |
| Hs3st-B Q9VWJ7 | ✗ | — | — |
| Chpf Q9VYH2 | ✗ | — | — |
| botv Q9XZ08 | ✗ | — | — |
| sotv Q9Y169 | ✗ | — | — |
| ttv Q9V730 | ✓ | ✓ | ✓ |
Linker tetrasaccharide synthesis, then heparan sulfate (Botv, Ttv-Sotv, Sfl, Hsepi, sulfotransferases) or chondroitin sulfate (Csgalnact, Chsy, Chpf, C4st) chain synthesis and modification.
Tout-velu and Sister of tout-velu act together as the heparan sulfate copolymerase.