Q92819 · HYAS2_HUMAN
- ProteinHyaluronan synthase 2
- GeneHAS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids552 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer (Probable) (PubMed:20507985, PubMed:21228273, PubMed:23303191, PubMed:32993960).
Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation (PubMed:20507985, PubMed:21228273, PubMed:8798477).
This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (By similarity).
Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation (PubMed:20507985, PubMed:21228273, PubMed:8798477).
This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (By similarity).
Catalytic activity
- [hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine = H+ + N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDPThis reaction proceeds in the forward direction.
[hyaluronan](n) RHEA-COMP:12583 + CHEBI:57705 = CHEBI:15378 + N-acetyl-β-D-glucosaminyl-(1→4)-[hyaluronan](n) RHEA-COMP:12585 + CHEBI:58223
Cofactor
Activity regulation
Regulated by several post-translational modifications such as ubiquitination/deubiquitination, phosphorylation and O-GlcNAcylation (PubMed:20507985, PubMed:21228273, PubMed:22887999, PubMed:28604766, PubMed:30394292, PubMed:32993960).
The enzymatic activity depends on the availability of UDP-GlcUA and UDP-GlcNAc (PubMed:22887999, PubMed:23303191).
The enzymatic activity depends on the availability of UDP-GlcUA and UDP-GlcNAc (PubMed:22887999, PubMed:23303191).
Pathway
Glycan biosynthesis; hyaluronan biosynthesis.
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHyaluronan synthase 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ92819
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-11 | Cytoplasmic | ||||
Sequence: MHCERFLCILR | ||||||
Transmembrane | 12-32 | Helical; Name=1 | ||||
Sequence: IIGTTLFGVSLLLGITAAYIV | ||||||
Topological domain | 33-45 | Extracellular | ||||
Sequence: GYQFIQTDNYYFS | ||||||
Transmembrane | 46-66 | Helical; Name=2 | ||||
Sequence: FGLYGAFLASHLIIQSLFAFL | ||||||
Topological domain | 67-374 | Cytoplasmic | ||||
Sequence: EHRKMKKSLETPIKLNKTVALCIAAYQEDPDYLRKCLQSVKRLTYPGIKVVMVIDGNSEDDLYMMDIFSEVMGRDKSATYIWKNNFHEKGPGETDESHKESSQHVTQLVLSNKSICIMQKWGGKREVMYTAFRALGRSVDYVQVCDSDTMLDPASSVEMVKVLEEDPMVGGVGGDVQILNKYDSWISFLSSVRYWMAFNIERACQSYFGCVQCISGPLGMYRNSLLHEFVEDWYNQEFMGNQCSFGDDRHLTNRVLSLGYATKYTARSKCLTETPIEYLRWLNQQTRWSKSYFREWLYNAMWFHKHHL | ||||||
Transmembrane | 375-395 | Helical; Name=3 | ||||
Sequence: WMTYEAIITGFFPFFLIATVI | ||||||
Topological domain | 396-402 | Extracellular | ||||
Sequence: QLFYRGK | ||||||
Transmembrane | 403-423 | Helical; Name=4 | ||||
Sequence: IWNILLFLLTVQLVGLIKSSF | ||||||
Topological domain | 424-429 | Cytoplasmic | ||||
Sequence: ASCLRG | ||||||
Transmembrane | 430-450 | Helical; Name=5 | ||||
Sequence: NIVMVFMSLYSVLYMSSLLPA | ||||||
Topological domain | 451-475 | Extracellular | ||||
Sequence: KMFAIATINKAGWGTSGRKTIVVNF | ||||||
Transmembrane | 476-496 | Helical; Name=6 | ||||
Sequence: IGLIPVSVWFTILLGGVIFTI | ||||||
Topological domain | 497-510 | Cytoplasmic | ||||
Sequence: YKESKRPFSESKQT | ||||||
Transmembrane | 511-531 | Helical; Name=7 | ||||
Sequence: VLIVGTLLYACYWVMLLTLYV | ||||||
Topological domain | 532-552 | Extracellular | ||||
Sequence: VLINKCGRRKKGQQYDMVLDV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 110 | Completely abolishes hyaluronan synthase activity. Not detected in cytoplasmic vesicles nor at cell membrane. Inability to travel from ER to Golgi. Unresponsive to AMPK-mediated inactivation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 190 | Completely abolishes hyaluronan synthase activity. Cumulates at plasma membrane. | ||||
Sequence: K → R | ||||||
Mutagenesis | 221 | Prevents O-GlcNAcylation. Increases protein stability. Reduces hyaluronan synthase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 221 | Increases protein degradation. Abolishes hyaluronan synthase activity. Does not affect subcellular location. | ||||
Sequence: S → D | ||||||
Mutagenesis | 221 | Increases protein degradation. Abolishes hyaluronan synthase activity. Does not affect subcellular location. | ||||
Sequence: S → E | ||||||
Mutagenesis | 328 | Abolishes hyaluronan synthase activity. | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 411 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000197173 | 1-552 | Hyaluronan synthase 2 | |||
Sequence: MHCERFLCILRIIGTTLFGVSLLLGITAAYIVGYQFIQTDNYYFSFGLYGAFLASHLIIQSLFAFLEHRKMKKSLETPIKLNKTVALCIAAYQEDPDYLRKCLQSVKRLTYPGIKVVMVIDGNSEDDLYMMDIFSEVMGRDKSATYIWKNNFHEKGPGETDESHKESSQHVTQLVLSNKSICIMQKWGGKREVMYTAFRALGRSVDYVQVCDSDTMLDPASSVEMVKVLEEDPMVGGVGGDVQILNKYDSWISFLSSVRYWMAFNIERACQSYFGCVQCISGPLGMYRNSLLHEFVEDWYNQEFMGNQCSFGDDRHLTNRVLSLGYATKYTARSKCLTETPIEYLRWLNQQTRWSKSYFREWLYNAMWFHKHHLWMTYEAIITGFFPFFLIATVIQLFYRGKIWNILLFLLTVQLVGLIKSSFASCLRGNIVMVFMSLYSVLYMSSLLPAKMFAIATINKAGWGTSGRKTIVVNFIGLIPVSVWFTILLGGVIFTIYKESKRPFSESKQTVLIVGTLLYACYWVMLLTLYVVLINKCGRRKKGQQYDMVLDV | ||||||
Modified residue | 110 | Phosphothreonine | ||||
Sequence: T | ||||||
Cross-link | 190 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Glycosylation | 221 | O-linked (GlcNAc) serine | ||||
Sequence: S | ||||||
Modified residue | 328 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylation at Thr-328 is essential for hyaluronan synthase activity (PubMed:32993960).
Phosphorylation at Thr-110 is required for transport from ER to Golgi (PubMed:30394292).
Phosphorylation at Thr-110 is required for transport from ER to Golgi (PubMed:30394292).
O-GlcNAcylation at Ser-221 increases the stability of HAS2 and plasma membrane localization.
Ubiquitination at Lys-190; this ubiquitination is essential for hyaluronan synthase activity and homo- or hetero-oligomerization. Can also be poly-ubiquitinated (PubMed:20507985).
Deubiquitinated by USP17 and USP4. USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains, whereas USP4 preferentially removes monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain (PubMed:28604766).
Deubiquitinated by USP17 and USP4. USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains, whereas USP4 preferentially removes monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain (PubMed:28604766).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homodimer; dimerization promotes enzymatic activity (PubMed:20507985, PubMed:25795779).
Forms heterodimer with HAS3 (PubMed:20507985, PubMed:25795779).
Forms heterodimer with HAS1 (PubMed:25795779).
Forms heterodimer with HAS3 (PubMed:20507985, PubMed:25795779).
Forms heterodimer with HAS1 (PubMed:25795779).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q92819 | HAS1 Q92839 | 9 | EBI-16628852, EBI-1052423 | |
BINARY | Q92819 | HAS3 O00219 | 10 | EBI-16628852, EBI-16628799 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length552
- Mass (Da)63,566
- Last updated1997-02-01 v1
- ChecksumEEEF58D97B131F9D
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U54804 EMBL· GenBank· DDBJ | AAC50692.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069353 EMBL· GenBank· DDBJ | AAH69353.1 EMBL· GenBank· DDBJ | mRNA | ||
BC109071 EMBL· GenBank· DDBJ | AAI09072.1 EMBL· GenBank· DDBJ | mRNA | ||
BC109072 EMBL· GenBank· DDBJ | AAI09073.1 EMBL· GenBank· DDBJ | mRNA |