O00219 · HYAS3_HUMAN
- ProteinHyaluronan synthase 3
- GeneHAS3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids553 (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. 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. This is one of three isoenzymes responsible for cellular hyaluronan synthesis.
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
The enzymatic activity depends on the availability of cytosolic levels of UDP-GlcUA and UDP-GlcNAc.
Pathway
Glycan biosynthesis; hyaluronan biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | early endosome | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | hyaluranon cable | |
Cellular Component | membrane | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | hyaluronan synthase activity | |
Molecular Function | identical protein binding | |
Biological Process | carbohydrate metabolic process | |
Biological Process | extracellular matrix assembly | |
Biological Process | extracellular polysaccharide biosynthetic process | |
Biological Process | hyaluronan biosynthetic process | |
Biological Process | positive regulation of DNA-templated transcription | |
Biological Process | positive regulation of hyaluranon cable assembly |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHyaluronan synthase 3
- 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 accessionO00219
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Golgi apparatus, trans-Golgi network membrane ; Multi-pass membrane protein
Note: Travels from endoplasmic reticulum (ER), Golgi to plasma membrane (PubMed:26883802).
Actives only when present in plasma membrane (By similarity).
O-GlcNAcylation controls its membrane localization (PubMed:26883802).
A rapid recycling of HAS3 between plasma membrane and endosomes is controlled by the cytosolic levels of UDP-GlcUA and UDP-GlcNAc (PubMed:26883802).
Actives only when present in plasma membrane (By similarity).
O-GlcNAcylation controls its membrane localization (PubMed:26883802).
A rapid recycling of HAS3 between plasma membrane and endosomes is controlled by the cytosolic levels of UDP-GlcUA and UDP-GlcNAc (PubMed:26883802).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-15 | Cytoplasmic | ||||
Sequence: MPVQLTTALRVVGTS | ||||||
Transmembrane | 16-36 | Helical; Name=1 | ||||
Sequence: LFALAVLGGILAAYVTGYQFI | ||||||
Topological domain | 37-44 | Extracellular | ||||
Sequence: HTEKHYLS | ||||||
Transmembrane | 45-65 | Helical; Name=2 | ||||
Sequence: FGLYGAILGLHLLIQSLFAFL | ||||||
Topological domain | 66-377 | Cytoplasmic | ||||
Sequence: EHRRMRRAGQALKLPSPRRGSVALCIAAYQEDPDYLRKCLRSAQRISFPDLKVVMVVDGNRQEDAYMLDIFHEVLGGTEQAGFFVWRSNFHEAGEGETEASLQEGMDRVRDVVRASTFSCIMQKWGGKREVMYTAFKALGDSVDYIQVCDSDTVLDPACTIEMLRVLEEDPQVGGVGGDVQILNKYDSWISFLSSVRYWMAFNVERACQSYFGCVQCISGPLGMYRNSLLQQFLEDWYHQKFLGSKCSFGDDRHLTNRVLSLGYRTKYTARSKCLTETPTKYLRWLNQQTRWSKSYFREWLYNSLWFHKHHL | ||||||
Transmembrane | 378-398 | Helical; Name=3 | ||||
Sequence: WMTYESVVTGFFPFFLIATVI | ||||||
Topological domain | 399-408 | Extracellular | ||||
Sequence: QLFYRGRIWN | ||||||
Transmembrane | 409-429 | Helical; Name=4 | ||||
Sequence: ILLFLLTVQLVGIIKATYACF | ||||||
Topological domain | 430-440 | Cytoplasmic | ||||
Sequence: LRGNAEMIFMS | ||||||
Transmembrane | 441-461 | Helical; Name=5 | ||||
Sequence: LYSLLYMSSLLPAKIFAIATI | ||||||
Topological domain | 462-473 | Extracellular | ||||
Sequence: NKSGWGTSGRKT | ||||||
Transmembrane | 474-494 | Helical; Name=6 | ||||
Sequence: IVVNFIGLIPVSIWVAVLLGG | ||||||
Topological domain | 495-515 | Cytoplasmic | ||||
Sequence: LAYTAYCQDLFSETELAFLVS | ||||||
Transmembrane | 516-536 | Helical; Name=7 | ||||
Sequence: GAILYGCYWVALLMLYLAIIA | ||||||
Topological domain | 537-553 | Extracellular | ||||
Sequence: RRCGKKPEQYSLAFAEV |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_049317 | 173 | in dbSNP:rs2232229 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 505 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, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000197178 | 1-553 | Hyaluronan synthase 3 | |||
Sequence: MPVQLTTALRVVGTSLFALAVLGGILAAYVTGYQFIHTEKHYLSFGLYGAILGLHLLIQSLFAFLEHRRMRRAGQALKLPSPRRGSVALCIAAYQEDPDYLRKCLRSAQRISFPDLKVVMVVDGNRQEDAYMLDIFHEVLGGTEQAGFFVWRSNFHEAGEGETEASLQEGMDRVRDVVRASTFSCIMQKWGGKREVMYTAFKALGDSVDYIQVCDSDTVLDPACTIEMLRVLEEDPQVGGVGGDVQILNKYDSWISFLSSVRYWMAFNVERACQSYFGCVQCISGPLGMYRNSLLQQFLEDWYHQKFLGSKCSFGDDRHLTNRVLSLGYRTKYTARSKCLTETPTKYLRWLNQQTRWSKSYFREWLYNSLWFHKHHLWMTYESVVTGFFPFFLIATVIQLFYRGRIWNILLFLLTVQLVGIIKATYACFLRGNAEMIFMSLYSLLYMSSLLPAKIFAIATINKSGWGTSGRKTIVVNFIGLIPVSIWVAVLLGGLAYTAYCQDLFSETELAFLVSGAILYGCYWVALLMLYLAIIARRCGKKPEQYSLAFAEV | ||||||
Glycosylation | 462 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
O-GlcNAcylation increases the hyaluronan synthase activity, HAS3 stability and its plasma membrane residence. The concentration of UDP-GlcNAc controls the level of O-GlcNAc modification.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O00219 | HAS1 Q92839 | 9 | EBI-16628799, EBI-1052423 | |
BINARY | O00219 | HAS2 Q92819 | 10 | EBI-16628799, EBI-16628852 | |
BINARY | O00219 | HAS3 O00219 | 10 | EBI-16628799, EBI-16628799 | |
BINARY | O00219-2 | APOL3 O95236-2 | 3 | EBI-17186025, EBI-11976321 | |
BINARY | O00219-2 | CMTM7 Q96FZ5 | 3 | EBI-17186025, EBI-2807956 | |
BINARY | O00219-2 | LHFPL5 Q8TAF8 | 3 | EBI-17186025, EBI-2820517 | |
BINARY | O00219-2 | NRAC Q8N912 | 3 | EBI-17186025, EBI-12051377 | |
BINARY | O00219-2 | PLP1 P60201-2 | 3 | EBI-17186025, EBI-12188331 | |
BINARY | O00219-2 | SYNGR1 O43759-2 | 3 | EBI-17186025, EBI-12187159 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O00219-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length553
- Mass (Da)62,998
- Last updated2008-09-23 v3
- Checksum82F3B0C932EE9EA3
O00219-2
- Name2
- Differences from canonical
- 247-553: ILNKYDSWISFLSSVRYWMAFNVERACQSYFGCVQCISGPLGMYRNSLLQQFLEDWYHQKFLGSKCSFGDDRHLTNRVLSLGYRTKYTARSKCLTETPTKYLRWLNQQTRWSKSYFREWLYNSLWFHKHHLWMTYESVVTGFFPFFLIATVIQLFYRGRIWNILLFLLTVQLVGIIKATYACFLRGNAEMIFMSLYSLLYMSSLLPAKIFAIATINKSGWGTSGRKTIVVNFIGLIPVSIWVAVLLGGLAYTAYCQDLFSETELAFLVSGAILYGCYWVALLMLYLAIIARRCGKKPEQYSLAFAEV → PPGKGMAVEDDQVQAAQVRATEAWSVHQRHVSREQ
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H3BRH5 | H3BRH5_HUMAN | HAS3 | 264 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_042022 | 247-553 | in isoform 2 | |||
Sequence: ILNKYDSWISFLSSVRYWMAFNVERACQSYFGCVQCISGPLGMYRNSLLQQFLEDWYHQKFLGSKCSFGDDRHLTNRVLSLGYRTKYTARSKCLTETPTKYLRWLNQQTRWSKSYFREWLYNSLWFHKHHLWMTYESVVTGFFPFFLIATVIQLFYRGRIWNILLFLLTVQLVGIIKATYACFLRGNAEMIFMSLYSLLYMSSLLPAKIFAIATINKSGWGTSGRKTIVVNFIGLIPVSIWVAVLLGGLAYTAYCQDLFSETELAFLVSGAILYGCYWVALLMLYLAIIARRCGKKPEQYSLAFAEV → PPGKGMAVEDDQVQAAQVRATEAWSVHQRHVSREQ | ||||||
Sequence conflict | 493 | in Ref. 1; AAF36984 | ||||
Sequence: G → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF232772 EMBL· GenBank· DDBJ | AAF36984.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291400 EMBL· GenBank· DDBJ | BAF84089.1 EMBL· GenBank· DDBJ | mRNA | ||
AC009027 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471092 EMBL· GenBank· DDBJ | EAW83247.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471092 EMBL· GenBank· DDBJ | EAW83248.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC021853 EMBL· GenBank· DDBJ | AAH21853.1 EMBL· GenBank· DDBJ | mRNA | ||
U86409 EMBL· GenBank· DDBJ | AAC51209.1 EMBL· GenBank· DDBJ | Genomic DNA |