HAS2
entrez
3037
canonical
uniprot
Q92819
canonical
ensembl
ENSG00000170961
resolver
ensp
ENSP00000306991
resolver
enst
ENST00000303924
resolver
genesymbol
HAS2
resolver
hgnc
HGNC:4819
resolver
uniprot
Q32MM3
resolver
uniprot_entry
HYAS2_HUMAN
resolver
uniprot_sec
Q32MM3
resolver
activity_regulation
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). {ECO:0000269|PubMed:20507985, ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:22887999, ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:28604766, ECO:0000269|PubMed:30394292, ECO:0000269|PubMed:32993960}.
uniprot
proteins
amino_acid_sequence
MHCERFLCILRIIGTTLFGVSLLLGITAAYIVGYQFIQTDNYYFSFGLYGAFLASHLIIQSLFAFLEHRKMKKSLETPIKLNKTVALCIAAYQEDPDYLRKCLQSVKRLTYPGIKVVMVIDGNSEDDLYMMDIFSEVMGRDKSATYIWKNNFHEKGPGETDESHKESSQHVTQLVLSNKSICIMQKWGGKREVMYTAFRALGRSVDYVQVCDSDTMLDPASSVEMVKVLEEDPMVGGVGGDVQILNKYDSWISFLSSVRYWMAFNIERACQSYFGCVQCISGPLGMYRNSLLHEFVEDWYNQEFMGNQCSFGDDRHLTNRVLSLGYATKYTARSKCLTETPIEYLRWLNQQTRWSKSYFREWLYNAMWFHKHHLWMTYEAIITGFFPFFLIATVIQLFYRGKIWNILLFLLTVQLVGLIKSSFASCLRGNIVMVFMSLYSVLYMSSLLPAKMFAIATINKAGWGTSGRKTIVVNFIGLIPVSVWFTILLGGVIFTIYKESKRPFSESKQTVLIVGTLLYACYWVMLLTLYVVLINKCGRRKKGQQYDMVLDV
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving HAS2 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1 intrachromosomal rearrangement with PLAG1. {ECO:0000269|PubMed:15642402}.
uniprot
proteins
ec_number
2.4.1.212
uniprot
proteins
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). {ECO:0000250|UniProtKB:P70312, ECO:0000269|PubMed:20507985, ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:23303191, ECO:0000269|PubMed:32993960, ECO:0000269|PubMed:8798477, ECO:0000305|PubMed:22887999, ECO:0000305|PubMed:30394292}.
uniprot
proteins
mass_dalton
63566
uniprot
proteins
mutagenesis
MUTAGEN 110; /note="T->A: 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."; /evidence="ECO:0000269|PubMed:21228273, ECO:0000269|PubMed:30394292"; MUTAGEN 190; /note="K->R: Completely abolishes hyaluronan synthase activity. Cumulates at plasma membrane."; /evidence="ECO:0000269|PubMed:20507985, ECO:0000269|PubMed:30394292"; MUTAGEN 221; /note="S->A: Prevents O-GlcNAcylation. Increases protein stability. Reduces hyaluronan synthase activity."; /evidence="ECO:0000269|PubMed:22887999, ECO:0000269|PubMed:30394292"; MUTAGEN 221; /note="S->D: Increases protein degradation. Abolishes hyaluronan synthase activity. Does not affect subcellular location."; /evidence="ECO:0000269|PubMed:30394292"; MUTAGEN 221; /note="S->E: Increases protein degradation. Abolishes hyaluronan synthase activity. Does not affect subcellular location."; /evidence="ECO:0000269|PubMed:30394292"; MUTAGEN 328; /note="T->A: Abolishes hyaluronan synthase activity."; /evidence="ECO:0000269|PubMed:32993960
uniprot
proteins
pathway_participation
PATHWAY: Glycan biosynthesis; hyaluronan biosynthesis. {ECO:0000269|PubMed:20507985}.
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:30394292, ECO:0000269|PubMed:32993960}.; PTM: O-GlcNAcylation at Ser-221 increases the stability of HAS2 and plasma membrane localization. {ECO:0000269|PubMed:22887999}.; PTM: Ubiquitination at Lys-190; this ubiquitination is essential for hyaluronan synthase activity and homo- or heterooligomerization. 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). {ECO:0000269|PubMed:20507985, ECO:0000269|PubMed:28604766}.
uniprot
proteins
protein_family
NodC/HAS family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15642402
uniprot
proteins
pubmed
20507985
uniprot
proteins
pubmed
21228273
uniprot
proteins
pubmed
22887999
uniprot
proteins
pubmed
23303191
uniprot
proteins
pubmed
25795779
uniprot
proteins
pubmed
28604766
uniprot
proteins
pubmed
30394292
uniprot
proteins
pubmed
32993960
uniprot
proteins
pubmed
8798477
uniprot
proteins
sequence_length
552
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22887999, ECO:0000269|PubMed:25795779, ECO:0000269|PubMed:30394292, ECO:0000269|PubMed:8798477}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:30394292}; Multi-pass membrane protein {ECO:0000255}. Vesicle {ECO:0000269|PubMed:30394292}. Golgi apparatus membrane {ECO:0000269|PubMed:25795779, ECO:0000269|PubMed:30394292}; Multi-pass membrane protein {ECO:0000255}. Lysosome {ECO:0000269|PubMed:30394292}. Note=Travels from endoplasmic reticulum (ER), Golgi to plasma membrane and either back to endosomes and lysosomes, or out into extracellular vesicles (PubMed:30394292). Post-translational modifications control HAS2 trafficking (PubMed:30394292). {ECO:0000269|PubMed:30394292}.
uniprot
proteins
transmembrane_region
TRANSMEM 12..32; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 46..66; /note="Helical; Name=2"; /evidence="ECO:0000255"; TRANSMEM 375..395; /note="Helical; Name=3"; /evidence="ECO:0000255"; TRANSMEM 403..423; /note="Helical; Name=4"; /evidence="ECO:0000255"; TRANSMEM 430..450; /note="Helical; Name=5"; /evidence="ECO:0000255"; TRANSMEM 476..496; /note="Helical; Name=6"; /evidence="ECO:0000255"; TRANSMEM 511..531; /note="Helical; Name=7"; /evidence="ECO:0000255
uniprot
proteins