Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P70312 (HYAS2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hyaluronan synthase 2

EC=2.4.1.212
Alternative name(s):
Hyaluronate synthase 2
Hyaluronic acid synthase 2
Short name=HA synthase 2
Gene names
Name:Has2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan. Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development. May also play a role in vasculogenesis. High molecular mass hyaluronan also play a role in early contact inhibition a process which stops cell growth when cells come into contact with each other or the extracellular matrix. Ref.9

Catalytic activity

UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-(nascent hyaluronan) = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-(nascent hyaluronan). Ref.8

UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-(nascent hyaluronan) = UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-(nascent hyaluronan). Ref.8

Cofactor

Magnesium.

Pathway

Glycan biosynthesis; hyaluronan biosynthesis.

Subcellular location

Membrane; Multi-pass membrane protein Probable.

Tissue specificity

Expressed in heart, brain, spleen, lung and skeletal muscle.

Developmental stage

Detected from E7.5 through birth. At E8.5, predominantly expressed in the epithelium of the foregut diverticulum, the cephalic mesenchyme, the allantois, and in the myocardium and endocardium of the heart. At E9.5, prominent expression is detected in cephalic, foregut and periaortic mesenchymes, the septum transversum and the cardiovascular system. Also present in the atrial and ventricular endothelium and the myocardium of the atrioventricular canal region. By E10.5, highly expressed in endothelial cells in the atrioventricular canal and outflow tract that transform into mesenchymal cells and invade the underlying matrix. Later, expressed by mesenchymal cells during elevation of the secondary palate and by hypertrophic chondrocytes within epiphysial growth plates. Ref.9

Disruption phenotype

Embryonic lethal. At day E9.5, the distribution of homozygous embryos approaches Mendelian frequency while only occasional viable embryos were found at E10.5. Embryos exhibited growth retardation, scant numbers of red blood cells, and lacked vitelline vessels in the yolk sac. The visceral endoderm and mesoderm forming the yolk sac was not fused except at discrete foci. The heart was thinwalled and relatively bloodless, and often exhibited marked pericardial swelling. The heart lacks cardiac jelly, endocardial cushions and trabeculae. A marked reduction in vessels in homozygous embryos is also observed. Somites were present but distorted. Some of the E9.5 embryos had failed to turn, and exhibited posterior defects as well as cephalic mesenchyme abnormalities. Ref.9

Sequence similarities

Belongs to the NodC/HAS family.

Biophysicochemical properties

Kinetic parameters:

KM=0.2 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2) Ref.8

KM=0.3 mM for UDP-Glc-UA (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)

Ontologies

Keywords
   Cellular componentMembrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionGlycosyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processatrioventricular canal development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

bone morphogenesis

Inferred from mutant phenotype PubMed 21246657. Source: MGI

cellular response to fluid shear stress

Inferred from electronic annotation. Source: Ensembl

cellular response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

cellular response to platelet-derived growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

endocardial cushion to mesenchymal transition

Inferred from mutant phenotype Ref.9. Source: UniProtKB

extracellular matrix assembly

Inferred from direct assay Ref.8. Source: UniProtKB

extracellular polysaccharide biosynthetic process

Inferred from direct assay Ref.8. Source: UniProtKB

hyaluronan biosynthetic process

Inferred from mutant phenotype Ref.9. Source: UniProtKB

hyaluronan metabolic process

Inferred from mutant phenotype PubMed 21246657. Source: MGI

kidney development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of monocyte aggregation

Inferred from electronic annotation. Source: Ensembl

positive regulation of urine volume

Inferred from sequence or structural similarity. Source: UniProtKB

renal water absorption

Inferred from sequence or structural similarity. Source: UniProtKB

vasculogenesis

Inferred from mutant phenotype Ref.9. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionhyaluronan synthase activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 552552Hyaluronan synthase 2
PRO_0000197174

Regions

Topological domain1 – 1111Cytoplasmic Potential
Transmembrane12 – 3221Helical; Name=1; Potential
Topological domain33 – 4513Extracellular Potential
Transmembrane46 – 6621Helical; Name=2; Potential
Topological domain67 – 374308Cytoplasmic Potential
Transmembrane375 – 39521Helical; Name=3; Potential
Topological domain396 – 4027Extracellular Potential
Transmembrane403 – 42321Helical; Name=4; Potential
Topological domain424 – 4296Cytoplasmic Potential
Transmembrane430 – 45021Helical; Name=5; Potential
Topological domain451 – 47525Extracellular Potential
Transmembrane476 – 49621Helical; Name=6; Potential
Topological domain497 – 51014Cytoplasmic Potential
Transmembrane511 – 53121Helical; Name=7; Potential
Topological domain532 – 55221Extracellular Potential

Experimental info

Sequence conflict1381M → I in AAC53309. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P70312 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: B840BABC6D2260D5

FASTA55263,510
        10         20         30         40         50         60 
MHCERFLCVL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG AFLASHLIIQ 

        70         80         90        100        110        120 
SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR KCLQSVKRLT YPGIKVVMVI 

       130        140        150        160        170        180 
DGNSDDDLYM MDIFSEVMGR DKSATYIWKN NFHEKGPGET EESHKESSQH VTQLVLSNKS 

       190        200        210        220        230        240 
ICIMQKWGGK REVMYTAFRA LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG 

       250        260        270        280        290        300 
DVQILNKYDS WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY 

       310        320        330        340        350        360 
NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ QTRWSKSYFR 

       370        380        390        400        410        420 
EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR GKIWNILLFL LTVQLVGLIK 

       430        440        450        460        470        480 
SSFASCLRGN IVMVFMSLYS VLYMSSLLPA KMFAIATINK AGWGTSGRKT IVVNFIGLIP 

       490        500        510        520        530        540 
VSVWFTILLG GVIFTIYKES KKPFSESKQT VLIVGTLIYA CYWVMLLTLY VVLINKCGRR 

       550 
KKGQQYDMVL DV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a putative mouse hyaluronan synthase."
Spicer A.P., Augustine M.L., McDonald J.A.
J. Biol. Chem. 271:23400-23406(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6J.
[2]Spicer A.P., Augustine M.L., McDonald J.A.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 138.
[3]"Coding sequence of a hyaluronan synthase homologue expressed during expansion of the mouse cumulus-oocyte complex."
Fueloep C., Salustri A., Hascall V.C.
Arch. Biochem. Biophys. 337:261-266(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CD-1.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Thymus.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[7]"Homologs of the Xenopus developmental gene DG42 are present in zebrafish and mouse and are involved in the synthesis of Nod-like chitin oligosaccharides during early embryogenesis."
Semino C.E., Specht C.A., Raimondi A., Robbins P.W.
Proc. Natl. Acad. Sci. U.S.A. 93:4548-4553(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 215-348.
Strain: Swiss Webster.
Tissue: Embryo.
[8]"Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties."
Itano N., Sawai T., Yoshida M., Lenas P., Yamada Y., Imagawa M., Shinomura T., Hamaguchi M., Yoshida Y., Ohnuki Y., Miyauchi S., Spicer A.P., McDonald J.A., Kimata K.
J. Biol. Chem. 274:25085-25092(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, KINETIC PARAMETERS.
[9]"Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme."
Camenisch T.D., Spicer A.P., Brehm-Gibson T., Biesterfeldt J., Augustine M.L., Calabro A. Jr., Kubalak S., Klewer S.E., McDonald J.A.
J. Clin. Invest. 106:349-360(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Web resources

Protein Spotlight

an unexpected turn of events - Issue 155 of December 2013

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U52524 mRNA. Translation: AAC53309.2.
U69695 mRNA. Translation: AAB17609.1.
AK079729 mRNA. Translation: BAC37733.1.
CH466545 Genomic DNA. Translation: EDL29280.1.
BC080281 mRNA. Translation: AAH80281.1.
U53222 Genomic DNA. Translation: AAC52651.1.
RefSeqNP_032242.3. NM_008216.3.
UniGeneMm.5148.

3D structure databases

ProteinModelPortalP70312.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

CAZyGT2. Glycosyltransferase Family 2.

PTM databases

PhosphoSiteP70312.

Proteomic databases

PRIDEP70312.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000050544; ENSMUSP00000062212; ENSMUSG00000022367.
GeneID15117.
KEGGmmu:15117.
UCSCuc007vsl.2. mouse.

Organism-specific databases

CTD3037.
MGIMGI:107821. Has2.

Phylogenomic databases

eggNOGCOG1215.
GeneTreeENSGT00390000010337.
HOGENOMHOG000112847.
HOVERGENHBG000189.
InParanoidQ68EF7.
KOK00752.
OMATAYIMGY.
OrthoDBEOG77WWBZ.
TreeFamTF332506.

Enzyme and pathway databases

BRENDA2.4.1.212. 3474.
UniPathwayUPA00341.

Gene expression databases

BgeeP70312.
CleanExMM_HAS2.
GenevestigatorP70312.

Family and domain databases

InterProIPR001173. Glyco_trans_2-like.
IPR026107. HAS/NodC.
IPR028371. HAS2.
[Graphical view]
PANTHERPTHR22913. PTHR22913. 1 hit.
PTHR22913:SF7. PTHR22913:SF7. 1 hit.
PfamPF00535. Glycos_transf_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio287534.
PROP70312.
SOURCESearch...

Entry information

Entry nameHYAS2_MOUSE
AccessionPrimary (citable) accession number: P70312
Secondary accession number(s): P70411, Q62405, Q68EF7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 102 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot