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Protein

Hyaluronan synthase 2

Gene

Has2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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).1 Publication
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).1 Publication

Cofactori

Kineticsi

  1. KM=0.2 mM for UDP-Glc-NAc (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)1 Publication
  2. KM=0.3 mM for UDP-Glc-UA (at pH 7.1 and 37 degrees Celsius, in the presence of 15 mM MgCl2)1 Publication

Pathwayi

GO - Molecular functioni

  1. hyaluronan synthase activity Source: UniProtKB

GO - Biological processi

  1. atrioventricular canal development Source: UniProtKB
  2. bone morphogenesis Source: MGI
  3. cell adhesion Source: GO_Central
  4. cellular response to fluid shear stress Source: Ensembl
  5. cellular response to interleukin-1 Source: Ensembl
  6. cellular response to platelet-derived growth factor stimulus Source: MGI
  7. cellular response to tumor necrosis factor Source: Ensembl
  8. endocardial cushion to mesenchymal transition Source: UniProtKB
  9. extracellular matrix assembly Source: UniProtKB
  10. extracellular polysaccharide biosynthetic process Source: UniProtKB
  11. hyaluronan biosynthetic process Source: UniProtKB
  12. hyaluronan metabolic process Source: MGI
  13. kidney development Source: Ensembl
  14. positive regulation of cell migration Source: MGI
  15. positive regulation of cell proliferation Source: MGI
  16. positive regulation of monocyte aggregation Source: MGI
  17. positive regulation of urine volume Source: UniProtKB
  18. renal water absorption Source: UniProtKB
  19. vasculogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.1.212. 3474.
UniPathwayiUPA00341.

Protein family/group databases

CAZyiGT2. Glycosyltransferase Family 2.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Has2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 15

Organism-specific databases

MGIiMGI:107821. Has2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei12 – 3221Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini33 – 4513ExtracellularSequence AnalysisAdd
BLAST
Transmembranei46 – 6621Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini67 – 374308CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei375 – 39521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini396 – 4027ExtracellularSequence Analysis
Transmembranei403 – 42321Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini424 – 4296CytoplasmicSequence Analysis
Transmembranei430 – 45021Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini451 – 47525ExtracellularSequence AnalysisAdd
BLAST
Transmembranei476 – 49621Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini497 – 51014CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei511 – 53121Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini532 – 55221ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 552552Hyaluronan synthase 2PRO_0000197174Add
BLAST

Proteomic databases

PRIDEiP70312.

PTM databases

PhosphoSiteiP70312.

Expressioni

Tissue specificityi

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

Developmental stagei

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.1 Publication

Gene expression databases

BgeeiP70312.
CleanExiMM_HAS2.
GenevestigatoriP70312.

Structurei

3D structure databases

ProteinModelPortaliP70312.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NodC/HAS family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1215.
GeneTreeiENSGT00390000010337.
HOGENOMiHOG000112847.
HOVERGENiHBG000189.
InParanoidiP70312.
KOiK00752.
OMAiTAYIMGY.
OrthoDBiEOG77WWBZ.
TreeFamiTF332506.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR001173. Glyco_trans_2-like.
IPR026107. HAS/NodC.
IPR028371. HAS2.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PANTHERiPTHR22913. PTHR22913. 1 hit.
PTHR22913:SF7. PTHR22913:SF7. 1 hit.
PfamiPF00535. Glycos_transf_2. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 2 hits.

Sequencei

Sequence statusi: Complete.

P70312-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MHCERFLCVL RIIGTTLFGV SLLLGITAAY IVGYQFIQTD NYYFSFGLYG
60 70 80 90 100
AFLASHLIIQ SLFAFLEHRK MKKSLETPIK LNKTVALCIA AYQEDPDYLR
110 120 130 140 150
KCLQSVKRLT YPGIKVVMVI DGNSDDDLYM MDIFSEVMGR DKSATYIWKN
160 170 180 190 200
NFHEKGPGET EESHKESSQH VTQLVLSNKS ICIMQKWGGK REVMYTAFRA
210 220 230 240 250
LGRSVDYVQV CDSDTMLDPA SSVEMVKVLE EDPMVGGVGG DVQILNKYDS
260 270 280 290 300
WISFLSSVRY WMAFNIERAC QSYFGCVQCI SGPLGMYRNS LLHEFVEDWY
310 320 330 340 350
NQEFMGNQCS FGDDRHLTNR VLSLGYATKY TARSKCLTET PIEYLRWLNQ
360 370 380 390 400
QTRWSKSYFR EWLYNAMWFH KHHLWMTYEA VITGFFPFFL IATVIQLFYR
410 420 430 440 450
GKIWNILLFL LTVQLVGLIK SSFASCLRGN IVMVFMSLYS VLYMSSLLPA
460 470 480 490 500
KMFAIATINK AGWGTSGRKT IVVNFIGLIP VSVWFTILLG GVIFTIYKES
510 520 530 540 550
KKPFSESKQT VLIVGTLIYA CYWVMLLTLY VVLINKCGRR KKGQQYDMVL

DV
Length:552
Mass (Da):63,510
Last modified:July 27, 2011 - v4
Checksum:iB840BABC6D2260D5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381M → I in AAC53309. (PubMed:8798545)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS27480.1.
RefSeqiNP_032242.3. NM_008216.3.
UniGeneiMm.5148.

Genome annotation databases

EnsembliENSMUST00000050544; ENSMUSP00000062212; ENSMUSG00000022367.
GeneIDi15117.
KEGGimmu:15117.
UCSCiuc007vsl.2. mouse.

Cross-referencesi

Web resourcesi

Protein Spotlight

an unexpected turn of events - Issue 155 of December 2013

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS27480.1.
RefSeqiNP_032242.3. NM_008216.3.
UniGeneiMm.5148.

3D structure databases

ProteinModelPortaliP70312.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

CAZyiGT2. Glycosyltransferase Family 2.

PTM databases

PhosphoSiteiP70312.

Proteomic databases

PRIDEiP70312.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050544; ENSMUSP00000062212; ENSMUSG00000022367.
GeneIDi15117.
KEGGimmu:15117.
UCSCiuc007vsl.2. mouse.

Organism-specific databases

CTDi3037.
MGIiMGI:107821. Has2.

Phylogenomic databases

eggNOGiCOG1215.
GeneTreeiENSGT00390000010337.
HOGENOMiHOG000112847.
HOVERGENiHBG000189.
InParanoidiP70312.
KOiK00752.
OMAiTAYIMGY.
OrthoDBiEOG77WWBZ.
TreeFamiTF332506.

Enzyme and pathway databases

UniPathwayiUPA00341.
BRENDAi2.4.1.212. 3474.

Miscellaneous databases

NextBioi287534.
PROiP70312.
SOURCEiSearch...

Gene expression databases

BgeeiP70312.
CleanExiMM_HAS2.
GenevestigatoriP70312.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR001173. Glyco_trans_2-like.
IPR026107. HAS/NodC.
IPR028371. HAS2.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PANTHERiPTHR22913. PTHR22913. 1 hit.
PTHR22913:SF7. PTHR22913:SF7. 1 hit.
PfamiPF00535. Glycos_transf_2. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 2 hits.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiHYAS2_MOUSE
AccessioniPrimary (citable) accession number: P70312
Secondary accession number(s): P70411, Q62405, Q68EF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: February 4, 2015
This is version 110 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.