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Protein

Hyaluronidase-2

Gene

Hyal2

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

Functioni

Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R (By similarity).By similarity

Catalytic activityi

Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei135 – 1351Proton donorBy similarity

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • hyaluronic acid binding Source: UniProtKB
  • hyaluronoglucuronidase activity Source: UniProtKB
  • hyalurononglucosaminidase activity Source: UniProtKB
  • receptor signaling protein tyrosine kinase inhibitor activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: MGI
  • transforming growth factor beta binding Source: BHF-UCL
  • virus receptor activity Source: UniProtKB

GO - Biological processi

  • carbohydrate metabolic process Source: InterPro
  • cartilage development Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: BHF-UCL
  • cellular response to tumor necrosis factor Source: Ensembl
  • cellular response to UV-B Source: UniProtKB
  • defense response to virus Source: UniProtKB
  • fusion of virus membrane with host plasma membrane Source: UniProtKB
  • glycosaminoglycan catabolic process Source: UniProtKB
  • hematopoietic progenitor cell differentiation Source: MGI
  • hyaluronan catabolic process Source: UniProtKB
  • monocyte activation Source: UniProtKB
  • multicellular organismal aging Source: MGI
  • multicellular organismal iron ion homeostasis Source: MGI
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of fibroblast migration Source: UniProtKB
  • negative regulation of MAP kinase activity Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of protein tyrosine kinase activity Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: UniProtKB
  • positive regulation of interleukin-8 secretion Source: UniProtKB
  • positive regulation of protein import into nucleus Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of urine volume Source: UniProtKB
  • renal water absorption Source: UniProtKB
  • response to antibiotic Source: Ensembl
  • response to reactive oxygen species Source: UniProtKB
  • response to virus Source: UniProtKB
  • skeletal system morphogenesis Source: MGI
  • transformation of host cell by virus Source: UniProtKB
  • viral entry into host cell Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase, Receptor

Enzyme and pathway databases

BRENDAi3.2.1.35. 3474.
ReactomeiREACT_353590. Hyaluronan uptake and degradation.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

Names & Taxonomyi

Protein namesi
Recommended name:
Hyaluronidase-2 (EC:3.2.1.35)
Short name:
Hyal-2
Alternative name(s):
Hyaluronoglucosaminidase-2
Gene namesi
Name:Hyal2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1196334. Hyal2.

Subcellular locationi

GO - Cellular componenti

  • anchored component of plasma membrane Source: UniProtKB
  • apical plasma membrane Source: UniProtKB
  • cell surface Source: BHF-UCL
  • cytoplasm Source: MGI
  • cytoplasmic membrane-bounded vesicle Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB
  • cytosol Source: UniProtKB
  • endocytic vesicle Source: UniProtKB
  • Golgi membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • membrane raft Source: UniProtKB
  • microvillus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 448428Hyaluronidase-2PRO_0000012101Add
BLAST
Propeptidei449 – 47325Removed in mature formSequence AnalysisPRO_0000012102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi47 ↔ 340By similarity
Glycosylationi74 – 741N-linked (GlcNAc...)1 Publication
Glycosylationi103 – 1031N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi211 ↔ 227By similarity
Glycosylationi357 – 3571N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi365 ↔ 376By similarity
Disulfide bondi370 ↔ 427By similarity
Glycosylationi390 – 3901N-linked (GlcNAc...)1 Publication
Disulfide bondi429 ↔ 438By similarity
Lipidationi448 – 4481GPI-anchor amidated asparagine; alternateSequence Analysis
Glycosylationi448 – 4481N-linked (GlcNAc...); alternateSequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PRIDEiO35632.

Expressioni

Tissue specificityi

Widely expressed. In the brain, expressed during embryonic stages but expression decreases after birth and is barely detectable in adult brain.1 Publication

Gene expression databases

BgeeiO35632.
CleanExiMM_HYAL2.
ExpressionAtlasiO35632. baseline and differential.
GenevisibleiO35632. MM.

Interactioni

Subunit structurei

Interacts with MST1R.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000010191.

Structurei

3D structure databases

ProteinModelPortaliO35632.
SMRiO35632. Positions 29-440.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini361 – 43979EGF-likeAdd
BLAST

Sequence similaritiesi

Belongs to the glycosyl hydrolase 56 family.Curated
Contains 1 EGF-like domain.Curated

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiNOG77606.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiO35632.
KOiK01197.
OMAiWGGEQCQ.
OrthoDBiEOG74J97S.
PhylomeDBiO35632.
TreeFamiTF321598.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR000742. EG-like_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O35632-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRAGLGPIIT LALVLEVAWA GELKPTAPPI FTGRPFVVAW NVPTQECAPR
60 70 80 90 100
HKVPLDLRAF DVKATPNEGF FNQNITTFYY DRLGLYPRFD AAGTSVHGGV
110 120 130 140 150
PQNGSLCAHL PMLKESVERY IQTQEPGGLA VIDWEEWRPV WVRNWQEKDV
160 170 180 190 200
YRQSSRQLVA SRHPDWPSDR VMKQAQYEFE FAARQFMLNT LRYVKAVRPQ
210 220 230 240 250
HLWGFYLFPD CYNHDYVQNW ESYTGRCPDV EVARNDQLAW LWAESTALFP
260 270 280 290 300
SVYLDETLAS SVHSRNFVSF RVREALRVAH THHANHALPV YVFTRPTYTR
310 320 330 340 350
GLTGLSQVDL ISTIGESAAL GSAGVIFWGD SEDASSMETC QYLKNYLTQL
360 370 380 390 400
LVPYIVNVSW ATQYCSWTQC HGHGRCVRRN PSANTFLHLN ASSFRLVPGH
410 420 430 440 450
TPSEPQLRPE GQLSEADLNY LQKHFRCQCY LGWGGEQCQR NYKGAAGNAS
460 470
RAWAGSHLTS LLGLVAVALT WTL
Length:473
Mass (Da):53,618
Last modified:November 15, 2002 - v2
Checksum:iDD433C9FFCF8147C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 272TA → KP in CAA03888 (PubMed:9790770).Curated
Sequence conflicti26 – 272TA → KP in CAA03889 (PubMed:9790770).Curated
Sequence conflicti193 – 1997YVKAVRP → LRQGSQT in CAA03888 (PubMed:9790770).Curated
Sequence conflicti250 – 2501Missing in CAA03888 (PubMed:9790770).Curated
Sequence conflicti269 – 2724SFRV → RFGG in CAA03888 (PubMed:9790770).Curated
Sequence conflicti355 – 3551I → V in AAK28481 (PubMed:11296287).Curated
Sequence conflicti383 – 3831A → V in CAA03888 (PubMed:9790770).Curated
Sequence conflicti383 – 3831A → V in CAA03889 (PubMed:9790770).Curated
Sequence conflicti416 – 4227ADLNYLQ → RDRQLPE in CAA03888 (PubMed:9790770).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ000059 mRNA. Translation: CAA03888.1.
AJ000060 Genomic DNA. Translation: CAA03889.1.
AF302843 mRNA. Translation: AAK28481.1.
AF302844 mRNA. Translation: AAK28482.1.
AF422177 mRNA. Translation: AAL17823.1.
CCDSiCCDS23496.1.
RefSeqiNP_034619.2. NM_010489.2.
XP_006511706.1. XM_006511643.2.
XP_006511707.1. XM_006511644.2.
XP_006511708.1. XM_006511645.2.
UniGeneiMm.440982.
Mm.4834.

Genome annotation databases

EnsembliENSMUST00000010191; ENSMUSP00000010191; ENSMUSG00000010047.
ENSMUST00000195752; ENSMUSP00000141280; ENSMUSG00000010047.
GeneIDi15587.
KEGGimmu:15587.
UCSCiuc009rlu.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ000059 mRNA. Translation: CAA03888.1.
AJ000060 Genomic DNA. Translation: CAA03889.1.
AF302843 mRNA. Translation: AAK28481.1.
AF302844 mRNA. Translation: AAK28482.1.
AF422177 mRNA. Translation: AAL17823.1.
CCDSiCCDS23496.1.
RefSeqiNP_034619.2. NM_010489.2.
XP_006511706.1. XM_006511643.2.
XP_006511707.1. XM_006511644.2.
XP_006511708.1. XM_006511645.2.
UniGeneiMm.440982.
Mm.4834.

3D structure databases

ProteinModelPortaliO35632.
SMRiO35632. Positions 29-440.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000010191.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

Proteomic databases

PRIDEiO35632.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000010191; ENSMUSP00000010191; ENSMUSG00000010047.
ENSMUST00000195752; ENSMUSP00000141280; ENSMUSG00000010047.
GeneIDi15587.
KEGGimmu:15587.
UCSCiuc009rlu.1. mouse.

Organism-specific databases

CTDi8692.
MGIiMGI:1196334. Hyal2.

Phylogenomic databases

eggNOGiNOG77606.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiO35632.
KOiK01197.
OMAiWGGEQCQ.
OrthoDBiEOG74J97S.
PhylomeDBiO35632.
TreeFamiTF321598.

Enzyme and pathway databases

BRENDAi3.2.1.35. 3474.
ReactomeiREACT_353590. Hyaluronan uptake and degradation.

Miscellaneous databases

NextBioi288580.
PROiO35632.
SOURCEiSearch...

Gene expression databases

BgeeiO35632.
CleanExiMM_HYAL2.
ExpressionAtlasiO35632. baseline and differential.
GenevisibleiO35632. MM.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR000742. EG-like_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase."
    Strobl B., Wechselberger C., Beier D., Lepperdinger G.
    Genomics 53:214-219(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
    Strain: 129/SvJ.
  2. "Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation."
    Rai S.K., Duh F.-M., Vigdorovich V., Danilkovitch-Miagkova A., Lerman M.I., Miller A.D.
    Proc. Natl. Acad. Sci. U.S.A. 98:4443-4448(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C3H and Czech II.
  3. "Transforming growth factor-beta1 blocks the enhancement of tumor necrosis factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts."
    Chang N.-S.
    BMC Cell Biol. 3:8-8(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Czech II.
  4. Cited for: REVIEW.
  5. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
    Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
    Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-74 AND ASN-390.

Entry informationi

Entry nameiHYAL2_MOUSE
AccessioniPrimary (citable) accession number: O35632
Secondary accession number(s): O35631, Q99MS9, Q99MT0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: July 22, 2015
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be lysosomal.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.