O35632 (HYAL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hyaluronidase-2
Short name=Hyal-2
EC=3.2.1.35

Alternative name(s):
Hyaluronoglucosaminidase-2

Gene names

Name:

Hyal2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Catalytic activity	Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
Subunit structure	Interacts with MST1R By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Tissue specificity	Widely expressed. In the brain, expressed during embryonic stages but expression decreases after birth and is barely detectable in adult brain. Ref.1
Sequence similarities	Belongs to the glycosyl hydrolase 56 family. Contains 1 EGF-like domain.
Caution	Was originally thought to be lysosomal.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	EGF-like domain Signal
Molecular function	Glycosidase Hydrolase Receptor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro cartilage development Inferred from sequence or structural similarity. Source: UniProtKB cellular response to UV-B Inferred from sequence or structural similarity. Source: UniProtKB cellular response to fibroblast growth factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB cellular response to interleukin-1 Inferred from sequence or structural similarity. Source: UniProtKB cellular response to transforming growth factor beta stimulus Inferred from direct assay PubMed 19366691. Source: BHF-UCL cellular response to tumor necrosis factor Inferred from electronic annotation. Source: Compara defense response to virus Inferred from direct assay PubMed 16191204. Source: UniProtKB hematopoietic progenitor cell differentiation Inferred from mutant phenotype PubMed 18772348. Source: MGI hyaluronan catabolic process Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB monocyte activation Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB multicellular organismal aging Inferred from mutant phenotype PubMed 18772348. Source: MGI multicellular organismal iron ion homeostasis Inferred from mutant phenotype PubMed 18772348. Source: MGI negative regulation of MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of fibroblast migration Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype PubMed 19366691. Source: BHF-UCL positive regulation of inflammatory response Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB positive regulation of interleukin-6 secretion Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB positive regulation of protein import into nucleus Inferred from direct assay PubMed 19366691. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19366691. Source: BHF-UCL positive regulation of urine volume Inferred from sequence or structural similarity. Source: UniProtKB renal water absorption Inferred from sequence or structural similarity. Source: UniProtKB response to antibiotic Inferred from electronic annotation. Source: Compara response to reactive oxygen species Inferred from sequence or structural similarity. Source: UniProtKB skeletal system morphogenesis Inferred from mutant phenotype PubMed 18772348. Source: MGI transformation of host cell by virus Inferred from sequence or structural similarity. Source: UniProtKB viral entry into host cell via membrane fusion with the plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from sequence or structural similarity PubMed 21740893. Source: UniProtKB anchored to plasma membrane Inferred from direct assay PubMed 21740893. Source: UniProtKB apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from direct assay PubMed 19366691. Source: BHF-UCL cytosol Inferred from sequence or structural similarity. Source: UniProtKB endocytic vesicle Inferred from sequence or structural similarity. Source: UniProtKB lysosome Inferred from sequence or structural similarity. Source: UniProtKB membrane raft Inferred from direct assay PubMed 21740893. Source: UniProtKB microvillus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	hyaluronic acid binding Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB hyaluronoglucuronidase activity Inferred from sequence or structural similarity. Source: UniProtKB hyalurononglucosaminidase activity Inferred from sequence or structural similarity PubMed 19443707. Source: UniProtKB receptor signaling protein tyrosine kinase inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB viral receptor activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 448	428	Hyaluronidase-2		PRO_0000012101
	Propeptide	449 – 473	25	Removed in mature form Potential		PRO_0000012102
Regions
	Domain	361 – 439	79	EGF-like
Sites
	Active site	135	1	Proton donor By similarity
Amino acid modifications
	Lipidation	448	1	GPI-anchor amidated asparagine Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	103	1	N-linked (GlcNAc...) Potential
	Glycosylation	357	1	N-linked (GlcNAc...) Potential
	Glycosylation	390	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	448	1	N-linked (GlcNAc...) Potential
	Disulfide bond	47 ↔ 340		By similarity
	Disulfide bond	211 ↔ 227		By similarity
	Disulfide bond	365 ↔ 376		By similarity
	Disulfide bond	370 ↔ 427		By similarity
	Disulfide bond	429 ↔ 438		By similarity
Experimental info
	Sequence conflict	26 – 27	2	TA → KP in CAA03888. Ref.1
	Sequence conflict	26 – 27	2	TA → KP in CAA03889. Ref.1
	Sequence conflict	193 – 199	7	YVKAVRP → LRQGSQT in CAA03888. Ref.1
	Sequence conflict	250	1	Missing in CAA03888. Ref.1
	Sequence conflict	269 – 272	4	SFRV → RFGG in CAA03888. Ref.1
	Sequence conflict	355	1	I → V in AAK28481. Ref.2
	Sequence conflict	383	1	A → V in CAA03888. Ref.1
	Sequence conflict	383	1	A → V in CAA03889. Ref.1
	Sequence conflict	416 – 422	7	ADLNYLQ → RDRQLPE in CAA03888. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O35632 [UniParc]. Last modified November 15, 2002. Version 2. Checksum: DD433C9FFCF8147C	FASTA	473	53,618
	10 20 30 40 50 60 MRAGLGPIIT LALVLEVAWA GELKPTAPPI FTGRPFVVAW NVPTQECAPR HKVPLDLRAF 70 80 90 100 110 120 DVKATPNEGF FNQNITTFYY DRLGLYPRFD AAGTSVHGGV PQNGSLCAHL PMLKESVERY 130 140 150 160 170 180 IQTQEPGGLA VIDWEEWRPV WVRNWQEKDV YRQSSRQLVA SRHPDWPSDR VMKQAQYEFE 190 200 210 220 230 240 FAARQFMLNT LRYVKAVRPQ HLWGFYLFPD CYNHDYVQNW ESYTGRCPDV EVARNDQLAW 250 260 270 280 290 300 LWAESTALFP SVYLDETLAS SVHSRNFVSF RVREALRVAH THHANHALPV YVFTRPTYTR 310 320 330 340 350 360 GLTGLSQVDL ISTIGESAAL GSAGVIFWGD SEDASSMETC QYLKNYLTQL LVPYIVNVSW 370 380 390 400 410 420 ATQYCSWTQC HGHGRCVRRN PSANTFLHLN ASSFRLVPGH TPSEPQLRPE GQLSEADLNY 430 440 450 460 470 LQKHFRCQCY LGWGGEQCQR NYKGAAGNAS RAWAGSHLTS LLGLVAVALT WTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Hyal2 -- less active, but more versatile?" Lepperdinger G., Mullegger J., Kreil G. Matrix Biol. 20:509-514(2001) [PubMed] [Europe PMC] [Abstract] 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, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00315535.
RefSeq	NP_034619.2. NM_010489.2.
UniGene	Mm.440982. Mm.4834.
3D structure databases
ProteinModelPortal	O35632.
SMR	O35632. Positions 29-440.
ModBase	Search...
Protein family/group databases
CAZy	GH56. Glycoside Hydrolase Family 56.
Proteomic databases
PRIDE	O35632.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000010191; ENSMUSP00000010191; ENSMUSG00000010047.
GeneID	15587.
KEGG	mmu:15587.
Organism-specific databases
CTD	8692.
MGI	MGI:1196334. Hyal2.
Phylogenomic databases
eggNOG	NOG77606.
HOGENOM	HOG000015133.
HOVERGEN	HBG052053.
InParanoid	O35632.
KO	K01197.
OMA	GWGGEQC.
OrthoDB	EOG4H463X.
Gene expression databases
ArrayExpress	O35632.
Bgee	O35632.
CleanEx	MM_HYAL2.
Genevestigator	O35632.
GermOnline	ENSMUSG00000010047. Mus musculus.
Family and domain databases
Gene3D	3.20.20.70. 1 hit.
InterPro	IPR013785. Aldolase_TIM. IPR000742. EG-like_dom. IPR017853. Glycoside_hydrolase_SF. IPR018155. Hyaluronidase. [Graphical view]
PANTHER	PTHR11769. PTHR11769. 1 hit.
Pfam	PF01630. Glyco_hydro_56. 1 hit. [Graphical view]
PIRSF	PIRSF038193. Hyaluronidase. 1 hit.
PRINTS	PR00846. GLHYDRLASE56.
SMART	SM00181. EGF. 1 hit. [Graphical view]
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	288580.
SOURCE	Search...

Entry information

Entry name

HYAL2_MOUSE

Accession

Primary (citable) accession number: O35632
Secondary accession number(s): O35631, Q99MS9, Q99MT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	November 15, 2002
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program