Q8SQG7 (HYAL2_SHEEP) 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

Ovis aries (Sheep)

Taxonomic identifier

9940 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Ovis

Protein attributes

Sequence length	476 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. Interacts with Jaagsiekte sheep retrovirus (JSRV) envelope proteins. Ref.2
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Miscellaneous	Acts as a receptor for the Jaagsiekte sheep retrovirus (JSRV), which induces ovine pulmonary adenocarcinoma. A possible mechanism is that binding to JSRV envelope proteins may liberate the oncogenic factor MST1R that is normally negatively regulated by HYAL2, leading to oncogenic transformation.
Sequence similarities	Belongs to the glycosyl hydrolase 56 family. Contains 1 EGF-like domain.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Membrane
Domain	EGF-like domain Signal
Molecular function	Glycosidase Hydrolase Receptor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
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 sequence or structural similarity. Source: UniProtKB hyaluronan catabolic process Inferred from sequence or structural similarity. Source: UniProtKB monocyte activation Inferred from sequence or structural similarity. Source: UniProtKB 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 inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-6 secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from sequence or structural similarity. Source: UniProtKB 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 reactive oxygen species Inferred from sequence or structural similarity. Source: UniProtKB 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	anchored to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB 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 sequence or structural similarity. 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. Source: UniProtKB hyaluronoglucuronidase activity Inferred from sequence or structural similarity. Source: UniProtKB hyalurononglucosaminidase activity Inferred from sequence or structural similarity. Source: UniProtKB receptor signaling protein tyrosine kinase inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB viral receptor activity Inferred from sequence or structural similarity. 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 – 451	431	Hyaluronidase-2		PRO_0000239065
	Propeptide	452 – 476	25	Removed in mature form Potential		PRO_0000239066
Regions
	Domain	364 – 442	79	EGF-like
Sites
	Active site	138	1	Proton donor By similarity
Amino acid modifications
	Lipidation	451	1	GPI-anchor amidated glycine Potential
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Glycosylation	360	1	N-linked (GlcNAc...) Potential
	Disulfide bond	47 ↔ 343		By similarity
	Disulfide bond	214 ↔ 230		By similarity
	Disulfide bond	368 ↔ 379		By similarity
	Disulfide bond	373 ↔ 430		By similarity
	Disulfide bond	432 ↔ 441		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q8SQG7 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 427C9277ACF7AAAA	FASTA	476	54,229
	10 20 30 40 50 60 MWTGLGPAVT LALVLVVAWA TELKPTAPPI FTGRPFVVAW DVPTQDCGPR HKMPLDPKDM 70 80 90 100 110 120 KAFDVQASPN EGFVNQNITI FYRDRLGMYP HFNSVGRSVH GGVPQNGSLW VHLEMLKGHV 130 140 150 160 170 180 EHYIRTQEPA GLAVIDWEDW RPVWVRNWQD KDVYRRLSRQ LVASHHPDWP PERIVKEAQY 190 200 210 220 230 240 EFEFAARQFM LETLRFVKAF RPRHLWGFYL FPDCYNHDYV QNWETYTGRC PDVEVSRNDQ 250 260 270 280 290 300 LSWLWAESTA LFPSVYLEET LASSTHGRNF VSFRVQEALR VADVHHANHA LPVYVFTRPT 310 320 330 340 350 360 YSRGLTGLSE MDLISTIGES AALGAAGVIL WGDAGFTTSN ETCRRLKDYL TRSLVPYVVN 370 380 390 400 410 420 VSWAAQYCSW AQCHGHGRCV RRDPNAHTFL HLSASSFRLV PSHAPDEPRL RPEGELSWAD 430 440 450 460 470 RNHLQTHFRC QCYLGWGGEQ CQWDRRRAAG GASGAWAGSH LTGLLAVAVL AFTWTS

References

[1]

"Mechanism of cell entry and transformation by enzootic nasal tumor virus." Dirks C., Duh F.-M., Rai S.K., Lerman M.I., Miller A.D. J. Virol. 76:2141-2149(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

[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: INTERACTION WITH JSRV ENVELOPE PROTEINS.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF411974 mRNA. Translation: AAL78386.1.
RefSeq	NP_001009754.1. NM_001009754.1.
UniGene	Oar.905.
3D structure databases
ProteinModelPortal	Q8SQG7.
ModBase	Search...
Protein family/group databases
CAZy	GH56. Glycoside Hydrolase Family 56.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	443154.
Organism-specific databases
CTD	8692.
Phylogenomic databases
HOVERGEN	HBG052053.
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...

Entry information

Entry name

HYAL2_SHEEP

Accession

Primary (citable) accession number: Q8SQG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	June 1, 2002
Last modified:	April 3, 2013
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program