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Q8SQG7

- HYAL2_SHEEP

UniProt

Q8SQG7 - HYAL2_SHEEP

Protein

Hyaluronidase-2

Gene

HYAL2

Organism
Ovis aries (Sheep)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 65 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    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 sitei138 – 1381Proton donorBy similarity

    GO - Molecular functioni

    1. hyaluronic acid binding Source: UniProtKB
    2. hyaluronoglucuronidase activity Source: UniProtKB
    3. hyalurononglucosaminidase activity Source: UniProtKB
    4. receptor signaling protein tyrosine kinase inhibitor activity Source: UniProtKB
    5. virus receptor activity Source: UniProtKB

    GO - Biological processi

    1. carbohydrate metabolic process Source: InterPro
    2. cartilage development Source: UniProtKB
    3. cellular response to fibroblast growth factor stimulus Source: UniProtKB
    4. cellular response to interleukin-1 Source: UniProtKB
    5. cellular response to transforming growth factor beta stimulus Source: UniProtKB
    6. cellular response to tumor necrosis factor Source: Ensembl
    7. cellular response to UV-B Source: UniProtKB
    8. defense response to virus Source: Ensembl
    9. fusion of virus membrane with host plasma membrane Source: UniProtKB
    10. glycosaminoglycan catabolic process Source: UniProtKB
    11. hematopoietic progenitor cell differentiation Source: Ensembl
    12. hyaluronan catabolic process Source: UniProtKB
    13. monocyte activation Source: UniProtKB
    14. multicellular organismal aging Source: Ensembl
    15. multicellular organismal iron ion homeostasis Source: Ensembl
    16. negative regulation of cell growth Source: UniProtKB
    17. negative regulation of fibroblast migration Source: UniProtKB
    18. negative regulation of MAP kinase activity Source: UniProtKB
    19. negative regulation of protein kinase B signaling Source: UniProtKB
    20. negative regulation of protein tyrosine kinase activity Source: UniProtKB
    21. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
    22. positive regulation of inflammatory response Source: UniProtKB
    23. positive regulation of interleukin-6 secretion Source: UniProtKB
    24. positive regulation of interleukin-8 secretion Source: UniProtKB
    25. positive regulation of protein import into nucleus Source: Ensembl
    26. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    27. positive regulation of urine volume Source: UniProtKB
    28. renal water absorption Source: UniProtKB
    29. response to antibiotic Source: Ensembl
    30. response to reactive oxygen species Source: UniProtKB
    31. response to virus Source: UniProtKB
    32. skeletal system morphogenesis Source: Ensembl
    33. transformation of host cell by virus Source: UniProtKB
    34. viral entry into host cell Source: UniProtKB

    Keywords - Molecular functioni

    Glycosidase, Hydrolase, Receptor

    Keywords - Biological processi

    Host-virus interaction

    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
    OrganismiOvis aries (Sheep)
    Taxonomic identifieri9940 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
    ProteomesiUP000002356: Chromosome 19

    Subcellular locationi

    Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity

    GO - Cellular componenti

    1. anchored component of external side of plasma membrane Source: Ensembl
    2. anchored component of plasma membrane Source: UniProtKB
    3. apical plasma membrane Source: UniProtKB
    4. cytoplasmic membrane-bounded vesicle Source: UniProtKB
    5. cytoplasmic vesicle Source: UniProtKB
    6. cytosol Source: UniProtKB
    7. endocytic vesicle Source: UniProtKB
    8. lysosome Source: UniProtKB
    9. membrane raft Source: UniProtKB
    10. microvillus Source: UniProtKB
    11. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2020Sequence AnalysisAdd
    BLAST
    Chaini21 – 451431Hyaluronidase-2PRO_0000239065Add
    BLAST
    Propeptidei452 – 47625Removed in mature formSequence AnalysisPRO_0000239066Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi47 ↔ 343By similarity
    Glycosylationi77 – 771N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi214 ↔ 230By similarity
    Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi360 – 3601N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi368 ↔ 379By similarity
    Disulfide bondi373 ↔ 430By similarity
    Disulfide bondi432 ↔ 441By similarity
    Lipidationi451 – 4511GPI-anchor amidated glycineSequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

    Interactioni

    Subunit structurei

    Interacts with MST1R By similarity. Interacts with Jaagsiekte sheep retrovirus (JSRV) envelope proteins.By similarity1 Publication

    Structurei

    3D structure databases

    ProteinModelPortaliQ8SQG7.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini364 – 44279EGF-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

    GeneTreeiENSGT00550000074476.
    HOVERGENiHBG052053.

    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.

    Q8SQG7-1 [UniParc]FASTAAdd to Basket

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    MWTGLGPAVT LALVLVVAWA TELKPTAPPI FTGRPFVVAW DVPTQDCGPR    50
    HKMPLDPKDM KAFDVQASPN EGFVNQNITI FYRDRLGMYP HFNSVGRSVH 100
    GGVPQNGSLW VHLEMLKGHV EHYIRTQEPA GLAVIDWEDW RPVWVRNWQD 150
    KDVYRRLSRQ LVASHHPDWP PERIVKEAQY EFEFAARQFM LETLRFVKAF 200
    RPRHLWGFYL FPDCYNHDYV QNWETYTGRC PDVEVSRNDQ LSWLWAESTA 250
    LFPSVYLEET LASSTHGRNF VSFRVQEALR VADVHHANHA LPVYVFTRPT 300
    YSRGLTGLSE MDLISTIGES AALGAAGVIL WGDAGFTTSN ETCRRLKDYL 350
    TRSLVPYVVN VSWAAQYCSW AQCHGHGRCV RRDPNAHTFL HLSASSFRLV 400
    PSHAPDEPRL RPEGELSWAD RNHLQTHFRC QCYLGWGGEQ CQWDRRRAAG 450
    GASGAWAGSH LTGLLAVAVL AFTWTS 476
    Length:476
    Mass (Da):54,229
    Last modified:June 1, 2002 - v1
    Checksum:i427C9277ACF7AAAA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF411974 mRNA. Translation: AAL78386.1.
    RefSeqiNP_001009754.1. NM_001009754.1.
    UniGeneiOar.905.

    Genome annotation databases

    EnsembliENSOART00000010462; ENSOARP00000010309; ENSOARG00000009614.
    GeneIDi443154.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF411974 mRNA. Translation: AAL78386.1 .
    RefSeqi NP_001009754.1. NM_001009754.1.
    UniGenei Oar.905.

    3D structure databases

    ProteinModelPortali Q8SQG7.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    CAZyi GH56. Glycoside Hydrolase Family 56.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSOART00000010462 ; ENSOARP00000010309 ; ENSOARG00000009614 .
    GeneIDi 443154.

    Organism-specific databases

    CTDi 8692.

    Phylogenomic databases

    GeneTreei ENSGT00550000074476.
    HOVERGENi HBG052053.

    Family and domain databases

    Gene3Di 3.20.20.70. 1 hit.
    InterProi IPR013785. Aldolase_TIM.
    IPR000742. EG-like_dom.
    IPR017853. Glycoside_hydrolase_SF.
    IPR018155. Hyaluronidase.
    [Graphical view ]
    PANTHERi PTHR11769. PTHR11769. 1 hit.
    Pfami PF01630. Glyco_hydro_56. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038193. Hyaluronidase. 1 hit.
    PRINTSi PR00846. GLHYDRLASE56.
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51445. SSF51445. 1 hit.
    PROSITEi PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiHYAL2_SHEEP
    AccessioniPrimary (citable) accession number: Q8SQG7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2006
    Last sequence update: June 1, 2002
    Last modified: October 1, 2014
    This is version 65 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3