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Protein

Hyaluronidase-2

Gene

HYAL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 Publications

Caution

Was originally thought to be lysosomal.Curated

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei135Proton donorBy similarity1

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: UniProtKB
  • transcription coactivator activity Source: Ensembl
  • 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: UniProtKB
  • cellular response to UV-B Source: UniProtKB
  • defense response to virus Source: Ensembl
  • fusion of virus membrane with host plasma membrane Source: UniProtKB
  • glycosaminoglycan catabolic process Source: UniProtKB
  • hematopoietic progenitor cell differentiation Source: Ensembl
  • hyaluronan catabolic process Source: UniProtKB
  • kidney development Source: UniProtKB
  • monocyte activation Source: UniProtKB
  • multicellular organism aging Source: Ensembl
  • multicellular organismal iron ion homeostasis Source: Ensembl
  • 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 by RNA polymerase II Source: BHF-UCL
  • positive regulation of urine volume Source: UniProtKB
  • renal water absorption Source: UniProtKB
  • response to antibiotic Source: UniProtKB
  • response to reactive oxygen species Source: UniProtKB
  • response to virus Source: UniProtKB
  • skeletal system morphogenesis Source: Ensembl
  • transformation of host cell by virus Source: UniProtKB
  • viral entry into host cell Source: UniProtKB

Keywordsi

Molecular functionGlycosidase, Hydrolase, Receptor

Enzyme and pathway databases

BioCyciMetaCyc:HS00926-MONOMER
BRENDAi3.2.1.35 2681
4.2.2.1 2681
ReactomeiR-HSA-2160916 Hyaluronan uptake and degradation
SignaLinkiQ12891

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
Lung carcinoma protein 2
Short name:
LuCa-2
Gene namesi
Name:HYAL2
Synonyms:LUCA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000068001.13
HGNCiHGNC:5321 HYAL2
MIMi603551 gene
neXtProtiNX_Q12891

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8692
OpenTargetsiENSG00000068001
PharmGKBiPA29572

Polymorphism and mutation databases

BioMutaiHYAL2
DMDMi311033483

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001209921 – 448Hyaluronidase-2Add BLAST428
PropeptideiPRO_0000012100449 – 473Removed in mature formSequence analysisAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi47 ↔ 340By similarity
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi103N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi211 ↔ 227By similarity
Glycosylationi357N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi365 ↔ 376By similarity
Disulfide bondi370 ↔ 427By similarity
Disulfide bondi429 ↔ 438By similarity
Lipidationi448GPI-anchor amidated glycineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

EPDiQ12891
MaxQBiQ12891
PaxDbiQ12891
PeptideAtlasiQ12891
PRIDEiQ12891
ProteomicsDBi59006

PTM databases

iPTMnetiQ12891
PhosphoSitePlusiQ12891

Expressioni

Tissue specificityi

Widely expressed. No expression detected in adult brain.1 Publication

Gene expression databases

BgeeiENSG00000068001
CleanExiHS_HYAL2
ExpressionAtlasiQ12891 baseline and differential
GenevisibleiQ12891 HS

Organism-specific databases

HPAiHPA036436

Interactioni

Subunit structurei

Interacts with MST1R.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • receptor tyrosine kinase binding Source: UniProtKB
  • transforming growth factor beta binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi114239, 15 interactors
IntActiQ12891, 13 interactors
STRINGi9606.ENSP00000350387

Structurei

3D structure databases

ProteinModelPortaliQ12891
SMRiQ12891
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini361 – 439EGF-likeAdd BLAST79

Sequence similaritiesi

Belongs to the glycosyl hydrolase 56 family.Curated

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiENOG410IECJ Eukaryota
ENOG410XPZT LUCA
GeneTreeiENSGT00550000074476
HOGENOMiHOG000015133
HOVERGENiHBG052053
InParanoidiQ12891
KOiK01197
OMAiWGGEQCQ
OrthoDBiEOG091G064G
PhylomeDBiQ12891
TreeFamiTF321598

Family and domain databases

Gene3Di3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR017853 Glycoside_hydrolase_SF
IPR018155 Hyaluronidase
PANTHERiPTHR11769 PTHR11769, 1 hit
PfamiView protein in Pfam
PF01630 Glyco_hydro_56, 1 hit
PIRSFiPIRSF038193 Hyaluronidase, 1 hit
PRINTSiPR00846 GLHYDRLASE56
SUPFAMiSSF51445 SSF51445, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q12891-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRAGPGPTVT LALVLAVSWA MELKPTAPPI FTGRPFVVAW DVPTQDCGPR
60 70 80 90 100
LKVPLDLNAF DVQASPNEGF VNQNITIFYR DRLGLYPRFD SAGRSVHGGV
110 120 130 140 150
PQNVSLWAHR KMLQKRVEHY IRTQESAGLA VIDWEDWRPV WVRNWQDKDV
160 170 180 190 200
YRRLSRQLVA SRHPDWPPDR IVKQAQYEFE FAAQQFMLET LRYVKAVRPR
210 220 230 240 250
HLWGFYLFPD CYNHDYVQNW ESYTGRCPDV EVARNDQLAW LWAESTALFP
260 270 280 290 300
SVYLDETLAS SRHGRNFVSF RVQEALRVAR THHANHALPV YVFTRPTYSR
310 320 330 340 350
RLTGLSEMDL ISTIGESAAL GAAGVILWGD AGYTTSTETC QYLKDYLTRL
360 370 380 390 400
LVPYVVNVSW ATQYCSRAQC HGHGRCVRRN PSASTFLHLS TNSFRLVPGH
410 420 430 440 450
APGEPQLRPV GELSWADIDH LQTHFRCQCY LGWSGEQCQW DHRQAAGGAS
460 470
EAWAGSHLTS LLALAALAFT WTL
Length:473
Mass (Da):53,860
Last modified:November 2, 2010 - v4
Checksum:iA8302738478BFE61
GO

Sequence cautioni

The sequence AAC28656 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti261 – 262SR → AL in CAA03924 (PubMed:9712871).Curated2
Sequence conflicti301 – 302RL → C in CAA03924 (PubMed:9712871).Curated2
Sequence conflicti375Missing in CAA03924 (PubMed:9712871).Curated1
Sequence conflicti378 – 379RR → PG in CAA03924 (PubMed:9712871).Curated2
Sequence conflicti450S → N in CAA03924 (PubMed:9712871).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02817018S → A5 PublicationsCorresponds to variant dbSNP:rs709210Ensembl.1
Natural variantiVAR_061193418I → L. Corresponds to variant dbSNP:rs35455589Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ000099 mRNA Translation: CAA03924.1
U09577 mRNA Translation: AAC62823.1
AK092449 mRNA Translation: BAG52554.1
AK127945 mRNA Translation: BAG54602.1
AC002455 Genomic DNA Translation: AAB67045.1
CH471055 Genomic DNA Translation: EAW65092.1
BC000692 mRNA Translation: AAH00692.1
AF070608 mRNA Translation: AAC28656.1 Different initiation.
CCDSiCCDS2818.1
RefSeqiNP_003764.3, NM_003773.4
NP_149348.2, NM_033158.4
XP_005265581.1, XM_005265524.2
XP_005265582.1, XM_005265525.2
UniGeneiHs.76873

Genome annotation databases

EnsembliENST00000357750; ENSP00000350387; ENSG00000068001
ENST00000395139; ENSP00000378571; ENSG00000068001
ENST00000442581; ENSP00000406657; ENSG00000068001
ENST00000447092; ENSP00000401853; ENSG00000068001
GeneIDi8692
KEGGihsa:8692
UCSCiuc003czv.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHYAL2_HUMAN
AccessioniPrimary (citable) accession number: Q12891
Secondary accession number(s): B3KRZ2, O15177, Q9BW29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 2, 2010
Last modified: July 18, 2018
This is version 168 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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