Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hyaluronidase-2

Gene

HYAL2

Organism
Homo sapiens (Human)
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.3 Publications

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
  • RNA polymerase II 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 from RNA polymerase II promoter 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
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase, Receptor

Enzyme and pathway databases

BioCyciMetaCyc:HS00926-MONOMER.
ZFISH: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

HGNCiHGNC:5321. HYAL2.

Subcellular locationi

GO - Cellular componenti

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

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...)Sequence analysis1
Glycosylationi103N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi211 ↔ 227By similarity
Glycosylationi357N-linked (GlcNAc...)Sequence 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.

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

WithEntry#Exp.IntActNotes
FHL3Q136433EBI-2806068,EBI-741101
KRTAP3-2Q9BYR73EBI-2806068,EBI-751260

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. 14 interactors.
IntActiQ12891. 11 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
Contains 1 EGF-like domain.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.
InterProiIPR013785. Aldolase_TIM.
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.
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.

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 → A.5 PublicationsCorresponds to variant rs709210dbSNPEnsembl.1
Natural variantiVAR_061193418I → L.Corresponds to variant rs35455589dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

ProteinModelPortaliQ12891.
SMRiQ12891.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114239. 14 interactors.
IntActiQ12891. 11 interactors.
STRINGi9606.ENSP00000350387.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

PTM databases

iPTMnetiQ12891.
PhosphoSitePlusiQ12891.

Polymorphism and mutation databases

BioMutaiHYAL2.
DMDMi311033483.

Proteomic databases

EPDiQ12891.
MaxQBiQ12891.
PaxDbiQ12891.
PeptideAtlasiQ12891.
PRIDEiQ12891.

Protocols and materials databases

DNASUi8692.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8692.
DisGeNETi8692.
GeneCardsiHYAL2.
H-InvDBHIX0003314.
HGNCiHGNC:5321. HYAL2.
HPAiHPA036436.
MIMi603551. gene.
neXtProtiNX_Q12891.
OpenTargetsiENSG00000068001.
PharmGKBiPA29572.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiHYAL2. human.
GeneWikiiHYAL2.
GenomeRNAii8692.
PROiQ12891.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068001.
CleanExiHS_HYAL2.
ExpressionAtlasiQ12891. baseline and differential.
GenevisibleiQ12891. HS.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
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.
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHYAL2_HUMAN
AccessioniPrimary (citable) accession number: Q12891
Secondary accession number(s): B3KRZ2, O15177, Q9BW29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 2, 2010
Last modified: November 30, 2016
This is version 159 of the entry and version 4 of the sequence. [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

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. 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

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 one 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.