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UniProtKB - Q12891 (HYAL2_HUMAN)
Protein
Hyaluronidase-2
Gene
HYAL2
Organism
Homo sapiens (Human)
Status
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 PublicationsCaution
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. EC:3.2.1.35
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 135 | Proton donorBy similarity | 1 |
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 production Source: UniProtKB
- positive regulation of interleukin-8 production 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
- viral entry into host cell Source: UniProtKB
Keywordsi
Molecular function | Glycosidase, Hydrolase, Receptor |
Enzyme and pathway databases
BRENDAi | 3.2.1.35, 2681 4.2.2.1, 2681 |
PathwayCommonsi | Q12891 |
Reactomei | R-HSA-2160916, Hyaluronan uptake and degradation |
SignaLinki | Q12891 |
Protein family/group databases
CAZyi | GH56, 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5321, HYAL2 |
MIMi | 603551, gene |
neXtProti | NX_Q12891 |
VEuPathDBi | HostDB:ENSG00000068001 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; GPI-anchor 1 Publication
Cytosol
- cytosol Source: BHF-UCL
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Golgi apparatus
- Golgi membrane Source: UniProtKB
Lysosome
- lysosome Source: UniProtKB
Nucleus
- RNA polymerase II transcription regulator complex Source: BHF-UCL
Plasma Membrane
- anchored component of external side of plasma membrane Source: UniProtKB
- anchored component of plasma membrane Source: UniProtKB
- apical plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
Other locations
- cell surface Source: UniProtKB
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB
- endocytic vesicle Source: BHF-UCL
- membrane raft Source: UniProtKB
- microvillus Source: BHF-UCL
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 8692 |
MalaCardsi | HYAL2 |
OpenTargetsi | ENSG00000068001 |
Orphaneti | 508476, Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome |
PharmGKBi | PA29572 |
Miscellaneous databases
Pharosi | Q12891, Tbio |
Chemistry databases
DrugBanki | DB08818, Hyaluronic acid |
Genetic variation databases
BioMutai | HYAL2 |
DMDMi | 311033483 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
ChainiPRO_0000012099 | 21 – 448 | Hyaluronidase-2Add BLAST | 428 | |
PropeptideiPRO_0000012100 | 449 – 473 | Removed in mature formSequence analysisAdd BLAST | 25 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 47 ↔ 340 | By similarity | ||
Glycosylationi | 74 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 103 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 211 ↔ 227 | By similarity | ||
Glycosylationi | 357 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 365 ↔ 376 | By similarity | ||
Disulfide bondi | 370 ↔ 427 | By similarity | ||
Disulfide bondi | 429 ↔ 438 | By similarity | ||
Lipidationi | 448 | GPI-anchor amidated glycineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, LipoproteinProteomic databases
EPDi | Q12891 |
jPOSTi | Q12891 |
MassIVEi | Q12891 |
MaxQBi | Q12891 |
PaxDbi | Q12891 |
PeptideAtlasi | Q12891 |
PRIDEi | Q12891 |
ProteomicsDBi | 59006 |
PTM databases
GlyGeni | Q12891, 3 sites |
iPTMneti | Q12891 |
PhosphoSitePlusi | Q12891 |
Expressioni
Tissue specificityi
Widely expressed. No expression detected in adult brain.1 Publication
Gene expression databases
Bgeei | ENSG00000068001, Expressed in right lung and 222 other tissues |
ExpressionAtlasi | Q12891, baseline and differential |
Genevisiblei | Q12891, HS |
Organism-specific databases
HPAi | ENSG00000068001, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Interacts with MST1R.
1 PublicationBinary interactionsi
Q12891
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
BioGRIDi | 114239, 162 interactors |
IntActi | Q12891, 31 interactors |
STRINGi | 9606.ENSP00000401853 |
Miscellaneous databases
RNActi | Q12891, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 361 – 439 | EGF-likeAdd BLAST | 79 |
Sequence similaritiesi
Belongs to the glycosyl hydrolase 56 family.Curated
Keywords - Domaini
EGF-like domain, SignalPhylogenomic databases
eggNOGi | ENOG502QUYI, Eukaryota |
GeneTreei | ENSGT01020000230364 |
HOGENOMi | CLU_036366_0_0_1 |
InParanoidi | Q12891 |
OMAi | FHCHCYQ |
OrthoDBi | 1096692at2759 |
PhylomeDBi | Q12891 |
TreeFami | TF321598 |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR017853, Glycoside_hydrolase_SF IPR018155, Hyaluronidase |
PANTHERi | PTHR11769, PTHR11769, 1 hit |
Pfami | View protein in Pfam PF01630, Glyco_hydro_56, 1 hit |
PIRSFi | PIRSF038193, Hyaluronidase, 1 hit |
PRINTSi | PR00846, GLHYDRLASE56 |
SUPFAMi | SSF51445, SSF51445, 1 hit |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS01186, EGF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
Q12891-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JBF5 | C9JBF5_HUMAN | Hyaluronidase | HYAL2 | 117 | Annotation score: | ||
C9JSD1 | C9JSD1_HUMAN | Hyaluronidase | HYAL2 | 81 | Annotation score: | ||
C9JSI7 | C9JSI7_HUMAN | Hyaluronidase | HYAL2 | 76 | Annotation score: | ||
C9K016 | C9K016_HUMAN | Hyaluronidase | HYAL2 | 121 | Annotation score: | ||
C9J700 | C9J700_HUMAN | Hyaluronidase-2 | HYAL2 | 47 | Annotation score: |
Sequence cautioni
The sequence AAC28656 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 261 – 262 | SR → AL in CAA03924 (PubMed:9712871).Curated | 2 | |
Sequence conflicti | 301 – 302 | RL → C in CAA03924 (PubMed:9712871).Curated | 2 | |
Sequence conflicti | 375 | Missing in CAA03924 (PubMed:9712871).Curated | 1 | |
Sequence conflicti | 378 – 379 | RR → PG in CAA03924 (PubMed:9712871).Curated | 2 | |
Sequence conflicti | 450 | S → N in CAA03924 (PubMed:9712871).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_028170 | 18 | S → A5 PublicationsCorresponds to variant dbSNP:rs709210Ensembl. | 1 | |
Natural variantiVAR_061193 | 418 | I → 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. |
CCDSi | CCDS2818.1 |
RefSeqi | NP_003764.3, NM_003773.4 NP_149348.2, NM_033158.4 XP_005265581.1, XM_005265524.2 XP_005265582.1, XM_005265525.2 |
Genome annotation databases
Ensembli | ENST00000357750.9; ENSP00000350387.4; ENSG00000068001.14 ENST00000395139.7; ENSP00000378571.3; ENSG00000068001.14 ENST00000442581.1; ENSP00000406657.1; ENSG00000068001.14 ENST00000447092.5; ENSP00000401853.1; ENSG00000068001.14 |
GeneIDi | 8692 |
KEGGi | hsa:8692 |
MANE-Selecti | ENST00000357750.9; ENSP00000350387.4; NM_003773.5; NP_003764.3 |
UCSCi | uc003czv.4, human |
Similar proteinsi
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. |
CCDSi | CCDS2818.1 |
RefSeqi | NP_003764.3, NM_003773.4 NP_149348.2, NM_033158.4 XP_005265581.1, XM_005265524.2 XP_005265582.1, XM_005265525.2 |
3D structure databases
AlphaFoldDBi | Q12891 |
SMRi | Q12891 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114239, 162 interactors |
IntActi | Q12891, 31 interactors |
STRINGi | 9606.ENSP00000401853 |
Chemistry databases
DrugBanki | DB08818, Hyaluronic acid |
Protein family/group databases
CAZyi | GH56, Glycoside Hydrolase Family 56 |
PTM databases
GlyGeni | Q12891, 3 sites |
iPTMneti | Q12891 |
PhosphoSitePlusi | Q12891 |
Genetic variation databases
BioMutai | HYAL2 |
DMDMi | 311033483 |
Proteomic databases
EPDi | Q12891 |
jPOSTi | Q12891 |
MassIVEi | Q12891 |
MaxQBi | Q12891 |
PaxDbi | Q12891 |
PeptideAtlasi | Q12891 |
PRIDEi | Q12891 |
ProteomicsDBi | 59006 |
Protocols and materials databases
Antibodypediai | 30889, 277 antibodies from 32 providers |
DNASUi | 8692 |
Genome annotation databases
Ensembli | ENST00000357750.9; ENSP00000350387.4; ENSG00000068001.14 ENST00000395139.7; ENSP00000378571.3; ENSG00000068001.14 ENST00000442581.1; ENSP00000406657.1; ENSG00000068001.14 ENST00000447092.5; ENSP00000401853.1; ENSG00000068001.14 |
GeneIDi | 8692 |
KEGGi | hsa:8692 |
MANE-Selecti | ENST00000357750.9; ENSP00000350387.4; NM_003773.5; NP_003764.3 |
UCSCi | uc003czv.4, human |
Organism-specific databases
CTDi | 8692 |
DisGeNETi | 8692 |
GeneCardsi | HYAL2 |
HGNCi | HGNC:5321, HYAL2 |
HPAi | ENSG00000068001, Tissue enhanced (lymphoid) |
MalaCardsi | HYAL2 |
MIMi | 603551, gene |
neXtProti | NX_Q12891 |
OpenTargetsi | ENSG00000068001 |
Orphaneti | 508476, Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome |
PharmGKBi | PA29572 |
VEuPathDBi | HostDB:ENSG00000068001 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QUYI, Eukaryota |
GeneTreei | ENSGT01020000230364 |
HOGENOMi | CLU_036366_0_0_1 |
InParanoidi | Q12891 |
OMAi | FHCHCYQ |
OrthoDBi | 1096692at2759 |
PhylomeDBi | Q12891 |
TreeFami | TF321598 |
Enzyme and pathway databases
BRENDAi | 3.2.1.35, 2681 4.2.2.1, 2681 |
PathwayCommonsi | Q12891 |
Reactomei | R-HSA-2160916, Hyaluronan uptake and degradation |
SignaLinki | Q12891 |
Miscellaneous databases
BioGRID-ORCSi | 8692, 9 hits in 1077 CRISPR screens |
ChiTaRSi | HYAL2, human |
GeneWikii | HYAL2 |
GenomeRNAii | 8692 |
Pharosi | Q12891, Tbio |
PROi | PR:Q12891 |
RNActi | Q12891, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000068001, Expressed in right lung and 222 other tissues |
ExpressionAtlasi | Q12891, baseline and differential |
Genevisiblei | Q12891, HS |
Family and domain databases
Gene3Di | 3.20.20.70, 1 hit |
InterProi | View protein in InterPro IPR013785, Aldolase_TIM IPR017853, Glycoside_hydrolase_SF IPR018155, Hyaluronidase |
PANTHERi | PTHR11769, PTHR11769, 1 hit |
Pfami | View protein in Pfam PF01630, Glyco_hydro_56, 1 hit |
PIRSFi | PIRSF038193, Hyaluronidase, 1 hit |
PRINTSi | PR00846, GLHYDRLASE56 |
SUPFAMi | SSF51445, SSF51445, 1 hit |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS01186, EGF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HYAL2_HUMAN | |
Accessioni | Q12891Primary (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: | May 25, 2022 | |
This is version 192 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Glycosyl hydrolases
Classification of glycosyl hydrolase families and list of entries - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families