Reviewed, UniProtKB/Swiss-Prot Q12891 (HYAL2_HUMAN)

Names and origin

Protein names

Recommended name:
    Hyaluronidase-2
      Short name=Hyal-2
    EC=3.2.1.35
Alternative name(s):
    Hyaluronoglucosaminidase-2
      Short name=LUCA-2

Gene names

Name:	HYAL2
Synonyms:	LUCA2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	473 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. Ref.1 Ref.7 Ref.8
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. Ref.8
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Ref.7
Tissue specificity	Widely expressed. No expression detected in adult brain. Ref.1
Sequence similarities	Belongs to the glycosyl hydrolase 56 family. Contains 1 EGF-like domain.
Caution	Was originally thought to be lysosomal.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal
Molecular function	Glycosidase Hydrolase Receptor
PTM	GPI-anchor Glycoprotein Lipoprotein
Gene Ontology (GO)
Biological process	glycosaminoglycan catabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosome Ref.1 Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	hyalurononglucosaminidase activity Ref.1 Traceable author statement. Source: ProtInc receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
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 – 448	428	Hyaluronidase-2		PRO_0000012099
	Propeptide	449 – 473	25	Removed in mature form Potential		PRO_0000012100
Regions
	Domain	361 – 439	79	EGF-like
Sites
	Active site	135	1	Proton donor By similarity
Amino acid modifications
	Lipidation	448	1	GPI-anchor amidated glycine Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	103	1	N-linked (GlcNAc...) Potential
	Glycosylation	357	1	N-linked (GlcNAc...) Potential
	Disulfide bond	47 ↔ 340		By similarity
	Disulfide bond	211 ↔ 227		By similarity
	Disulfide bond	365 ↔ 376		By similarity
	Disulfide bond	370 ↔ 427		By similarity
	Disulfide bond	429 ↔ 438		By similarity
Natural variations
	Natural variant	18	1	A → S: dbSNP rs709210. Ref.2 Ref.3		VAR_028170
Experimental info
	Sequence conflict	261 – 262	2	SR → AL in CAA03924. Ref.1
	Sequence conflict	301 – 302	2	RL → C in CAA03924. Ref.1
	Sequence conflict	375	1	Missing in CAA03924. Ref.1
	Sequence conflict	378 – 379	2	RR → PG in CAA03924. Ref.1
	Sequence conflict	450	1	S → N in CAA03924. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q12891-1 [UniParc]. Last modified November 15, 2002. Version 3. Checksum: 79DBD0B560B0BF8E	FASTA	473	53,844
	10 20 30 40 50 60 MRAGPGPTVT LALVLAVAWA MELKPTAPPI FTGRPFVVAW DVPTQDCGPR LKVPLDLNAF 70 80 90 100 110 120 DVQASPNEGF VNQNITIFYR DRLGLYPRFD SAGRSVHGGV PQNVSLWAHR KMLQKRVEHY 130 140 150 160 170 180 IRTQESAGLA VIDWEDWRPV WVRNWQDKDV YRRLSRQLVA SRHPDWPPDR IVKQAQYEFE 190 200 210 220 230 240 FAAQQFMLET LRYVKAVRPR HLWGFYLFPD CYNHDYVQNW ESYTGRCPDV EVARNDQLAW 250 260 270 280 290 300 LWAESTALFP SVYLDETLAS SRHGRNFVSF RVQEALRVAR THHANHALPV YVFTRPTYSR 310 320 330 340 350 360 RLTGLSEMDL ISTIGESAAL GAAGVILWGD AGYTTSTETC QYLKDYLTRL LVPYVVNVSW 370 380 390 400 410 420 ATQYCSRAQC HGHGRCVRRN PSASTFLHLS TNSFRLVPGH APGEPQLRPV GELSWADIDH 430 440 450 460 470 LQTHFRCQCY LGWSGEQCQW DHRQAAGGAS EAWAGSHLTS LLALAALAFT WTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity." Lepperdinger G., Strobl B., Kreil G. J. Biol. Chem. 273:22466-22470(1998) [PubMed: 9712871] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"LUCA2 (HYAL2, lysosomal hyaluronidase) a novel human cDNA with homology to human PH-20 gene is homozygously deleted in small cell lung cancer and located in 3p21.3." Chen J., Bader S., Latif F., Duh F.-M., Lerman M.I., Minna J.D. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-18. Tissue: Placenta.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-18.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-473. Tissue: Brain.
[6]	"Hyal2 -- less active, but more versatile?" Lepperdinger G., Mullegger J., Kreil G. Matrix Biol. 20:509-514(2001) [PubMed: 11731268] [Abstract] Cited for: REVIEW.
[7]	"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: 11296287] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus." Danilkovitch-Miagkova A., Duh F.-M., Kuzmin I., Angeloni D., Liu S.-L., Miller A.D., Lerman M.I. Proc. Natl. Acad. Sci. U.S.A. 100:4580-4585(2003) [PubMed: 12676986] [Abstract] Cited for: FUNCTION, INTERACTION WITH MST1R.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ000099 mRNA. Translation: CAA03924.1. U09577 mRNA. Translation: AAC62823.1. AC002455 Genomic DNA. Translation: AAB67045.1. BC000692 mRNA. Translation: AAH00692.1. AF070608 mRNA. Translation: AAC28656.1.
RefSeq	NP_003764.3. NP_149348.2.
UniGene	Hs.76873
3D structure databases
HSSP	HSSP built from PDB template 1FCQ based on UniProtKB Q08169.
ModBase	Search...
Proteomic databases
PRIDE	Q12891.
Genome annotation databases
Ensembl	ENSG00000068001. Homo sapiens. [Contig view]
GeneID	8692.
KEGG	hsa:8692.
Organism-specific databases
GeneCards	GC03M050330.
H-InvDB	HIX0003314.
HGNC	HGNC:5321. HYAL2.
MIM	603551. gene.
PharmGKB	PA29572.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q12891.
HOVERGEN	Q12891.
Gene expression databases
ArrayExpress	Q12891.
CleanEx	HS_HYAL2.
GermOnline	ENSG00000068001. Homo sapiens.
Family and domain databases
InterPro	IPR013785. Aldolase_TIM. IPR006210. EGF. IPR000742. EGF_3. IPR013032. EGF_like_reg_CS. IPR001968. Glyco_hydro_56. IPR017430. Glyco_hydro_56_Hyaluronidase. [Graphical view]
Gene3D	G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.
PANTHER	PTHR11769. Glyco_hydro_56. 1 hit.
Pfam	PF01630. Glyco_hydro_56. 1 hit. [Graphical view]
PIRSF	PIRSF038193. Hyaluronidase. 1 hit.
PRINTS	PR00846. GLHYDRLASE56.
ProDom	PD003549. Glyco_hydro_56. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00070. Hyaluronidase.
NextBio	32597.
SOURCE	Search...

Entry information

Entry name

HYAL2_HUMAN

Accession

Primary (citable) accession number: Q12891
Secondary accession number(s): O15177, Q9BW29

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	November 15, 2002
Last modified:	December 16, 2008
This is version 82 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)