Q12891 (HYAL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hyaluronidase-2
Short name=Hyal-2
EC=3.2.1.35

Alternative name(s):
Hyaluronoglucosaminidase-2
Lung carcinoma protein 2
Short name=LuCa-2

Gene names

Name:	HYAL2
Synonyms:	LUCA2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.9 Ref.10
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.10
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor Ref.9.
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.
Sequence caution	The sequence AAC28656.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal
Molecular function	Glycosidase Hydrolase Receptor
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome cartilage development Inferred from expression pattern PubMed 11944887. Source: UniProtKB cellular response to UV-B Inferred from direct assay PubMed 21699545. Source: UniProtKB cellular response to fibroblast growth factor stimulus Inferred from direct assay PubMed 19577615. Source: UniProtKB cellular response to interleukin-1 Inferred from direct assay PubMed 18390475. Source: UniProtKB cellular response to transforming growth factor beta stimulus Inferred from direct assay PubMed 19366691. Source: BHF-UCL cellular response to tumor necrosis factor Inferred from expression pattern PubMed 18390475. Source: UniProtKB defense response to virus Inferred from electronic annotation. Source: Compara hematopoietic progenitor cell differentiation Inferred from electronic annotation. Source: Compara hyaluronan catabolic process Inferred from direct assay PubMed 17170110PubMed 19443707PubMed 20554532PubMed 21699545. Source: UniProtKB kidney development Inferred from sequence or structural similarity. Source: UniProtKB monocyte activation Inferred from direct assay PubMed 19443707. Source: UniProtKB multicellular organismal aging Inferred from electronic annotation. Source: Compara multicellular organismal iron ion homeostasis Inferred from electronic annotation. Source: Compara negative regulation of MAP kinase activity Inferred from direct assay Ref.10. Source: UniProtKB negative regulation of cell growth Inferred from direct assay PubMed 18725949. Source: UniProtKB negative regulation of fibroblast migration Inferred from direct assay PubMed 19577615. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from direct assay Ref.10. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of inflammatory response Inferred from direct assay PubMed 19443707. Source: UniProtKB positive regulation of interleukin-6 secretion Inferred from direct assay PubMed 19443707. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from direct assay PubMed 19443707. Source: UniProtKB positive regulation of protein import into nucleus Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of urine volume Inferred from sequence or structural similarity. Source: UniProtKB renal water absorption Inferred from sequence or structural similarity. Source: UniProtKB response to antibiotic Inferred from expression pattern PubMed 11944887. Source: UniProtKB response to reactive oxygen species Inferred from direct assay PubMed 20554532. Source: UniProtKB skeletal system morphogenesis Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome transformation of host cell by virus Inferred from direct assay Ref.9. Source: UniProtKB viral entry into host cell via membrane fusion with the plasma membrane Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from sequence or structural similarity PubMed 21740893. Source: UniProtKB anchored to external side of plasma membrane Inferred from direct assay Ref.9PubMed 16191204PubMed 20554532. Source: UniProtKB apical plasma membrane Inferred from direct assay PubMed 20554532. Source: UniProtKB cytosol Inferred from direct assay PubMed 19366691. Source: BHF-UCL endocytic vesicle Inferred from direct assay PubMed 19366691. Source: BHF-UCL endoplasmic reticulum Non-traceable author statement PubMed 16191204. Source: UniProtKB lysosome Inferred from direct assay PubMed 16600643Ref.1. Source: UniProtKB membrane raft Inferred from direct assay PubMed 21740893. Source: UniProtKB microvillus Inferred from direct assay PubMed 19366691. Source: BHF-UCL perinuclear region of cytoplasm Inferred from direct assay PubMed 16600643. Source: UniProtKB
Molecular_function	hyaluronic acid binding Inferred from direct assay Ref.10PubMed 19443707. Source: UniProtKB hyaluronoglucuronidase activity Inferred from direct assay PubMed 21699545. Source: UniProtKB hyalurononglucosaminidase activity Inferred from direct assay PubMed 11944887PubMed 16600643PubMed 17170110PubMed 18390475PubMed 19443707PubMed 20554532Ref.1. Source: UniProtKB receptor signaling protein tyrosine kinase inhibitor activity Inferred from direct assay Ref.10. Source: UniProtKB transforming growth factor beta binding Inferred from sequence or structural similarity. Source: BHF-UCL viral receptor activity Inferred from direct assay Ref.9PubMed 16191204. Source: UniProtKB
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	S → A. Ref.1 Ref.3 Ref.5 Ref.6 Ref.7 Corresponds to variant rs709210 [ dbSNP | Ensembl ].		VAR_028170
	Natural variant	418	1	I → L. Corresponds to variant rs35455589 [ dbSNP | Ensembl ].		VAR_061193
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 [UniParc]. Last modified November 2, 2010. Version 4. Checksum: A8302738478BFE61	FASTA	473	53,860
	10 20 30 40 50 60 MRAGPGPTVT LALVLAVSWA 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANT ALA-18.
[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]. Tissue: Placenta.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-18. Tissue: Placenta and Synovium.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-18.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-18. Tissue: Kidney.
[7]	Yu W., Gibbs R.A. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-473, VARIANT ALA-18. Tissue: Brain.
[8]	"Hyal2 -- less active, but more versatile?" Lepperdinger G., Mullegger J., Kreil G. Matrix Biol. 20:509-514(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"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: FUNCTION, SUBCELLULAR LOCATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MST1R.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00021531.
RefSeq	NP_003764.3. NM_003773.4. NP_149348.2. NM_033158.4.
UniGene	Hs.76873.
3D structure databases
ProteinModelPortal	Q12891.
SMR	Q12891. Positions 29-439.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12891. 4 interactions.
STRING	9606.ENSP00000350387.
Protein family/group databases
CAZy	GH56. Glycoside Hydrolase Family 56.
Polymorphism databases
DMDM	311033483.
Proteomic databases
PaxDb	Q12891.
PRIDE	Q12891.
Protocols and materials databases
DNASU	8692.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357750; ENSP00000350387; ENSG00000068001. ENST00000395139; ENSP00000378571; ENSG00000068001. ENST00000442581; ENSP00000406657; ENSG00000068001. ENST00000447092; ENSP00000401853; ENSG00000068001. ENST00000571614; ENSP00000460851; ENSG00000261921. ENST00000572136; ENSP00000458862; ENSG00000261921. ENST00000575564; ENSP00000461372; ENSG00000261921. ENST00000576042; ENSP00000460938; ENSG00000261921.
GeneID	8692.
KEGG	hsa:8692.
UCSC	uc003czv.3. human.
Organism-specific databases
CTD	8692.
GeneCards	GC03M050355.
H-InvDB	HIX0003314.
HGNC	HGNC:5321. HYAL2.
HPA	HPA036436.
MIM	603551. gene.
neXtProt	NX_Q12891.
PharmGKB	PA29572.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77606.
HOGENOM	HOG000015133.
HOVERGEN	HBG052053.
InParanoid	Q12891.
KO	K01197.
OMA	GWGGEQC.
OrthoDB	EOG4H463X.
PhylomeDB	Q12891.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00926-MONOMER.
BRENDA	4.2.2.1. 2681.
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
ArrayExpress	Q12891.
Bgee	Q12891.
CleanEx	HS_HYAL2.
Genevestigator	Q12891.
GermOnline	ENSG00000068001. Homo sapiens.
Family and domain databases
Gene3D	3.20.20.70. 1 hit.
InterPro	IPR013785. Aldolase_TIM. IPR000742. EG-like_dom. IPR017853. Glycoside_hydrolase_SF. IPR018155. Hyaluronidase. [Graphical view]
PANTHER	PTHR11769. PTHR11769. 1 hit.
Pfam	PF01630. Glyco_hydro_56. 1 hit. [Graphical view]
PIRSF	PIRSF038193. Hyaluronidase. 1 hit.
PRINTS	PR00846. GLHYDRLASE56.
SMART	SM00181. EGF. 1 hit. [Graphical view]
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. False negative. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL4952.
DrugBank	DB00070. Hyaluronidase.
GenomeRNAi	8692.
NextBio	32597.
SOURCE	Search...

Entry information

Entry name

HYAL2_HUMAN

Accession

Primary (citable) accession number: Q12891
Secondary accession number(s): B3KRZ2, O15177, Q9BW29

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

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.