Reviewed, UniProtKB/Swiss-Prot Q6YGZ1 (HPSE_MOUSE)

Names and origin

Protein names

Recommended name:
    Heparanase
    EC=3.2.-.-
Alternative name(s):
    Endo-glucoronidase
Cleaved into the following 2 chains:
    1- Recommended name:
            Heparanase 8 kDa subunit
    2- Recommended name:
            Heparanase 50 kDa subunit

Gene names

Name:	Hpse
Synonyms:	Hpa

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	535 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	Endoglycosidase which is a cell surface and extracellular matrix-degrading enzyme. Cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Also implicated in the extravasation of leukocytes and tumor cell lines. Contributes to metastasis and angiogenesis By similarity.
Enzyme regulation	Inhibited by EDTA and activated by calcium and magnesium By similarity. Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin.
Subunit structure	The active heterodimer is composed of the 8 and 50 kDa subunits, the proteolytic products. Ref.2
Subcellular location	Lysosome membrane; Peripheral membrane protein By similarity. Secreted By similarity. Note: Secreted, internalised and transferred to late endosomes/lysosomes as a proheparanase. In lysosomes, it is processed into the active form, the heparanase. The uptake or internalisation of proheparanase is mediated by HSPGs. Heparin appears to be a competitor and retain proheparanase in the extracellular medium By similarity.
Post-translational modification	Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, 8 kDa and 50 kDa product. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme By similarity. N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility. Ref.2
Sequence similarities	Belongs to the glycosyl hydrolase 79 family.
biophysicochemical properties	pH dependence: Optimum pH is 5.

Ontologies

Keywords
Cellular component	Lysosome Membrane Secreted
Domain	Signal
Ligand	Calcium Magnesium
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Cellular component	lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix Ref.1 Traceable author statement. Source: MGI
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW hydrolase activity, acting on glycosyl bonds Inferred from electronic annotation. Source: InterPro magnesium ion binding 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 – 27	27	By similarity
	Chain	28 – 101	74	Heparanase 8 kDa subunit		PRO_0000042263
	Propeptide	102 – 149	48	Linker peptide By similarity		PRO_0000042264
	Chain	150 – 535	386	Heparanase 50 kDa subunit		PRO_0000042265
Regions
	Region	150 – 154	5	Heparin/HS-binding By similarity
	Region	262 – 272	11	Heparin/HS-binding By similarity
Sites
	Active site	217	1	Proton donor Potential
	Active site	335	1	Nucleophile Potential
Amino acid modifications
	Glycosylation	154	1	N-linked (GlcNAc...)
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	230	1	N-linked (GlcNAc...) Potential
	Glycosylation	451	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	206	1	K → R in AAN41636. Ref.3
	Sequence conflict	212	1	W → S in AAN41636. Ref.3
	Sequence conflict	230 – 232	3	NGS → DGL Ref.1
	Sequence conflict	230 – 232	3	NGS → DGL Ref.2
	Sequence conflict	230 – 232	3	NGS → DGL Ref.4
	Sequence conflict	335	1	E → K in AAN41636. Ref.3
	Sequence conflict	342	1	G → A in AAN41636. Ref.3
	Sequence conflict	455	1	Y → H Ref.1
	Sequence conflict	455	1	Y → H Ref.2
	Sequence conflict	455	1	Y → H Ref.4
	Sequence conflict	531	1	V → I Ref.1
	Sequence conflict	531	1	V → I Ref.2
	Sequence conflict	531	1	V → I Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q6YGZ1-1 [UniParc]. Last modified October 11, 2005. Version 2. Checksum: AF19B28B7CD03F7B	FASTA	535	60,050
	10 20 30 40 50 60 MLRLLLLWLW GPLGALAQGA PAGTAPTDDV VDLEFYTKRP LRSVSPSFLS ITIDASLATD 70 80 90 100 110 120 PRFLTFLGSP RLRALARGLS PAYLRFGGTK TDFLIFDPDK EPTSEERSYW KSQVNHDICR 130 140 150 160 170 180 SEPVSAAVLR KLQVEWPFQE LLLLREQYQK EFKNSTYSRS SVDMLYSFAK CSGLDLIFGL 190 200 210 220 230 240 NALLRTPDLR WNSSNAQLLL DYCSSKGYNI SWELGNEPNS FWKKAHILIN GSQLGEDFVE 250 260 270 280 290 300 LHKLLQRSAF QNAKLYGPDI GQPRGKTVKL LRSFLKAGGE VIDSLTWHHY YLNGRIATKE 310 320 330 340 350 360 DFLSSDVLDT FILSVQKILK VTKEITPGKK VWLGETSSAY GGGAPLLSNT FAAGFMWLDK 370 380 390 400 410 420 LGLSAQMGIE VVMRQVFFGA GNYHLVDENF EPLPDYWLSL LFKKLVGPRV LLSRVKGPDR 430 440 450 460 470 480 SKLRVYLHCT NVYHPRYQEG DLTLYVLNLH NVTKYLKVPP PLFRKPVDTY LLKPSGPDGL 490 500 510 520 530 LSKSVQLNGQ ILKMVDEQTL PALTEKPLPA GSALSLPAFS YGFFVIRNAK VAACI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis." Hulett M.D., Freeman C., Hamdorf B.J., Baker R.T., Harris M.J., Parish C.R. Nat. Med. 5:803-809(1999) [PubMed: 10395326] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: SJL/J. Tissue: Spleen.
[2]	"Cloning, expression, and purification of mouse heparanase." Miao H.-Q., Navarro E., Patel S., Sargent D., Koo H., Wan H., Plata A., Zhou Q., Ludwig D., Bohlen P., Kussie P. Protein Expr. Purif. 26:425-431(2002) [PubMed: 12460766] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 28-57 AND 150-179, GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT. Strain: FVB. Tissue: Embryo.
[3]	"Processing of macromolecular heparin by heparanase." Gong F., Jemth P., Galvis M.L.E., Vlodavsky I., Horner A., Lindahl U., Li J.-P. J. Biol. Chem. 278:35152-35158(2003) [PubMed: 12837765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Thymus.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF359507 mRNA. Translation: AAQ15188.1. AY077467 mRNA. Translation: AAL76083.1. AY151051 mRNA. Translation: AAN41636.1. AK040471 mRNA. Translation: BAC30600.1. AK154628 mRNA. Translation: BAE32725.1.
IPI	IPI00170098.
RefSeq	NP_690016.1.
UniGene	Mm.265786
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GH79. Glycoside Hydrolase Family 79.
PTM databases
PhosphoSite	Q6YGZ1.
Genome annotation databases
Ensembl	ENSMUSG00000035273. Mus musculus. [Contig view]
GeneID	15442.
KEGG	mmu:15442.
Organism-specific databases
MGI	MGI:1343124. Hpse.
Phylogenomic databases
HOGENOM	Q6YGZ1.
HOVERGEN	Q6YGZ1.
Gene expression databases
ArrayExpress	Q6YGZ1.
Bgee	Q6YGZ1.
CleanEx	MM_HPSE.
GermOnline	ENSMUSG00000035273. Mus musculus.
Family and domain databases
InterPro	IPR005199. Glyco_hydro_79_N. [Graphical view]
PANTHER	PTHR14363. Glyco_hydro_79_N. 1 hit.
Pfam	PF03662. Glyco_hydro_79n. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	288230.
SOURCE	Search...

Entry information

Entry name

HPSE_MOUSE

Accession

Primary (citable) accession number: Q6YGZ1
Secondary accession number(s): Q8K3K3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	October 11, 2005
Last modified:	April 14, 2009
This is version 39 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)