Reviewed, UniProtKB/Swiss-Prot Q71RP1 (HPSE_RAT)

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:	Hep

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	536 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 laminarin sulfate and, to a lower extent, by heparin and sulfamin By similarity. Activated by calcium and magnesium. Inhibited by EDTA.
Subunit structure	The active heterodimer is composed of the 8 and 50 kDa subunits, the proteolytic products By similarity.
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 By similarity.
Sequence similarities	Belongs to the glycosyl hydrolase 79 family.

Ontologies

Keywords
Cellular component	Lysosome Membrane Secreted
Domain	Signal
Ligand	Calcium Magnesium
Molecular function	Hydrolase
PTM	Glycoprotein
Gene Ontology (GO)
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW heparanase activity Ref.2 Inferred from direct assay. Source: RGD 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 – 28	28	By similarity
	Chain	29 – 102	74	Heparanase 8 kDa subunit		PRO_0000042266
	Propeptide	103 – 150	48	Linker peptide By similarity		PRO_0000042267
	Chain	151 – 536	386	Heparanase 50 kDa subunit		PRO_0000042268
Regions
	Region	151 – 155	5	Heparin/HS-binding By similarity
	Region	263 – 273	11	Heparin/HS-binding By similarity
Sites
	Active site	218	1	Proton donor Potential
	Active site	336	1	Nucleophile Potential
Amino acid modifications
	Glycosylation	155	1	N-linked (GlcNAc...) By similarity
	Glycosylation	193	1	N-linked (GlcNAc...) By similarity
	Glycosylation	210	1	N-linked (GlcNAc...) By similarity
	Glycosylation	452	1	N-linked (GlcNAc...) By similarity
Experimental info
	Sequence conflict	15	1	G → R in AAF04563. Ref.2
	Sequence conflict	227	1	H → Q in AAF04563. Ref.2
	Sequence conflict	350	1	D → N in AAF04563. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q71RP1-1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: C434E04CF536EA4D	FASTA	536	60,480
	10 20 30 40 50 60 MLRPLLLLWL WGRLGALTQG TPAGTAPTKD VVDLEFYTKR LFQSVSPSFL SITIDASLAT 70 80 90 100 110 120 DPRFLTFLGS PRLRALARGL SPAYLRFGGT KTDFLIFDPN KEPTSEERSY WQSQDNNDIC 130 140 150 160 170 180 GSERVSADVL RKLQMEWPFQ ELLLLREQYQ REFKNSTYSR SSVDMLYSFA KCSRLDLIFG 190 200 210 220 230 240 LNALLRTPDL RWNSSNAQLL LNYCSSKGYN ISWELGNEPN SFWKKAHISI DGLQLGEDFV 250 260 270 280 290 300 ELHKLLQKSA FQNAKLYGPD IGQPRGKTVK LLRSFLKAGG EVIDSLTWHH YYLNGRVATK 310 320 330 340 350 360 EDFLSSDVLD TFILSVQKIL KVTKEMTPGK KVWLGETSSA YGGGAPLLSD TFAAGFMWLD 370 380 390 400 410 420 KLGLSAQLGI EVVMRQVFFG AGNYHLVDEN FEPLPDYWLS LLFKKLVGPK VLMSRVKGPD 430 440 450 460 470 480 RSKLRVYLHC TNVYHPRYRE GDLTLYVLNL HNVTKHLKLP PPMFSRPVDK YLLKPFGSDG 490 500 510 520 530 LLSKSVQLNG QTLKMVDEQT LPALTEKPLP AGSSLSVPAF SYGFFVIRNA KIAACI

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]. Tissue: Placenta.
[2]	"Characterization of heparanase from a rat parathyroid cell line." Podyma-Inoue K.A., Yokote H., Sakaguchi K., Ikuta M., Yanagishita M. J. Biol. Chem. 277:32459-32465(2002) [PubMed: 12077130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF359508 mRNA. Translation: AAQ15189.1. AF184967 mRNA. Translation: AAF04563.1.
IPI	IPI00214945.
RefSeq	NP_072127.1.
UniGene	Rn.6392
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GH79. Glycoside Hydrolase Family 79.
Genome annotation databases
Ensembl	ENSRNOG00000002188. Rattus norvegicus. [Contig view]
GeneID	64537.
KEGG	rno:64537.
Organism-specific databases
RGD	61969. Hpse.
Phylogenomic databases
HOVERGEN	Q71RP1.
Gene expression databases
ArrayExpress	Q71RP1.
GermOnline	ENSRNOG00000002188. Rattus norvegicus.
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	613394.

Entry information

Entry name

HPSE_RAT

Accession

Primary (citable) accession number: Q71RP1
Secondary accession number(s): Q9QZF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	July 5, 2004
Last modified:	June 16, 2009
This is version 36 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)